Bioscientist Issue 6 - Aligning with Innovation

THE SALFORD BIOMEDICINE SOCIETY MAGAZINE

OCT 2024 | ISSUE 6

A LIGNING WITH I NNOVATION

Charles delves into the risks and benefits of machine learning in cardiovascular research.

Julia highlights the importance of conscious sustainable choices for a better tomorrow.

ISSUU.COM/BIOSCIENTISTMAGAZINE OPENJOURNALS.SALFORD.AC.UK/BIOSCIENTIST

Sara Alnasir Kassam and Wiktoria Wisniewska CO-EDITORS-IN-CHIEF

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The Bioscientist Magazine is now also an official Open Access Journal!

You can follow this link or scan the QR code below to access the journal.

The Bioscientist Magazine Team has teamed up with the University of Salford’s Library Team to create a journal containing all the articles ever published within the Bioscientist Magazine.

The articles in this issue are intended for both leisure and supplementary reading. You may find some articles interesting and useful to use in your assignments. The journal now offers a chance for you to cite the article. Each article has been assigned a DOI to make citation easier. The articles are also searchable using the Library Search tool to help you find the articles.

We would love to hear your thoughts about the Magazine and the journal site. You may contact us via email on bioscientistmagazine@salford.ac.uk or you can use the contact form on the journal website.

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Dearest readers, old and new, of the Bioscientist Magazine.

It has been three years and three issues since we, Sara and Wiktoria, assumed the role of Co-Editors-in-Chief of the Bioscientist.

It has been an utmost pleasure to take over from the previous editors, bring our new perspectives forward, and see the publication soar to new heights under our tenure.

Some of our highlights include the transition of the publication from a digital magazine to a Diamond Open Access Journal, which requires maintaining a high standard via peer reviewing. Our student publication was featured in the inaugural Salford Authors events, where we spoke about the publication’s journey up until that point. Our recent issue has seen the largest writer pool so far, and our issues continue to feature a plethora of internal as well as external contributors for our writers to connect with.

We have sincerely enjoyed carrying the legacy established by our legacy editors. We hope that we have done well to maintain the standards that were set all the way back in 2020.

As we continue our professional development, we have made a decision to collectively step back from our roles and pass over the roles to new and enthusiastic editors - Dilruba Boksh and Noor Ali Najam. We trust that they will continue to expand the magazine's potential and we have absolutely no doubts that the legacy will carry on.

Thank you for your continued support and we hope to see more and more of you working closely with Dilruba and Noor to take the publication to newer heights.

Sara A Kassam & Wiktoria Wisniewska Co-editors-in-chief Bioscientist: The Salford Biomedicine Society Magazine

Pictured: Dilruba Boksh (on the left) Noor-ul-Ain Ali Najam (on the right)

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BIOSCIENTIST MAGAZINE

CONTENTS I EDITORS' NOTE II PUBLICATION PLATFORM III SPECIAL ANNOUNCEMENT

42

BIOMEDICINE 2 SCIENCE IN THE NEWS

100

Ozempic and weight loss Food safety assurancde using bacteriophages Mapping the infection pathways in a placenta Neuralink and dementia Ancient DNA - bethics with sequencing the DNA of extinct species

26 RESEARCH SPOTLIGHT

20

Using bioluminescence in MRI New screening trial for prostate cancer Pregabalin

35 TOPICS IN BIOMEDICINE

2 26 BIOLUMINESCENCE IN MRI Explore how bioluminescence allows MRI to be a non-invasive diagnostic tool

An insight into clinical trials: perpsectives and practices Recreational drug use and it’s ethical impacts on fertility Challenging the physiology we see in film Ethics in Biological Sciences Explained Sustainable development goals AI in cardiovascular research

SALFORD SCIENCE

58

58 THE ETHICAL IMPLICATIONS OF AI

AI IN HEALTHCARE

62 INFLUENCING PARLIAMENT TO

Discussing AI in healthcare with Prof Andy Miah

IN HEALTHCARE

SEE THE IMPORTANCE OF GENETICS

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BIOSCIENTIST MAGAZINE

SALFORD SCIENCE

THE BIOMEDICINE SOCIETY

65 ACCESS GRANTED

96 PRESIDENT’S ROUND UP

68 FOETAL ALCOHOL SPECTRUM

97 BIODEBATE

DISORDER

71 CELASTROL AS A POTENTIAL

PHARMACEUTICAL FOR MEDULLOBLASTOMA THERAPY

98 EVENTS ROUND UP WITH BEHIND THE SCENES

99 BIOART COMPETITON

100 FEAR AND TRIUMPH CAREERS

101 BIOSPORTS ROUNDUP 102 12HR BOOK CLUB CHALLENGE

75 IDENTIFYING BLOOD GROUPS USING VR

78 THE NEED OF BIOMEDICAL SCIENTISTS TO HAVE THE RIGHT SKILLS

81 EMPLOYABILITY SKILLS

98

82 QUALIFYING AS A SCIENCE TEACHER

84 MILITARY HEALTHCARE ETHICS

STUDENTS 87 PROGRAMME LEADER’S ADDRESS 89 COFFEE WITH CAROLINE 91 MY PLACEMENT EXPERIENCE 92 BIOMEDICAL SCIENCE DAY 2024 94 MY JOURNEY TO SALFORD AS A DEGREE APPRENTICE

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89

75

COFFEE WITH CAROLINE

BLOOD GROUPING WITH VR

In conversation with Ashleigh Bowskill, discussing the theme of resilience and Dr Topham’s Coffee with Caroline support sessions

Discover how NHSBT uses a VRbased MetaVerse App to train biomedical scientists to perform blood grouping accurately

pg.2 SCIENCE IN THE NEWS Read about Ozempic and whether it is a weight loss drug that is truly effective, using bacteriophages to screen for disease causing organisms in food and the links between Elon Musk’s innovation Neuralink and neurodegenerative disease Dementia along with the use of placentas to explore pathways of infections in the human body.

pg.26 RESEARCH SPOTLIGHT A section highlighting novel research done in the last few years. Here you can discover how magnetic resonance imaging is enhanced through the use of bioluminescence, what the drug Pregabalin does and outlining the details on a new and potentially promising trial for prostate cancer.

pg.35 TOPICS IN BIOMEDICINE Let’s dive deeper into the fields of biomedicine.

Readers can explore topics such as United Nations Sustainable Development Goals, how AI is used in the cardiovascular research field, how physiology, portrayed in film, can be used in physiology education along with the ethical implications of recreational drug use on male fertility.

pg.58 SALFORD SCIENCE Insights from the academics, researchers and staff based at the University of Salford. Read about Prof Miah’s perspectives on AI in healthcare, how scientific research is affected by open access journal publishing, combatting childhood brain cancers with phytochemicals and the ethics linked with FASD.

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SCIENCE IN THE NEWS

Ozempic: Revolutionary Weight Loss Drug or Too Good to Be True?

BY IRAM SHAKIL

Abstract The drug Ozempic, also known as semaglutide, has gained popularity in recent years due to its rapid weight loss effects. It was first created as a treatment for patients with type 2 diabetes suffering with obesity.

Numerous studies including metaanalyses have found that semaglutide is effective in achieving weight loss but also has adverse gastrointestinal effects such as nausea, diarrhoea and vomiting.

It has been seen to influence the brain, as semaglutide crosses the blood-brain barrier to reduce satiety centres that in turn reduce appetite, which further supports weight loss.

Although semaglutide has adverse effects, some studies have shown that it may help patients who have cardiovascular disease reduce cardiovascular events such as myocardial infarction. Ozempic has been proven to be effective as a weight loss treatment despite its side effects and more studies are being done to see how long-term use may affect patients.

What is Ozempic and how does it work?

Ozempic is the brand name for the glucagon-like peptide-1 (GLP-1) agonist semaglutide made by the company Novo Nordisk¹³.

Ozempic was recently approved for human consumption by the US Food and Drug Association (FDA) in 2021⁴. Its main medical use is as a drug to help patients manage type 2 diabetes⁶.

Semaglutide has gained popularity over the last few years as a weight loss treatment for those without type 2 diabetes too through prescription from a doctor.

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It was developed from a previously used GLP-1 agonist, liraglutide, made by the same company e-company¹¹. However, liraglutide must be administered through daily injections, while semaglutide can be administered weekly due to its longer halflife. It can also be administered orally when given with the absorption enhancer sodium N-[8-(2-hydroxybenzoyl) aminocaprylate (SNAC). Semaglutide is a peptide that has a similar structure to the human (GLP-1) receptor. GLP-1 stimulates the secretion of insulin and inhibits glucagon without causing hypoglycaemia⁹. However, GLP-1 has a short half-life of only a few minutes so GLP-1 agonists like semaglutide were developed to help patients with type 2 diabetes lose weight quicker. These agonists also delay gastric emptying and reduce appetite by inducing satiety. They stimulate satiety in the brain directly, through crossing the blood-brain barrier and indirectly through neural afferents¹⁵.

How effective is Ozempic for weight loss?

Numerous studies have been conducted to evaluate the efficacy of semaglutide for weight loss. A meta-analysis was carried out to discover the effects of semaglutide for weight loss in patients without type 2 diabetes.

Four studies with 3,613 participants were analysed¹⁵. Across the studies 2,350 were given semaglutide and 1,263 were given a placebo. The metaanalysis found that there was an 11.85% mean difference in weight loss between the semaglutide and placebo groups across all four trials. This shows that semaglutide causes significant weight loss compared to the placebo so is effective for people without type 2 diabetes. Another study showed that semaglutide also effects energy intake as lunch energy intake was 35% lower in the semaglutide group compared to the placebo group³.

It also showed that there was a lower intake of energy of high fat foods meaning semaglutide reduces appetite and hunger.

Metabolic rate did not differ between treatments showing that weight loss was not due to increased energy expenditure but rather a decrease in energy intake.

However, weight was shown to have come back after discontinuing the treatment, meaning patients must take semaglutide permanently to retain the weight loss, this is known as ‘Ozempic rebound’ although it can come about with any brand of semaglutide¹⁴.

What

are

the

advantages

and

disadvantages of taking Ozempic?

The advantages and disadvantages of semaglutide were analysed to understand its side effects and whether any significant harm could come to patients who take it.

A review on the risk of developing gastrointestinal adverse effects showed that the semaglutide group were 1.59 times more likely to develop these compared to the placebo group¹⁵. Over the four trials the semaglutide group were more twice as likely to stop treatment due to these adverse effects, 6% of the semaglutide group discontinued use compared to only 2.9% of the placebo group. Another study found that nausea was the most common side effect found in patients who were prescribed semaglutide at 44%¹⁰. Other adverse effects were found such as diarrhoea, vomiting and abdominal pain affecting 30%, 24% and 20% respectively in clinical trials. A real-life study found that 49% of patients experienced adverse effects which caused 3% of patients to discontinue treatment resulting in less weight loss⁵. In laboratory mice it was found that some developed thyroid C-cell tumours which was because of higher doses of semaglutide administered¹⁰. This means people with a family history of medullary thyroid carcinoma are discouraged from taking semaglutide¹².

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Long-term studies show that after 1 year 24%-26% baseline weight was lost compared to only 15%-17% baseline weight after 10 years⁷. An advantage of taking semaglutide include the evidence of it reducing cardiovascular events in patients with type 2 diabetes¹. A SELECT trial suggested that semaglutide may have an impact on cardiovascular events in obese patients without type 2 diabetes, but the results of this trial are yet to be published⁸.

These trials showed that major adverse cardiovascular events were reduced by 20% in those taking semaglutide but admits more research is needed to assess the risks of semgalutide as a treatment for this.

Semaglutide also proves to be more effective than other Type 2 diabetes treatments such as metformin and thiazolidinediones as it induced more weight loss without the risk of hypoglycaemia².

Although these advantageous effects lifestyle changes should also be made such as eating healthier as these are important in tackling obesity too.

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Conclusion In conclusion, Ozempic (semaglutide) is shown to be a viable option for weight loss both in people with and without type 2 diabetes. Although, there are adverse side effects such as nausea, vomiting and diarrhoea there are benefits to taking Ozempic. Along with the weight loss semaglutide has been seen to reduce cardiovascular effects. However, some of these studies have been funded by Novo Nordisk so there may be some bias and hesitation with publishing any negative results. Ozempic has been proven to be effective in short-term trials, but more longterm studies need to be done to fully understand the effects of semaglutide on patients with and without type 2 diabetes.

The SELECT trial will be the first trial to evaluate this and its results are set to be published soon⁸. As Ozempic is being approved for adolescents, more research is being done to assess the paediatric benefits and limitations of semaglutide for the treatment of paediatric obesity¹⁶.

References: 1.

Amaro, A., Sugimoto, D., & Wharton, S. (2022). Efficacy and safety of semaglutide for weight management: evidence from the STEP program.

Postgrad Med, 134(sup1), 5-17. https://doi.org/10.1080/00325481.2022.2147326 2.

Aroda, V. R., Ahmann, A., Cariou, B., Chow, F., Davies, M. J., Jódar, E., Mehta, R., Woo, V., & Lingvay, I. (2019). Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: Insights from the SUSTAIN 1-7 trials. Diabetes Metab, 45(5), 409418. https://doi.org/10.1016/j.diabet.2018.12.001 3.

Blundell, J., Finlayson, G., Axelsen, M., Flint, A., Gibbons, C., Kvist, T., & Hjerpsted, J. B. (2017). Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab, 19(9), 1242-1251. https://doi.org/10.1111/dom.12932 4.

Chao, A. M., Tronieri, J. S., Amaro, A., & Wadden, T. A. (2023).

Semaglutide for the treatment of obesity. Trends Cardiovasc Med, 33(3), 159-166. https://doi.org/10.1016/j.tcm.2021.12.008 5. Ghusn, W., De la Rosa, A., Sacoto, D., Cifuentes, L., Campos, A., Feris, F., Hurtado, M. D., & Acosta, A. (2022). Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity. JAMA Network Open, 5(9), e2231982e2231982. https://doi.org/10.1001/jamanetworkopen.2022.31982 6. Goldenberg, R. M., & Steen, O. (2019). Semaglutide: Review and Place in Therapy for Adults With Type 2 Diabetes. Can J Diabetes, 43(2), 136-145. https://doi.org/10.1016/j.jcjd.2018.05.008 7. Kanerva, N., Larsson, I., Peltonen, M., Lindroos, A. K., & Carlsson, L. M. (2017). Changes in total energy intake and macronutrient composition after bariatric surgery predict long-term weight outcome: findings from the Swedish Obese Subjects (SOS) study.

Am J Clin Nutr, 106(1), 136-145. https://doi.org/10.3945/ajcn.116.149112 8.

Lingvay, I., Brown-Frandsen, K., Colhoun, H. M., Deanfield, J., Emerson, S. S., Esbjerg, S., Hardt-Lindberg, S., Hovingh, G. K., Kahn, S. E., Kushner, R. F., Lincoff, A. M., Marso, S. P., Fries, T. M., Plutzky, J., Ryan, D. H., & Group, t. S. S. (2023). Semaglutide for cardiovascular event reduction in people with overweight or obesity: SELECT study baseline characteristics.

Obesity, 31(1), 111-122. https://doi.org/https://doi.org/10.1002/oby.23621 9.

Monami, M., Dicembrini, I., Marchionni, N., Rotella, C. M., & Mannucci, E. (2012). Effects of glucagon-like peptide-1 receptor agonists on body weight: a meta-analysis. Exp Diabetes Res, 2012, 672658. https://doi.org/10.1155/2012/672658 10. Moyad, M. A. (2023). Embracing the Pros and Cons of the New Weight Loss Medications (Semaglutide, Tirzepatide, Etc.). Current Urology Reports, 24(11), 515-525. https://doi.org/10.1007/s11934-02301180-7 11. Smits, M. M., & Van Raalte, D. H. (2021). Safety of Semaglutide.

Front Endocrinol (Lausanne), 12, 645563. https://doi.org/10.3389/fendo.2021.645563 12. Smits, M. M., & Van Raalte, D. H. (2021). Safety of Semaglutide [Review].

Frontiers in endocrinology, 12. https://www.frontiersin.org/journals/endocrinology/articles/10.3389 /fendo.2021.645563 13. Suran, M. (2023). As Ozempic's Popularity Soars, Here's What to Know About Semaglutide and Weight Loss. Jama, 329(19), 16271629. https://doi.org/10.1001/jama.2023.2438 14. Suran, M. (2023). As Ozempic’s Popularity Soars, Here’s What to Know About Semaglutide and Weight Loss. JAMA, 329(19), 16271629. https://doi.org/10.1001/jama.2023.2438 15. Tan, H. C., Dampil, O. A., & Marquez, M. M. (2022). Efficacy and Safety of Semaglutide for Weight Loss in Obesity Without Diabetes: A Systematic Review and Meta-Analysis. J ASEAN Fed Endocr Soc, 37(2), 65-72. https://doi.org/10.15605/jafes.037.02.14 Wahi, G., St-Pierre, J., Johnston, B. C., Fitzpatrick-Lewis, D., Usman, A., Sherifali, D., Merdad, R., Esmaeilinezhad, Z., Birken, C. S., Hamilton, J., Henderson, M., Moore, S. A., Ball, G. D. C., & Morrison, K. M. (2024). Effectiveness of pharmacological interventions for managing obesity in children and adolescents: A systematic review and meta-analysis framed using minimal important difference estimates based on GRADE guidance to inform a clinical practice guideline.

Pediatr Obes, e13169. https://doi.org/10.1111/ijpo.13169

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SCIENCE IN THE NEWS

Bacteriophages: A Natural and Effective tool for Foodborne Pathogens

BY UMMAD TARIQ

Abstract Food safety is a major concern around the world, with millions of people suffering from foodborne illnesses each year. Traditional techniques of ensuring food safety, such as pasteurisation and chemical preservatives, have limitations, prompting the search for new solutions.

Bacteriophages, which are viruses that particularly target and kill bacteria, represent a possible alternative. This article investigates the use of bacteriophages to improve food safety by describing their mechanisms of action, uses in different food industries, benefits over old approaches, and obstacles.

Bacteriophages are very selective to harmful bacteria, minimising contamination while neither hurting beneficial microbiota nor modifying food characteristics. ListShield™, a phage preparation, can efficiently decrease pathogens including Listeria, Salmonella, and E. coli in meat, poultry, fresh vegetables, dairy products, and seafood.

While bacteriophages provide a novel and natural alternative, regulatory constraints, potential bacterial resistance, and public image all pose barriers to their widespread implementation. Continued research and education are critical for overcoming these limitations and using bacteriophages to improve global food safety.

Food safety is a crucial global concern, with 600 million cases of people suffering from foodborne illnesses each year and 420,000 dying from them¹³. Traditional treatments, such as pasteurisation and chemical preservatives have proven useful, although they have limitations. Whilst pasteurisation is successful at killing many diseases, it can occasionally change the flavour, texture, and nutritional value of food¹⁸. Chemical preservatives, on the other hand, can cause the development of resistant bacterial strains and pose possible health hazards when consumed over time.

These resistant bacterial strains are detrimental to immunological health because they can render normal therapies ineffective, resulting in more severe and persistent infections that are difficult to cure³⁰.

For example, several bacterial strains recovered from seafood revealed that a large percentage of the isolates tested (75.86%) were resistant to at least one antibiotic or biocide, which is a type of chemical preservative used in food, with 6.90% resistant to at least three biocides and three antibiotics¹¹. Bacteriophages, viruses that specifically target and kill bacteria, are one novel option that is becoming increasingly popular.

This article investigates how bacteriophages can improve food safety, including their mechanisms, applications, and potential problems.

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What are Bacteriophages?

Bacteriophages are viruses that infect bacteria.

Discovered in the beginning of the 20th century, they are extremely specific to their bacterial hosts, making them suitable for targeting harmful bacteria while preserving beneficial microflora. These viruses strictly stick to the bacterial cells and introduce their own genetic material into them. The phage then hijacks the bacterial machinery and allows for viral replication, eventually leading to cell lysis and death².

As the number of phage particles inside the bacterium rises, the cell's structural integrity deteriorates. Finally, the bacterial cell lyses, or bursts, releasing a new generation of phages into the surrounding environment¹. These freshly generated phages can then infect neighbouring bacterial cells, repeating the cycle and effectively lowering bacterial numbers⁹.

As self-propagating antibacterial agents, when the cell ruptures, additional bacteriophages are released, which can infect other bacterial cells.

This cycle of infection and lysis enables bacteriophages to rapidly multiply at the site of infection, effectively eliminating specific bacterial populations. Their ability to selfreplicate provides a long-term antibacterial impact, as new waves of phages continue to target and eradicate remaining dangerous bacteria, potentially providing a broader and long-lasting treatment to bacterial infections than traditional antibiotics¹⁰. Furthermore, 59 clinical studies completed between 2000 and 2021 were evaluated and discovered that 79% of 1,904 patients with chronic and drugresistant infections improved after receiving phage treatment, while 87% of the target bacteria were eradicated in 1,461 cases³⁵.

Figure 1: A diagram showing the different stages a bacteriophage undergoes during the lytic cycle³

Mechanisms of Action Bacteriophages undergo a lytic cycle, which is a multi-step process that starts with the phage adhering to receptors on the bacterial cell surface³⁶. This attachment is extremely precise, frequently requiring interactions between phage tail fibres and bacterial surface proteins or polysaccharides³⁴. Once the phage has successfully attached, it injects its DNA into the host cell, causing the bacterial machinery to copy its genetic material and make phage proteins. During this stage, the bacterial cell's usual processes are disturbed as it is reprogrammed to form new phage particles⁹.

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Applications in Food Safety Meat and Poultry Processing Phages can be used on raw meat and poultry to minimise infections such as Salmonella and E. coli. Studies have demonstrated that using phages during processing reduces bacterial levels significantly¹². For example, a 90% reduction in Salmonella in chickens treated with a specific phage mixture was found¹⁴.

The most prevalent phages employed in these applications are those that target Salmonella, Listeria, and E. coli. Actual phages employed include Felix O1 and SJ2 for Salmonella, P100 for Listeria monocytogenes, and T4 and T7 for E. coli³⁷.

Furthermore, phage cocktails, which include many phages, can be more effective than single-phage therapies. This is because they can target a wider spectrum of bacterial strains within a species, lowering the risk of bacterial resistance and giving a more thorough strategy to bacterial eradication¹.

Phage cocktails take advantage of the unique processes of many phages, increasing the overall efficacy of the therapy and assuring a more powerful reduction in bacterial contamination².

In the case of cheese production, phages are added to milk or curds to eliminate unwanted bacteria that can outcompete or infect beneficial lactic acid bacteria. Phages contribute to the microbial ecosystem balance required for optimum cheese fermentation by lowering the population of spoilage bacteria²⁹. This leads to a more uniform product with improved texture, flavour, and safety. Furthermore, phages can be utilised selectively to target certain spoilage organisms while preserving the beneficial bacteria required for cheese manufacturing, improving the overall quality and safety of the finished product²⁹.

Seafood Phages can lower infections in raw and undercooked fish, including Vibrio species⁹. A study found that phage spraying reduced Vibrio vulnificus levels in oysters by 99%¹⁹.

Fresh Produce Contaminated fresh vegetables are a common cause of foodborne illness.

Phages can be sprayed on fruits and vegetables to kill surface germs, increasing shelf life, and ensuring safety³³. In a study, the use of phages on cantaloupes and apples drastically reduced Listeria monocytogenes numbers²⁰. .

Dairy Products Phages are used in cheese production to reduce spoilage bacteria, hence enhancing product quality and safety¹².

Bacteriophages have been employed successfully to treat lactic acid bacterial infections in cheese, resulting in a higherquality product⁵. Phages like phiIPLA-RODI and phage P008 are unique to Lactococcus and Lactobacillus species²³. These phages target spoilage bacteria, which may negatively affect cheese texture, flavour, and overall quality⁸.

Figure 2: An image of a bacteriophage-based tool, ListShield™, used to mitigate Listeria contamination in ready-to-eat foods using six naturally occurring bacteriophages, ListShield™ works by lysing Listeria bacteria without affecting food quality¹⁶.

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Fresh Produce: Contaminated fresh vegetables are a common cause of foodborne illness.

Phages can be sprayed on fruits and vegetables to kill surface germs, increasing shelf life, and ensuring safety³³. In a study, the use of phages on cantaloupes and apples drastically reduced Listeria monocytogenes numbers²⁰.

Dairy Products: Phages are used in cheese production to reduce spoilage bacteria, hence enhancing product quality and safety¹².

Bacteriophages have been employed successfully to treat lactic acid bacterial infections in cheese, resulting in a higherquality product⁵. Phages like phiIPLA-RODI and phage P008 are unique to Lactococcus and Lactobacillus species²³.

These phages target spoilage bacteria, which may negatively affect cheese texture, flavour, and overall quality⁸.

Reducing Antibiotic Resistance: Phage therapy offers a different treatment option compared to antibiotics, helping combat the growing issue of antibiotic resistance³³. Unlike antibiotics, which frequently exert broad selected pressure that might lead to widespread antibiotic resistance, phages are very particular in their target bacteria, reducing overall selective pressure on bacterial populations²¹. This selectivity helps to sustain beneficial bacteria and decreases the possibility of acquiring resistant strains.

However, it is crucial to remember that phage genomes are still not entirely known, and the topic of phage resistance requires further investigation⁶. Some bacteria can develop resistance to phages, and bacteriophages can transport resistance mechanisms between bacterial cells during infection. This means that, like antibiotics, phages have the potential to propagate resistance if not managed effectively²².

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Using phage cocktails, which are mixtures of different phages, can help mitigate this risk. Phage cocktails target multiple bacterial strains and reduce the likelihood of resistance developing, as it is more difficult for bacteria to simultaneously develop resistance to several phages³⁹.

Despite this, the possibility of resistance remains, and ongoing research is necessary to fully understand and address these concerns.

Challenges and Considerations Regulatory Hurdles: Regulatory approval for phage uses in food differs by area, with some needing rigorous testing to assure safety and efficacy¹². For example, the European Food Safety Authority (EFSA) sets strict standards for innovative food additives, which might hinder the approval process. For a food additive to be authorised, the EFSA requires detailed information about its identity, manufacturing process, chemical composition, stability, and reactivity and destiny in foods. This includes specific safety data, such as its genotoxic potential and other toxicological facts essential to its safety³⁸.

Phages must meet strict criteria to protect human health. The EFSA's Panel on Food additions and Flavourings (FAF) conducts safety evaluations, reviewing both novel additions and any new uses of existing additives. This extensive review method protects consumer health by guaranteeing that phages and other food additives do not harm food safety or quality³⁸.

Bacterial Resistance: Bacteria can develop resistance to both antibiotics and bacteriophages. It has been suggested that continued research and the development of phage combinations are necessary to prevent resistance⁹. Some researchers found that mixing numerous bacteriophages can reduce the probability of resistance²⁷.

This is because using a diverse cocktail of phages targets bacteria via various methods, making it more difficult for the bacteria to build resistance to all the phages in the mixture.

Public Perception: The acceptability of bacteriophages in food products is crucial. Educating the public about the safety and benefits of bacteriophages is critical for overcoming scepticism³³. It was found that, while consumers are first sceptical, education dramatically boosts acceptability²⁶. A variety of factors contribute to public scepticism of bacteriophages in food items, including a lack of information, safety concerns, issues about naturalness, and questions about efficacy¹⁵.

Many people are unfamiliar with bacteriophages and their significance in treating bacterial infections or improving food safety³¹. The concept of employing viruses, even good ones, is frequently misinterpreted, causing doubt²⁸.

Safety issues are also prominent, with some consumers concerned about the potential side effects or long-term health consequences of eating phage-treated foods¹⁵.

However, studies showed that educating consumers addressed the knowledge gaps in consumers by significantly improving the acceptance of phage-based treatments²⁵. While bacteriophages exist naturally in the environment and the human gut, many consumers prefer raw and minimally processed meals⁷.

Furthermore, there is scepticism about bacteriophages' efficacy, especially in compared to known techniques like as antibiotics or chemical preservatives⁷. People may be sceptical that phages can effectively replace established ways for combating bacterial contamination, which could hinder the adoption of phage-based therapies and goods.

To address public concerns about bacteriophages, educational campaigns are essential. Providing clear, accessible information on how phages work and emphasizing that they are naturally occurring in our environment and bodies can help reduce apprehension⁴.

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Sharing scientific data, such as research showing that phage intake has no harmful health impacts, can help to establish trust. For example, regulatory agencies like as the FDA and EFSA have previously approved phage applications as safe, which might be mentioned to comfort customers².

Transparency in how corporations utilise phages, combined with labelling that emphasises their natural and tailored effect, might also appeal to health-conscious customers, encouraging greater acceptance³³.

Phage Therapy in the UK Phage therapy is gaining popularity in the UK; however, it is not yet widely available. It is generally used in clinical settings to treat antibiotic-resistant infections, particularly when other therapies fail. Furthermore, phage therapy in the UK is overseen by health agencies such as the EFSA and must adhere to strict regulatory criteria to ensure safety and efficacy. Clinical research and compassionate use situations are closely monitored. When it comes to research and development, the UK is heavily involved in phage research, with several organisations like biotechnology companies investigating its applications in health and food safety²⁴.

The economic impact of phage therapy in the UK is expected to keep growing as antibiotic resistance becomes a more important concern. The global phage therapy market could generate hundreds of millions of pounds in revenue, driven by demand for innovative antimicrobial therapies and food safety solutions¹⁷.

Conclusion Bacteriophages represent a possible approach for improving food safety by addressing the limitations of previous technologies and providing a natural, effective means of combating foodborne diseases. Continued research, regulatory support, and public education are critical to the widespread application of phage technology in the food business. These developments may make phage applications more practical and acceptable, potentially revolutionising both food safety and medical treatments.

References 1. Abd-Allah, I. M., El-Housseiny, G. S., Yahia, I. S., Aboshanab, K. M., & Hassouna, N. A.(2021). Rekindling of a Masterful Precedent; Bacteriophage: Reappraisal and Future Pursuits [Review]. Frontiers in Cellular and Infection Microbiology, 11. https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2021.635597 2. Abedon, S. T., Danis-Wlodarczyk, K. M., & Wozniak, D. J. (2021). Phage Cocktail Development for Bacteriophage Therapy: Toward Improving Spectrum of Activity Breadth and Depth. Pharmaceuticals, 14(10).

3. Adesanya, O., Oduselu, T., Akin-Ajani, O., Adewumi, O. M., & Ademowo, O. G. (2020). An exegesis of bacteriophage therapy: An emerging player in the fight against anti-microbial resistance. AIMS Microbiology, 6(3), 204-230. https://doi.org/10.3934/microbiol.2020014 4. Batinovic, S., Wassef, F., Knowler, S. A., Rice, D. T. F., Stanton, C. R., Rose, J., Tucci, J., Nittami, T., Vinh, A., Drummond, G. R., Sobey, C. G., Chan, H. T., Seviour, R. J., Petrovski, S., & Franks, A. E. (2019).

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8. Fernández, L., Escobedo, S., Gutiérrez, D., Portilla, S., Martínez, B., García, P., & Rodríguez, A. (2017). Bacteriophages in the Dairy Environment: From Enemies to Allies. Antibiotics, 6(4).

9. García, P., Martínez, B., Obeso, J. M., & Rodríguez, A. (2008). Bacteriophages and their application in food safety. Letters in Applied Microbiology, 47(6), 479-485. https://doi.org/10.1111/j.1472765X.2008.02458.x 10. García, R., Latz, S., Romero, J., Higuera, G., García, K., & Bastías, R. (2019). Bacteriophage Production Models: An Overview [Mini Review]. Frontiers in Microbiology, https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.01187 11. Giacometti, F., Shirzad-Aski, H., & Ferreira, S. (2021). Antimicrobials and Food-Related Stresses as Selective Factors for Antibiotic Resistance along the Farm to Fork Continuum. Antibiotics, 10(6).

12. Hagens, S., & Loessner, M. J. (2007). Application of bacteriophages for detection and control of foodborne pathogens. Applied Microbiology and Biotechnology, 76(3), 513-519. https://doi.org/10.1007/s00253-007-1031-8 13. Havelaar, A. H., Kirk, M. D., Torgerson, P. R., Gibb, H. J., Hald, T., Lake, R. J., Praet, N., Bellinger, D. C., de Silva, N. R., Gargouri, N., Speybroeck, N., Cawthorne, A., Mathers, C., Stein, C., Angulo, F. J., Devleesschauwer, B., & on behalf of World Health Organization Foodborne Disease Burden Epidemiology Reference, G. (2015). World Health Organization Global Estimates and Regional Comparisons of the Burden of Foodborne Disease in 2010. PLoS Medicine, 12(12), e1001923. https://doi.org/10.1371/journal.pmed.1001923 14. Higgins, J. P., Higgins, S. E., Guenther, K. L., Huff, W., Donoghue, A. M., Donoghue, D. J., & Hargis, B. M. (2005). Use of a specific bacteriophage treatment to reduce Salmonella in poultry products12.

Poultry Science, 84(7), 1141-1145. https://doi.org/https://doi.org/10.1093/ps/84.7.1141 15. Imran, A., Shehzadi, U., Islam, F., Afzaal, M., Ali, R., Ali, Y. A., Chauhan, A., Biswas, S., Khurshid, S., Usman, I., Hussain, G., Zahra, S. M., Shah, M. A., & Rasool, A. (2023). Bacteriophages and food safety: An updated overview. Food Science & Nutrition, 11(7), 3621-3630. https://doi.org/https://doi.org/10.1002/fsn3.3360 16. Intralytix Inc. (2024). Bacteriophage Home - Intralytix, Inc. Retrieved 02/10/2024 from https://www.intralytix.com/ 17. Jones, J. D., Trippett, C., Suleman, M., Clokie, M. R. J., & Clark, J. R. (2023). The Future of Clinical Phage Therapy in the United Kingdom. Viruses, 15(3).

18. Koutsoumanis, K., Alvarez-Ordóñez, A., Bolton, D., Bover-Cid, S., Chemaly, M., Davies, R., De Cesare, A., Herman, L., Hilbert, F., Lindqvist, R., Nauta, M., Peixe, L., Ru, G., Simmons, M., Skandamis, P., Suffredini, E., Castle, L., Crotta, M., Grob, K., . . . Efsa Panel on Biological Hazards. (2022). The efficacy and safety of high-pressure processing of food. EFSA Journal, 20(3), e07128. https://doi.org/10.2903/j.efsa.2022.7128 19. Letchumanan, V., Chan, K.-G., Pusparajah, P., Saokaew, S., Duangjai, A., Goh, B.-H., Ab Mutalib, N.-S., & Lee, L.-H. (2016). Insights into Bacteriophage Application in Controlling Vibrio Species [Review].

Frontiers in Microbiology, 7. https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2016.01114 20. Leverentz, B., Conway, W. S., Alavidze, Z., Janisiewicz, W. J., Fuchs, Y., Camp, M. J., Chighladze, E., & Sulakvelidze, A. (2001). Examination of Bacteriophage as a Biocontrol Method for Salmonella on Fresh-Cut Fruit: A Model Study. Journal of Food Protection, 64(8), 1116-1121. https://doi.org/https://doi.org/10.4315/0362-028X-64.8.1116 21. Li, N., Zeng, Y., Wang, M., Bao, R., Chen, Y., Li, X., Pan, J., Zhu, T., Hu, B., & Tan, D. (2022). Characterization of Phage Resistance and Their Impacts on Bacterial Fitness in Pseudomonas aeruginosa.

Microbiology Spectrum, 10(5), e02072-02022. https://doi.org/10.1128/spectrum.02072-22 22. Lin, D. M., Koskella, B., & Lin, H. C. (2017). Phage therapy: An alternative to antibiotics in the age of multi-drug resistance. World J Gastrointest Pharmacol Ther, 8(3), 162-173. https://doi.org/10.4292/wjgpt.v8.i3.162 23. Lv, R., Gao, X., Zhang, C., Lian, W., Quan, X., Guo, S., & Chen, X. (2023). Characteristics and Whole-Genome Analysis of Limosilactobacillus fermentum Phage LFP02. Foods, 12(14).

24. Mboowa, G. (2023). Reviewing the journey to the clinical application of bacteriophages to treat multi-drug-resistant bacteria. BMC Infectious Diseases, 23(1), 654. https://doi.org/10.1186/s12879-023-08621-1 25. McCammon, S., Makarovs, K., Banducci, S., & Gold, V. (2023). Phage therapy and the public: Increasing awareness essential to widespread use. PLoS ONE, 18(5), e0285824.https://doi.org/10.1371/journal.pone.0285824 26. Moye, Z. D., Woolston, J., & Sulakvelidze, A. (2018). Bacteriophage Applications for Food Production and Processing. Viruses, 10(4).

27. Oechslin, F. (2018). Resistance Development to Bacteriophages Occurring during Bacteriophage Therapy. Viruses, 10(7).

28. Principi, N., Silvestri, E., & Esposito, S. (2019). Advantages and Limitations of Bacteriophages for the Treatment of Bacterial Infections [Review]. Frontiers in Pharmacology, 10. https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00513 29. Ranveer, S. A., Dasriya, V., Ahmad, M. F., Dhillon, H. S., Samtiya, M., Shama, E., Anand, T., Dhewa, T., Chaudhary, V., Chaudhary, P., Behare, P., Ram, C., Puniya, D. V., Khedkar, G. D., Raposo, A., Han, H., & Puniya, A. K. (2024). Positive and negative aspects of bacteriophages and their immense role in the food chain. npj Science of Food, 8(1), 1. https://doi.org/10.1038/s41538-023-00245-8 30. Salam, M. A., Al-Amin, M. Y., Salam, M. T., Pawar, J. S., Akhter, N., Rabaan, A. A., & Alqumber, M. A. A. (2023). Antimicrobial Resistance: A Growing Serious Threat for Global Public Health. Healthcare, 11(13).

31. Sillankorva, S. M., Oliveira, H., & Azeredo, J. (2012). Bacteriophages and Their Role in Food Safety. International Journal of Microbiology, 2012(1), 863945. https://doi.org/https://doi.org/10.1155/2012/863945 32. Sulakvelidze, A., Alavidze, Z., & Morris, J. G. (2001). Bacteriophage Therapy. Antimicrobial agents and chemotherapy, 45(3), 649-659. https://doi.org/10.1128/aac.45.3.649-659.2001 33. Summers, W. C. (2001). Bacteriophage Therapy. Annual Review of Microbiology, 55(Volume 55, 2001), 437-451. https://doi.org/10.1146/annurev.micro.55.1.437 34. Taslem Mourosi, J., Awe, A., Guo, W., Batra, H., Ganesh, H., Wu, X., & Zhu, J. (2022). Understanding Bacteriophage Tail Fiber Interaction with Host Surface Receptor: The Key “Blueprint” for Reprogramming Phage Host Range. International journal of molecular sciences, 23(20).

35. Uyttebroek, S., Chen, B., Onsea, J., Ruythooren, F., Debaveye, Y., Devolder, D., Spriet, I., Depypere, M., Wagemans, J., Lavigne, R., Pirnay, J.-P., Merabishvili, M., De Munter, P., Peetermans, W. E., Dupont, L., Van Gerven, L., & Metsemakers, W.-J. (2022). Safety and efficacy of phage therapy in difficult-to-treat infections: a systematic review. The Lancet Infectious Diseases, 22(8), e208-e220. https://doi.org/10.1016/S1473-3099(21)00612-5 36. Venturini, C., Petrovic Fabijan, A., Fajardo Lubian, A., Barbirz, S., & Iredell, J. (2022). Biological foundations of successful bacteriophage therapy. EMBO Molecular Medicine, 14(7), e12435. https://doi.org/https://doi.org/10.15252/emmm.202012435 37. Vinner, G. K., Rezaie-Yazdi, Z., Leppanen, M., Stapley, A. G. F., Leaper, M. C., & Malik, D.J. (2019). Microencapsulation of Salmonella-Specific Bacteriophage Felix O1 Using Spray-Drying in a pHResponsive Formulation and Direct Compression Tableting of Powders into a Solid Oral Dosage Form. Pharmaceuticals, 12(1).

38. Younes, M., Aquilina, G., Castle, L., Degen, G., Fowler, P. J., Fernandez, M. J. F., Fürst, P., Gundert-Remy, U., Gürtler, R., Husøy, T., Manco, M., Mennes, W., Moldeus, P., Passamonti, S., Shah, R., WaalkensBerendsen, I., Wölfle, D., Wright, M., Benigni, R., . . Efsa Panel on Food Additives Flavourings. (2022). Scientific Guidance on the data required for the risk assessment of flavourings to be used in or on foods. EFSA Journal, 20(12), e07673. https://doi.org/https://doi.org/10.2903/j.efsa.2022.7673 39. Zou, X., Xiao, X., Mo, Z., Ge, Y., Jiang, X., Huang, R., Li, M., Deng, Z., Chen, S., Wang, L., & Lee, S. Y. (2022). Systematic strategies for developing phage resistant Escherichia coli strains. Nature Communications, 13(1), 4491. https://doi.org/10.1038/s41467-022-31934-9

SCIENCE IN THE NEWS

Mapping the Infection Pathways in Human Placentas

BY OMOTOYOSI OSALAYE

Abstract This review explores the intricate mechanisms by which pathogens breach the placental barrier, a critical interface between mother and foetus. Despite its robust defensive structures, including the syncytiotrophoblast and underlying tissues, various microorganisms have evolved strategies to penetrate this barrier, leading to severe maternal and foetal health complications. The article examines three main categories of pathogens — bacterial, viral, and parasitic — and their distinct infection pathways.

Notable examples include Listeria monocytogenes' use of surface proteins for cellular invasion, cytomegalovirus' manipulation of trophoblasts, and Toxoplasma gondii's evasion of immune responses. The impact of these infections on maternal and foetal health is substantial, potentially resulting in preeclampsia, preterm labour, congenital anomalies, and long-term developmental issues. Current research utilises advanced technologies such as highresolution imaging, single-cell sequencing, and organoid models to elucidate molecular mechanisms and develop targeted therapies.

The review concludes by highlighting the importance of understanding pathogenplacenta interactions for developing effective preventive measures, early detection techniques, and safe treatment options during pregnancy.

Future directions emphasise the need for translational research to bridge laboratory findings with clinical practice, potentially reducing the burden of placental infections and their associated complications.

Keywords: placenta, infection pathways, maternal-foetal health, pathogens, immunology, pregnancy complications, translational research.

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Introduction The placenta, a remarkable organ unique to pregnancy, serves as a vital interface between mother and foetus. Its primary functions include facilitating nutrient and gas exchange while simultaneously acting as a formidable barrier against potentially harmful pathogens⁴. Despite its robust defensive mechanisms, certain microorganisms have evolved strategies to breach this barrier, leading to severe maternal and foetal health complications¹³. This article explores the intricate pathways through which infections can affect the human placenta, drawing on recent scientific findings and understanding.

The Placental Barrier: Structure and Function The placenta's role in pregnancy extends far beyond its nutritional functions. It employs a sophisticated array of physical, cellular, and immunological defences to protect the developing foetus¹¹. The placental barrier comprises multiple layers, including the syncytiotrophoblast, which is directly exposed to maternal blood, and underlying cytotrophoblasts and stromal tissues¹⁶. Collectively, these layers form a formidable obstacle against invading pathogens. Additionally, the maternal immune system plays a crucial role in this defence, maintaining a delicate balance between tolerance to foetal antigens and readiness to combat infections¹⁰.

Pathogen

Categories

and

Infection

Mechanisms Despite these defences, various pathogens have developed mechanisms to penetrate the placental barrier and infect the foetus.

These pathogens are typically categorised into three main groups: bacterial, viral, and parasitic. Each group employs distinct strategies to evade the immune responses at the maternal-foetal interface and ensure their transmission to the foetus.

Bacterial Infections Bacterial pathogens such as Listeria monocytogenes and Treponema pallidum (the causative agent of syphilis) have been well documented in their ability to cross the placental barrier. L. monocytogenes, for instance, utilises surface proteins, primarily Internalin A (InlA), to bind E-cadherin on trophoblasts, triggering receptor-mediated endocytosis⁸.

Once internalised, L. monocytogenes escapes the phagosome using listeriolysin O (LLO), replicates in the cytoplasm, and spreads cell-to-cell via ActAmediated actin polymerisation.

This mechanism enables the pathogen to breach the placental barrier, potentially reaching foetal tissues⁷. Once inside, it can evade immune responses and proliferate, leading to severe complications such as preterm birth and neonatal sepsis¹³. The disruption of the placental barrier by bacteria can also trigger inflammatory responses that harm both mother and foetus.

Prevention and management strategies for bacterial infections include antibiotic treatment, proper food hygiene, and regular prenatal check-ups.

Viral Infections Viral infections, particularly those caused by cytomegalovirus (CMV) and Zika virus, have evolved mechanisms to breach the placenta and cause congenital infections.

After maternal infection, CMV spreads through the blood to the placenta where the virus enters trophoblasts via receptor binding, endocytosis, or membrane fusion, facilitated by the viral glycoprotein B (gB), Once inside, CMV hijacks the cellular machinery for replication.

Infected trophoblasts spread the virus to adjacent cells, disrupting placental barrier function¹⁴.

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This process enables CMV to cross from infected placental cells to foetal circulation, potentially resulting in severe foetal complications such as hearing loss and developmental delays¹⁵. Similarly, Zika virus has been shown to cause significant neurological damage by crossing the placenta and infecting foetal neural tissues1.

Prevention and management of viral infections often involve hygiene practices, mosquito control in endemic areas, and, when applicable, antiviral treatments.

Parasitic Infections Parasitic infections, exemplified by Toxoplasma gondii, the causative agent of toxoplasmosis, can also invade the placenta through direct cellular invasion, infected immune cell transport, or paracellular routes, in which the parasite employs specialised proteins, notably ROP18 (rhoptry protein 18), to form a moving junction with host cell membranes, facilitating entry. T. gondii evades both maternal and foetal immune responses, enabling replication within placental cells⁹. This invasion can lead to severe outcomes such as miscarriage, stillbirth, and congenital defects⁶. Preventive measures include avoiding undercooked meat and cat litter, while management often involves antiparasitic medications when infection is detected.

Impact on Maternal and Fatal Health Placental infections profoundly impact maternal and foetal health through multiple mechanisms. Maternally, infections can trigger systemic inflammation, vascular dysfunction, and uterine contractions, potentially leading to preeclampsia, preterm labour, and in severe cases, maternal sepsis and mortality¹². Fetally, pathogens crossing the placenta can cause direct tissue damage, while placental dysfunction restricts nutrient and oxygen transfer, resulting in growth restriction.

Infections during critical developmental periods may lead to congenital anomalies.

The foetal inflammatory response can damage developing organs, particularly the rain. Additionally, placental structural damage alters gene expression, and vascular changes which further compromise foetal development, and long-term consequences include developmental delays and increased susceptibility to diseases in adulthood¹⁰.

This interconnected process underscores the critical need for prevention and early intervention in placental infections.

Figure 1: Depicting how infections affect pregnancy outcomes and the placental defence mechanisms.

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On the left, infections from sources like STDs, bacterial vaginosis, and dysbiotic microbiota activate Toll-like receptors (TLRs), leading to the release of proinflammatory cytokines (IL1β, IL6, IL8, TNFα, CCL2). This shifts the immune response from tolerogenic to immunogenic, resulting in foetal injuries, membrane rupture, and possibly miscarriage or preterm birth. On the right, the placenta defends against infections using exosomes, cytokines, and antimicrobial peptides.

However, pathogens like Zika, Toxoplasma gondii, and Listeria monocytogenes can breach these defences, causing vertical transmission and placental damage due to an aberrant pro-inflammatory response¹⁰.

Current Research and Challenges Several charitable organizations, such as March of Dimes and Tommy's in the UK, are dedicated to improving pregnancy health and reducing the incidence of birth defects, including those caused by placental infections.

These organizations play a crucial role in funding research, raising awareness, and providing support to affected families.

Current research on placental infections utilizes advanced technologies to elucidate molecular mechanisms and develop targeted therapies.

High-resolution imaging, single-cell sequencing, and organoid models provide deeper insights into infection processes, in which these methods enable detailed study of pathogen-host interactions, cellular responses, and potential intervention points¹⁷.

Detection methods include non-invasive prenatal testing (NIPT), amniocentesis, and chorionic villus sampling, although these methods involve ethical considerations and potential risks. Researchers are leveraging genomics, proteomics, and transcriptomics to better understand placental invasion and immune evasion strategies of pathogens5.

This comprehensive approach aims to enhance diagnostic accuracy and develop specific treatments while carefully navigating the complex ethical landscape of prenatal testing and intervention.

Conclusion and Future Directions Understanding pathogen-placenta interactions is pivotal for developing effective strategies against placental infections.

Recent advances in molecular and cellular biology have shed light on the complex maternal-foetal interface, paving the way for targeted interventions. Future research should prioritize enhancing preventive measures, refining early detection techniques, and exploring safe treatment options during pregnancy. Key focus areas include further elucidating on placental invasion mechanisms, improving placental barrier function, and identifying non-invasive biomarkers. Advanced technologies, such as organoid models and artificial intelligence (AI) offer promising avenues for drug screening and predictive diagnostics².

Translational research will be vital in bridging laboratory findings with clinical practice, leading to evidence-based guidelines for managing placental infections³.

As our understanding deepens, we move closer to more effective strategies for ensuring healthy pregnancies and positive outcomes for both mothers and their children. This multi-faceted approach holds the potential to significantly reduce the burden of placental infections and their associated complications.

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References: 1. Acosta-Reyes, J., Navarro, E., Herrera, M. J., Goenaga, E., Ospina, M. L., Parra, E., Mercado, M., Chaparro, P., Beltran, M., Gunturiz, M. L., Pardo, L., Valencia, C., Huertas, S., Rodríguez, J., Ruiz, G., Valencia, D., Haddad, L. B., Tinker, S. C., Moore, C. A., & Baquero, H. (2017). Severe Neurologic Disorders in 2 Fetuses with Zika Virus Infection, Colombia. Emerging infectious diseases, 23(6), 982-984. https://doi.org/10.3201/eid2306.161702 2. Bai, L., Wu, Y., Li, G., Zhang, W., Zhang, H., & Su, J. (2024). AI-enabled organoids: Construction, analysis, and application. Bioactive Materials, 31, 525-548. https://doi.org/https://doi.org/10.1016/j.bioactmat.2023.09.005 3. Bauman, M. D., & Van de Water, J. (2020). Translational opportunities in the prenatal immune environment: Promises and limitations of the maternal immune activation model. Neurobiol Dis, 141, 104864. https://doi.org/10.1016/j.nbd.2020.104864 4. Burton, G. J., & Fowden, A. L. (2015). The placenta: a multifaceted, transient organ. Philos Trans R Soc Lond B Biol Sci, 370(1663), 20140066. https://doi.org/10.1098/rstb.2014.0066 5. Choi, S., Khan, T., Roberts, R. M., & Schust, D. J. (2022). Leveraging Optimized Transcriptomic and Personalized Stem Cell Technologies to Better Understand Syncytialization Defects in Preeclampsia [Review]. Frontiers in Genetics, 13. https://doi.org/10.3389/fgene.2022.872818 6. Deganich, M., Boudreaux, C., & Benmerzouga, I. (2023). Toxoplasmosis Infection during Pregnancy. Tropical Medicine and Infectious Disease, 8(1).

7. Eallonardo, S. J., & Freitag, N. E. (2024). Crossing the Barrier: A Comparative Study of Listeria monocytogenes and Treponema pallidum in Placental Invasion. Cells, 13(1).

8. Johnson, L. J., Azari, S., Webb, A., Zhang, X., Gavrilin, M. A., Marshall, J. M., Rood, K., & Seveau, S. (2021). Human Placental Trophoblasts Infected by Listeria monocytogenes Undergo a Pro-Inflammatory Switch Associated With Poor Pregnancy Outcomes [Original Research]. Frontiers in Immunology, 12. https://doi.org/10.3389/fimmu.2021.709466 9. Kato, K. (2018). How does <i>Toxoplama gondii</i> invade host cells?

Journal of Veterinary Medical Science, 80(11), 1702-1706. https://doi.org/10.1292/jvms.18-0344 10. Kumar, M., Saadaoui, M., & Al Khodor, S. (2022). Infections and Pregnancy: Effects on Maternal and Child Health [Review]. Frontiers in Cellular and Infection Microbiology, 12. https://www.frontiersin.org/journals/cellular-and-infectionmicrobiology/articles/10.3389/fcimb.2022.873253 11. Li, X., Li, Z.-H., Wang, Y.-X., & Liu, T.-H. (2023). A comprehensive review of human trophoblast fusion models: recent developments and challenges. Cell Death Discovery, 9(1), 372. https://doi.org/10.1038/s41420-023-01670-0 12. MacIntyre, D. A., Chandiramani, M., Lee, Y. S., Kindinger, L., Smith, A., Angelopoulos, N., Lehne, B., Arulkumaran, S., Brown, R., Teoh, T. G., Holmes, E., Nicoholson, J. K., Marchesi, J. R., & Bennett, P. R. (2015). The vaginal microbiome during pregnancy and the postpartum period in a European population. Scientific reports, 5(1), 8988. https://doi.org/10.1038/srep08988 13. Megli, C. J., & Coyne, C. B. (2022). Infections at the maternal–fetal interface: an overview of pathogenesis and defence. Nature Reviews Microbiology, 20(2), 67-82. https://doi.org/10.1038/s41579-021-00610-y 14. Narang, K., Cheek, E. H., Enninga, E. A. L., & Theiler, R. N. (2021).

Placental Immune Responses to Viruses: Molecular and HistoPathologic Perspectives. International journal of molecular sciences, 22(6).

15. Pontes, K. F., Nardozza, L. M., Peixoto, A. B., Werner, H., Tonni, G., Granese, R., & Araujo Júnior, E. (2024). Cytomegalovirus and Pregnancy: A Narrative Review. Journal of Clinical Medicine, 13(2).

16. Silini, A. R., Di Pietro, R., Lang-Olip, I., Alviano, F., Banerjee, A., Basile, M., Borutinskaite, V., Eissner, G., Gellhaus, A., Giebel, B., Huang, Y.-C., Janev, A., Kreft, M. E., Kupper, N., Abadía-Molina, A. C., Olivares, E. G., Pandolfi, A., Papait, A., Pozzobon, M., . . . Parolini, O. (2020). Perinatal Derivatives: Where Do We Stand? A Roadmap of the Human Placenta and Consensus for Tissue and Cell Nomenclature [Review]. Frontiers in bioengineering and biotechnology, 8. https://www.frontiersin.org/journals/bioengineering-andbiotechnology/articles/10.3389/fbioe.2020.610544 17. Zhao, Z., Chen, X., Dowbaj, A. M., Sljukic, A., Bratlie, K., Lin, L., Fong, E. L. S., Balachander, G. M., Chen, Z., Soragni, A., Huch, M., Zeng, Y. A., Wang, Q., & Yu, H. (2022). Organoids. Nature Reviews Methods Primers, 2(1), 94. https://doi.org/10.1038/s43586-022-00174-y

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SCIENCE IN THE NEWS

Neuralink and Dementia

BY FAATIMA PATEL

Brain-computer interfaces (BCIs) came into development in the late 1960s and early 1970s. Over the decades, as technology has progressed, humanity has quickly reached the point where these devices that are generally seen as dangerous can now be implanted in a human brain to be tested and trialled. BCIs come in many forms to aid people with debilitating conditions and disabilities to communicate, move, and perhaps even improve memory. One such device is the ‘Link’ produced by Neuralink.

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Currently, the device is being trialled on two patients that are quadriplegic, to help them move and regain their autonomy. Eventually, it is hoped that patients with illnesses such as dementia will be trialled and tested; however, there are concerns related to the invasive nature of the device. The general public are worried about what the companies who implant the devices may do with the data, as well as how accessible and affordable it will be.

Neuralink is a piece of neurotechnology, specifically an implantable brain-computer interface in the form of a chip that would be surgically implanted into the brain of a patient founded by Elon Musk in 2016. This technology aims to allow humans to communicate with computers. Human trials are currently ongoing with the first patient having received an implanted chip. As of August 2024, a second patient has successfully received the implant¹². The patient has been using computer-aided design (CAD) to design 3D objects, which they then 3D-print, suggesting the implant is working as intended, allowing patients to control devices as they wish.

By next year, Neuralink aims to have 11 patients implanted, and by 2030, the aim is to have 22,000 patients receive implants⁶.

The goal of Neuralink is to enable patients with mobility problems and degenerative memory issues to regain their mobility and ability to retain information. This will be achieved by having the chip read the electrical impulses fired by the neurons, which will in turn create a reaction, such as controlling prosthetics, devices, or software.

Elon Musk believes it will revolutionise the treatment of Dementia, and possibly cure it; however, there are ethical considerations and risks involved with the surgery itself, as it is an invasive process.

There are many forms of dementia, with Alzheimer’s disease thought to be the most common form. Many of the diseases that fall under the umbrella of dementia are caused by an abnormal build-up of proteins in the brain¹⁰. Different types of dementia can also

After that, the decoded signals are transmitted back to the brain using electrical stimulation⁴. In essence, the chips are controlled by the users’ thoughts.

The chip is surgically implanted into the cerebral cortex, which is the area of the brain responsible for memory, learning, and emotion. BCIs could possibly enhance cognitive functions that are damaged due to dementia; however, current clinical trials with “the Link” have been focused on patients with motor neurone diseases. As human trials are only beginning, not much information has been released, and there has yet to be any news from Neuralink on the use of the BCI in patients with degenerative cognitive diseases. As a result, it is only speculation that Musk’s BCI could help treat dementia¹⁴.

be caused by damage to different areas of the brain. For example, Alzheimer’s disease is thought to be caused by high levels of the protein beta-amyloid, which is made by the breakdown of the larger protein amyloid precursor, both inside and outside brain cells, hindering their ability to communicate¹³. It is the brain cells in the hippocampus that are responsible for learning and memory that are often the first to be damaged². Though there are treatments for the different types of dementia, due to it being caused by many diseases, such as Alzheimer’s, frontotemporal dementia, dementia with Lewy Bodies etc, there is no definitive cure³.

Musk’s BCI, named ‘the Link’, chip uses thin, flexible threads that contain 1,024 electrodes⁵. These electrodes are what record the neural activity of the neurons and nerve cells that send electrical signals across the body to control bodily functions. It is described as “cosmetically invisible”¹². The chip itself is around the size of a coin and works by recording the electrical signals and then decoding them.

Figure 1: A diagram of the wireless Link implant, displaying the four layers, including the neural threads that are inserted into the motor cortex¹¹.

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According to Elon Musk on the 29th of January 2024, a BCI has been implanted in a patient for the first time¹⁵. The patient suffers from severe paralysis, and it is hoped he will be able to control devices, such as computers and tablets, with his thoughts alone. Unfortunately, there is a lack of information regarding the research being conducted, as well as the trial itself7.

This has caused some researchers to be concerned due to the communication of scientific news being relayed through social media instead of traditional peerreviewed publications.

Furthermore, Neuralink’s lack of transparency is a violation of ethical guidelines assigned to all biomedical research⁸. There has, however, been reported success with a BSI (brain-spine implant) in a patient who suffered an incomplete cervical spinal cord injury due to a biking accident ten years prior. The patient, a 38-year-old male, took part in Stimulation Movement Overground (STIMO) – BSI clinical trial⁹.

The trial included a five-month neurorehabilitation programme, where the patient would receive epidural electrical stimulation to their spinal cord. The BSI works by restoring communication between the brain and the spinal cord by building a digital bridge between them. Now, the patient can walk naturally with the aid of the BSI. Furthermore, the patient can walk assisted with crutches while the BSI is switched off, and the BSI has remained stable for over one year⁹.

An online cross-sectional survey, involving 326 adults between the ages of 20 and 40 was completed in 2021, within five countries in the Middle East and North Africa. Many of the participants believe that brain chip implants would help in processing data, treating disabilities such as epilepsy, improve cognitive function mimic lost brain functions, or even an alternative method to drug delivery systems1. It was revealed 54.6% of the study participants stated they have heard about the ‘Brain Chip Implants’, and 6.1% stated they knew of the importance of the implants. Moreover, whilst 6.1% had confirmed they would use it, only 2.5% of the participants thought brain implants would be safe.

Concerns were shown about the possible loss of autonomy and privacy due to the invasive nature of brain chip implants as a means of gathering data¹. Society still has not caught up with the recent surge of technological development, and so many still struggle to comprehend what BCIs are and what they’re used for. In terms of legality, it would take time for the Link to be commercially available in most countries due to concerns of privacy and data breaches. In addition to this, ethically speaking, it should be discussed whether the virtually invasive nature of the Link feeding data back to Neuralink warrants the physically invasive nature of the surgery to implant the device in the first place. Overall, the use of brain implants raises the issue of numerous social, legal, and ethical questions.

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References: 1. Abdelnaby, R., Amer, S. A., Mekky, J., Mohamed, K., Dardeer, K., Hassan, W., Alafandi, B., & Elsayed, M. (2022). Brain Chip Implant: Public’s knowledge, Attitude, and Determinants. A Multi-Country Study, 2021. Open Access Macedonian Journal of Medical Sciences, 10(B), 2489-2497. https://doi.org/10.3889/oamjms.2022.9982 2. Alzheimer's Association. (2024). Alzheimer's and Dementia - What is Dementia? Retrieved 23/10/2024 from https://www.alz.org/alzheimers-dementia/what-isdementia 3. Alzheimer's Association. (2024). What is Dementia? - Types of Dementia. Retrieved 23/10/2024 from https://www.alz.org/alzheimers-dementia/what-isdementia/types-of-dementia 4. Becher, B. (2023). What Is Neuralink? What We Know So Far. Retrieved 22/10/2024, from https://builtin.com/hardware/what-is-neuralink 5. Capitol Technology University. (2024). Neuralink's Brain Chip: How It Works and What It Means. Capitology. https://www.captechu.edu/blog/neuralinks-brain-chiphow-it-works-and-what-it-means 6. Carter, T. (2024). Elon Musk says Neuralink is looking for a 2nd participant for its brain implant. https://www.businessinsider.com/elon-musk-neuralinklooking-second-participant-brain-implant-2024-5 7. Drew, L. (2024). Elon Musk's Neuralink brain chip: what scientists think of first human trial. Nature. https://doi.org/10.1038/d41586-024-00304-4 8. Hart, R. (2024). Experts Criticize Elon Musk’s Neuralink Over Transparency After Billionaire Says First Brain Implant Works. Retrieved 23/10/2024, from https://www.forbes.com/sites/roberthart/2024/02/26/expert s-criticize-elon-musks-neuralink-over-transparency-afterbillionaire-says-first-brain-implant-works/ 9. Lorach, H., Galvez, A., Spagnolo, V., Martel, F., Karakas, S., Intering, N., Vat, M., Faivre, O., Harte, C., Komi, S., Ravier, J., Collin, T., Coquoz, L., Sakr, I., Baaklini, E., HernandezCharpak, S. D., Dumont, G., Buschman, R., Buse, N., . . .

Courtine, G. (2023). Walking naturally after spinal cord injury using a brain–spine interface. Nature, 618(7963), 126133. https://doi.org/10.1038/s41586-023-06094-5 10. National Health Service (NHS). (2024). Causes of dementia.

Retrieved 23/10/2024 from https://www.nhs.uk/conditions/dementia/aboutdementia/causes/ 11. Neuralink. (2021). Pager Plays MindPong. https://neuralink.com/blog/pager-plays-mindpong/ 12. Neuralink. (2024). Pioneering Brain Computer Interfaces.

Retrieved 23/10/2024 from https://neuralink.com/ 13. NIH National Institute on Aging. (2022). What Is Dementia?

Symptoms, Types, and Diagnosis. National Institutes of Health. Retrieved 22/10/2024 from https://www.nia.nih.gov/health/alzheimers-anddementia/what-dementia-symptoms-types-and-diagnosis 14. Penick, H. (2020). Will Neuralink Cure Dementia? https://getneuralnet.com/will-neuralink-cure-dementia/ 15. Reed, J., & McFadden, J. (2024). Neuralink: Can Musk's brain technology change the world? Retrieved 23/10/2024, from https://www.bbc.co.uk/news/health-68169082

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SCIENCE IN THE NEWS

Genetic Chronicles: Stories Written in Ancient DNA

Abstract

Introduction to Ancient DNA

This article focuses on the way ancient DNA research has reshaped our understanding of human history, as well as explore the ethical concerns surrounding aDNA research. As scientists uncover genetic information from long-extinct populations, ethical dilemmas related to consent, cultural sensitivity, and the potential for misuse of genetic data arise. This piece sheds light on the balance between scientific advancement and respect for the communities connected to these ancient remains, as well as address the responsibilities researchers have toward descendant communities to guide ethical aDNA research.

Ancient DNA (aDNA) refers to the genetic material extracted from biological remains such as bones, hair bulbs, skin fragments, teeth, sediments, etc., dating to the last tens of thousands of years or older. Due to its great age and environmental exposure, aDNA is subject to degradation, particularly fragmenting into short 50-100 base pairs, undergoing post-mortem mutations (e.g., cytosine deamination), and environmental contamination³.

This article has been reviewed by Assoc.

Prof. Robin Beck, Reader in Biology, University of Salford. The Editorial Team would like to thank him for his time and contributions.

Keywords: ancient DNA, aDNA, ethical research, biological remains, genome sequencing, cultural heritage, ancestry, migration patterns, kinship analysis, human evolution, infectious diseases, genetic data, consent, indigenous communities, cultural sensitivity

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These considerations complicate the research and result in additional methodical approaches to avoid misleading conclusions³. Initial aDNA research began in 1984 with the extraction and sequencing of short mitochondrial fragments from the quagga (Equus quagga quagga), an extinct subspecies of zebra⁹, followed by Svante Pääbo’s paper where the first sequence of ancient human DNA from an Egyptian mummy was published¹¹. Pääbo has been a pioneer in aDNA studies and has contributed greatly to the expansion and recognition of the field of paleogenomics.

The fragile nature of aDNA makes it difficult to analyse the samples by introducing various methodological assumption liberties, difficulties in dating samples (for example, by carbon dating), and ethical considerations relating to ownership.

Decoding

aDNA:

Methods,

Limits

&

Applications While vague in definition, generally the term aDNA encompasses DNA recovered from any postmortem material which has not been specifically preserved for later use. As described above, these samples are subject to degradation, meaning that it is often challenging to establish a precise timeframe of the sample based on the genetic material alone⁵. Apart from the biological material itself, the environment where the remains have been found can be associated with a particular time period, providing an indirect age for the sample. The combination of multidisciplinary DNA genotyping, radiocarbon dating, and dendrochronology assessments are often used and compared to other historical evidence to provide a narrow date range for the age of the sample⁶.

Nowadays, the technology used includes utilisation of sterile facilities, nextgeneration high throughput sequencing which has been shown to work most efficiently on short DNA sequences, as well as novel statistical tools that can reliably estimate the sequence damage in aDNA⁵.

While there have been attempts to standardise criteria in the design of aDNA research, these have often proved impractical and a ‘common-sense approach’ acknowledging the contamination issue appears to be significantly more feasible for a larger number of studies⁵.

Another crucial consideration involves the awareness of taphonomic bias, which relates to burial, decay, and preservation processes, and analytical procedures bias relating to the extraction, amplification, and identification of the aDNA samples⁷. The main origin of bias in the study of ancient samples revolve around the source of the material, the methodology and efficiency of the DNA transfer, the preservation conditions of the sample, and the assumption that these have remained constant throughout time⁷.

On a more technical scale, a controversial aspect of aDNA research is the assumption of molecular rates of change. These include genetic diversity, the mutation rates of natural alleles, substitution rates, etc., which often assume an equilibrium between mutation and genetic drift over time5. Most of the aDNA work utilises mtDNA (mitochondrial DNA), as it is relatively easy to amplify.

When dealing with trace quantities of preserved DNA, standard methods of genetic sequencing such as PCR introduce a major risk of accidentally sequencing contaminants as opposed to the aDNA itself⁵.

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Prior to aDNA research, studies focusing on the rates of change of mitochondrial loci sometimes resulted in conflicting values;, for example, estimates for the mutation rate of the hypervariable region 1 of the mitochondrial genome have ranged between 2% to 10% per million years;, however, recent estimates over shorter timeframes for intraspecific comparisons that use aDNA methodology differ greatly from those obtained via phylogenetic methods using DNA from living individuals⁵.

Promisingly, findings like these have the capacity to be rectified as novel bioinformatics tools enable the re-evaluation of published data. The BMC Genomic Data in particular encourages the submission of ancient DNA Data Notes³.

Alongside recent advancements in nextgeneration sequencing technologies and bioinformatic research, the analyses of aDNA have achieved significant scholarly attention as they have the capacity to revolutionise our perception of human evolution, plant and animal domestication, the origins and the evolution of pathogens and microbiomes, migration patterns, and many more (see Figure 1)³. At present, genome-scale data has been obtained from thousands of palaeobiological samples, and the number of ancient biological tissues that are suitable for genome sequencing is continuously increasing, hence promising realistic nearfuture advancements³.

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Figure 1: Applications of ancient DNA analysis. This chart outlines possible areas whereby ancient DNA implementation would shape the fields of anthropology and palaeobiology³.

Recent Discoveries in aDNA Research Research team led by the Francis Crick Institute have identified a prehistoric person with mosaic Turner syndrome who is assumed to have lived around 2500 years ago, an Early Medieval Period individual with Jacob’s syndrome, three people with Klinefelter’s syndrome, and an Iron Age infant with Down’s syndrome². These individuals have been analysed as a part of the Thousand Ancient British Genomes project and have been found at sites in Oxford, Somerset, Yorkshire, and Lincoln. All have been buried within the guidelines of society’s customs at the time, but without any possessions that could inform us about their lives. The findings surrounding atypical autosomal and sex chromosome karyotypes aided in the understanding of past perceptions of biological sex, as well as diverse biological traits².

Since polygenic risk scores are already utilised as routine assessments by the NHS, ancient genomics data bring about the potential to reconstruct the history of human health over time, particularly the sought-after link between genomic diversity and disease. The oldest nuclear genome from the Homo genus was retrieved from a 430,000-year-old-Neanderthal¹⁰.

While aDNA has been obtained from various parts of the world, there is a general northern hemisphere bias in the data which needs to be addressed. The potential of studying Neanderthal DNA arises from the introgression of Neanderthal DNA which forms a small proportion of modern human DNA, where research has revealed genes of major physiological relevance10. Recent paleogenomics studies have determined that 3% of people of European ancestry have a TYK2 P1104A tuberculosis risk variant which has evolved under strong selection pressure over two millennia. This finding reflects the pressure imposed by M. tuberculosis epidemics and would not have been brought to attention with sole modern DNA studies¹⁰. Interestingly, it has been established that a Neanderthal haplotype encompassing the antiviral OAS1 gene is linked to protection against severe COVID-19¹². These findings have the potential to redefine our understanding of immunity and shape our strategies for tacking infectious diseases.

Cultural Sensitivity: Ownership of aDNA Data Arguably the biggest concern surrounding aDNA is lack of means to obtained informed consent from test subjects and ownership of genomic data.

The general principle is to ensure that paleogenomic researchers consider the ethical and cultural issues before, during, and after the study has been undertaken, and they must consult with the communities the remains have been found around⁴.

In the past, destruction of relics, defiling of holy places, and misrepresenting the remains have discouraged ethnic communities from consenting to such studies⁴. For example, in 1996, archaeologists assembled a nearly complete skeleton consisting of more than 300 bones found along the edge of the Columbia River, an area local to at least four Indigenous groups. The remains have been referred to as the Kennewick Man, or the Ancient One. One archaeologist called James C. Chatters, has suggested that Kennewick Man may have been European due to certain “Caucasoid” features like his skull morphology.

When the remains have been found to be older than Chatters expected, the realised that this is not the person he suspected Kennewick Man to be. By suggesting that Kennewick Man was European, Chatters undermined the claim of Indigenous groups which stated that the skeletal remains belonged to them under the Native American Graves Protection and Repatriation Act (NAGPRA)⁸.

This act clearly declares that the remains must be returned to a tribe if they were found to be culturally related. Court rulings denied the tribes’ claims and granted scientists access to the bones, while Chatters was not part of the lawsuit, he was able to study the remains and published his book in 2002.

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Jerome Rose, an osteologist, was called to analyse the remains, concluded that the skeleton belongs to a Native American from the Great Plains, which is consistent with the time and location where the remains were found⁸.

Paulette Steeves, an Indigenous (Cree-Métis) archaeologist at Algoma University in Canada (and one of Rose's former students) said this when referring to Rose's work on Kennewick Man: “[the archaeologists] tried to disenfranchise Kennewick Man from the local Indigenous communities⁸.”

In 2015, thanks to modern genome sequencing technology using one of the individual’s hand bones, Kennewick Man has been definitively linked with, and returned to, the Indigenous Columbia Basin tribes. At his burial site, more than 200 tribal members have gathered, displaying the impact of this situation on their culture. Paulette Steeves, Rose’s former student, said “Genetics . . . obviously showed later on that this person definitely was linked to those tribal communities and he was buried, but for how many years did [they] suffer? That’s the kind of damage that researchers and archaeologists and geneticists can do⁸.”

Chatters argues that he did not deny the tribe ownership, instead he did not agree with the refusal to not let Kennewick Man to tell his story. The burial itself provided psychological relief to the tribal group; however, due to the unpleasant circumstances surrounding it, the stigma prohibited scientists from reviewing the burial site and answering important historical questions⁸.

Furthermore, literature reports that genetic findings may result in repression of such communities through communal or personal convictions, or perpetrating falsifying narratives through the misuse of genetic data for determining group belonging¹.

Some experts believe that it is not appropriate for these data to be used as an “arbiter of identity” and to avoid exercising extreme and misguided determination of claim to ancient heritage¹. In addition, when conducting culturally sensitive studies, researchers should inform the communities that the genetic findings may be inconsistent with the communities’ beliefs. While the scientific analyses are reported as scholarly outputs, a study highlights that “they do not discredit, diminish, or decrease the importance of traditional expertise and deeply held beliefs”, and other lines of evidence should be reported alongside genetic analyses to reflect the complexity of factors that played a role in shaping those traditions¹.

To address these ethical concerns, protective guidelines like NAGPRA ensure an alliance between scientists and Indigenous communities, where ethical and cultural implications are considered to develop strategies regarding communication and handling of the sensitive data, Indigenous community engagement, making sure they are fully aware of the process to maximise informed consent, and also tackling long-term responsibilities that arise from the genetic findings⁴. In these studies, the main priority lies with community engagement that involves Indigenous scholars and stakeholders⁴.

More specifically, the widespread argument is that “(1) researchers must ensure that all regulations were followed in the places where they work and from which the human remains derived; (2) researchers must prepare a detailed plan prior to beginning any study; (3) researchers must minimize damage to human remains; (4) researchers must ensure that data are made available following publication to allow critical re-examination of scientific findings; and (5) researchers must engage with other stakeholders from the beginning of a study and ensure respect and sensitivity to stakeholder perspectives¹.”

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Every aDNA researcher must commit to adhering to these and is expected to promote a high ethical standard in aDNA research on human remains¹.

In conclusion, the field of ancient DNA has changed enormously since its beginnings, both in aspects of technological advancements and in ethical considerations.

Ever since the field gained historic recognition through Svante Pääbo’s paleogenetic research on Neanderthals, it has consistently reached new milestones in terms of increased technical accuracy and sparking curiosity for insights into human migration patterns, cultural heritage, and even the impact of genetic diversity on infectious diseases. The field continues to expand, and with that, scientists learn to develop initiatives to establish and strengthen the dialogues between researchers, Indigenous peoples, and interdisciplinary specialists, ultimately elevating the domain of knowledge while ensuring a respectful and considerate approach.

References: 1. Alpaslan-Roodenberg, S., Anthony, D., Babiker, H., Bánffy, E., Booth, T., Capone, P., Deshpande-Mukherjee, A., Eisenmann, S., Fehren-Schmitz, L., Frachetti, M., Fujita, R., Frieman, C. J., Fu, Q., Gibbon, V., Haak, W., Hajdinjak, M., Hofmann, K. P., Holguin, B., Inomata, T., . . . Zahir, M. (2021).

Ethics of DNA research on human remains: five globally applicable guidelines.

Nature, 599(7883), 41-46. https://doi.org/10.1038/s41586-021-04008-x 2. Anastasiadou, K., Silva, M., Booth, T., Speidel, L., Audsley, T., Barrington, C., Buckberry, J., Fernandes, D., Ford, B., Gibson, M., Gilardet, A., Glocke, I., Keefe, K., Kelly, M., Masters, M., McCabe, J., McIntyre, L., Ponce, P., Rowland, S., . . .

Skoglund, P. (2024). Detection of chromosomal aneuploidy in ancient genomes. Communications Biology, 7(1), 14. https://doi.org/10.1038/s42003-023-05642-z 3. Chen, N., & Nedoluzhko, A. (2023). Ancient DNA: the past for the future.

BMC Genomics, 24(1), 309. https://doi.org/10.1186/s12864-023-09396-0 4. Dalal, V., Pasupuleti, N., Chaubey, G., Rai, N., & Shinde, V. (2023). Advancements and Challenges in Ancient DNA Research: Bridging the Global North–South Divide. Genes, 14(2).

5. de Bruyn, M., Hoelzel, A. R., Carvalho, G. R., & Hofreiter, M. (2011). Faunal histories from Holocene ancient DNA. Trends in Ecology & Evolution, 26(8), 405-413. https://doi.org/https://doi.org/10.1016/j.tree.2011.03.021 6. Domínguez-Delmás, M., Schroeder, H., Kuitems, M., Haneca, K., Archangel, S., van Duin, P., & Piena, H. (2023). A stepwise multidisciplinary approach to determine the date and provenance of historical wooden objects. Journal of Cultural Heritage, 62, 430-440. https://doi.org/https://doi.org/10.1016/j.culher.2023.06.023 7. Giguet-Covex, C., Ficetola, G. F., Walsh, K., Poulenard, J., Bajard, M., Fouinat, L., Sabatier, P., Gielly, L., Messager, E., Develle, A. L., David, F., Taberlet, P., Brisset, E., Guiter, F., Sinet, R., & Arnaud, F. (2019). New insights on lake sediment DNA from the catchment: importance of taphonomic and analytical issues on the record quality.

Scientific reports, 9(1), 14676. https://doi.org/10.1038/s41598019-50339-1 8. Heidt, A. (2022). Ancient DNA Boom Underlines a Need for Ethical Frameworks.

Retrieved 17/10/2024, from https://www.the-scientist.com/ancient-dna-boomunderlines-a-need-for-ethical-frameworks-69645 9. Higuchi, R., Bowman, B., Freiberger, M., Ryder, O. A., & Wilson, A. C. (1984). DNA sequences from the quagga, an extinct member of the horse family. Nature, 312(5991), 282284. https://doi.org/10.1038/312282a0 10. Kerner, G., Choin, J., & Quintana-Murci, L. (2023). Ancient DNA as a tool for medical research. Nature medicine, 29(5), 1048-1051. https://doi.org/10.1038/s41591-023-02244-4 11. Pääbo, S. (1985). Molecular cloning of Ancient Egyptian mummy DNA. Nature, 314(6012), 644-645. https://doi.org/10.1038/314644a0 12. Zeberg, H., & Pääbo, S. (2021). A genomic region associated with protection against severe COVID-19 is inherited from Neandertals. Proceedings of the National Academy of Sciences, 118(9), e2026309118. https://doi.org/10.1073/pnas.2026309118

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RESEARCH SPOTLIGHT

USING BIOLUMINESCENCE IN MAGNETIC RESONANCE IMAGING

BY NASHAF AZIZ Abstract Magnetic resonance imaging (MRI) is a powerful medical diagnostic tool that provides detailed images of tissues and organs. However, conventional MRI has limitations in sensitivity and specificity that can be overcome by integrating bioluminescence. This article explores the innovative application of bioluminescence in MRI, discusses its mechanisms, advantages, and potential clinical applications.

Bioluminescence can be particularly beneficial for cancer patients, in preclinical studies, In neurological research and diagnostics.

Individuals with genetic disorders, Patients with certain implanted medical devices such as pacemakers or cochlear implants, may not be able to undergo MRI due to the strong magnetic fields involved. Bioluminescence-based MR can revolutionize non-invasive diagnostics and personalized medicine by improving contrast and enabling molecular imaging.

By adding bioluminescent molecules such as luciferin and luciferase, which emit the light through the biochemical reactions to MRI, researchers aim to improve contrast and provide more accurate imaging capabilities.

These molecules could significantly advance medical imaging, offering deeper insights into health and disease. Utilizing strong magnetic fields and radiofrequency waves, MRI produces high-resolution images of soft tissues, making it particularly effective for examining the brain, spinal cord, muscles, and joints. This is done by aligning hydrogen nuclei in the body and detecting the signals they emit¹⁰.

KEYWORDS: Bioluminescence, MRI, molecular imaging, contrast enhancement, non-invasive diagnostics, personalized medicine, fatty acid reductase complex, luciferin.

Introduction Magnetic resonance imaging (MRI) has become a cornerstone of modern medical diagnosis, known for its ability to produce high-resolution images of internal structures and to visualise detailed internal structures without the use of ionizing radiation⁶. Despite its advantages, MRI has problems with sensitivity and specificity, especially in differentiating between different tissue types and detecting small or early-stage abnormalities.

Bioluminescence, the emission of light from living organisms, offers a new approach to overcome these limitations.

Figure 1: Standard MRI Scan showing high-resolution images of internal structures, commonly used in medical diagnostics to visualise tissues and organs¹⁵.

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Mechanisms of Bioluminescence in MRI Bioluminescence occurs when certain enzymes known as luciferases catalyse reactions with substrates called luciferins, emitting light as a result. In the context of MRI, bioluminescent molecules can be modified to target specific cells, tissues, or molecular pathways. When these molecules interact with their targets, the emitted light can be detected and used to amplify the MRI signal¹⁷.

Bioluminescent probes Bioluminescent probes are designed emit light in response to specific biological processes¹⁸.

These probes can be combined with magnetic nanoparticles or various agents that can be seen with MRI. The bioluminescence signal can be converted into an MRI signal, improving image quality, and providing additional information about the biological environment.

Figure 2: Mechanism of Bioluminescence in Firefly Luciferase.

Firefly bioluminescence involves the enzyme luciferase catalysing a reaction where D-luciferin, in the presence of ATP and oxygen, is converted into an excited molecule. As this molecule returns to its ground state, it emits visible light, typically yellow green. This process is highly efficient, allowing fireflies to produce light with minimal energy loss¹³.

Advantages of Bioluminescence-Enhanced MRI Molecular imaging Bioluminescence enables molecular imaging, which allows specialists to visualise and monitor molecular processes over time. This capability is important in oncology as it can be used to track tumour growth, metastasis, and response to treatment. Bioluminescence MRI focuses on specific biomarkers that can provide information about the molecular basis of disease¹².

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Specialists are generally required to use bioluminescence-based molecular imaging effectively, given the complexity of the technology and the depth of understanding needed to interpret the results accurately.

Bioluminescence magnetic resonance is very promising for cancer diagnosis. Bioluminescent studies focus on tumour-specific markers that can show malignant cells with high accuracy, allowing early detection and accurate diagnosis of cancer. This technology makes it possible to assess the effectiveness of cancer treatment in real time to create a personalized treatment plan.

Figure 3: Time-lapse Imaging of Tumour Growth Using Bioluminescence MRI, Early frames capture the initial, small tumour, while later frames show increased bioluminescent signals as the tumour grows larger⁸.

Improved imaging One of the main advantages of incorporating bioluminescence into MRI is the significantly improved contrast. Traditional MRI relies on differences in fluid content and tissue density to produce contrast. Bioluminescence provides a different layer of information on molecular and cellular activity, which can accurately distinguish between healthy and dead tissue Non-invasive and safe The biomolecules used in MRI are non-toxic and do not require ionizing radiation, so this procedure is safe for patients. The non-invasive nature of bioluminescence MRI means it can be used for repeated imaging over time, which is important for monitoring disease progress and treatment effectiveness Clinical Applications: Musculoskeletal Disorders Joint Disorders MRI is frequently used to assess joint problems, including ligament tears, meniscus injuries, and cartilage damage, particularly in the knee, shoulder, and spine⁵.

Spinal Conditions MRI is crucial in diagnosing herniated discs, spinal stenosis, and other spinal cord abnormalities, aiding in both conservative and surgical treatment planning.

Neurological Disorders In neurological studies, bioluminescence MRI can be used to study brain function and monitor neurological diseases.

By focusing on neurotransmitter activity or specific neural pathways, researchers can understand conditions such as Alzheimer's disease, Parkinson's disease, and epilepsy. This approach can aid in development of targeted treatments and provide insights into the progression of these diseases¹⁴.

Brain Function Mapping MRI is used to map brain activity by detecting changes in blood flow, particularly useful in presurgical planning for epilepsy or brain tumour surgeries².

Psychiatric Research MRI is increasingly used in research to study brain function in psychiatric disorders such as depression, schizophrenia, and anxiety¹⁹.

Figure 4: This image showcases various brain scanning techniques, illustrating the different methods used to visualize brain structures and functions, providing unique insights into brain anatomy and activity, essential for diagnosing neurological conditions and studying brain functions⁵.

This non-invasive technique is critical for evaluating conditions like cardiomyopathies, coronary artery disease, and congenital heart defects. Additionally, MRI can detect inflammatory cytokines like interleukin-1β (IL-1β) and tumour necrosis factoralpha (TNF-α), which are central to the progression of atherosclerosis, enabling early detection of plaque formation. MRI can visualise apoptotic processes in heart tissue after myocardial infarction and detect oxidative stress, both of which are critical for understanding the progression of heart failure. This approach provides a non-invasive, sensitive method to detect molecular and structural changes in cardiovascular diseases, aiding in early diagnosis and treatment monitoring⁷.

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Figure 5: This image illustrates a cardiac MRI, providing a detailed view of the heart’s anatomy and function¹¹.

Future Challenges and Opportunities Biodynamics is important in MRI, but there are also challenges that need to be addressed. These includes developing better bioluminescence probes, ensuring the stability and biocompatibility of these probes, and integrating bioluminescence detection with current MRI techniques. Bioluminescence probes can degrade over time due to chemical reactions with the biological environment or imaging equipment, leading to diminished luminescence Probes may also undergo photobleaching when exposed to light, which reduces their luminescence Probes must remain stable in the complex physiological environment, including varying pH levels, ionic strength, and temperatures³. To ensure biocompatibility probes are coated with biocompatible materials like polyethylene glycol (PEG) to minimize immune reactions. Employing non-toxic luciferins and luciferases reduces potential harm¹⁶. Adhering to regulatory guidelines ensures probes are safe for clinical use. Future research will focus on overcoming these obstacles and expanding the clinical use of bioluminescence MRI. Conclusion The introduction of bioluminescence in magnetic resonance imaging represents a major advance in medical imaging. By enhancing contrast and enabling molecular imaging, bioluminescence MRI can improve the accuracy and effectiveness of diagnosis and treatment monitoring. Current research and development in bioluminescence MRI include advancements in probes, integration with MRI, and biocompatibility and stability.

Major UK universities and research centres are advancing bioluminescence MRI technology, funded by UK Research and Innovation (UKRI) and through collaborative efforts among academic and healthcare institutions. Funding for bioluminescence MRI research in the UK comes primarily from UKRI, including grants from the Medical Research Council (MRC). Major UK universities, research centres, and healthcare institutions are also involved, with collaborative efforts supported by both public and private sector funding. This financial backing is crucial for advancing bioluminescence MRI technology, particularly in developing better probes, improving MRI integration, and ensuring biocompatibility, ultimately pushing the technology toward clinical application. As research progresses, this innovative approach could revolutionise non-invasive diagnostics and personalised medicine, bringing new hope for patients and doctors.

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References: 1.Andelovic, K., Winter, P., Jakob, P. M., Bauer, W. R., Herold, V., & Zernecke, A. (2021).

Evaluation of Plaque Characteristics and Inflammation Using Magnetic Resonance Imaging. Biomedicines, 9(2).

2.Bates, E., Wilson, S. M., Saygin, A. P., Dick, F., Sereno, M. I., Knight, R. T., & Dronkers, N. F. (2003). Voxel-based lesion-symptom mapping. Nat Neurosci, 6(5), 448-450. https://doi.org/10.1038/nn1050 3.Brodl, E., Winkler, A., & Macheroux, P. (2018). Molecular Mechanisms of Bacterial Bioluminescence.

Comput Struct Biotechnol J, 16, 551-564. https://doi.org/10.1016/j.csbj.2018.11.003 4.Busse, A., Rajagopal, R., Yücel, S., Beller, E., Öner, A., Streckenbach, F., Cantré, D., Ince, H., Weber, M.-A., & Meinel, F. G. (2020). Cardiac MRI—Update 2020. Der Radiologe, 60(1), 33-40. https://doi.org/10.1007/s00117-020-00687-1 5.Cejvanovic, S., Sheikh, Z., Hamann, S., & Subramanian, P. S. (2024). Imaging the brain: diagnosis aided by structural features on neuroimaging studies. Eye (Lond), 38(12), 2380-2391. https://doi.org/10.1038/s41433-024-03142-w 6.Grover, V. P., Tognarelli, J. M., Crossey, M. M., Cox, I. J., Taylor-Robinson, S. D., & McPhail, M. J. (2015). Magnetic Resonance Imaging: Principles and Techniques: Lessons for Clinicians.

J Clin Exp Hepatol, 5(3), 246-255. https://doi.org/10.1016/j.jceh.2015.08.001 7.A Heart to Heart Discussion: Cardiac MRI. (2017). In D. W. McRobbie, E. A. Moore, M. J. Graves, & M. R. Prince (Eds.), MRI from Picture to Proton (3 ed., pp. 269-287).

Cambridge University Press. https://doi.org/10.1017/9781107706958.017 8.Koessinger, A. L., Koessinger, D., Stevenson, K., Cloix, C., Mitchell, L., Nixon, C., Gomez-Roman, N., Chalmers, A. J., Norman, J. C., & Tait, S. W. G. (2020). Quantitative in vivo bioluminescence imaging of orthotopic patient-derived glioblastoma xenografts. Scientific reports, 10(1), 15361. https://doi.org/10.1038/s41598-020-72322-x 9.Koff, M. F., Burge, A. J., Koch, K. M., & Potter, H. G. (2017). Imaging near orthopedic hardware. J Magn Reson Imaging, 46(1), 24-39. https://doi.org/10.1002/jmri.25577 10. Le, D., Dhamecha, D., Gonsalves, A., & Menon, J. U. (2020). Ultrasound-Enhanced Chemiluminescence for Bioimaging.

Front Bioeng Biotechnol, 8, 25. https://doi.org/10.3389/fbioe.2020.00025 11. Maceira, A. M., Joshi, J., Prasad, S. K., Moon, J. C., Perugini, E., Harding, I., Sheppard, M. N., Poole-Wilson, P. A., Hawkins, P. N., & Pennell, D. J. (2005). Cardiovascular Magnetic Resonance in Cardiac Amyloidosis. Circulation, 111(2), 186-193. https://doi.org/10.1161/01.CIR.0000152819.97857.9D 12. Massoud, T. F., & Gambhir, S. S. (2003). Molecular imaging in living subjects: seeing fundamental biological processes in a new light. Genes Dev, 17(5), 545-580. https://doi.org/10.1101/gad.1047403 13. Nakatsu, T., Ichiyama, S., Hiratake, J., Saldanha, A., Kobashi, N., Sakata, K., & Kato, H. (2006). Structural basis for the spectral difference in luciferase bioluminescence.

Nature, 440(7082), 372-376. https://doi.org/10.1038/nature04542 14. Seiler, A., Nöth, U., Hok, P., Reiländer, A., Maiworm, M., Baudrexel, S., Meuth, S., Rosenow, F., Steinmetz, H., Wagner, M., Hattingen, E., Deichmann, R., & Gracien, R.-M. (2021). Multiparametric Quantitative MRI in Neurological Diseases [Mini Review].

Frontiers in Neurology, 12. https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2021.640239 15. Summers, P., Saia, G., Colombo, A., Pricolo, P., Zugni, F., Alessi, S., Marvaso, G., Jereczek-Fossa, B. A., Bellomi, M., & Petralia, G. (2021). Whole-body magnetic resonance imaging: technique, guidelines and key applications.

Ecancermedicalscience, 15, 1164. https://doi.org/10.3332/ecancer.2021.1164 16. Syed, A. J., & Anderson, J. C. (2021). Applications of bioluminescence in biotechnology and beyond [10.1039/D0CS01492C]. Chemical Society Reviews, 50(9), 5668-5705. https://doi.org/10.1039/D0CS01492C 17. Weissleder, R., & Ntziachristos, V. (2003). Shedding light onto live molecular targets. Nature medicine, 9(1), 123-128. https://doi.org/10.1038/nm0103-123 18. Yang, J., Chen, Z., Yang, Y., Zheng, B., Zhu, Y., Wu, F., & Xiong, H. (2024).

Visualization of Endogenous Hypochlorite in Drug-Induced Liver Injury Mice via a Bioluminescent Probe Combined with Firefly Luciferase mRNA-Loaded Lipid Nanoparticles.

Analytical Chemistry, 96(18), 6978-6985. https://doi.org/10.1021/acs.analchem.4c00008 Zhang, W., Yang, C., Cao, Z., Li, Z., Zhuo, L., Tan, Y., He, Y., Yao, L., Zhou, Q., Gong, Q., Sweeney, J. A., Shi, F., & Lui, S. (2023). Detecting individuals with severe mental illness using artificial intelligence applied to magnetic resonance imaging.

EBioMedicine, 90, 104541. https://doi.org/10.1016/j.ebiom.2023.104541

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RESEARCH SPOTLIGHT

BY AREEBA KHALID Prostate cancer is the most diagnosed cancer in men, mainly those over 50. In the UK, an average of 52,000 men are diagnosed with prostate cancer each year, and about 12,000 men die from it⁹. Prostate cancer often shows little to no symptoms in its early stages. The TRANSFORM Trial is a research project worth £42 million, launched by Prostate Cancer UK, with the sole purpose of finding the best way to screen men through an easy and less stressful diagnosis¹⁰.

Prostate cancer begins when some cells develop mutations in their DNA and start growing and dividing uncontrollably, causing normal healthy cells to die. Cancer cells will continue to grow and divide creating a tumour that can spread over time, to other tissues and organs such as the bladder, bones, lymph nodes, pelvic wall, lungs, and rectum.

Prostate cancer metastasis can rarely occur in the kidneys and spleen³. Some of the symptoms of prostate cancer include blood in semen and urine, weak flow, bladder not fully emptied, and prolonged duration of urination.

Some advanced symptoms, indicating the cancer has spread, include involuntary weight loss, reduced appetite, and pain in the testicles, back and bone⁵. It can also become metastatic, meaning it spreads to other organs, such as the bladder or, in some cases, to the bloodstream⁸.

On average, it takes two to four weeks to be diagnosed with prostate cancer following different tests and biopsies. Generally, a positive biopsy indicates the presence of cancer cells. The cancer is graded by factors such as how quickly the cells are likely to grow and how aggressive the cells are. These scores are known as the Grade Group².

Currently, there is no definitive test or screening for prostate cancer. However, it is possible to determine the risks by simple factors that include PSA Levels and results of prostate examinations.

Depending on the results of the previous tests, Multiparametric Magnetic Resonance Imaging (mpMRI) is performed.

The mpMRI scan is preferred as it gives a more detailed image of the prostate gland, and it helps the doctor check for abnormalities, decide whether a biopsy is needed and if needed from which area is best to take it, if the cancer has spread².

One of the limitations is that it cannot surely confirm if there is cancer, which is why a transperineal or transrectal biopsy is needed accordingly⁴.

The TRANSFORM Trial’s main purpose is to find an effective screening method which will improve diagnostic rates, without making the patient undergo unnecessary procedures that can also lead to mental distress².

Figure 1: A visual depiction of the cellular progression of prostate cancer¹¹.

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Other risk factors include ethnic groups. Black men are more likely to get prostate cancer than any other ethnic group; currently, in the UK, 1 in 4 black men are more likely to get prostate cancer in their lives, with reasons not yet determined.

The reasons are not fully known but as age increases, the risk of getting prostate cancer increases too. Most men get diagnosed between the age of 70 and 74 years. Family history and genetics are also key risk factors. The genes determine the growth, functions, and development of the body; if gene variation occurs, it often leads to cancer. In the case of prostate cancer, a BRCA1 or BRCA2 gene variation leads to the disease⁸. BRCA genes work by preventing cancer cell growth, and make sure healthy cells are growing normally. People with the BRCA2 gene variant are more likely to develop prostate cancer than those with the BRCA1 variation.

Although there is no clear evidence, some researchers suggest that the BRCA1 or BRCA2 gene variation can also increase the possibility of developing this disease at a young age as well as the disease becoming aggressive and spreading more⁸.

Figure 2: An image of a histology section showing the comparison between healthy/normal prostate tissue and cancerous prostate tissue⁶.

References:

A large number of men are expected to take part in the TRANSFORM Trial. The trial will compare the most effective tests and provide definitive evidence indicating the best way to screen for prostate cancer; the trial will try to reduce patient death by up to 40%⁷.

This trial consists of two stages: Stage one – this stage will consist of researching different screening options that include PSA blood tests, faster MRI scans (also known as ‘Prostagram’) as well as genetic testing to identify men that are at higher risk. The effectiveness of these new techniques will be evaluated through comparison with the NHS's existing diagnostic procedure to choose who should progress to the trial's next phase.

Approximately 12,500 men will be requited, and this stage itself may take three years to complete by providing initial results¹⁻⁷.

Stage two – this stage will consist of utilising the most effective methods found in stage one.

300,000 men are projected to participate. The trial is estimated to run for a minimum of 15 years to determine if the screening can lower prostate cancer related deaths as well as improve quality of life; it will also unveil whether patients will suffer consequences from unnecessary procedures (biopsies and invasive treatment). Most importantly, it will help identify the least harmful tests and procedures that enable the diagnosis of major cancers such as prostate cancer¹-⁷.

The TRANSFORM Trial will contribute to the largest prostate cancer biomarkers in the world by collecting various samples, such as images and data, from over 250,000 men.

This will help researchers make major discoveries that will guide the diagnosis and treatment of prostate cancer¹-⁷.

1. Atkins, V., & Department of Health and Social Care. (2023). Biggest prostate cancer screening trial in decades to start in UK https://www.gov.uk/government/news/biggest-prostate-cancer-screening-trial-in-decades-to-start-in-uk 2. Cancer Research UK. (2022). Tests for prostate cancer. Retrieved 30/10/2024 from https://www.cancerresearchuk.org/aboutcancer/prostate-cancer/getting-diagnosed/tests-for-prostate-cancer 3. Giridhar, K. (2023). Prostate cancer metastasis: Where does prostate cancer spread? Mayo Clinic. Retrieved 30/10/2024 from https://www.mayoclinic.org/diseases-conditions/prostate-cancer/expert-answers/prostate-cancer-metastasis/faq-20058270 4. Gravestock, P., Shaw, M., Veeratterapillay, R., & Heer, R. (2022). Chapter 12 - Prostate Cancer Diagnosis: Biopsy Approaches. In Urologic Cancers. https://doi.org/10.36255/exon-publications-urologic-cancers-prostate-cancer-biopsy 5. National Health Service (NHS). (2021). Symptoms - prostate cancer. Retrieved 30/10/2024 from https://www.nhs.uk/conditions/prostatecancer/symptoms/ 6. Newman, M. E. (2024, 17/10/2024). Study suggests a healthy diet may help keep low grade prostate cancer from progressing to more dangerous states during active surveillance https://www.hopkinsmedicine.org/news/newsroom/news-releases/2024/10/study-suggests-ahealthy-diet-may-help-keep-low-grade-prostate-cancer-from-progressing-to-more-dangerous-states-during-active-surveillance 7. O'Hare, R. (2024). New prostate cancer screening trial could save thousands of lives. Retrieved 30/10/2024, from https://www.imperial.ac.uk/news/253035/new-prostate-cancer-screening-trial-could/ 8. Prostate Cancer UK. (2022). About Prostate Cancer. Retrieved 30/10/2024 from https://prostatecanceruk.org/prostate-information-andsupport/risk-and-symptoms/about-prostate-cancer 9. Prostate Cancer UK. (2022). Are you at risk? Retrieved 30/10/2024 from https://prostatecanceruk.org/prostate-information-andsupport/risk-and-symptoms/are-you-at-risk 10. Prostate Cancer UK. (2024). TRANSFORM Trial. Retrieved 30/10/2024 from https://prostatecanceruk.org/research/transform-trial 11. Saranyutanon, S., Srivastava, S. K., Pai, S., Singh, S., & Singh, A. P. (2020). Therapies Targeted to Androgen Receptor Signaling Axis in Prostate Cancer: Progress, Challenges, and Hope. Cancers, 12(1).

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RESEARCH SPOTLIGHT

BY ELOGHOSA OHONBA

Abstract Pregabalin, a GABA analog originally developed as an anticonvulsant, has recently gained widespread use in managing neuropathic pain and fibromyalgia. Despite its therapeutic evidence, recent studies suggest that pregabalin has abuse potential especially among individuals with prior history of drug abuse and those using opioids. While pregabalin is a controlled substance in the UK and USA, its misuse continues to rise. Case reports show that even patients without a history of substance abuse can experience withdrawal symptoms, including agitation and insomnia, upon discontinuation, suggesting the potential for dependence even at therapeutic doses. This article examines the pharmacological action of pregabalin, the pattern of abuse and how the issue of pregabalin abuse and misuse can be addressed by prescribers and healthcare policy makers.

Pregabalin, popularly marketed as Lyrica, is a lipophilic analog of GABA (gamma amino-butyric acid) and is structurally similar to Gabapentin. It is currently indicated in the management of neuropathic pain, fibromyalgia, partial seizures, and epilepsy⁴. Pregabalin is believed to exert its pharmacological effects by acting on voltage gated calcium channels in the central nervous system inhibiting the influx of Calcium ions (Ca²⁺) into the nerves leading to a decrease in the release of excitatory neurotransmitters¹.

However, a recent case study demonstrated that at normal therapeutic doses of pregabalin for the management of neuropathic pain, patients developed symptoms such as shortness of breath, agitation, insomnia, and psychotic-like symptoms upon abrupt discontinuance⁷. This indicates that at normal therapeutic dose of pregabalin, patients with no history of substance abuse tend to develop dependence and withdrawal symptoms upon abrupt withdrawal.

This is particularly significant, as most studies and reports of pregabalin abuse misuse the reason of substance abuse as a risk factor⁶. It should however be stated that while the sample size for the study was limited and no follow-up study has been conducted on it, it raises concern and points to a neglected area of research.

The reasons for the growing trend of pregabalin dependence and misuse are not clearly defined but contributing factors to the rising incidence includes ease of obtaining large quantities without a prescription with pregabalin prescriptions increasing by 5% between 2021 and 2022 in the UK³.

Additionally, off-label use and lack of thorough understanding about the abuse potential of pregabalin by both prescribers and patients alike⁵.

In recent times, pregabalin has been classified as a Class C Schedule drug in the UK and a Schedule V drug in the United States⁵. This classification indicates that pregabalin cannot be purchased over the counter, and possession or sharing of the drug is only legal with a valid prescription.

Although pregabalin is currently not listed as a substance of abuse, recent studies have revealed that pregabalin has abuse potential, which is exacerbated in patients with a history of substance abuse disorder, as well as patients administered pregabalin along with opioids².

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This places a clear responsibility on prescribers and healthcare professionals when prescribing pregabalin as patients may be unaware of the dependency potential of the medication. Additionally, since pregabalin has a soothing and calming effect, patients may be oblivious to the starting point of dependence, as most patients on pregabalin tend to take them daily.

Prescribers and pharmacists should exercise more caution when prescribing pregabalin to patients already taking opioids as this exponentially increases the abuse potential of pregabalin5.

Prescribers would need to take into cognizance history of substance abuse before prescribing pregabalin and necessitate routine monitoring of patients taking pregabalin to adequately monitor the onset of dependence as well as consider alternatives to pregabalin.

This routine monitoring should involve constant medication review, preferably monthly for patients on long-term therapy and educating them on the signs of dependence.

Furthermore, more intentional steps should be employed in tapering off patients on already high doses of pregabalin as opposed to abrupt discontinuation to prevent the development of withdrawal symptoms.

For patients without any history of substance abuse who need to be started on pregabalin therapy for management of chronic neuropathic pain, prescribers can start therapy by prescribing low doses of the medication with adequate patient counselling to ensure patients do not develop dependence.

Policymakers also have a role to play by establishing a patient registry solely for tracking use and outcome of pregabalin.

More epidemiological surveys that monitor the prevalence rate of pregabalin abuse and dependence should be carried out to make informed decisions on policies to guide pregabalin prescription among prescribers.

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References:

1. Baidya, D. K., Agarwal, A., Khanna, P., & Arora, M. K. (2011).

Pregabalin in acute and chronic pain. Journal of Anaesthesiology Clinical Pharmacology, 27(3). https://journals.lww.com/joacp/fulltext/2011/27030/pregabalin_in_a cute_and_chronic_pain.3.aspx 2. Bonnet, U., & Scherbaum, N. (2017). How addictive are gabapentin and pregabalin? A systematic review. European Neuropsychopharmacology, 27(12), 1185-1215. https://doi.org/https://doi.org/10.1016/j.euroneuro.2017.08.430 3. Care Quality Commission. (2022). National trends in the prescribing of controlled drugs. Retrieved 13/10/2024 from https://www.cqc.org.uk/publications/safer-managementcontrolled-drugs-annual-update-2022/national-trends-prescribingcontrolled-drugs 4. Chiappini, S., & Schifano, F. (2016). A Decade of Gabapentinoid Misuse: An Analysis of the European Medicines Agency’s ‘Suspected Adverse Drug Reactions’ Database. CNS Drugs, 30(7), 647-654. https://doi.org/10.1007/s40263-016-0359-y 5. Evoy, K. E., Morrison, M. D., & Saklad, S. R. (2017). Abuse and Misuse of Pregabalin and Gabapentin. Drugs, 77(4), 403-426. https://doi.org/10.1007/s40265-017-0700-x 6. Grosshans, M., Lemenager, T., Vollmert, C., Kaemmerer, N., Schreiner, R., Mutschler, J., Wagner, X., Kiefer, F., & Hermann, D. (2013). Pregabalin abuse among opiate addicted patients.

European Journal of Clinical Pharmacology, 69(12), 2021-2025. https://doi.org/10.1007/s00228-013-1578-5 Ishikawa, H., Takeshima, M., Ishikawa, H., Ayabe, N., Ohta, H., & Mishima, K. (2021). Pregabalin withdrawal in patients without psychiatric disorders taking a regular dose of pregabalin: A case series and literature review. Neuropsychopharmacology Reports, 41(3), 434-439. https://doi.org/https://doi.org/10.1002/npr2.12195

TOPICS IN BIOMEDICINE

INSIGHTS INTO CLINICAL TRIALS: PERSPECTIVES AND PRACTICES

BY WIKTORIA WISNIEWSKA AND SARA ALNASIR KASSAM TRANSCRIBED BY DILRUBA BOKSH Issue 6 Co-Editors-in-Chief Wiktoria Wisniewska and Sara Alnasir Kassam had the pleasure of having a conversation with Dr Jonathan Bannard-Smith and Professor Mahesh Nirmalan regarding Clinical Trials and their importance in developing lifesaving treatments and answering clinical questions. Dr Jonathan Bannard-Smith is a Critical Care & Anaesthesia Consultant at Manchester University NHS Foundation Trust. Professor Mahesh Nirmalan is a medical education professor, an Honorary Critical Care Medicine Consultant at Manchester Royal Infirmary, and Former Vice Dean for social responsibility at the University of Manchester.

Sara: Can you explain what clinical trials are and what they entail?

Jonathan: Clinical trials aim to test various methods of diagnosing and treating patients and their influence on patient outcomes.

Classically, you can think of it as a comparison between two methods. In a clinical setting, these methods are applied to patients, and their progress is monitored to determine if the different approaches lead to different results. It's a structured experiment to identify the most effective treatments for specific conditions.

Wiktoria: What was your involvement in clinical trials?

Jonathan: My first exposure to clinical trials was at international meetings where the results of trials were presented, and I found them fascinating. While many early critical care trials revealed no difference between treatment groups, they have allowed us to refine our practice toward efficient and effective care.

I was fascinated by how these experiments were organised and conducted across multiple countries, involving large communities of clinical professionals and thousands of patients.

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After completing my training, I decided to work with a prominent trialist in Australia known for conducting extensive trials in our field. Upon returning to Manchester about ten years ago, I decided to focus on conducting clinical trials here and becoming part of the UK community dedicated to addressing these bedside questions. I believe this is where all clinical trials should begin.

In the ICU, we often treat patients with critical and life-threatening conditions.

However, it may surprise many that much of what we do lacks solid evidence in improving patient outcomes.

Many treatments are empirical, based on scientific rationale and physiological principles to support patients until they recover.

However, there remains uncertainty about whether these treatments genuinely benefit patients and if the benefits of treatment outweigh potential harm due to side effects.

Countless questions arise at the bedside— when to administer a treatment, whether to wait or act immediately—that could easily become clinical trials. Therefore, the starting point for clinical trials is often the questions that arise directly from patient care.

Mahesh: Medical practices were often based solely on scientific theories for several decades. For example, if a treatment was found to lower blood pressure, it was frequently implemented without considering potential side effects.

However, every treatment carries risks along with its benefits, and the overall balance is crucial. Thus, there was a growing consensus that real evidence from large cohorts of people was necessary before adopting new practices. This approach is known as evidence-based medicine, emphasising the importance of empirical evidence over theoretical assumptions. This context laid the foundation for introducing clinical trials, which have since played a dominant role in medical decision-making.

Sara: How important is it for these trials to be conducted ethically and morally, in your opinion?

Jonathan: Ethical and legal regulatory standards govern all our research, whether it involves enrolling patients on ventilators in the ICU or testing cell cultures in the lab.

Everything must be conducted ethically. This is somewhat different from how you design a trial. It's essential to start with a clear research question and be thoroughly knowledgeable about the current evidence base surrounding that question. Suppose a question has already been answered through previous research it may not be necessary to repeat this work.

It's beneficial because we can change practice or apply that answer without wasting time and resources on unnecessary trials. Understanding the context of your research question is essential before embarking on a new trial.

Mahesh: The term 'ethics' can be defined narrowly or broadly as necessary. For example, when conducting a clinical trial, the obvious question is whether it will harm people. Therefore, an independent panel needs to evaluate the balance of risk versus benefit, as the person conducting the trial is likely to emphasise its benefits. Another aspect is whether people feel coerced into participating, maybe via financial incentives or fear. The doctor-patient or healthcare professional-patient relationship creates a power hierarchy, and patients might feel obliged to participate, fearing that refusal could affect the care they receive. This indirect pressure can make individuals feel obliged to participate even if it goes against their beliefs.

Large clinical trial companies or pharmaceutical firms might offer financial inducements to participants, which can also prove problematic. Individuals who typically wouldn't have access to personal data will review patient notes, raising concerns about confidentiality. This potential for breach of confidentiality underscores the importance of ethical review processes, which, though timeconsuming, are essential to protect the integrity of the patient-doctor relationship. In clinical trials, stringent protocols are implemented to safeguard patient data from unauthorised access or breaches. Only the clinical team responsible for patient care can access identifiable patient information.

Research teams, integrated within the clinical setting, undergo training identical to that of clinical staff.

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Identifiable data is only accessed when necessary. After uploading, the data undergoes meticulous de-identification (encryption), ensuring complete anonymity and security in the study database. This process complies with UK laws, including the Data Protection Act Sara: Does the standardisation of legislation and uniform guidance by ethics committees aid in risk mitigation? How do you handle tough conversations with patients and their families?

Jonathan: The process undergoes rigorous scrutiny. For example, when seeking regulatory approval for a Phase I clinical trial involving a new drug's first dose in a critically ill patient on a ventilator, I expect extensive questioning about safety and preclinical data. The project will be reviewed by specific ethics committees and regulatory approval panels, such as those focused on paediatric patients, individuals with mental illness, and critical care research.

In critical care, we often enrol participants who cannot consent, such as sedated patients on life support. We adhere to an ethical protocol to enrol these patients and seek their consent after recovering. The UK has robust guidelines and a strong track record for ethical conduct of research involving such vulnerable patient groups.

Engaging with patients is essential. Once a research question is identified and existing evidence is reviewed, the next step is patient involvement. In the UK, we excel in patient and public engagement and involvement. We collaborate with patient groups who have undergone similar care pathways to co-design clinical trials and apply for funding with their input. This partnership helps us understand patients' questions if approached to join a clinical trial. This engagement is crucial to designing a clinical trial. It is carried out in tandem with consultations with statisticians and health economists.

Mahesh: An essential component of our approval process is the provision of a detailed information leaflet that outlines all potential risks, regardless of their severity or frequency. This leaflet must be given to participants well in advance, allowing ample time for them to read, understand, and consider the information. They should also have the chance to ask questions before agreeing to participate and signing the consent form. This is known as the informed consent process, a cornerstone of ethical conduct of research.

In our projects, dedicated teams are trained to assist participants through the informed consent process. It's unacceptable to ask someone to join a study on short notice, as this could exert undue pressure.

Participants must receive the information leaflet at least 24 to 72 hours beforehand. The leaflet includes contact details for any questions they may have. Only after a thorough review and consideration should participants sign the consent form. This ensures they are fully informed and willing to consent.

Sara: In the context of the UK, what additional safeguards should be implemented to protect vulnerable individuals, such as those with cognitive impairments, during their participation in clinical trials?

Jonathan: In the ethics application process, researchers must articulate precisely how their experimental design deviates from standard care for patients with a specific illness within the healthcare system. This involves specifying every alteration, such as additional blood pressure management, new questionnaires, blood sampling, or extra diagnostics like X-rays. Each deviation must be justified with a solid evidence-based rationale, weighing its benefits against any potential burdens for the patient. Ethics committees are crucial in evaluating these justifications, ensuring that proposed changes are proportionate to the study's objectives and do not unnecessarily burden participants. This approach aims to streamline clinical trials by gathering essential data while minimising unnecessary data collection, thereby optimising efficiency in research practices.

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Wiktoria: When an established drug is proven effective for a disease under study, would it be ethically justified to incorporate a placebo into the trial design?

Jonathan: When evaluating a new drug, the ethical consideration for using a placebo arises. Typically, comparing the latest treatment with the established one or in other words, comparing the added benefits of using the new drug against standard care only would be the standard approach under these circumstances.

Placebos traditionally come into play when no existing treatment exists for the studied condition. However, there is a shifting perspective on the necessity of placebos, especially given their high costs and the logistical challenges of blinding participants and assessors in trials. They can be costly and might not always be essential, especially when blinding is feasible among patients, assessors, and statisticians.

Wiktoria: Do the participants have any entitlement to access this proven treatment once the trial has concluded?

Mahesh: When conducting a clinical trial, our goal is to demonstrate the effectiveness of a drug in achieving specific outcomes.

However, even if the trial shows promising results, we cannot immediately implement widespread changes in medical practice. In the United Kingdom, a structured process follows to ensure that any new treatment is not only effective but also socially/culturally viable, and economically viable or cost effective. This decision-making process is overseen by the National Institute for Health and Care Excellence (NICE). This additional rigorous evaluation ensures that broader considerations of effectiveness and acceptability in the healthcare landscape and inform decisions regarding new treatments.

Jonathan: In academic research, particularly in clinical trials, evaluating costeffectiveness often involves considerations beyond the trial's immediate objectives. As researchers, our primary focus is designing and conducting trials to evaluate treatments and report outcomes. Whether a treatment merits public funding falls under the purview of external bodies such as NICE.

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JIn commercially funded research, especially in critical fields such as cancer or rare degenerative diseases, contractual agreements often govern interactions between participants and drug providers. For instance, in double-blind randomised controlled trials (RCTs), participants may receive either the treatment or a placebo. Suppose the treatment proves effective and is approved. In that case, participants who received the placebo might be able to receive the active treatment first. These potential benefits must be agreed before-hand and are carefully regulated under ethical and contractual guidelines, including participants consenting to receive trial updates and treatment alternatives.

However, providing treatments post-trial raises ethical and scientific complexities, potentially compromising the trial's blinding. Despite these complexities, such practices aim to balance scientific integrity with providing potential benefits to participants engaged in pivotal research efforts.

Sara: When the vaccine was developed in high-stakes situations like the global COVID-19 pandemic, would it typically undergo a clinical trial under normal circumstances? How do we uphold efficacy and ethical standards during such critical times?

Jonathan: During the COVID-19 pandemic in the UK, all trials on vaccines and new treatments strictly followed standard practices and regulatory protocols. Despite the urgency of the pandemic, all necessary steps were followed without cutting corners. This focused approach and a surge in eligible participants facilitated rapid advancements in our research. Despite the urgency of the situation to our knowledge, all regulatory approvals from bodies like the MHRA (Medicines and Healthcare Products Regulatory Agency) and HRA (Health Research Authority) were rigorously adhered to, ensuring the integrity and safety of the trials.

The Medicines and Healthcare Products Regulatory Agency (MHRA) scrutinises clinical drug trials. Other bodies may be involved in changes in care pathways. Overall, the Health Research Authority (HRA) is the umbrella organisation for health research in the UK, integrated within NHS infrastructure. This structure supports a unified network of ethics committees, ensuring they adhere to the same guidelines and laws with similar compositions and operating practices.

Mahesh: In fact, there was considerable pressure, especially with certain medications other than vaccines, to bypass the trials and proceed directly because of the urgency and fatal nature of the disease. A notable example is hydroxychloroquine. However, the UK generally resisted such pressures and adhered to the established processes and good practice.

Jonathan: After administering a new trial, one of our primary concerns is monitoring adverse events to determine if any short- or long-term harm may be related to their research participation or their underlying illness. We swiftly identified adverse events during the COVID-19 trials due to the extensive recruitment efforts and rapid vaccine administration. This resulted in rapid changes to the vaccine formulation to prevent recurrence. This process would have been much slower in traditional vaccine trials due to longer intervals between adverse events. Despite criticisms, particularly regarding now-withdrawn vaccines using older technology, our approach enabled us to establish the safety profile much quicker due to the high volume of participants involved simultaneously. It highlights that our research isn't solely about efficacy but also focuses on long-term safety considerations.

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Wiktoria: How are participants screened to ensure their eligibility, mainly when testing a drug for multifactorial conditions?

Jonathan: We generally use a mnemonic called PICO (Population, Intervention, Comparison, Outcome) to guide the screening process for clinical trials. It's crucial to describe the population sampled for a clinical trial clearly and to ensure that it closely matches the end population that might be prescribed the new diabetic drug.

For instance, in sepsis trials, there is no definitive diagnostic test. Instead, we rely on a set of inclusion criteria that patients must meet and exclusion criteria that would exclude them. Creating these criteria involves balancing broad and narrow definitions. A broad inclusion criterion might yield a diverse study population with high external validity, meaning the results widely apply to realworld settings. Conversely, narrow inclusion criteria focus on a specific patient population, offering high internal validity (strength of the study results) but may be less applicable in everyday clinical practice.

Sara: How can researchers ensure that the selection of participants for clinical trials is fair and unbiased, representing the diversity of the population?

Jonathan: From an NHS perspective, ensuring fair and unbiased participant selection in clinical trials is crucial. Our policy is that every patient who enters our facilities is given the opportunity to be included in appropriate trials. We conduct comprehensive screenings daily, from Monday to Friday, particularly in the ICU, to identify eligible participants without discrimination. We make a concerted effort to avoid discrimination of any kind.

For instance, if participant information sheets are only available in English, are lengthy, and require a high reading level, individuals who are non-native English speakers or have lower literacy levels may be excluded. Similarly, suppose follow-up procedures require participants to return to the hospital.

However, they cannot do so due to distance or lack of transportation. In that case, these participants are effectively excluded from the study.

Mahesh: Moreover, when the study is written up as a report or formal paper, the results section typically includes a detailed description of the study population. This description typically includes details such as the mean or median age, the age range, and various demographic characteristics.

Comparing the study population's demographics to the general population. This practice helps control for demographic variables and ensures that the study's findings are accurately contextualised.

Sara: Could you explain how the integration of machine learning and deep learning might improve the success rate of clinical trials if implemented successfully?

Jonathan: AI has immediate potential to enhance the efficiency and costeffectiveness of clinical trials. For instance, electronic patient records (EPRs) already streamline patient screening, automatically identifying eligible candidates based on specific criteria like antibiotic prescriptions for infections. This automation saves time and labour. Additionally, AI could facilitate faster data transfer and transcription, further optimising trial processes.

Moreover, AI could facilitate data management and transfer improvements, further optimising trial operations.

However, challenges remain, particularly in integrating and harmonising data across different healthcare settings and regions.

Current data systems are not yet fully interconnected at the level required for comprehensive analysis and personalised decision-making.

Looking ahead, younger generations of healthcare professionals may increasingly rely on AI at the bedside to inform clinical decisions. Yet, AI is unlikely to replace the human element of patient care, which involves nuanced decision-making and compassionate communication with patients and families. As such, while AI offers promising advancements, its role will complement rather than replace healthcare professionals in delivering patient-centred care.

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Mahesh: Throughout history, every technological advancement has sparked fear and anxiety about potential disruptions and consequences. Artificial intelligence (AI) is no different. The consensus is that AI holds immense potential benefits but also risks causing harm. Like any technology, its outcomes depend on how humanity chooses to utilise it, and the regulatory frameworks put in place Sara: How can we ensure patient data protection amidst concerns about AI's susceptibility to cyberattacks and other security risks?

Jonathan: Within the UK healthcare infrastructure, NHS digital plays a crucial role.

Suppose we can effectively harmonise data across different platforms. In that case, we can achieve labour-saving efficiencies in the short term, with long-term benefits expected from harmonising data across different NHS platforms. However, as you have pointed out data security is important and is an absolute priority for the NHS. Several systems are in place in our own Trusts, Universities and the wider NHS to ensure data security. Specialist units and experts are employed to ensure that all precautions are in place to protect the integrity of data, and these systems are subject to regular audits and checks by internal and external authorities.

The Editorial Team and the writers would like to thank Professor Niroshini Nirmalan for her assistance with establishing a connection with the featured collaborators for this article.

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TOPICS IN BIOMEDICINE

BY EGHOSA ENORIOMWANIHA

Abstract Recreational drugs are mainly used by young people and they are legal and illegal substances taken by individuals for pleasure rather than medical purposes. In England, the most used recreational drug is cannabis among other drugs including cocaine, codeine, ecstasy, alcohol, and nicotine.

Recreational drugs can have a negative influence on men’s sperm by reducing its quality and having an impact on male hormones like testosterone which is necessary for the regulation of the male reproductive system. There are limited studies on the effects of recreational drugs on sperm but there is evidence that demonstrates the negative influence of these drugs on sperm and the male reproductive system. It also relates to health ethics and parental responsibility as it can have a negative impact on their future children leading to the importance of informing the public about the consequences of recreational drugs on the male reproductive system.

What are Recreational Drugs?

Recreational drugs are legal and illegal substances taken by individuals for pleasure rather than medical purposes⁸. They are mainly used by young adults for reasons such as curiosity on the drug’s effect on their wellbeing by making them feel happy or relaxed, or to help them to forget about their personal problems or circumstances⁹. One study reported that 9.5% of the population aged 16 to 59 (around 3.1 million people) and 17.6% of individuals aged 16 to 24 (about 1 million individuals) disclosed using drugs at some point in the year that ended in March 2023¹⁵.

There are many different types of recreational drugs, but the most common drug used in England is cannabis. Research shows 15.4% of those in the 16–24 age group and 7.6% of those in the 16–59 age group confirmed that they consumed the drug at some point in their life¹⁵. Some other examples of common recreational drugs include cocaine, codeine, ecstasy, alcohol, and nicotine.

The effects on recreational drugs on sperm Many people are not aware that apart from the negative effects previously mentioned, recreational drugs can also influence men’s sperm by reducing its quality which could lead to fertility issues in the future.

Recreational drugs have a negative impact on hormones such as testosterone, luteinizing hormone (LH), gonadotropin releasing hormone, and follicle stimulating hormone (FSH) which are necessary for the effective regulation of the male reproductive system, leading to changes in the spermatozoa and male fertility¹².

Cannabis Studies have demonstrated that the use of cannabis, which is also known as marijuana, is linked to the inhibition of LH, FSH and testosterone levels in the bloodstream⁷. Researchers observed that men who smoked cannabis more than once a week suffered from lower sperm concentrations, total sperm counts, motile sperm percentages, and morphologically average sperm percentages⁶. Regular use of cannabis, more than once per week was associated with a 28% decrease in sperm concentration and a 29% decrease in total sperm count, according to a Danish study²⁰. However, research found that gradually stopping cannabis use can reduce these effects, so this is possibly reversible. Based on the study's findings, men who quit smoking cannabis for 77 days produced sperm that lacked most of the known alterations that were evident during their active cannabis usage¹³.

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Cocaine Frequent cocaine use has been associated with lower sperm mobility and concentration as well as a rise in the percentage of sperm with abnormal morphology⁷. Both short-term and long-term cocaine usage damages the ultrastructure of the testes and reduces spermatogenesis. Cocaine triggers cell death, vacuoles, and lipid droplets, which instantly interrupt spermatogenesis and tubule formation⁷. Men who had used cocaine for five years or longer were twice as likely to have poor sperm motility, according to research conducted on male patients at a Yale infertility clinic⁴. The limited information available on how cocaine affects spermatogenesis is obtained from research conducted on animals found that rats that were given large doses of cocaine had reduced seminiferous tubule dimensions and a lower likelihood of pregnancy¹⁸.

Although some effects, primarily decreased motility, are still observed, research indicates that relatively low dosages of cocaine are unlikely to have an enormous effect on sperm quality²¹.

Additionally, some evidence indicates that the alterations are temporary, restoring to normal sperm quality once the use of cocaine is stopped²¹.

Alcohol Alcohol use has been associated with sexual dysfunction, which has been linked to male infertility. This includes issues with arousal and desire as well as erectile and ejaculatory impotence. It has been shown that persistent and excessive alcohol use decreases the levels of gonadotropin and testosterone in the blood, shrinks the testicles, reduces sperm production, and causes low sperm quality⁷. When compared to males who consumed 1-4 units per week, it was found that men who usually consumed more than 40 units per week had a 33% decline in sperm concentration¹⁰.

Alcohol consumption has been linked to impairment of the majority of semen parameters, despite no consistent doseresponse pattern¹⁷. Infertile patients in the "daily drinkers" group had poorer semen quality and hormonal characteristics in comparison to all other groups, according to the same study's results. Also, couples where the male drank over 20 units of alcohol a week had a noticeably longer time frame before getting pregnant¹⁷. Evidence suggests that alcohol abstinence can facilitate rapid changes in sperm quality, shown by the return of normal semen parameters within three months of the absence of alcohol¹⁹.

Codeine

Nicotine

While codeine has been demonstrated to increase male libido and sexual activity, It may also significantly lower copulatory efficiency and reproductive indices¹. Longterm codeine usage has been demonstrated to result in testicular degeneration, reduced sperm quality, and the development of oxidative sperm DNA damage and apoptosis⁷.

It was discovered that at 4 mg/kg b.w., codeine caused a 25% and 30% reduction in sperm plasma membrane integrity in 30 and 60 minutes, compared at 10 mg/kg b.w., which caused a 35% and 42% decline in 30 and 60 minutes². These findings indicated that the poor membrane integrity observed with codeine use was dose-dependent².

One of the most harmful components in cigarette smoke is nicotine. There have been concerns about its impact on the male reproductive system as it was found that nicotine reduced the number of spermatocytes and spermatids³. Because the testes are affected by cigarette smoke, continuous exposure to it changes the shape of spermatogenic cells and interferes with spermatogenesis and sperm production, all of which directly contribute to male infertility³.

In addition, testosterone, pituitary gonadotropins, and the antioxidant status of the testicles are all altered by nicotine.

Research revealed that the density of sperm in smokers was 13%–17% lower compared to nonsmokers¹¹.

Ecstasy The effects of ecstasy were investigated in animal research, which revealed an increased incidence of tubular degeneration, damage to sperm DNA and interstitial oedema in the testes, although sperm motility and morphology were unaffected on all tested levels⁴.

Testicular damage was also demonstrated in another study involving male rats, where the higher levels of reactive oxygen species (ROS) produced by nicotine targeted the polyunsaturated fatty acids (PUFA) in the testes membrane, eventually resulting in the impairment of testicular function and structure³.

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This means low sperm quality caused by nicotineinduced oxidative damage could be the cause of the structural damage to the testicles and an impairment of the testes' normal function.

Any male who stops smoking at least three months prior conception will have better sperm with a higher possibility of fertilising an egg. This means that quitting smoking can reverse its effects on sperm²².

How do recreational drugs and its effects on sperm relate to ethics?

Individuals who take recreational drugs often believe that there are no negative effects from regular use or that the effects do not have any major consequences¹⁴. Although it is known that there are limited studies on the effects of recreational drugs on sperm and fertility because of ethical concerns and insufficient reporting of the problem, there is still strong evidence that demonstrates that using recreational drugs can have a negative influence on sperm and the male reproductive system in general¹⁸.

From an ethical standpoint, recreational drugs have an impact on sperm quality which influences the chances of conceiving and giving birth to healthy children apart from causing issues in men’s reproductive health¹⁸. Equally, in terms of parental responsibility, future fathers should responsibly prevent unhealthy behaviours like recreational drugs that could cause their future children to face developmental or overall health issues due to the sperm quality¹⁶.

Recreational drug usage can cause problems in the future because the parent might not be able to give their child a safe and healthy environment. The reason behind this is that drug usage may eventually make it difficult for a parent to provide for their child's necessities and could cause doubt on their ability to keep their child safe⁵.

Everyone should be informed and aware about the risks and consequences of these and its impact on fertility and child health. This demonstrates that it is ethically necessary to inform the public about the harmful consequences of recreational drugs on the reproductive system by putting in place initiatives and raising awareness to reduce its incidence.

This also leads to ethical issues concerning informed consent due to the lack of public health education as individuals cannot make the right decision due to not being appropriately informed about the risk of recreational drugs on their own health and the health of their unborn child⁴.

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References 1. Ajayi, A. F., & Akhigbe, R. E. (2020). Assessment of sexual behaviour and fertility indices in male rabbits following chronic codeine use. Andrology, 8(2), 509-515. https://doi.org/https://doi.org/10.1111/andr.12717 2. Ajayi, A. F., & Akhigbe, R. E. (2020). Codeine-induced sperm DNA damage is mediated predominantly by oxidative stress rather than apoptosis. Redox Report, 25(1), 33-40. https://doi.org/10.1080/13510002.2020.1752003 3. Budin, S. B., Kho, J. H., Lee, J. H., Ramalingam, A., Jubaidi, F. F., Latif, E. S., Zainalabidin, S., Taib, I. S., & Mohamed, J. (2017). Low-dose nicotine exposure induced the oxidative damage of reproductive organs and altered the sperm characteristics of adolescent male rats. The Malaysian journal of medical sciences, 24(6), 50-57. https://doi.org/10.21315/mjms2017.24.6.6 4. Fronczak, C. M., Kim, E. D., & Barqawi, A. B. (2012). The Insults of Illicit Drug Use on Male Fertility.

Journal of Andrology, 33(4), 515-528. https://doi.org/https://doi.org/10.2164/jandrol.110.011874 5. Gumbrill-Ward, H. (2022). The impact of drug abuse in child arrangement matters. Retrieved 11/09/2024 from https://www.familylawpartners.co.uk/blog/the-impact-of-drug-abuse-in-childarrangement-matters 6. Gundersen, T. D., Jørgensen, N., Andersson, A.-M., Bang, A. K., Nordkap, L., Skakkebæk, N. E., Priskorn, L., Juul, A., & Jensen, T. K. (2015). Association Between Use of Marijuana and Male Reproductive Hormones and Semen Quality: A Study Among 1,215 Healthy Young Men. American Journal of Epidemiology, 182(6), 473-481. https://doi.org/10.1093/aje/kwv135 7. Hamed, M. A., Ekundina, V. O., & Akhigbe, R. E. (2023). Psychoactive drugs and male fertility: impacts and mechanisms. Reproductive Biology and Endocrinology, 21(1), 69. https://doi.org/10.1186/s12958-023-01098-2 8. Hawkes, N. (2016). Sixty seconds on . . . psilocybin. BMJ, 353, i2775. https://doi.org/10.1136/bmj.i2775 9. Hazell, T., & Tidy, C. (2022). Recreational drugs. Retrieved 11/09/2024, from https://patient.info/healthy-living/recreational-drugs 10. Jensen, T. K., Gottschau, M., Madsen, J. O. B., Andersson, A.-M., Lassen, T. H., Skakkebæk, N. E., Swan, S. H., Priskorn, L., Juul, A., & Jørgensen, N. (2014). Habitual alcohol consumption associated with reduced semen quality and changes in reproductive hormones; a cross-sectional study among 1221 young Danish men. BMJ Open, 4(9), e005462. https://doi.org/10.1136/bmjopen-2014005462 11. Kovac, J. R., Khanna, A., & Lipshultz, L. I. (2015). The effects of cigarette smoking on male fertility.

Postgraduate Medicine, 127(3), 338-341. https://doi.org/10.1080/00325481.2015.1015928 12. Lampiao, F., Lockey, T., Jana, C. E., Lee, D. M., & du Plessis, S. S. (2014). Drugs: Recreational and Performance Enhancing Substance Abuse. In S. S. du Plessis, A. Agarwal, & J. E. S. Sabanegh (Eds.), Male Infertility: A Complete Guide to Lifestyle and Environmental Factors (pp. 93-104).

Springer New York. https://doi.org/10.1007/978-1-4939-1040-3_7 13. Lopez, S. (2021). Smoking Abstinence Could Lower Effects of Cannabis on Sperm https://psychiatry.duke.edu/news/smoking-abstinence-could-lower-effects-cannabis-sperm 14. NIDA. (2018). Understanding Drug Use and Addiction DrugFacts. https://nida.nih.gov/publications/drugfacts/understanding-drug-use-addiction 15. Office For National Statistics. (2023). Drug misuse in England and Wales: year ending March 2023. https://www.ons.gov.uk/peoplepopulationandcommunity/crimeandjustice/articles/drugmisusein englandandwales/yearendingmarch2023#main-points 16. Pickard, H. (2017). Responsibility without Blame for Addiction. Neuroethics, 10(1), 169-180. https://doi.org/10.1007/s12152-016-9295-2 17. Sansone, A., Di Dato, C., de Angelis, C., Menafra, D., Pozza, C., Pivonello, R., Isidori, A., & Gianfrilli, D. (2018). Smoke, alcohol and drug addiction and male fertility. Reproductive Biology and Endocrinology, 16(1), 3. https://doi.org/10.1186/s12958-018-0320-7 18. Schifano, N., Chiappini, S., Mosca, A., Miuli, A., Santovito, M. C., Pettorruso, M., Capogrosso, P., Dehò, F., Martinotti, G., & Schifano, F. (2022). Recreational Drug Misuse and Its Potential Contribution to Male Fertility Levels’ Decline: A Narrative Review. Brain Sciences, 12(11).

19. Sermondade, N., Elloumi, H., Berthaut, I., Mathieu, E., Delarouzière, V., Ravel, C., & Mandelbaum, J. (2010). Progressive alcohol-induced sperm alterations leading to spermatogenic arrest, which was reversed after alcohol withdrawal. Reproductive BioMedicine Online, 20(3), 324-327. https://doi.org/https://doi.org/10.1016/j.rbmo.2009.12.003 20. Srinivasan, M., Hamouda, R. K., Ambedkar, B., Arzoun, H. I., Sahib, I., Fondeur, J., Escudero Mendez, L., & Mohammed, L. (2021). The Effect of Marijuana on the Incidence and Evolution of Male Infertility: A Systematic Review. Curēus, 13(12), e20119. https://doi.org/10.7759/cureus.20119 21. Testhim. Cocaine and Male Fertility. https://testhim.com/news/lifestyle/cocaine-and-male-fertility 22. YourFertility. (2018). Smoking. Retrieved 11/09/2024 from https://www.yourfertility.org.au/everyone/drugs-chemicals/smoking

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TOPICS IN BIOMEDICINE

Challenging the Physiology We See in Film

BY SARA ALNASIR KASSAM

Sara: First, where did you get the inspiration for this module? As in, why teach Physiology through film? Áine: I've been teaching a module in integrative physiology for about 20 years. I developed this module because students often tend to think about different physiological systems in isolation, and can struggle with bringing different aspects of physiology together and thinking about how the body works as a whole integrated organism, which is the key to Physiology. I put a module together where students would look at broad questions or case studies that would challenge them to integrate their entire knowledge of physiology. In recent years, I started bringing questions about film into the module.

I was inspired by Professor Mike Tipton, a brilliant physiologist who works on the Physiology of extreme environments. He mentioned to me that he was the physiology consultant on the film ‘Everest’. He's got a brilliant lab in Portsmouth where researchers can model extreme environments, different atmospheric pressures, temperatures, etc. And he actually had the actors from the film in there to simulate the experience of being at altitude to help their performance. And first of all, I thought, what a cool thing to do. And second, I thought that would be a fascinating integrative-type question.

Through this approach, the students watch films that I assign to them and think about what would actually happen physiologically in those situations and also whether the portrayal makes sense to them as physiologists.

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I developed it so that the film questions are done by the students at the last stage of the module, and they present their findings via individual oral presentations. It's getting them to think about integrating physiology in a different and fun way.

Sara: What was your students' consensus when you asked them how they found this particular way of learning physiology? What was their response to it? Áine: Yeah, they love it. I surveyed them and made a word cloud of their responses; the word that came up most often was "fun". The students prepare really good PowerPoint presentations and often put in little clips and diagrams. It helped them to think about Physiology from a different angle. Some of them did believe that it was a lot of fun, but maybe they didn't learn as much as they did from some of the other sessions that were a lot more structured.

But generally, they like it as a way of finishing off the module with something a bit different.

Sara: Let's talk about your talk at the Physiological Society meeting at Salford. It was titled 'What Volume Is Ryan Reynolds?'. I read that title in the programme book and asked, "Hang on a minute, why are we talking about Ryan Reynolds?" Can you tell our readers the story behind your talk? Áine: Yeah. I have great fun when trying to think of new films every year. Physiology encompasses everything, and there are a lot of movies that concentrate on particular diseases, for example, while some focus on extreme events. Buried is one of them. Buried is about an American in Iraq who gets kidnapped for ransom, and he gets buried alive in a coffin. He wakes up in the coffin and only has a phone that he can use to communicate with people. But the film is done in real-time, over 90 minutes - you spend 90 minutes with him in the coffin. So, the challenge for the students is to ask if the portrayal of what's happening to him is accurate physiologically.

The title for the talk came from the title of a slide that the student who studied that film last year included in her presentation (Figure 1). It was, "What volume is Ryan Reynolds?" because she needed that information to figure out how long his oxygen would last, when he would get hypoxic and when is would be hyperventilating and so on. So she calculated, the volume of the coffin and how much air would be in that? But it's not just air because Ryan Reynolds displaces some of the air. So, what volume is Ryan Reynolds? When you take him into account, how much air is there and how much oxygen is there?

Spoiler alert: in the film, Ryan Reynold’s character dies because the coffin collapses, and sand comes inside and suffocates him.

But according to her calculations, he should have been unconscious within an hour and therefore the film couldn't have been 90 minutes long. But that's just according to her calculations - the class then had a discussion to determine whether we thought her conclusion was correct.

Figure 1: Photograph of Professor Kelly’s student, presenting her talk titled “What Volume Is Ryan Reynolds?”, duly inspiring Prof Kelly’s talk at The Physiological Society meeting at the University of Salford in May 2024. Photo Credit: Professor Áine Kelly.

Sara: Do you think Physiology is depicted accurately in films? Áine: I think it depends. Some films do it better than others. Everest did it very well because they got Mike on board as an expert to discuss things.

Sometimes, some aspects of Physiology are depicted well, but not others. So, for example the reactions to changing temperatures, activation of the sympathetic nervous system, etc. Sometimes, these things are plot devices if you like, and other times the film is trying to depict something real.

Some of the films I chose are based on real-life events, and again, the extreme Physiology ones are usually the coolest. We can compare 127 Hours and Titanic, for example. In some films, they try to depict the Physiology well, because that tells part of the story or helps to tell the story. Sometimes it's just sort of an incidental little plot point.

Sara: If we were to look at general public education of physiology using films, would these depictions be ethical, with the potential of the assumption that the physiology depicted is wholly accurate? Áine: The module has thrown up a few surprising ethical questions in the years I've been doing this. I think if the filmmakers are portraying a disease or a real-life situation that people can find themselves in, an attempt really should be made to be accurate. If it's something like the HIV AIDS as depicted in Dallas Buyers Club or dementia or Parkinson’s Disease, that really does impact on people's lives, I think the film makers should try to be as accurate as they possibly can in terms of depicting diagnosis and symptoms and drug treatments etc.

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Sara: Having them talk about the ethical side of physiology, has it enhanced your students as student scientists, do you think? Áine: I didn't ask that that question directly, but I would hope so. Hopefully they already have a lot of skills and a lot of knowledge by that stage as the students who take this module are final year students. They can draw on a lot of knowledge in these discussions. I think it's important to think about things like ethics because science doesn't exist in a vacuum - it has to apply to society. So I think it's important that we think about these issues and how we use science to better society.

I've tried to keep the films I choose realistic. So I haven't gone into zombie Physiology or superhero Physiology. You could go down that road in terms of what might be physiologically possible for humans above and beyond what's possible for us now. But I've sort of stayed away from that. I mean, I've tried to keep it within the realms of realistic physiology, but that's not augmented in any way.

Sara: Do you think using films with augmented physiology could be something you would be willing to experiment with? Áine: Definitely. I'd be interested to see what the students come up with because of course, in this, the students are the ones who do all the work! I just assign the films and then can sit back to see all the brilliant work they've done and have an interesting discussion afterwards.

Sara: would you like to leave our readers with any final thoughts? Which films would you recommend, to help people learn about physiology? And what approach would you recommend they take? Áine: I like some of the extreme Physiology ones like ‘127 Hours' or 'Buried'. That might not be everyone’s cup of tea. But everywhere you look, there's Physiology. You can probably find some physiology in any film, as long as they're not just animations or something like that. If there are living beings on the screen and moving around in the world, then Physiology is there.

Sara: Thank you so much, Áine. I loved learning about the inspiration behind your use of film to teach physiology. Thank you so much for joining me today. I appreciate your time.

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TOPICS IN BIOMEDICINE

Uncovering Ethics In Bioscience

BY ANISE YOUNIS Ethics is a recurrent conversation in science, with the advancement of new technologies, cellular research and clinical trials, we find ourselves asking how well the population of service users are really protected.

Nowadays, concerns arise about how well our privacy is being protected and how our consent and safeguarding is being prioritised. While the additions of new laws and regulations aim to protect human rights, they raise the all-important question in the world of bioethics about the responsibility of scientists and institutions: How well can these organisations ensure the protection of service users while keeping pace with novel scientific inventions?

This article had a contribution from and has been reviewed by Professor Harry Witchel, a renowned Doctor of Physiology and Neuroscience, currently teaching at Brighton and Sussex Medical School. By sharing his expertise, he has provided a better understanding of ethics and decision making of scientists over time.

The Editorial Team would like to thank Prof Witchel for his time and expertise that he has shared.

Ethics through time To understand the fundamentals of ethics and the evolution of law over time, it is important to discuss prior civilisations where legal systems and moral codes naturally differed.

Early descriptors of ethics The birth of ethics comes from an era where humans began to reflect on what behaviours were in the best interest of life. According to the World History Encyclopaedia, the oldest known code of law was written by King UrNammu in 2100-2050 BCE a Sumerian king who presented 57 laws to his people⁵. King UrNammu presented the idea that this code was written by the gods sharing ideas that all subjects are equal disregarding social status.

Another early surviving document from the Egyptians supported ideas of ideal conduct and societal behaviour for boys⁹. Arguably, this document only focused on how to achieve social favour and did not delve into ethics but conveyed ideas about not passing judgement and how others should be treated.

Later on, around 350 BCE, Aristotle wrote describing the theory of Nicomachean Ethics as the nature of human actions derived from the concept of happiness³. The preface of the discussion highlights the difference in opinion surrounding the best interest for mankind and how disagreement may be resolved. Ideally all of humankind would have the same ideals whereby the same morals and values are shared, in this way there would never be a difference in opinions and conflict would consistently be avoided.

This however, is impossible, the difference in culture, religious belief and social etiquette paired with the ability of man to have free will ensures there will always be differences in values. For instance, female genital mutilation (FGM) is considered the social norm in some regions of Africa, the Middle east and Asia¹¹. Most contemporary Western societies consider this practice highly unethical practice, as this is a clear violation of human rights for girls and women. It goes without saying that societies have their reasons for such practices, traditional patriarchal societies have associated the practice with coming of age in preparation for marriage to prevent fornication and foster fidelity¹¹. There are no religious scripts that advocate for the practice, but it is believed that there is religious support.

The 13th century philosopher, Thomas Aquinas discussed that there exists two forms of law: an eternal law, which is an omnipotent God's law governing the universe and a natural law which humans acknowledge through reason⁶. The idea that God ordains humans to ultimate happiness may, for certain groups of people, result in the addition of practices that are thought to please the God in which they follow¹. One can argue, FGM is an example of this.

Many other ethically questionable practices learnt about in history result in the addition of new laws to prevent such disasters from recurring.

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Past unethical disasters and their implications It is apparent that rules are added to prevent the recurrence of historical mishaps and ethical disasters, mishaps that question the idea that decisions are made in the best interest of humankind- eugenics was the prime example. In the year 1883 Sir Francis Galton invented the term "eugenics", which was defined as the selection of desirable characteristics to better equip latter generations¹⁰. This term, which was initially accepted by scientists and political leaders, rapidly degenerated as a fundamental science after the Nazis used eugenics in an attempt to eradicate many groups of people (Jews, Roma, the disabled, homosexuals) who they viewed as undesirable for the human gene-pool². The publication by Kevles highlights the practice of eugenics from the 1930s 1970s in Sweden, where 60,000 people were sterilised in an attempt to prevent the number of infants born with genetic disorders. In many societies these practices were driven by a superiority complex of particular races over others. This gave life to negative eugenics, the belief that the quality of the human-race may be improved by eliminating ‘inferior’ people. That poses the question, who is allowed to decide which group of people are inferior?

In recent times there has been the abolishment of deep-rooted societal ideas, this is all to say that we as humans acknowledge our belief is altered by the development and discoveries of new theories and ideas.

The Impact of ethical theories on novel science Variations of regulations and laws exist to protect patients in multiple ways with new regulations being implemented the moment a practice goes wrong – to prevent recurrence. The Centres for Disease Control and Prevention (CDC) alongside the Federation of State medical boards (US), The Health and Care Professions council (UK) and even the United Nations are examples of organisations that work in the best interest to protect human rights and regulate the use of certain technology in scientific practice.

Even with these heavy regulations what is currently deemed as unethical practices still occur unnoticed until it is uncovered.

A 2018 report of the first gene-edited infants shocked the world of science and bioethics as we know it. Scientist He Jiankui was responsible for using clustered regularly interspaced short palindromic repeats (CRISPR) to alter the lives of twin girls. By disabling the C-C Motif Chemokine Receptor 5 (CCR5) which is a HIV co-receptor enabling the entry of HIV into host cells, Jiankui was able to make these children immune to HIV4. In the UK, The Human Fertilisation and Embryology (HFE) Act prohibits the insertion of an embryonic cell with an altered germline DNA into a woman. Similarly, the Chinese Ethics Guiding Principles for Research on Embryonic Stem Cells banned research of embryos in vitro 14 days after conception, and its implantation into a uterus⁸.

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This research faced much global backlash with many scientists in agreement that this action was not morally or ethically sound; from birth, the lives of these children are the result of a science experiment; however, their lives are a testament to the functional ability of scientific technology. Finally, one could argue that not intervening when it is known that quality of life could be greatly improved is not ethically correct.

The new generation of scientists alongside established governing bodies are now responsible for deciding how novel technologies should be implemented in modern medical treatments. As a scientist or someone who can understand the gravity of some of these new advancements there are a few things to consider: Is it ethical to prevent the use of new technologies when it is certain they could considerably alter patient diagnosis and treatment for the better? Is it ethical to prevent the use of gene editing in cases like the one above, removing the need for treatment by preventing the disease?

Or has science gone too far, and should this practice be prevented?

A quote from Edward Osborne Wilson, American sociobiologist, stated “We have palaeolithic emotions, medieval institutions and godlike technology. It is terrifically dangerous and now it is approaching a point of crisis overall⁷.” How can we utilise new technology in a way that is not harmful to prevent unethical mishaps?

References 1. Floyd, S. (n.d.). Thomas Aquinas: Moral Philosophy. Retrieved 30/10/2024, from https://iep.utm.edu/thomasaquinasmoral-philosophy/#H4 2. Kevles, D. J. (1999). Eugenics and human rights. BMJ, 319(7207), 435. https://doi.org/10.1136/bmj.319.7207.435 3. Kraut, R. (2022). Aristotle's Ethics. https://plato.stanford.edu/archives/fall2022/entries/aristotle-ethics 4. Lopalco, L. (2010). CCR5: From Natural Resistance to a New Anti-HIV Strategy. Viruses, 2(2), 574-600.

5. Mark, J. J. (2021). Code of Ur-Nammu. Retrieved 30/10/2024 from https://www.worldhistory.org/Code_of_Ur-Nammu/ 6. New Advent. (1920, 2017). Question 94. The natural law. New Advent LLC. https://www.newadvent.org/summa/2094.htm 7. Oxford Reference. (2016). Edward O. Wilson 1929 - American sociobiologist. In S. Ratcliffe (Ed.), Oxford Essential Quotations (Vol. 4). Oxford University Press. https://www.oxfordreference.com/display/10.1093/acref/9780191826719.001.0001/q-oro-ed4-00016553 8. Raposo, V. L. (2019). The First Chinese Edited Babies: A Leap of Faith in Science. JBRA Assist Reprod, 23(3), 197-199. https://doi.org/10.5935/1518-0557.20190042 9. Singer, P. (2024). The history of Western ethics. Britannica. Retrieved 30/10/2024 from https://www.britannica.com/topic/ethics-philosophy/The-history-of-Western-ethics 10. Wilson, P. K. (2024). Eugenics. Britannica. Retrieved 30/10/2024 from https://www.britannica.com/science/eugenicsgenetics 11. World Health Organization. (2024). Female genital mutilation. Retrieved 30/10/2024 from https://www.who.int/news-room/fact-sheets/detail/female-genital-mutilation

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TOPICS IN BIOMEDICINE

Sustainable Development Goals Humanising Science Beyond the Lab

BY JULIA CASSEROTI

The United Nations (UN) has developed 17 objectives to improve education, health and sanitation, poverty, hunger, etc. These objectives are called Sustainable Development Goals (SDGs). This article mainly focused on SDG 3, which promotes ideal health and well-being, where scientific contribution has been essential to its development. Nevertheless, barriers to poverty seen in Sub-Saharan regions have limited further advancements, requiring social protection programme investment through the government. Expansion of HIV treatments, such as Cabenuva, has reduced AIDS-related deaths by 50%, although eradication of social discrimination is essential to surpass the AIDS-related stigma present since the 1980s. An estimated 80% of women will be content with their reproductive health by 2030, for instance, due to the development of the HPV vaccine, which prevents cervical cancer. A drastic decline in vaccination is still observed, which calls for more efficient vaccination incentives. Lastly, the article focused on goal 12, highlighting the importance of replacing medical plastic with biodegradable materials such as starch to ensure a more sustainable and eco-friendly environment. In the next six years, economic and socio-protective regulations will be needed as a starting point for the SDG targets to be possible to reach by 2030.

A lot has been discussed recently about a more sustainable future and its vital importance within society. Nevertheless, what is sustainability, and how can we achieve it? Sustainability is a broad term encompassing social, political, environmental, and economic interconnections and integrations to come to fruition⁷. It is the knowledge of sustainability’s promise and capacity for transformation towards an ideal quality of life that confronts and tackles current global challenges such as poverty. This has become of interest to United Nations (UN) members, who want to explore and establish sustainable development goals (SDGs) to achieve this. The 17 sustainable development goals and 169 targets were created in September 2015 at a sustainable development conference held in Rio de Janeiro, with aims to improve factors such as education, health and sanitation to ensure the same standard quality globally, eradicate poverty and hunger and promote world peace by 2030⁴. With just six years to 2030, how far are we achieving these goals? What are the scientific research contributions towards the attainment of these goals?

As it has emerged in biomedical science, it is our core interest and need to keep abreast of goal three of the SDGs, which refers to promoting good health and wellbeing¹¹. According to the 2023 SDGs progress report by the United Nations, we can observe considerable progress towards goal three. For instance, it is reported that among members of the UN, 73% have fought or are working to reduce the mortality rate among children under five, fulfilling objective 3.2. However, among the remaining 27%, approximately 4/5 of the countries are concentrated in the subSaharan region, which stands out as one of the regions of extreme poverty globally.

Perhaps the possible progress towards improvement would be correlated to goal one, which aims to eradicate poverty and raise the economy of such societies, thus promoting and ensuring improvement in health. Nevertheless, this reality seems distant when looking at the data reports from the UN, which estimate that 575 million people live in precarious situations and that this number will not improve unless governments invest more in social protection programmes for further progress¹².

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Science has revolutionised the world and brought unimaginable benefits to society; its health benefits are no exception. As mentioned, there are still changes that need to occur to ensure the promotion of ideal health and wellbeing globally. Even so, the substantial assistance scientists can provide in ameliorating healthcare cannot go unnoticed. This can be evidenced, for example, through advances in HIV treatment, which, according to statistics from the United Nations, have reduced approximately half of the deaths related to AIDS (advanced state of HIV) between 2010 and 2021¹². New HIV treatment, such as retroviral injections, made this reduction possible Take Cabenuva as an example, which involves a combination of ART therapy drugs, Integrase inhibitors and NNRTIs that prevent viral replication⁵. The New England Journal of Medicine has shown this to maintain viral levels at undetectable levels. This is beneficial in the prevention of HIV progression and transmission⁹-¹⁰. Despite such benefits, social discrimination and AIDS-related stigma have created barriers to access to treatment. The “bad label” that the name AIDS carries originate from its discovery in the 80s when it was called “gay-related immune disease”, which imposed shame on infected people and has limited their search for treatment, even to this day⁶. To seek progress in ending the AIDS epidemic reported by objective 3.3 of the UN, it will be necessary to impose stricter laws against discrimination, especially within the healthcare sector, and to implement cautious monitoring measures. This will be an arduous and laborious task, considering insufficient and unreliable data on discrimination across countries².

Moreover, access to women's reproductive healthcare has positively increased, which will make it possible for approximately 80% of women to feel satisfied by 2030. The invention of the HPV vaccine is considered one of the revolutionary milestones in advancing female reproductive health. This vaccine helps prevent cervical cancer, which has been common among women and is administered during early adolescence (ages 12-13) as a preventative measure. However, recent data from the United Nations highlights the decline in childhood vaccination, estimating that 21 million children will not receive essential health vaccines in 2022.

Despite the HPV vaccine being introduced in 67% of UN member countries as part of their immunisation campaigns, it covers only 15% of the population.

Implementing health information systems through technology can be crucial in increasing vaccination coverage13.

Implementing health information systems through technology can play a pivotal role in increasing vaccination coverage. An article published in 2021 in the British Journal of Medicine has shown the effectiveness of SMS reminder messages in improving vaccination rates in lower to middle-income countries. These quick, direct messages enhance communication between patients and healthcare providers, making access to vaccination information more efficient³.

Sustainability is often linked to ecological sustainability, which seeks to guarantee the performance of human activities that respect the limits of the environment. Goal 12 of the Sustainable Development Goals (SDGs) considers the importance of sustainable material production, minimising waste, and using eco-friendly, renewable resources¹².

In the daily operations of biomedical scientists, laboratories frequently use disposable materials, particularly plastics. Research shows that plastic accounts for approximately 30% of medical waste worldwide, with the UK producing 133,000 tonnes annually. This plastic waste in syringes, blood sampling tubes, and gloves significantly contributes to global warming by releasing greenhouse gases.

Furthermore, exposure to certain plastics has been linked to cancers such as leukaemia and lymphoma¹. Given these environmental and health concerns, it is crucial to implement measures to reduce plastic use in alignment with Goal 12. This can be done by utilising the three Rs of waste management: reduce, reuse, and recycle. For example, reducing plastic consumption can be achieved by converting its usage to other material sources. In the UK, plastic waste bins have been replaced by paper-based bins. Additionally, biodegradable plastics made from corn are a potential solution, though they may disrupt food supplies⁸.

What can be concluded is that over the next six years, extensive and arduous work will be needed to achieve the SDGs, most of which will come from the government through economic and socioprotective measures. Significant advances have been seen in the healthcare sector, corresponding to SDG 3, where gradual improvement is expected.

However, when observing global poverty indices related to SDG 1 and its tendency for nonimprovement, this raises concerns about the possibility of it being an unachievable goal for the United Nations by 2030. It requires more difficult measures to implement and change than those for SDG 12.

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References 1. Davey, M. (2023). Plastics cause wide-ranging health issues from cancer to birth defects, landmark study finds. The Guardian. https://www.theguardian.com/environment/2023/ma r/29/plastics-cause-wide-ranging-health-issues-fromcancer-to-birth-defects-landmark-study-finds 2. European Centre for Disease Prevention and Control.

(2024). Evidence brief: Progress towards reaching the Sustainable Development Goals related to HIV in the EU/EEA. https://www.ecdc.europa.eu/en/publicationsdata/evidence-brief-progress-towards-reachingsustainable-development-goals-related 3. Eze, P., Lawani, L. O., & Acharya, Y. (2021). Short message service (SMS) reminders for childhood immunisation in low-income and middle-income countries: a systematic review and meta-analysis.

BMJ Global Health, 6(7), e005035. https://doi.org/10.1136/bmjgh-2021-005035 4. Imaz, M., & Sheinbaum, C. (2017). Science and technology in the framework of the sustainable development goals. World Journal of Science, Technology and Sustainable Development, 14(1), 2-17. https://doi.org/10.1108/WJSTSD-04-2016-0030 5. International Association of Providers of AIDS Care.

(2024). Cabenuva. Retrieved 02/10/2024 from https://www.iapac.org/fact-sheet/cabenuva/ 6. King, N. (2012). HIV/AIDS + education: Lessons from the 1980s + the gay male community in the United States. UN Chronicle, 48(1), 16-17. https://doi.org/https://doi.org/10.18356/85e9f37b-en 7. Ortúzar, J. d. D. (2019). Sustainable Urban Mobility: What Can Be Done to Achieve It? Journal of the Indian Institute of Science, 99. https://doi.org/10.1007/s41745-019-00130-y 8. Rizan, C., Mortimer, F., Stancliffe, R., & Bhutta, M. F. (2020). Plastics in healthcare: time for a reevaluation. Journal of the Royal Society of Medicine, 113(2), 49-53. https://doi.org/10.1177/0141076819890554 9. Skinner, G., & Malebranche, D. (2021, 30th May 2024).

Cabenuva for HIV Treatment: What You Need to Know. The Body. Retrieved 02/10/2024 from https://www.thebody.com/health/hiv-cabenuva 10. Toegel, F., Rodewald, A. M., Novak, M. D., Pollock, S., Arellano, M., Leoutsakos, J. M., Holtyn, A. F., & Silverman, K. (2022). Psychosocial Interventions to Promote Undetectable HIV Viral Loads: A Systematic Review of Randomized Clinical Trials. AIDS Behav, 26(6), 1853-1862. https://doi.org/10.1007/s10461-02103534-z 11. United Nations. (2015, 19th October 2023).

Sustainable Development Goals - Goal 3: Ensure healthy lives and promote well-being for all ages.

Retrieved 02/10/2024 from https://www.un.org/sustainabledevelopment/health/ 12. United Nations. (2023). The Sustainable Development Goals Report 2023: Special Edition. https://unstats.un.org/sdgs/report/2023 13. United Nations. (2024). The Sustainable Development Goals Report 2024. https://unstats.un.org/sdgs/report/2024

TOPICS IN BIOMEDICINE

AI in Cardiovascular Research

Cardiovascular research encompasses a vast array of challenges such as including the development of effective therapeutics and access to them, education about cardiovascular pathologies, and the implications of cost. But what if the problems we are trying to solve could be addressed with the use of artificial intelligence (AI)? This article explores how AI is currently being utilised in some medical fields and is continuously being improved for greater precision to aid in advancements in biological understanding⁴.

AI is technology that is used to solve problems by simulating human intelligence, allowing us to perform data handling in a more rapid but accurate manner. This can be beneficial in diagnostics, therapeutics, and management of existing healthcare data, which is what AI is currently being used for. AI is an umbrella term which encompasses many subcategories. These include machine learning, natural language processing and rule based expert systems.

Machine learning uses data and algorithm analysis which allows learning without the need to explicitly program technology, fundamentally ascertaining new outcomes and performing complex tasks. Machine learning models are trained to use large data sets including ECG data via techniques like parallelisation6. This involves integrating a variety of methods such as specialised algorithms, workload split across generators and utilising graphics processing units (GPUs), effectively, combining these techniques together improve the efficiency, speed and accuracy of large datasets and provide high sensitivity and specificity. The specialised algorithms used are specifically designed to carry out thorough analysis and the software trains the machines.

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For example, within a study using unsupervised learning, the machine was trained without ECG recordings and is trained in annotations performed by cardiologists that would be used in recordings and identifying cardiovascular conditions like arrythmias. Unsupervised learning utilises clustered input which effectively groups similar datapoints together and can then learn based on the annotations for when scanning through ECG datasets. AI is also trained through deep convolutional neural networks which scan through data and predict clinical outcomes, and this can be applied to ECG datasets to predict conditions such as left ventricular dysfunction¹-².

Natural language processing is when technology is used to generate language and uses data for computers to comprehend linguistics and interpret this information. Rule- based expert systems exploit data using a set of rules to determine decision-making and employ logical reasoning to execute outcomes.

Currently ongoing studies using AI in areas of cardiovascular research, diagnosis and therapeutics are being developed.

One major study has involved the diagnosis of an asymptomatic left ventricular dysfunction (ALVD). ALVD is a type of heart failure resulting in reduced blood flow through the left ventricle leading to loss of contractility, ultimately progressing to chronic heart failure. AI was used within the study via an electrocardiogram (ECG) to determine patient risk of developing the disease within asymptomatic patients and had high levels of accuracy, thus delivering beneficial outcomes within cardiovascular diagnosis.

AI can however pose algorithmic bias and unintentionally propagate health disparities due to biased training in datasets. For example, racial bias was observed in the US when additional healthcare needs wrongly underestimated over 50% of black patients were not in need⁹. This bias presented major bias due to healthcare inequality and prioritised healthcare costs rather than healthcare needs.

Using AI across various demographics could open the possibility of data collection bias whether this be sampling or measurements, for example⁸. This may occur in countries with lower socio-economic status as access to healthcare facilities may already be scarce and the patient data used may not be representative of the entire population, creating disproportion in how the algorithms generate outcomes. Meanwhile, measurement bias is another potential risk that may arise and has been observed in a study where men were given more lipid lowering medications than women due to cardiovascular disease risk being higher statistically in men⁵. Many examples of bias from AI data can arise and therefore, it is advantageous for a global effort amongst clinicians, governments, and healthcare institutions to work collaboratively to harness the benefits that AI models can achieve.

Another study where AI has been used in cardiovascular research has been in atrial fibrillation (AF) diagnosis where the sensitivity rate was 82.3% and specificity rate was 83.4%².

AF an irregularity and rapid heart rhythm that can lead to other complications such as stroke, heart failure, and other cardiopathies.

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AF is a common cardiopathy, often asymptomatic and underdiagnosed. The study used machine learning to shed a light on identifying patients in ECG recordings.

Moreover, other studies have shown AI modelling to be highly feasible in cardiovascular magnetic resonance imaging with predication of cardiovascular function in acute myocardial infarction patients³. The study performed a clinical trial which had shown that with multivariable modelling, outcomes for diagnosis and assessment with p-values <0.0010.0048. Therefore, AI enhances the diagnostic accuracy, and these studies are amongst many other cardiovascular studies using AI modelling which have obtained significantly higher sensitivity and specificity rates than with clinical only input⁷-¹⁰. AI clearly shows increased accuracy and can identify cardiovascular abnormalities that may be unnoticed by human judgement and intelligence, but it has its limitations. When using AI within healthcare systems, informed consent tends to be compromised due to the complexity of platform sharing. There is not always a way to mitigate lack of informed consent in some scenarios. For example, a patient may be entirely unaware of what AI is and may receive proposed treatment for preventing embolic stroke by utilising AI to analyse patient data.

This also raises ethical considerations around the clinical efficacy of AI algorithms. How likely it is that the situation be misjudged, and will patients be given unnecessary treatments?

When contemplating the use of AI, legal and regulatory requirements are standard in validating the models for healthcare use.

Regulatory bodies such as the Food and Drug Administration (FDA) have provided additional guidance for AI to be used within medical devices which includes having a premarketing review to reflect on any modifications that may need to be made and to risk assess the impact on the public¹². The additional guidance is to be utilised alongside with the traditional framework for regulation of medical devices.

The legal implications of AI include privacy of data, intellectual property rights, accountability, transparency, and algorithm disgorgement.

The FDA, therefore, covers all these aspects within its "Artificial Intelligence and Machine Learning Software as a Medical Device Action Plan", which minimises and mitigates the legal implications.

The FDA targets AI generated diagnoses and informed consent by having additional scrutiny and tighter regulations when it comes to AI in healthcare.

Despite there being risks to using AI in cardiovascular research, the overall benefits outweigh the risks involved. However, it is important to use AI sensibly within cardiovascular research and harness the beneficial outcomes by proceeding with caution. AI should be viewed as a complementary tool as clinician judgment is important. Clinicians should, therefore, be trained in data analysis and AI methodology as machines follow a different logical pathway than the human brain¹¹.

References: 1. Attia, Z. I., Kapa, S., Lopez-Jimenez, F., McKie, P. M., Ladewig, D. J., Satam, G., Pellikka, P. A., EnriquezSarano, M., Noseworthy, P. A., Munger, T. M., Asirvatham, S. J., Scott, C. G., Carter, R. E., & Friedman, P. A. (2019). Screening for cardiac contractile dysfunction using an artificial intelligence–enabled electrocardiogram. Nature medicine, 25(1), 70-74. https://doi.org/10.1038/s41591-018-0240-2 2. Attia, Z. I., Noseworthy, P. A., Lopez-Jimenez, F., Asirvatham, S. J., Deshmukh, A. J., Gersh, B. J., Carter, R. E., Yao, X., Rabinstein, A. A., Erickson, B. J., Kapa, S., & Friedman, P. A. (2019). An artificial intelligence-enabled ECG algorithm for the identification of patients with atrial fibrillation during sinus rhythm: a retrospective analysis of outcome prediction. The Lancet, 394(10201), 861-867. https://doi.org/10.1016/S0140-6736(19)31721-0 3. Backhaus, S. J., Aldehayat, H., Kowallick, J. T., Evertz, R., Lange, T., Kutty, S., Bigalke, B., Gutberlet, M., Hasenfuß, G., Thiele, H., Stiermaier, T., Eitel, I., & Schuster, A. (2022). Artificial intelligence fully automated myocardial strain quantification for risk stratification following acute myocardial infarction. Scientific reports, 12(1), 12220. https://doi.org/10.1038/s41598-022-16228-w 4. Gaetani, M., Mazwi, M., Balaci, H., Greer, R., & Maratta, C. (2024). Artificial intelligence in medicine and the pursuit of environmentally responsible science. The Lancet Digital Health, 6(7), e438-e440. https://doi.org/10.1016/S2589-7500(24)00090-6 5. Li, S., Fonarow, G. C., Mukamal, K. J., Liang, L., Schulte, P. J., Smith, E. E., DeVore, A., Hernandez, A. F., Peterson, E. D., & Bhatt, D. L. (2016). Sex and Race/Ethnicity–Related Disparities in Care and Outcomes After Hospitalization for Coronary Artery Disease Among Older Adults. Circulation: Cardiovascular Quality and Outcomes, 9(2_suppl_1), S36-S44. https://doi.org/10.1161/CIRCOUTCOMES.115.002621 6. Martínez-Sellés, M., & Marina-Breysse, M. (2023). Current and Future Use of Artificial Intelligence in Electrocardiography. Journal of Cardiovascular Development and Disease, 10(4).

7. Mohsen, F., Al-Saadi, B., Abdi, N., Khan, S., & Shah, Z. (2023). Artificial Intelligence-Based Methods for Precision Cardiovascular Medicine. Journal of Personalized Medicine, 13(8).

8. Nazer, L. H., Zatarah, R., Waldrip, S., Ke, J. X. C., Moukheiber, M., Khanna, A. K., Hicklen, R. S., Moukheiber, L., Moukheiber, D., Ma, H., & Mathur, P. (2023). Bias in artificial intelligence algorithms and recommendations for mitigation.

PLOS Digital Health, 2(6), e0000278. https://doi.org/10.1371/journal.pdig.0000278 9. Obermeyer, Z., Powers, B., Vogeli, C., & Mullainathan, S. (2019). Dissecting racial bias in an algorithm used to manage the health of populations.

Science, 366(6464), 447-453. https://doi.org/10.1126/science.aax2342 10. Singh, M., Kumar, A., Khanna, N. N., Laird, J. R., Nicolaides, A., Faa, G., Johri, A. M., Mantella, L. E., Fernandes, J. F. E., Teji, J. S., Singh, N., Fouda, M. M., Singh, R., Sharma, A., Kitas, G., Rathore, V., Singh, I. M., Tadepalli, K., Al-Maini, M., . . . Suri, J. S. (2024). Artificial intelligence for cardiovascular disease risk assessment in personalised framework: a scoping review. eClinicalMedicine, 73. https://doi.org/10.1016/j.eclinm.2024.102660 11. Tikhomirov, L., Semmler, C., McCradden, M., Searston, R., Ghassemi, M., & Oakden-Rayner, L. (2024).

Medical artificial intelligence for clinicians: the lost cognitive perspective. The Lancet Digital Health, 6(8), e589-e594. https://doi.org/10.1016/S2589-7500(24)00095-5 12. US Food and Drug Administration. (2024). Artificial Intelligence and Machine Learning in Software as a Medical Device. Retrieved 13/10/2024 from https://www.fda.gov/medical-devices/softwaremedical-device-samd/artificial-intelligence-and-machine-learning-software-medicaldevice#regulation

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SALFORD SCIENCE

Ethical Implications of AI in Healthcare: An Introductory Piece PROFESSOR ANDY MIAH IN CONVERSATION WITH ROBIN MEKVAN

The ethical implications of integrating Artificial Intelligence (AI) into healthcare have raised significant concerns. With the advancement of AI technology and its increasing integration into medical procedures, there is a pressing worry about the potential for AI systems to perpetuate existing biases and inequalities. This concern is rooted in the possibility of unfair treatment of specific patient demographics, which could worsen existing health disparities.

In this interview, Robin Mekvan spoke with Professor Andy Miah, the Chair of Science Communication and Future Media at the University of Salford. Professor Miah also directs the SciComm Space and leads the Metaverse Special Interest Group, along with overseeing the ENGAGEMENT FORUM that focuses on Community and Public Engagement. As the university's AI Ethics lead, he actively promotes responsible AI integration while advising global organisations on the ethical considerations of emerging technologies.

Can you start by telling us a bit about your background and brief knowledge in the ethical implications of AI in healthcare?

My background is in the ethics of emerging technologies. I have written about genetics, biotechnology and, of course, artificial intelligence.

Recently, my focus has been on the gains associated with further integrating biotechnology with digital technologies and this is where AI has become a major influence, but at the heart of everything I do are questions about the ethical implication of recent technology. Some of my recent work has examined the ethical implications of brain implants, for example. I have always been interested in the boundary between therapy and enhancement - when does technology take us beyond just repair into an entire range of capabilities? My research investigates the implications of that ethically and it is part of my wider interest in how we think about our relationship with technology more generally, how should humanity use technology? What are the limits of that use? What are the concerns we have about it? Additionally, how can it allow us to also evolve? Fundamentally, these are questions about how humanity can flourish and what makes a good life.

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How do you think AI is transforming the healthcare industry? What are some of the most significant benefits and challenges that come with this transformation?

We must recognize that the healthcare sector, to serve an increasingly aging population with increasing numbers of medical challenges, is entirely reliant on the technological efficiencies of artificial intelligence. If we want a healthcare service that is available to everybody at the point of need, rather than dependent on private healthcare, then the only way we can service this need is by achieving greater efficiencies within the system. And those efficiencies operate on three distinct levels.

One is a human resource efficiency; how can we ensure that we have a workforce that is able to function effectively? Another is a technological efficiency; how can we make sure that the infrastructure that underpins healthcare is optimal for delivery? But the third one, and this for me, is the more critical one: how can we ensure there are data efficiencies within the system? And what we have seen over the last 15 years, with the rise of data driven economies, is that companies that have the data are most able to provide the best service.

However, if we progressively use third party companies to drive healthcare innovation as an infrastructure, then the risk to public health care is huge, as it has progressively diminishing capability, as more of that data is owned by a third party to whom we are now increasingly beholden to make any kind of efficiencies at all.

So, with all of this in mind, the role of artificial intelligence - which still is very much treated as a panacea for society – is huge and we need to ensure that public health provision can take a leading role in those developments. The impact of this technology is something that is already having dramatic consequences for healthcare and creating a lot of optimism for its future.

What are some of the most pressing ethical concerns surrounding the use of AI in healthcare? How do you think these concerns can be addressed?

Some of the more prominent conversations are about the disruption to the workforce. for example, in 2020, the World Health Organization launched its first digital healthcare worker, an AI chat bot driven through a semi realistic avatar with which you could have a conversation about your condition. And it was quite a limited trial, but they wanted to see if it could supplement or even replace some of the existing healthcare provision.

You could argue that such examples potentially reducing the important nuances of good healthcare practice and risks losing some crucial elements, like the human touch. But you could also argue that, in fact, for many people, the current system of healthcare provision is not working very effectively. So, they wanted to explore whether it could be a more effective way of doing that.

A notable example is obesity. So, many parts of the world are experiencing an obesity crisis, and countries are reverting to drugs to address this problem, which is a model that many clinicians are concerned about. The general predisposition towards finding a drug to treat a problem is something that people are quite anxious about as a behavioural expectation. Yet, we have spent half a century driving treatments through pharmaceutical solutions, because of their efficiencies and we are now seeing this potential for addressing obesity. And whilst there is a lot of complexity this subject, an appetite supressing drug seems like an innovative idea. However, we might also apply AI to understand the complex behavioural characteristic of problematic eating, and this could be helpful to many people to assist in their weight loss, without needing to resort to drugs.

More generally, the ethical implications associated with AI derive in healthcare relate to the impact on the healthcare sector. AI will undoubtedly transform the workforce in a huge way, but that does not necessarily mean a reduction. If you look at the World Economic Forum, it published a report a couple of years ago which argued that eighty-seven million jobs are in jeopardy because of AI, but ninety-five million jobs are likely to be created by AI. So, on balance, it is likely that we will have more jobs rather than less jobs.

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But what you need to do is make sure that you can transition people from their existing work into an AI based work experience. And that is often the hard part when you look at the economics of the labour force, as transitioning people into new skills is a really challenging task and the fair treatment of employees is paramount in that process. So, these are critical risks that are fundamental to how governments must start to think about the implications of AI, because if your AI crashes your economy, you have got lots of other problems as well.

Going back to the point about looking at this from a macro perspective, you must address that first; the primary responsibility is to ensure the stability of an economy which is intimately tied to the stability of prospects of healthcare. People that have no jobs and have no income have extremely limited health prospects. Once you have thought about that, you then must look at the specific applications of AI, whether they are undermining a range of health or ethical concerns. We have a reasonable proposition for that in Europe now with the EU AI Safety Act, which has demarcated various levels of ethical concern. So, it has a graded system for assessing what level of ethical concern is appropriate to whatever application and put in place some specific recommendations for things that we do not do.

For example, an AI system should not discriminate between people based on their demographic circumstances. If an AI is unmonitored and unmanaged, where you cannot see clearly what impacts it is having on the people whose lives are affected by its use, then that is something that would fail the test of meeting the ethical standards of the EU Safety Act. That is crucial.

One of the things that is critical, but which is often overlooked is how we consider informal experiences of healthcare provision. We look at that the health profession as if it represents the whole problem, when a lot of what is taking place is happening well outside of that sphere. Many people are using health related digital systems that have an entire range of implications for their own health and wellbeing, but also allow companies to determine a full range of health insights by looking at the data.

Examples like Spotify are platforms where health related information is being gathered by non-health related applications that, in my mind, is potentially the biggest part of the health data that we both need, but also is being exploited by commercial companies without any real insight from the user.

The same is true with things like Google, and Strava exercise applications, which are now full of a full range of health data, which we simply click, accept to, and go along with. But of course, is underpinning the business model of those organizations. So, when we think about the ethics of the future of health applications of AI, we must look far beyond just what the healthcare system is looking at from a governance perspective, because in my mind, that is a bigger part of the puzzle.

How do you think healthcare organizations can balance the need to collect and analyse substantial amounts of patient data with the need to protect patient privacy and ensure data security?

One of the key cornerstones of good practice is patient involvement in all these discussions. We see examples of that within the scientific profession and we need to apply those insights and best practices into health AI. If you look at such journals as the British Medical Journal, it is an increasing expectation that authors include patients within their research process. This is very well established now and has emerged as a critical component of ethical practice.

When you start to think about the potential AI applications, we should be mindful to make sure that the public are involved in those conversations.

So, the first starting point is to ask questions about whether the research community is engaging with the public about discover applications to find out both the concerns that people may have, but also to help them design solutions that are in keeping with those ethical and moral concerns. If you can use AI to draw upon data to develop earlier insights into cancer diagnosis, I think most potential or existing cancer patients would say, that sounds brilliant. And I think in many cases, that is the case, but it is still important to engage the public on these matters, because it is often their data that is required to achieve that.

What are some of the potential risks and consequences of data breaches or misuse of patient data in AI-powered healthcare systems?

There are two key risks associated with the use of data. One is whether the modelling is ineffective. The presumption is - and it is a misleading idea - that AI is necessarily going to be smarter than the human.

One of the risks is around how we model AI and how we engage with the AI itself, from the perspective of the governance of healthcare, and getting that wrong is a huge risk because people do not know what the optimal model is yet.

There are very few clinicians within the NHS that are interacting with AI patient data. So, we have not even begun the process of working out what should be the nature of the clinician’s interaction with AI data when it comes to patient care. The NHS is also still quite primitive in its use of digital technology and this needs to change. If you go into most hospitals, the IT infrastructure is far less effective than the latest technology and it is not all excessive cost either. For example, there has been various interesting articles in the BMJ recently which talk about whether doctors should be allowed to use WhatsApp during their clinical observations and that sort of tells you the level of conversation that we are at. It is incredibly early stage and extremely far behind where we should be as a digital conversation in healthcare. I would say that the immediate risks, in fact, are less to do with deployment and more to do with not being able to critically and rapidly engaged with the pace of change of technology in this sector. It has been quite well recognized that, not only has the NHS been far behind digitally, but it is also at risk of becoming further behind if it does not utilize the AI effectively.

Who should be held accountable when AI systems make mistakes or cause harm to patients, and how can we ensure that accountability in these situations?

I would urge that we look at accountability from the perspective of formal governance of healthcare and all other health related data together, because not only can we gain greater insights into how best to develop healthcare by looking at those two elements, but it also explains the complexity of this problem. If you look at what healthcare tries to do and what it is tried to do, especially over the last 30 years, we have had a strong focus on preventive medicine. We want to make sure that people do not establish habits that lead to health care burdens, but the only way you can do that is by accessing them in aspects of their life that are outside of health care.

Where is the NHS finding opportunities to talk to patients about healthcare, health risk prevention or reduction? It must look elsewhere, when interaction is very minimal with patients, which means it must grapple with all that health-related data that exists within social media to maximize those opportunities.

When it comes to how the NHS deploys specific AI based applications, the emphasis will have to be specific, and the example of genetic counselling is a great comparison here.

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When the prospect of harnessing insights from genetic information became a reality twenty or so years ago, it was never the case that you could simply give someone a genetic test and expect that to be beneficial without further support in understanding what to do with that information.

In many cases, the information created new burdens that required support to think through.

We now have quite established and rigorous systems of genetic counselling to help people come to terms with the implications of what that data means about them and we may a kind of AI counselling to help people work through the implications of health insights that arise through a similar process. And that's the conversation that still hasn't begun, and perhaps is something that is a service that should be delivered in combination with healthcare professionals, both to diminish the burden on the NHS, but also to recognize that there's distinct consequences to people interacting with AI that will have an impact on the healthcare system as well.

How do you think we can ensure that the benefits of AI in healthcare are equitably distributed and accessible to all patients, regardless of their background or socioeconomic status?

I think the first thing to recognize is that we do not have that already, in a pre-AI world. Often, the immediate response that people have to AI is that it could create greater inequalities, which is often the same case with concerns about technology. I believe that AI will deliver greater equality, greater justice in healthcare, but this requires vigilance and monitoring, but also understanding the complexities of injustice. The current healthcare system cannot deliver healthcare justice presently and we need to look at this critically - at what is not working presently - and appreciate where that can be improved by technology. There is more research that is illuminating the degree of biases that exist within the profession, not just at the clinical level, but also at the at the bureaucratic level as well.

There is a good chance that AI improves those situations, because it will help us identify those injustices, based on being able to more adequately analyse data and examine those injustices.

Now, a lot of our data is determined by quite a limited human resource that has capacity to do that research and generate those insights. I think again, the optimist in me thinks that we can design an awareness of that into the system so the AI can be informed by those potential risks, and both monitor for it, but also adjust for it.

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If you think about AI and what it could do, AI designed with these sorts of questions in mind, these sorts of concerns, would be able to reveal that distinction and that difference and flag it up as a potential bias. Following through from the methodology that this research has developed, it would be able to more effectively test whether the questions are working. I am optimistic that, with our awareness of those ethical concerns about injustice in mind, it has the capacity to deliver a far more efficient and effective way of monitoring for them, because now, we are not particularly good at that.

In conclusion, is there anything else you would like to add about the ethical implications of AI in healthcare, or any concluding thoughts you would like to share with our readers?

Well, I think the first thing I would say is that everybody needs to be part of this journey. A lot of work is needed to make sure that people are part of the transformation to society that is happening through AI. I speak to many people about their use of ChatGPT, which, of course, is the most common application that is out there. Most people are still using it like Google, but the best way to use it, is not like Google at all. There is a huge amount of work to help people understand what is possible with even that application. That application is one of 1000s of applications that are out there now. So that is a huge chunk of work for society to do to make sure that the population understands what can be done to improve people's lives because of these technologies.

My advice would be to make sure you complete your training with a degree of AI literacy that will allow you to bring that innovation into your sector. If you are going into biotechnology, make sure you graduate with biotechnology skills around AI integrations that will both allow you to make more useful contributions to your sector, but it will also allow you to be ready for the future of your sector too.

Artificial intelligence will not replace your job, but people who know how to us artificial intelligence will replace those who do not.

The final thing I would add to that is, do not just look to your narrow sector for guidance, look at what is happening around your entire industry and beyond.

More generally, discover the companies that are doing the best work ethically, but more importantly, the companies that are developing AI for the right reasons and have the best values to underpin that work.

SALFORD SCIENCE

Influencing Parliament to See the Importance of Genetics INTERVIEW WITH PROF ARIJIT MUKHOPADHAYAY BY SANARIA FATHULLA Genetic sequencing, especially whole genome sequencing, has become a groundbreaking method for improving public health. While still in development, it has limitations and challenges that all stakeholders need to overcome and adapting to. For integration of these developments into current and future healthcare policies, it is crucial that scientists keep the parliament informed and involved. This is done through the British Society of Genomic Medicine (BSGM) to ensure informed decisions are being made with the public’s interest at the forefront. This interview with Dr Arijit Mukhopadhyay will shed light on the current development of genetics, its integration into public healthcare and potential challenges that arise from it.

Sanaria Fathulla: How do you think 100,000 Genome Project will be implemented? Do you think there will be any restrictions?

Arijit Mukhopadhyay: The implementation will happen over a long period of time. I am not aware of the exact specifics since I am not involved in the project. If you find a variant from the sequence data, that is usually not enough. If you find a variant with a known mutation for a particular disease, you will be able to predict, with high accuracy, that the individual will have the disease in the future.

However, you will not be able to tell how that person has inherited the disease unless you sequence the parents. Even if the disease is dominant or recessive, the parents (one or both) maybe completely unaffected. That is why when the 100,000-genome project has recruited individuals, they must take unaffected family members as well, because the ability of anybody to assign a variant with a pathology is crucially dependent on the relative comparison with the absence of the variant in unaffected members. Eventually, the goal is to be able to make genotype-to-phenotype correlation.

Now to answer your question, is it fully integrated, I do not think so. It is a slow ongoing process, but it is happening as we speak. It is a five-year project where the sequencing project was completed but done at various times. Some genomes were sequenced in year one, and some in year five so discoveries form year one would have progressed further.

When a genetic counsellor counsels one of these patients, they will have the backstory and they will know the clinical diagnosis, they know the sample, they know the genome sequencing results so that is the way it is integrated.

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Further integration that goes beyond the NHS, which I hope will happen, is when the findings are published, and new mutations are included in the public databases, meaning that anyone will be able to query a particular gene on NCBI and check which other variants are disease-causing. This has not happened yet. However, not every genome from the 100,000 Genome project will have a conclusive answer, as they might have variants of unknown significance (VUS).

Many variants will be catalogued as VUS, some of which will have functions assigned as more sequences are deposited in the public domain.

SF: What made you decide to contribute to the BSGM and why is it important?

AM: The official society that is tasked with making these understandings available to the public and the ministry, and to the administrators, is called the British Society of Genomic Medicine (BSGM). I am a member of that society; it relates to what I do. They put out a call to all members more than five years ago when the UK had decided to be out of the European Union. At the same time, the new GDPR (General Data Protection Regulation) law was introduced by the EU, which UK had decided to follow. This understanding of that legal/political scenario is important because a question came from this. If the 100,000 Genomes Project is happening today and tomorrow, the longtime result is that everyone might have their genome sequenced at some point in time, what about the privacy of that data? The previous policy was not fit for purpose.

That is why the document was made. I was interested because of how society changes with technological development and now you are hearing about AI, Chat GPT. Because this was right in my domain of expertise, I wanted to be part of that narrative. Having said that I was part of the subcommittee so if you see the document, you will see my name in the acknowledgements. My contribution was looking at the technical accuracy of the genetic sequencing bit of that documentation and correcting a few things in that draft. It was quite humbling going through this process of everybody’s contribution. My contribution was important, but small.

Updating such documents is important because Parliament is representative of the public. The NHS has faced multiple legal cases and litigations from members of the public, suing for not having the information they think they deserved due to lack of understanding. Parliament is final policy makers or approvers of new guidelines but lacks technical knowledge in the areas that are everchanging and need updating. That is why if it is a significant change that is happening in any area that is going to impact a larger portion of the public life, informing parliament is vital.

SF: Do you think the parliament should be able to have more say in genetics and its implications? Is there any right answer?

AM: Currently, the parliament should have a say but that is not specific to genetics. As I was saying, they are the policy approvers so they also have a say in any change in broader policies so GDPR, change in healthcare, how much of genomics will come into the forefront of healthcare all that will be governed by the parliamentarians so yes, they should have a say.

We, as domain experts, through societies such as BSGM must be responsible for giving the right information to the parliamentarians.

SF: Who should have access to that data?

AM: The basic principle is that any personal information, you should be the decider of who should be able to get it. Having said that, it is actually a can of worms. In a sense, let us say, you are getting your genome sequencing done and there is a variant that puts you at a high risk of a certain disease when you are 50 years old. You chose not to reveal that to anyone, then when you are 50 years old, and if you have that disease and are unable to do your job. Your employers would need to support your wellbeing, but the work is suffering. So, what is the right answer?

Especially if it is a private health insurance, or if it is your employers, should they have known before they employed you?

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SF: What are the main problems in terms of consent and confidentiality hindering progress in making genetics a wide stream concept in healthcare/public?

AM: A General understanding and awareness about the pros and cons. What genetic info can tell and what it cannot tell. That’s the biggest thing lacking which you asked me earlier why I’m interested in engaging in such conversations, whether it’s part of my role in the subcommittee or in conversations like this, it’s part of that process I feel responsible that I should be engaging in any way to increase understanding and awareness of this. Until we have a general understanding of genetic data and what it means, we cannot have this public debate of who should have access.

SF: Do you think the public mindset on consent/confidentiality will change in the future?

AM: Although they are public documents, members of the public will never find the document due to lack of publicity. They do not feature in the front page of the newspaper; it is not the mainstream public information. The world has changed forever postpandemic, people have become more aware of biomedical research and its potential. The 100,000 Genome Project is a very visible project so in that respect, people are now familiar with the technologies of genetics, but it stops there.

It is difficult to say, it will depend on the individual.

People who are more aware will be able to make an informed choice. People who are less aware will simply say no or yes without understanding or they will depend on somebody to make the choice.

People are not sure or do not feel comfortable sharing any private information, not just genetic data, worried about it getting misused or abused. As the technological risk is increasing, the technological protection is also improving. It will be a lengthy process, but it largely depends on the individual’s ability to understand the risk and benefits and give an informed choice.

SF: In the future, how do you think genetics will be used?

AM: The NHS published a document in 2016, proposing that genomics will be the first layer of healthcare. If you think of the current healthcare process, when you have a problem, you contact your GP, and the GP prescribes tests and medicine. At the very end, they can prescribe a genetic test as a last resort because it is expensive and complicated, it is not something you can buy a medicine with prescription and then feel better.

The new genome generation is a future looking document proposing that a newborn baby will have their genome sequenced and any health condition that arises in their life will be seen as the first layer of information. The 100,000 Genome website today has100,000 newborn genome sequencing programmes. It is already in the process, and I think genomics will become the first step in public health soon.

SF: How do you think the NHS/government will be monitoring the data locally and internationally?

AM: It boils down to whoever pays to generate the data and receives the custody of the data. It does not mean they are free to share, but they have access to the data. Because the 100,000 Genome project is funded by the NHS, they are the custodian of the data but that does not mean NHS will be able to hold onto it forever. How it should be monitored depends on the funders, but a larger dialogue surrounds human genome sequence, because it is a naturally occurring phenomenon and it cannot be patented. NHS cannot monetise it therefore NHS will not be able to sell it to a third party or ask for something in return because it cannot be patented or monetised. Every big pharma company like GSK and Johnson & Johnson hold onto thousands of genome sequencing data of their own. They cannot monetise the data, but they can make profit off making drugs because they are a private company. The NHS cannot do the same, the indirect profit will be that public health will be improved. How it will be monitored is a complicated question to answer. I think large bodies such as the NHS, NIH, US, EU health care services, key representations from other nations must come together and form data policies so that most of this data is used for the greater good. Policy making is not my expertise, so I cannot say, I can only say it should be used for greater good.

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SALFORD SCIENCE

Access Granted: Discovering the Significance of Open Publishing INTERVIEW WITH WENDY TAYLOR & TRACY BREHENY BY WIKTORIA WISNIEWSKA

The ‘Bioscientist’ magazine is a fully open access journal available on the Salford Open Journals platform, led for students, by students. Our CoEditor-in-Chief Wiktoria Wisniewska had the pleasure to interview Wendy Taylor, an Open Research Coordinator at the University of Salford, and Tracy Breheny, Academic Support Librarian, about open access publishing and its benefits for scientific communication and student learning.

Wiktoria: Could you please introduce yourselves and your roles at our university?

Wendy: My name is Wendy, and I am an Open Research Coordinator publishing at the University of Salford. I support postgraduate students and academic staff in publishing their research open access, disseminate it, and share it with the world. I am part of the library’s open research team, which assists researchers, not only with open access and publishing but also with making their data open and managing their research data.

Tracy: My name is Tracy, and I am an Academic Support Librarian supporting the School of Science, Engineering & Environment. I help students, academic staff, and researchers develop their information literacy and research skills. I offer guidance and support in finding academic information, referencing, and maintaining academic integrity. I also manage the Science, Engineering & Environment collections. I am part of the Library, Careers & Enterprise Team.

Wiktoria: In your own words, what would you say Open Access is and how is it different from traditional subscription-based model?

Wendy: Open Access enables anyone, anywhere in the world, to read research material as long as they have access to the Internet. They do not need to be part of a library or an academic institution that pays for a library subscription to access that content.

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This reduces international barriers and allows charitable groups, members of the public, and others to view this material, not just the academic community. If the research is published with a Creative Commons license, it can be reused and built upon, leading to further innovation. Studies show that Open Access content is cited more than subscription content, which makes sense because it is freely available and, therefore, more likely to be picked up and cited. The benefits extend not only to the researchers themselves but also to society as a whole.

Wiktoria: What are the challenges behind using Open Access and how are they being addressed?

Wendy: There are different routes to Open Access.

One option is Gold Open Access, where the publisher makes the content openly accessible. This usually requires a fee called an article processing charge (APC), which averages around £2,000–£3,000 but can cost up to £10,000. Depending on the author’s funding to pay this Open Access charge, they may or may not be able to publish with that journal. We have a number of deals with publishers that enable our corresponding authors from Salford to publish Gold Open Access for free, and these are all listed on our website. These deals are intended to move journals away from being subscription-based to becoming fully Open Access journals. Over time, more content will be published as Open Access, and eventually, the journal will flip, no longer depending on the subscription model. The aim was for journals to become fully Open Access, but studies show that this is taking much longer than previously hoped, so as a sector, we are exploring other models to enable Open Access publishing.

For example, another model is Diamond Open Access, where, like Gold Open Access, the publisher makes the work Open Access, but there isn’t a fee for the author, allowing them to publish in that journal without worrying about funding. These Diamond journals are funded through different business models that are more sustainable and equitable than the traditional Gold Open Access model.

The final model is Green Open Access. In this model, the accepted version of the paper—the final peer-reviewed version before any formatting by the publisher—can be made Open Access in our repository, USIR, at no cost to the author.

When authors sign a contract with a journal, they usually transfer their copyright to the publisher, who then decides whether there is an embargo on open access and determines the license terms. There is a strong push at the moment to have Open Access available immediately upon publication, with a clear Creative Commons license to enable maximum reuse of the research. We aim to enable all of our researchers to make their work Open Access in this way, which is why we prefer equitable and sustainable open access models.

Wiktoria: What rights do the authors have to their content?

Wendy: When you sign a contract with a publisher, you are signing over the copyright of that work to them. The publisher then becomes the copyright owner and determines how the work is used. If an author wants to reuse it in any way, they have to contact the publisher and ask for permission because they’ve lost control of their rights. There is a significant movement called Plan S, started by a group of funders, including UKRI and the Wellcome Trust. Plan S enables authors to retain their rights so that works can be made immediately Open Access with a CC BY license.Plan S funder policies state that when an author submits a paper, they must include a statement within the paper indicating that any accepted papers resulting from the submission can be made immediately Open Access with a CC BY license in a repository.

Starting with Edinburgh, many institutions have developed institutional rights retention policies to enable their authors to retain their rights, and Salford is in the process of working towards implementing its own policy.

Wiktoria: Could you tell us more about the licensing that our ‘Bioscientist’ magazine currently operates under?

Wendy: The ‘Bioscientist’ runs on Salford Open Journals, an open-source platform. This means that Salford maintains and manages it without relying on a commercial organization for any part of the publishing process. The journals on the platform operate as Diamond Open Access publications, providing immediate Open Access without any charges to authors for either access or publishing.

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The system includes publishing workflows that simplify the process from article submission to full publication. These workflows incorporate the allocation of a digital object identifier (DOI), a persistent identifier for each article, and allow editors to assign various types of licenses. For this material, the Creative Commons license is most appropriate, which is why it is used for the magazine. This license is the most permissive, requiring that anyone reusing the content attributes the author to ensure they receive credit for their work.

The journal titles are assigned an ISSN, a unique identifier that is considered best practice in article publishing. Additionally, the system connects with ORCID, a unique identifier for researchers.

These features enable authors to adhere to best practices from the start. By including these identifiers, the article metadata is harvested by Google Scholar and the university library catalogue search, which increases the reach and engagement of the articles and provides analytics on views and downloads displayed on the article pages. Each article also has the option to generate citations in different styles, allowing your work to be recognized and referred to. This setup allows our students to publish using best practices in a straightforward and accessible manner.

Tracy: As an author, you benefit from having your work widely accessible. Not only do you gain visibility and reach through Google Scholar and the library catalogue (Library Search), but you also have the opportunity to develop your skills by using a publishing platform like this. As an editor, you engage in various publishing processes, such as peer review and article management, which will strengthen your research skills over time. If you’re an Early Career Researcher, you might not be fully aware of all the Open Access options Wendy mentioned earlier. It is important for us to make you aware of and inform you about the options that best fit your research. We are here to support you in making these choices.

Wiktoria: Can our students count on library support with starting their own journal publications?

Tracy: Yes, of course. It is a university wide platform, so if any ideas come forward to the library, we'll be able to look at those individually.

Wiktoria: Thank you, that was very informative. Lastly, if a student wanted to access a journal locked behind the paywall, could the library gain access to this specific material?

Tracy: We have systems in place to obtain resources for students. If there is a specific journal article you need from a subscription-based journal that we do not have access to, we can request it for you. We offer a service called ‘You Want It,’ where you can place resource requests.

This service typically handles individual articles or book chapters, rather than whole journal access.

It is free for students, researchers, and staff to use, though there is a cost to the university.

If a journal or resource subscription is deemed beneficial for the university's teaching, learning, and research purposes, we have a separate process for evaluating these requests. This involves a series of checks to assess content coverage, accessibility, cost, and other factors.

This process is longer, whereas if you encounter a paywall when trying to access a single journal article or book chapter, we can facilitate that through the ‘You Want It’ service.

There are also other ways that our students can access resources, so feel free to check these out: You Want It’ service Our ‘You Want It’ service enables you to request articles from subscription-based journals and books/chapters that the university doesn't have access to. This is free to use for students, researchers, and staff. You can access the service https://www.salford.ac.uk/library/findhere: resources/you-want-it-service

Lean Library Lean Library is a browser extension that simplifies accessing articles, journals, and databases, making research easier, especially off-campus.

Lean Library can be accessed here: https://www.salford.ac.uk/library/findresources/lean-library Unpaywall Unpaywall is an open database giving access to free scholarly articles. It has a browser plugin that allows users to access full-text PDFs of resources easily and quickly, for free, when available. You can access this here: https://unpaywall.org/

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University of Salford Institutional Repository (USIR) USIR is an Open Access showcase for the published research output of the university. Our collection contains a wide range of research across multiple formats and subject areas and can be accessed here https://salfordrepository.worktribe.com/ Open Access Support We have lots of support with Open Access available for PGRs and academic staff. You can find out more here: https://www.salford.ac.uk/library/openresearch/open-access/support-for-open-accessfunding

SALFORD SCIENCE

What is Foetal Alcohol Spectrum Disorder and its ethical impacts on society?

ELAINE COATES IN CONVERSATION WITH DR DAVID JUNIOR GILBERT Foetal Alcohol Spectrum Disorder (FASD) is a range of neurological and physical conditions caused by prenatal exposure to alcohol. Alcohol can damage developing cells in various ways, and the impact will vary depending on the amount, duration and timing of the alcohol exposure. There is no safe limit, but women may be unaware of the risks or may drink before they realise they are pregnant.

Dr David Junior Gilbert is part of the multi-disciplinary FASD research group at the University of Salford, which investigates various aspects of FASD. Dr Gilbert’s research is specifically focuses on the behavioural impacts. This article describes his current research into suggestibility and confabulation in adolescents with FASD, and how this affects their vulnerability, particularly in interactions with the criminal justice system. Greater awareness of FASD among social workers, medical professionals and within the justice system will help to facilitate earlier intervention and enable affected individuals more appropriately supported.

Foetal Alcohol Spectrum Disorder (FASD) is a range of conditions caused by exposure to alcohol in the womb, impacting neurological and physical development. It is estimated to affect 2-3% of children in the UK⁷, and these children are far more likely to encounter the criminal justice system (CJS) than children without FASD³. Elaine Coates spoke to Salford research fellow Dr David Junior Gilbert about the research being done at Salford on FASD. What is FASD? FASD encompasses a range of closely related brain and body disorders caused by prenatal alcohol exposure (PAE). Alcohol is known to be a teratogen, meaning that it can cause defects in developing cells. If a baby is exposed to alcohol in the womb, irrespective of the trimester when that happens, they may be born with the condition. It can affect any part of the body but particularly affects the brain, with reduced brain volumes and white matter abnormalities in the hippocampus and corpus callosum⁸. Individuals with FASD often have executive function disorder, so they struggle to regulate their own behaviour. They may be impulsive and have difficulty understanding the consequences of their actions. At the far end of the FASD spectrum, children with Fetal Alcohol Syndrome (FES) often have characteristic malformed facial features including small eyes, a thin upper lip and smooth philtrum and may also have damage to visual, auditory and other organ systems⁹.

There is currently no treatment for FASD, but early diagnosis and intervention can help parents access appropriate support. There is some evidence that nutritional supplements during pregnancy can reduce the damage caused by PAE⁸. A recent small study found that FAS impacted children who received choline supplements during early childhood had improved cognitive development and executive function compared to a control group⁴.

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Mechanisms of alcohol damage Alcohol increases free radicals, highly reactive molecules which can react with biological macromolecules, affecting their function. When the balance of free radicals compared to antioxidants is disrupted, this is referred to as oxidative stress.

Developing cells can be affected in many different ways and there may be different impacts depending on the amount, duration and timing of the alcohol exposure Free radical damage to proteins and lipids can disrupt membrane functions and cell signalling. Critical cell cycle control proteins may be compromised, which can result in cells maturing early or in the cell cycle stalling, or in inappropriate cell differentiation. Alcohol can also affect DNA methylation and histone methylation, resulting in changes in gene expression¹.

Alcohol directly damages mitochondria, disrupting the electron transport chain and leading to increased cellular apoptosis. In the developing brain, increased apoptosis of glial cells may be the cause of the reduced brain density associated with FASD. Neurotransmitter systems may also be affected, resulting in behavioural impacts throughout life¹.

How did Dr Gilbert become interested in FASD? Dr Gilbert initially trained as a biochemist in Nigeria.

He worked for a few years for a pharma company, where he worked with physicians and clinicians with a drug portfolio mainly aimed at improving quality of life for people with serious or terminal conditions. He decided to pursue a Masters and obtained a scholarship to the University of Salford to complete a Master’s in Public Health supervised by Professor Penny Cook who leads the Salford FASD research group. The Salford research group is a multidisciplinary team with expertise on different aspects of FASD research, ranging from prevalence and epidemiology, genetics, trauma, interventions to support those with FASD, to social workers and criminal justice research. The group is regarded as the largest and most expert research group on FASD in Europe.

When Dr Gilbert decided to specialise in FASD, he says he was inspired by three words: Misdiagnosis – Individuals with FASD are often misdiagnosed with autism, ADHD or personality disorders, because of lack of awareness of FASD. Missed diagnosis – individuals may not be diagnosed with any condition, and so receive no support Under diagnosis – due to lack of resources. There is only one specialist clinic in the UK, in Surrey. There has been very little research to establish the extent of FASD. For his PhD, Dr Gilbert interviewed parents of children with FASD, and the children themselves, about their experiences. Dr Gilbert work provided the first experimental evidence of interrogative suggestibility in adolescents with FASD . Individuals with FASD demonstrated a significantly higher level of suggestibility compared to the control group². Dr Gilbert has now been awarded a 5-year research fellowship to expand on this work, recruiting subjects from the US, Canada, Australia, New Zealand and the Republic of Ireland, to investigate the vulnerabilities of individuals with FASD to and within the justice system.

FASD and the Criminal Justice System In New Zealand, a teenager with FASD falsely confessed to having been involved in the rape and murder of a woman because he wanted to claim a $20,000 reward and thought he would be immune from prosecution. Over 20 years later the conviction was quashed⁶.

People with FASD are more likely to have high rates of adverse childhood experience, and FASD adds another layer of adversity compounding their vulnerability. Problems with impulse-control and executive function mean these individuals are more likely to encounter the CJS.

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They are then vulnerable because their higher suggestibility means they are more likely to agree to suggestions put to them, or to say what they think interviewers want to hear. Some parents interviewed

by Dr Gilbert reported than their child would “say Yes to anything”. They may struggle to understand complex questions and may be easily manipulated.

In research not yet published, Dr Gilbert has also looked at confabulation. Confabulation is when people make things up to fill in gaps in their memory, and don’t realise they are doing so. People with FASD have poor memory recall and have a higher rate of confabulation.

There is a need for increased awareness of FASD within the CJS, and an understanding of the increased vulnerability of impacted individuals whether as suspects, witnesses, of victims of crimes, in order to avoid false confessions or miscarriages of justice. Dr Gilbert emphatically says that individuals with FASD are not criminals, it is their diagnosis that provides a context to behaviours relevant to the justice system. Also, these individuals have strengths which should be leveraged upon to create custodial, sentencing and rehabilitation plans.

How is Salford making a difference?

Dr Gilbert hopes his research will lead to better understanding of FASD, and for professionals within the justice system to be more aware of the vulnerabilities of FASD impacted individuals and not take things at face value. It is important for example to avoid leading questions in interviews, and for sentencing and rehabilitation plans to provide appropriate support.

Salford researchers have also been working with the Greater Manchester Combined Authority on a major intervention called the Alcohol Exposed Pregnancy programme. No woman wants to harm their baby – they either do not know they are pregnant, are not aware of the harm alcohol can do, or they need help and support to control their alcohol intake. The programme has already trained hundreds of social care staff to equip them to have conversations around the harms of alcohol during pregnancy, and has provided screening, support and early interventions⁵.

Further Information This short video by the FASD Salford group gives an overview of their research.

More on Dr Gilbert’s research: https://www.salford.ac.uk/our-staff/david-junior-gilbert

References: 1. Abdul-Rahman, O. A., & Petrenko, C. L. M. (2023). Fetal alcohol spectrum disorders : a multidisciplinary approach (1st 2023. ed.).

Springer International Publishing.

2. Gilbert, D. J., Allely, C. S., Gudjonsson, G., Mukherjee, R. A. S., & Cook, P. A. (2024). Immediate and repeat interrogative suggestibility in a sample of adolescents with fetal alcohol spectrum disorder. Diversity & Inclusion Research, 1(1), e12007.

3. Gilbert, D. J., Allely, C. S., Mukherjee, R. A. S., & Cook, P. A. (2022). Foetal alcohol spectrum disorder and Investigative interviewing: A systematic review highlighting clinical and legal implications and recommendations. Behavioral Sciences & the Law, 40(1), 170-185.

4. Gimbel, B. A., Anthony, M. E., Ernst, A. M., Roediger, D. J., de Water, E., Eckerle, J. K., Boys, C. J., Radke, J. P., Mueller, B. A., Fuglestad, A. J., Zeisel, S. H., Georgieff, M. K., & Wozniak, J. R. (2022). Long-term follow-up of a randomized controlled trial of choline for neurodevelopment in fetal alcohol spectrum disorder: corpus callosum white matter microstructure and neurocognitive outcomes. Journal of Neurodevelopmental Disorders, 14(1), 59.

5. Greater Manchester Integrated Care Partnership. (2022). “A very positive and rapid influence on change” – reflecting on work to reduce alcohol exposed pregnancies in Greater Manchester. Retrieved 11/09/2024 from 6. Hansen, R. (2016). Report for Minister of Justice on Compensation Claim by Teina Anthony Pora.

7. McCarthy, R., Mukherjee, R. A. S., Fleming, K. M., Green, J., Clayton-Smith, J., Price, A. D., Allely, C. S., & Cook, P. A. (2021).

Prevalence of fetal alcohol spectrum disorder in Greater Manchester, UK: An active case ascertainment study. Alcoholism: Clinical and Experimental Research, 45(11), 2271-2281.

8. Popova, S., Dozet, D., Shield, K., Rehm, J., & Burd, L. (2021). Alcohol’s impact on the fetus. Nutrients, 13(10), 3452.

9. Riley, E. P., Infante, M. A., & Warren, K. R. (2011). Fetal Alcohol Spectrum Disorders: An Overview. Neuropsychology Review, 21(2), 73-80.

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SALFORD SCIENCE

Celastrol as a Potential Phytopharmaceutical for Medulloblastoma Therapy: Assessing Efficacy and Cardiotoxicity

BY ALVINA IMRAN

Cancer remains a pervasive global health challenge associated with substantial mortality. While current chemotherapy treatments are efficacious, they frequently entail significant off-target effects, notably hepatotoxicity, neurotoxicity, and cardiotoxicity, impacting long-term patient survival. Childhood cancers, including medulloblastoma, present additional complexities due to the heightened susceptibility of these individuals to these off-target effects³. Thus, a compelling need exists to evaluate novel therapeutics with heightened efficacy and diminished off-target effects.

This article has been reviewed by Dr Matthew Jones, Lecturer in Biomedicine (Physiology), University of Salford. The Editorial Team would like to thank him for his time and contributions.

Phytopharmaceuticals, biologically active compounds derived from plant origins, provide a diverse array of potential therapeutic agents¹.

Celastrol, a pentacyclic triterpene extracted from the species Tripterygium wilfordii, has demonstrated anti-inflammatory and antioxidant properties in vitro and exhibited anti-cancer properties against diverse cancer types². This collaborative study with KidsCan Children’s Cancer Research and funded by a Biochemical Society Summer Research Studentship focuses on evaluating celastrol against medulloblastoma, emphasizing its efficacy against various subtypes and its potential for inducing cardiotoxicity.

The research unveils celastrol's potent cytotoxicity against medulloblastoma cells, particularly the group 3 medulloblastoma cell line HD-MB03.

Celastrol demonstrates effectiveness with EC50 values (The concentration required to decrease viability by 50%) below 0.5μM (Figure 1A), through the induction of apoptotic cell death. Subsequent investigations extended to the Sonic Hedgehog medulloblastoma subtype, DAOY (Figure 1B), with similar findings observed validating celastrol's efficacy across different medulloblastoma subtypes.

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The observed irreversible cytotoxicity after 24 hours of treatment with concentrations exceeding 500nM (Figures 1C-D), and fluorescent microscopy visualising the activation of Caspases 3 and 7, provide supporting evidence of irreversible caspase-mediated apoptotic cell death induced by celastrol in numerous medulloblastoma subtypes (Figure 2). These data position celastrol as a promising chemotherapeutic agent for medulloblastoma treatment.

As a part of this project, we also sought to preliminarily investigate the potential side effects of celastrol by evaluating its toxicity towards cardiac cells. This analysis explored the cardiotoxic potential of celastrol using an in vitro model of cardiotoxicity utilising H9c2 cardiac myoblasts. Results of these investigations indicate that concentrations greater than 2μM induce cardiotoxicity after 72 hours of treatment (Figure 3) highlighting some selectivity towards medulloblastoma cells but also highlighting potential cardiotoxicity at higher concentrations.

This underscores the need for meticulous assessment of potential side effects of novel compounds early in the drug development pipeline.

Beyond its potential clinical application, the project encouraged scientific exploration of compounds derived from traditional medicine for therapeutic potential, an underexploited source of novel therapeutic compounds, and began to develop an understanding of their molecular mechanisms of action. The development of an in vitro model of cardiotoxicity for simultaneous screening of therapeutic and cardiotoxic potential holds promise for revolutionizing drug development, especially considering the relatively fewer off-target effects associated with phytochemicals compared to synthetic compounds.

The project has equipped me with a diverse set of practical and transferable skills crucial for embarking on a research career.

From fundamental laboratory techniques to advanced methodologies like time-lapse live-cell microscopy and flow cytometry, I have gained proficiency and resilience in problem-solving.

Workshops and presentations have further contributed to the development of my analytical and communication skills, priming me for postgraduate research opportunities or industrial research positions.

In conclusion, celastrol emerges as a promising and comparatively safe phytopharmaceutical candidate for medulloblastoma treatment.

Ongoing research aims to delve into the molecular mechanisms of action and explore nano-encapsulation strategies to enhance potency and minimize off-target effects. The findings underscore the broader applicability of in vitro models for simultaneous screening of therapeutic and cardiotoxic potential, paving the way for the development of novel compounds in the realm of cancer therapeutics.

The author would like to thank the Biochemical Society for awarding her with the Biochemical Society Summer Studentship which enabled this research to be conducted and for exposure to be gained in academic research. Additionally, the author extends appreciation to Dr. Matthew Jones for endorsing her application for the studentship.

Through his support, the author delivered an oral presentation summarizing the findings and conclusions to the research laboratory team and a broader academic audience. His guidance provided the author with valuable insights into the daily responsibilities of a research scientist involved in interdisciplinary research, an experience made possible by this studentship opportunity.

Figure 1: The cytotoxic effects of celastrol against medulloblastoma subtypes. (A & B) Dose-response curves comparing the cytotoxicity of celastrol and against HD-MB03 (Panel A) and DAOY (Panel B) cell lines following treatment for 24 (Red), 48 (Blue) and 72 hours (Black). (C) Representative crystal violet staining images showing HD-MB03 colonies arising after celastrol wash-out over 10 days of recovery. Pre-treatments with celastrol were carried out over 48 hours before washout. (D) Corresponding Mean ± SD crystal violet absorbance derived from 6 independent repeats. All data compared to vehicle alone (0.5 % v/v DMSO). Statistical significance (P < 0.05) was determined following a one-way ANOVA with a Tukey’s post-hoc test **P < 0.01; ***P < 0.001; **** P < 0.0001. n = 6 independent repeats for all experiments.

Figure 2: The effects of celastrol on caspase-mediated apoptosis. Specimen light and fluorescent micrographs (100x total magnification) showing the activation of Caspases 3/7 following staining with Invitrogen Cell Event Caspase-3/7 detection agent following treatment with Celastrol (0.25, 0.5 and 1 µM) for 24 hours. Scale bars = 200 µm.

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References: 1. Lim, C. L., Raju, C. S., Mahboob, T., Kayesth, S., Gupta, K. K., Jain, G. K., . . . Nissapa. (2022, January 12). Precision and Advanced Nano-Phytopharmaceuticals for Therapeutic Applications.

Nanomaterials (Basel, Switzerland), 12(2), 238.

2. Shi, J., Li, J., Xu, Z., Chen, L., Luo, R., Zhang, C., . . . Fu, C. (2020, November 18). Celastrol: A Review of Useful Strategies Overcoming its Limitation in Anticancer Application . Frontiers in pharmacology, 11, 558741.

3. Zahnreich, S., & Schmidberger, H. (2021, May 26). Childhood Cancer: Occurrence, Treatment and Risk of = Primary Malignancies. Cancers, 13(11), 2607.

Figure 3: The cardiotoxic effects of celastrol. Doseresponse curves comparing the cytotoxicity of celastrol against H9c2 terminally differentiated cardiac myocytes following treatment for 72 hours. Statistical significance (P < 0.05) was determined following a one-way ANOVA with Dunnett’s post-hoc test. * P < 0.05, **P < 0.01; **** P < 0.0001. n = 6 independent repeats for all experiments.

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pg. 75 CAREER STORIES VIRTUAL BLOOD GROUPING TRAINING Let’s explore a novel tool developed by NHS Blood and Transport through a conversation with Alison Hines, a clinical training and education mentor based in NHSBT Bristol.

pg. 77 CAREER ADVICE THE SKILLS OF A BIOMEDICAL SCIENTIST Read about a conversation between Dr Victoria Chalker and biomedical science apprentice Lloyd exploring the skills that are required for all biomedical scientists to have in a technologically advancing world.

pg. 80 CAREER ADVICE DEVELOPING EMPLOYABILITY SKILLS Paula, a Careers Consultant, shares 4 ways that can be used to develop employability skills that will be crucial in the world of work after graduation.

pg. 81 CAREER INSIGHTS TEACHING SCIENCE IN HIGH SCHOOL We hear from a high school teacher who qualified to teach science in a local secondary school. She talks about her journey so far and shares some advice for aspiring teachers.

pg. 83 CAREER INSIGHTS MILITARY HEALTHCARE ETHICS Ethics in the military is explored, which is governed by several regulations. A comparison is established between medical practice in a civilian setting and in a military setting.

CAREER STORIES

ALISON HINES IN CONVERSATION WITH AYESHA NAEEM Alison Hines is a clinical training and educational manager who is currently working with the NHS Blood & Transplant department in Filton (Bristol). NHS Blood Transplant has recently introduced a VR (Virtual reality) training programme that enhances knowledge on blood transfusion education². This program can be accessed on the Meta Quest APP Lab store. The NHSBT blood identification app gives learners an insight into the processes of correct blood group and educates them on the consequences of administering a transfusion following incorrect blood group identification. In addition to realistic simulations that highlight the grave consequences of mistakes, it also provides quick feedback. This app aims to provide an immersive hands-on learning experience as well as raises awareness of transfusion science encouraging recruitment in this field to help overcome staffing shortages in transfusion laboratories.

Tell us about your educational background what made you join blood transfusion and what aspects of blood grouping amaze you?

I have been a biomedical scientist for 15 years now. My interest in haematology and transfusion stemmed from having a relative diagnosed with a haematological condition, which sparked my passion for this field. As I progressed in my career, I became more focused on the blood transfusion side, which led me to work for NHS Blood and Transplant in one of the specialist labs here in Bristol.

Eventually, I transitioned into training others in this area instead. What amazes me about blood grouping is the sheer number of blood groups that exist. Most people are familiar with ABO and antigen D (when referring to being Rh-positive or negative), but there are hundreds of different antigens on red blood cells. In fact, there are over forty different blood group systems. New discoveries are constantly being made in blood transfusion, and that is what makes it such an exciting area to work in.

Explain the main purpose of using virtual reality in the blood grouping programme introduced by NHS? We brought in the virtual reality training programme as a proof of concept to show that it is possible to train people in specialist techniques using virtual reality. We have found that this package that we developed is useful for various audiences, from people who have no experience of blood grouping to experienced scientists because it introduces the techniques to someone who has not been trained. For experienced scientist, it provides the patient aspect where they are interacting with a patient in the package, and it is taking them back to our core purpose of saving lives and improving patients' lives. Thus, it is beneficial for a variety of reasons.

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Why was the Meta Quest app lab store chosen as a VR training platform?

It was exceedingly difficult to find a suitable platform, particularly in health in healthcare, to host your apps, there is not a national NHS platform available to host things that we could easily access, so we needed to make it available to people nationally and internationally. It was suggested that the Meta Quest app lab store was the only option for us. This makes it an easy, accessible platform. For the future, we are hoping that as we continue to work with Institute of Biomedical Science, there will be a place where we can host all apps to do with biomedical science in one place.

Can you walk us through the experience of using VR training app and what does a training session look like?

The training session is designed to take around 10 to 15 minutes to complete, and it walks you through meeting your patients at the beginning and performing ABO grouping by the tile technique. First, you get all your reagents out of the fridge and prepare them. You can then interpret your test results and compare these to a table. In case you are not sure about what is how to interpret those results, then you go on to select blood for transfusing to your patients and then you take that blood to the patient's bedside and start that transfusion. You see the process from beginning to end, performing the testing through to the transfusion of the units that you selected.

Depending on the blood that you chose to get from the fridge, you may save your patient's life, or you may have What we call a negative outcome where you are told that there have been some complications, and you are walked through what happens when there is an incompatible transfusion. What makes this package good for training is that it allows people to fail in a safe way because they can select an incorrect unit for transfusion and no patient will be harmed by that.

It is particularly good for helping people to try a process multiple times and learn from it.

Figure 1: Performing ABO grouping by the tile technique¹ How does the app enhance the experience of handling lab equipment?

In the experience, we introduce each piece of lab equipment and explained to people what each piece of equipment was and how it is used. For example, they use pipettes in this exercise, and we have managed to use haptic feedback so that people can tell if they are perpetuating too hard and potentially overdispensing their reagents and when they're mixing their reagents, they are given feedback through the handsets as to whether they are doing it correctly. Users feel as if they are truly performing the test whilst wearing the headsets and using the handsets.

What kind of issues does the VR training software aim to resolve within the field of transfusion?

In the field of transfusion, there is a lot of pressure on the hospital transfusion labs and on our reference labs where there is a shortage of highly qualified biomedical scientists. This is putting a huge training burden on hospitals to train their staff up to an experienced level. The virtual reality packages that we have been working on are trying to address that training gap so that people can enter the blood transfusion laboratory; after completing some virtual reality training They will be much more prepared to learn those individual laboratory processes because they have already been introduced to them over and over in virtual reality. We also hope to develop transfusion laboratory hub where people can have training, can meet in the virtual world.

How did the app help you reduce the risk of associated with mismatched transfusion?

We do not expect the app to fully replace the actual training within the transfusion laboratories, but we hope that the app provides a better understanding of the ABO blood grouping process and the need to select compatible units. Though the app, user experience negative outcome at the end of an incompatible unit is transduced. In a hospital transfusion lab, there are lots of processes in place to prevent an incompatible unit from being issued for a patient. The app reinforces this knowledge, making people aware of the safety repercussions. By practicing frequently in the app, it becomes difficult to make mistakes, particularly in the lab setting.

Have you observed any improvements since the app has launched?

At the moment, we are doing some research into the benefits of virtual reality training and what we found is that it is relieving some of the pressure on laboratories. We have two projects on the go, one that involves the blood identification app and one that involves a cross-matching package.

Both have found that people who have completed the virtual reality training were ready and confident when they went into the lab to perform the real test. Those who completed the training came in with prior experience and required less instruction on the technique and procedure, reducing the need for extensive explanations in the laboratory. This frees up time for specialists to focus more on patient work, as well as on training in laboratory processes, rather than having to explain all the foundational knowledge associated with the procedure.

References 1. Evans, R., & NHS Blood and Transport. (2024). Virtual Reality training - Blood typing. Retrieved 29/08/2024 from https://hospital.blood.co.uk/the-update/virtual-reality-training/ 2. NHS Blood and Transport. (2024). NHS Blood and Transplant now using virtual reality training for blood transfusion matching. Retrieved 29/08/2024, from https://www.nhsbt.nhs.uk/news/nhs-blood-and-transplant-now-using-virtualreality-training-for-blood-transfusion-matching/

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CAREER ADVICE

The Need For Biomedical Scientists To Have The Right Skills DR VICTORIA CHALKER, DEPUTY CHIEF SCIENTIFIC OFFICER FOR NHS ENGLAND IN CONVERSATION WITH LLOYD MCLEGGON-WATKINSON Biomedical scientists play a pivotal role in the care and management of patients that is rarely seen in the public eye; it is also a specialist area that is constantly evolving. The nature of this evolution requires that registered Biomedical Scientists continually work towards achieving a skillset suitable for a continually developing speciality. These skills may begin to be acquired early in education and firmly established into a career and beyond. The dynamic nature of the sector often requires the integration of innovative technology, methodology and evidence-based practice to be implemented which requires Biomedical Scientists to continuously work to obtain updated knowledge in an ever-changing environment. Lloyd Mcleggon-Watkinson, a Biomedical Science Apprentice at the University of Salford, spoke with Dr Victoria Chalker, the Deputy Chief Scientific Officer for NHS England, to get to know how healthcare science has evolved over time but also about the importance of Biomedical Scientists updating their skills and practices for a modern laboratory setting.

The Editors would like to thank Professor Richard Birtles (The University of Salford) for connecting us with Dr Victoria Chalker. Additional thanks go to Kim Allen, Alex Wilson and the NHS Communications Team, David Wells (Chief Executive of the Institute of Biomedical Science) and Sue Jones (Executive Head of Education – Institute of Biomedical Science) for reviewing this article and providing their insights.

Lloyd: Please introduce yourself to our readers and tell us a little bit about your role.

Victoria: My name is Dr Victoria Chalker; I am the current Deputy Chief Scientific Officer in NHS England. I am not a Biomedical Scientist, but I am a Clinical Scientist, and I have spent several decades of my life working very closely with Biomedical Scientists. I have worked in various areas, such as the UK Health Security Agency, NHS Blood and Transplant, and NHS England. In all of those, I have worked with Biomedical Scientists who are delivering high quality healthcare for patients.

Lloyd: Your current role as the Deputy Chief Scientific Officer, how is that linked to the work of biomedical scientists?

Victoria: We have quite a lot of interactions with Biomedical Scientists because Biomedical Scientists are part of the healthcare science family. In healthcare science, we have more than fifty types of scientists operating. Our personnel range from bioinformaticians, clinical engineers, medical physicists, epidemiologists, to Biomedical Scientists who form one of our largest staff groups; the HCPC reported in March 2023 that there are 27,067 Biomedical Scientists registered with them. Biomedical Scientists work in hospital laboratories, providing services such as infectious disease testing, blood typing and other testing, immunology, and biochemistry, which are important for people in hospital, informing clinicians on the required treatments of patients.

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Additional areas that Biomedical Scientists work in include histology, cytology, transfusion, and genomics. Tests are needed by the public, 24 hours a day, 365 days of the year. Information that is used nationally for our surveillance of infectious diseases relies on Biomedical Scientists undertaking the tests in a high-quality way and reporting those tests through to the epidemiologists undertaking analysis.

Biomedical Scientists also provide emergency out-of-hours tests for services and patients on the weekends and late at night as well.

Lloyd: There has been an increase in awareness of the profession, especially since COVID. However, there is still work to do.

What do you think could help?

Victoria: Biomedical Science is a profession that is more than one hundred years old, and we have the Institute of Biomedical Science as one of the longest standing professional bodies with a strong history of tradition, skilled and proud members. The profession can provide an amazingly rewarding career. If you look at the history of Biomedical Science, many biomedical scientists have contributed the development of sterile technique, vaccines and much more. Over many years Biomedical Scientists have taken the country through the creation of techniques and processes that ensure high laboratory quality, which we still use today.

Lloyd: How can we improve the understanding of biomedical science for young people and the public?

Victoria: We can do it in a number of ways: we need to talk to teachers. We need to talk to universities as well. Not all biomedical science degrees are accredited; 62% of all BSc Biomedical Science(s) courses are accredited, so around sixtyfour are officially IBMS-accredited. I think it would be helpful if that was better articulated to young people when they are choosing their options, with more information now being circulated on sites such as UCAS to make prospective students aware of what is required. If they want to be accredited as a Biomedical Scientist, or if universities could increase the extension of Biomedical Science degrees so that they are all accredited, we would then be able to help students not start studying before realising that the degree is not accredited.

Also, we need to be better at articulating the rewarding careers that people can have, to teachers, and focusing on showcasing the great work that our Biomedical Scientists do.

I think we need flexible entry for Biomedical Science, and we need for people to be able to enter the profession and be supported during the work to gain accredited status; this is done through the four routes to registration. We do that in the NHS and other organisations; we take people with non-accredited degrees and earlier in their careers and help support them through the process. I recently met a biomedical scientist who has been supporting the NHS for forty years and did his A levels and biomedical science degree and other training qualifications all supported on the job. We have a strong tradition of training people on the job.

Biomedical scientists do not just work in the NHS, they also support other organisations and academia. Having both accredited and nonaccredited degrees is helpful for people to study a breadth of science, which we need as a society.

Lloyd: The NHS Long Term Workforce Plan gives enough description of the future of developing and retaining its staff to better protect and improve the health service. Point #18 of the plan relates to the continuation of science, research and technology, digital and data development. Will there be a greater initiative and support for CPD to ensure skill development and retention?

Victoria: CPD is essential for all our scientists to ensure that they are actively learning on the job, but also working with the most up-to-date quality and safety standards and procedures to translate our research into the care that the patients need.

There should be an ongoing focus on CPD for all our staff to make sure everyone is performing as well as they can.

All the organisations that I have worked in, support staff in many ways. For example, the apprentice route for training is open to staff members in the NHS. I undertook an apprenticeship as part of my role when I was in UKHSA, and they are not necessarily purely science focused.

There are degree apprenticeships that are science-focused, and they can help you on your route to become a Biomedical Scientist. There is a breadth of apprenticeships that are available in the system now to support the development of staff; we need to help them, help our patients. One person in my team is undertaking a data analytics apprenticeship.

Lloyd: On the topic of equality, diversity, and inclusion, which are key principles that form the foundation of the NHS? What is in place to ensure groups obtain and retain their skills as biomedical scientists?

Victoria: All staff should be supported to be competent in their practises that they are undertaking, and continuous professional development is part of that process. The retention of skills is something that if you are a biomedical scientist is iterative; we are all constantly learning, and science is constantly changing. It is important that we have a diverse and broad community of scientists to bring a breadth of thought that we would not necessarily have otherwise. Everybody who wants to become a biomedical scientist should be supported to consider if it is the right role for them and be supported to obtain the qualifications. We need biomedical scientists across the country. It is important we help people aspire to be biomedical scientists.

It is about role modelling and communicating and there are things we can do to help do that.

For example, last year, I went to a school in Bradford where I used to play sport when I was younger. There, I talked to the students about my career to help them aspire to work in science.

When I speak to young people and teachers about the breadth of science, not many of them are aware of the whole variety of scientists that we employ in government and in the NHS. We really need to get better at communicating what we do and the scientists we need. We do have a truly diverse community in the workforce, but it can always be improved.

Lloyd: My next question now, as an apprentice, I do have an appreciation of being able to work in the NHS trained laboratories whilst undertaking the Biomedical science degree. Do you think that post graduate apprenticeships will take a greater role going forward in enhancing the knowledge and skillsets of registered biomedical scientists?

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Victoria: Absolutely. There are already available postgraduate qualifications for biomedical scientists supported by the IBMS such as the specialist portfolios. Our biomedical scientists, advanced clinical can undertake many qualifications with the IBMS. An additional option is to undertake the STP (scientist training pathway) programme and then progress to become consultant level scientists. There is also an equivalence route for clinical scientists, and this is the Certificate of Attainment by Equivalence for Clinical Scientist (CEP). A CEP can be done in the field of laboratory management as well. Postgraduate training is also open for biomedical scientists to apply for, but there are also other forms of postgraduate education, such as undertaking research or PhD qualifications if that is something that they really want to do.

to make sure that with everything we do, patient safety and patient care is at the heart of it.

We have people who work in things like communication of science, or the regulation of science, safety and quality regulation or accreditation services. We even have people who go on if they are interested to take their science degree, whatever that may be, and then undertake law to advise on intellectual property.

My advice to aspirant biomedical scientists who want to broaden their portfolio is that there are many different careers in science that your biomedical science provides a solid foundation for. We have also got areas of emerging science where we need biomedical scientists going forward, which are interesting and innovative areas that will help patients for the future.

Victoria: Reading scientific papers and abstracts is an effective way to get a broad understanding of different sort of research techniques and methodologies, and the structure of how different protocols, studies and clinical trials have been established and set up. If there is one area you are interested in, you can always read around that, contact the lead researcher or researchers on the team and ask them to talk to you about it. Most scientists are quite willing to talk about their own research to others. It is good to be aware of who the experts are in the field and where are they located in the world. Research skills and a final year research project are embedded in all BSc (Hons) degrees for students and apprentices to allow as many students as possible to gain valuable experience in the laboratory space.

Lloyd: Speaking of emerging sectors, how is artificial intelligence being introduced into the NHS laboratory settings and how does the NHS support recent graduates to make the best use of AI? Victoria: We can certainly use improved machine learning and digital capabilities in the science that we undertake. The scope for AI to influence practise is potentially quite large.

However, it is going to take time to make sure that these processes are done in a regulated and quality assured manner, that people are trained to understand how they work, as well as make sure they are working as expected with safety and quality being built into any systems.

The NHS is investing a lot in digital transformation, including training staff in AI, as well as digital pathology. In fact, I was sent an AI framework just yesterday, with learning opportunities for staff, not just those in science to understand how AI could really transform what we are doing. You can find out more about the NHS viewpoint on AI and machine learning on the NHS England website. AI and Machine Learning is something that might help transform some of the areas that we work on, but we need

It is important to note that not all biomedical science will be or can be replaced by AI. We still need subject matter experts; not all techniques are undertaken digitally. There are a lot of physiological based sciences that are needed to support patients. I do not want scientists to be put off from undertaking biomedical science because they are not as excited or interested in AI. We need we need a whole breadth of expertise and specialists, including those with digital and AI capability, which is why there are many different pathways to follow.

Lloyd: Do you have any advice for biomedical science students, including myself, who are working to gain skills and experience to prepare for medical laboratory or research work?

Often, it is about increasing your own knowledge, and that is really through learning from others through attending conferences etc. Scientific conferences are important, such as the IBMS Congress. There are local, regional, or national level conferences that people can attend, to increase their scientific knowledge and build a network. If you are early in your career, it will hold you in good stead over a number of years. I am still in contact with people I started working with decades ago.

People should not be afraid to fail; you should not be afraid to ask questions. No question is a stupid question. You can also apply for grants. I applied for and received my first grant when I was a junior scientist to help me with a discrete piece of research.

The lessons I learned in going through that application process held me in good stead because it helped me look at how to structure research applications, how to communicate, and how to plan and undertake the study, considering its financial, ethical and governance requirements. For young scientists, there are grants available to support them with undertaking basic level of research to start. If you do not have experience writing grants, there will be someone in your organisation who is experienced at it, who can help you and advise you on that.

CAREER ADVICE

Employability Skills – What are they and how can you develop them as a student?

BY PAULA COURCHENE Paula Courchene, who is a Careers Consultant in the University of Salford’s School of Science, Engineering and Environment, shares her tips on how to become more employable. She emphasises the current competitive nature of the job market and suggests ways to develop skills needed in the world of work. She works closely with the careers team who provide career and employability support to all students at the University. You may contact them via careersandenterprise@salford.ac.uk.

Employers value your degree and the range of transferable or ‘employability’ skills you gain throughout your course. During your degree, you will develop a number of technical and job-specific skills, such as lab techniques and report writing. Alongside this, you will use soft skills, for example, time management to manage deadlines and critical analysis to complete assignments. Combined, all of these are important and can demonstrate to an employer your potential to be effective in the workplace.

We know that the graduate job market is competitive, so while you are studying for your degree and picking up this broad set of employability skills, consider what else you can do to enhance your employability and make yourself stand out from the crowd. There are many activities you can get involved with outside of your studies. Below you will find four suggestions of activities that can develop your employability: 1. Gain work experience.

Work experience comes in many forms, such as an integrated placement, like the IBMS or a research placement, an internship, volunteering, or part-time employment. It could involve applying for positions of responsibility within the university, like a course or student representative role. Any experience you gain can be added to your CV and used in applications and interviews.

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2. Engage with the support offered through your department and university.

Throughout the year, many academic departments organise lab visits, industry speakers, and career festivals. Speak to your academic team to see what is on offer, as these are great CPD opportunities where you can enhance your knowledge about the sector and start to network with professionals. As well as departmentalspecific support, seek out your Careers Service, as they usually offer workshops, events, and one-to-one advice and guidance appointments to help you explore your career options and develop job-seeking skills.

3. Become a student professional body.

member

of

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Many courses are accredited by the leading professional body in that sector. The IBMS is a great example of this, and if you are studying an eligible degree, you can apply for student membership. This will give you access to industry updates, CPD webinars, and career resources. Membership shows your interest and commitment to keeping up to date with the sector and is a great addition to your CV. 4. Take up extra-curricular activities.

Universities offer many different societies, sports, and clubs; there is something for everyone. What’s more, if you can’t find exactly what you want, you can use your initiative and entrepreneurial skills to start your own! Extra-curricular activities can be a great way to collaborate with peers, learn new skills, and show employers what interests you outside of your studies.

University of Salford students and graduates can get in touch with the Careers & Enterprise Team for further information by visiting their website.

CAREER INSIGHTS

Diving Deep – Qualifying as a Science Teacher

BY DILRUBA BOKSH Meet Thasmiah Khanom, a dedicated science teacher making a real difference in secondary education.

With a BSc in Biological Sciences from Queen Mary University and a PGCE from Greenwich University, Thasmiah has risen through the ranks to become the Head of Biology at a secondary school.

Additionally, she plays a crucial role as an AQA examiner for GCSE and A-Level biology. In an interview with second-year BSc Biomedical Science student Dilruba Boksh, Thasmiah shares her journey into teaching, the challenges she has overcome, and what keeps her motivated in the classroom. She also offers valuable advice for those considering a career in teaching, drawing on her journey and the insights she has gained along the way.

Could you share a bit about your educational background and explain what inspired you to pursue a career in teaching science?

I completed a BSc in Biological Science from Queen Mary University of London. I then decided to take some time out to explore my interests. As I have always had an interest in the education sector, I decided to see if I would enjoy being in the classroom, so I completed a year of unqualified teaching and academic mentoring. Throughout this year, I realized that I really enjoyed being in the classroom and sharing my passion for science, especially biology, with future generations. I then decided to complete my PGCE (Postgraduate Certificate in Education) the following year.

Can you describe your PGCE journey and what it took for you, as a recent graduate, to apply and succeed?

During my time working in a school, I encountered teachers who had pursued various routes into teaching, such as Teach First, School Direct, and the more traditional PGCE. This exposure allowed me to evaluate the advantages and disadvantages of each pathway and select the one that best aligned with my goals. Ultimately, I chose the PGCE route, as it offered extensive opportunities to experience different school environments through placements. The PGCE is a year-long program featuring placements in two different schools, each with distinct educational settings. This setup offers handson classroom experience, allowing you to teach several hours weekly with the support of a dedicated mentor. The ongoing feedback on my lessons proved crucial, significantly advancing my development, and refining my teaching abilities. The PGCE also involves university-level coursework, requiring critical writing and assignments for different modules, which further develops your academic and professional skills.

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What is the best part of your job, and what challenges have you overcome in your teaching career?

I enjoy building rapport with students and their families, witnessing their success and sharing in that achievement. If you stay at a school for a long period, you start to see siblings of your former students, and it is really rewarding to see their success and hear about what the older students are doing in life. As a teacher, spending significant time with students allows me to impact not only their academic achievements but also their personal development. I love that aspect of the job. The most challenging aspect of the job is managing various tasks throughout the day, such as marking, providing feedback, and handling other administrative duties.

However, the time spent teaching in the classroom is perhaps the easiest and most enjoyable part of the job, making the rest of the responsibilities worthwhile.

How excited are you about your new role as Head of Biology? Also, could you share how long it takes and what it involves to progress in the teaching field?

I always love a good challenge, so I am looking forward to it. I have always enjoyed planning curricula and observing how they are delivered and their impact on students. While completing my PGCE, I was recruited as a science teacher to undergo my NQT (Newly Qualified Teacher) training (now known as ECT, Early Career Teacher). During my NQT induction year, I was promoted to KS3 Coordinator for Science. I held this role for three years because it was important to support a cohort throughout KS3 (Year 7 to Year 9). Now, I am excited to take on the role of Head of Biology for a new challenge. On career progression there is no fixed timeline. Typically, you start with two years as an ECT. After this period, you can apply for middle leadership positions. Once you demonstrate success as a middle leader, you can then progress to senior leadership roles. The progression to each level depends on individual achievements and readiness, rather than a predefined timeframe.

How has your experience as an AQA examiner shaped your teaching approach, and what is the pathway to becoming one?

I have just become an AQA examiner, and this is my first set of marking. To become an AQA examiner, you typically need to have one or two years of classroom experience. You can express your interest on the AQA website, and if there are any job openings, they will contact you. You then send your CV and application, selecting the subject you want to mark. The reason I wanted to become an examiner is to learn from expert examiners, specifically, to understand what they look for in mark schemes and see the types of answers students across the country are writing.

This experience allows me to bring valuable insights into my teaching, ultimately benefiting my students.

Do you think there are any drawbacks to a career in teaching?

Like in any other career, there are some drawbacks. Especially at the beginning, teaching can be very time-consuming, and finding a good work-life balance may be challenging. This is why many new teachers experience burnout quickly.

Initially, you want to give it your all, but by the end of the two years, you might feel like you cannot continue. This challenge contributes to the high turnover rate among teachers. However, with time, experience, and an excellent team, it does get better.

Besides academic learning, what other qualities or experiences from your school and university life have you integrated into your teaching career?

There are a lot of transferable skills that I picked up along the way. For example, I still remember how my biology teacher in secondary school taught certain topics, and I try to integrate those methods into my own teaching.

One of the most important skills I picked up from university is working collaboratively as part of a team. It is crucial to work as a team to achieve the best outcomes for students, and the group presentations from university really helped me understand how to effectively collaborate in large teams and consider everyone's ideas.

How can undergraduate students determine if teaching is the right career for them, and what advice do you have for aspiring teachers?

Before committing to becoming a teacher, it is crucial to experience a classroom from a teacher's perspective. That is why I did not go straight to a PGCE, even though it was one of my options. I wanted to see if teaching is something I could do for the rest of my life. I had volunteered in schools and tutored from a young age, but that experience is different from standing in front of a classroom of 30 students all day. Teaching is a demanding role, so shadowing a teacher for at least a week can provide insight into its requirements. My best recommendation would be to work as a teaching assistant (TA) for a year before entering teacher training. While it might be challenging to find a job as an unqualified teacher, TA positions are more accessible. This role exposes you to various teaching styles and often involve supporting our most vulnerable students, including those with special educational needs and disabilities (SEND). This experience helps you learn adaptive teaching, a crucial standard in the profession.

I have always noticed that PGCE students with TA experience perform better than those who go straight into the program. They are more prepared and have a better understanding of classroom dynamics.

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CAREER INSIGHTS

Military Healthcare Ethics - Practicing Healthcare Ethically in a Military Setting

BY BLESSING AKPEJI Military healthcare operates differently from medical healthcare. Even though they provide the same services, treating sick and wounded patients, military healthcare is governed by different ethics. To practice as a Military healthcare professional, crucial skills are needed. Military healthcare professionals are bound by medical ethics of saving lives first and being loyal to their country on the war front. Even though they are not involved in fighting on the war front, they make equally essential decisions regarding who gets to be treated and even save the enemy. This article expands on some of the crucial needs and requirements necessary to practice as a military healthcare professional and how different this is from civilian medical practice.

Being a healthcare professional has been said to be one of the most rewarding and fulfilling roles as you save the lives of others. Being in the military has a different twist to the picture. As military personnel, you lay your life on the frontline to fight for your people, and as medical personnel, you are there to save every life you can, often under extreme and challenging conditions.

Military healthcare professionals, including doctors, nurses, or biomedical scientists, must adapt to the tenets of a military environment.

They may operate in various work settings, ranging from well-equipped military hospitals, remote relief areas with limited resources, and field hospitals in conflict zones or war fronts.

Medical ethics is governed based on certifications of qualifications and competence done by relevant professional bodies, such as the General Medical Council for Medical Doctors and the Health Professional Council for Biomedical Scientists.

The Geneva Conventions and other international humanitarian laws mainly govern military healthcare professionals. This is the basis of the term “Dual Loyalty” associated with Military medical healthcare professionals because they are in between two principles in practice, which may become conflicting as they must uphold national security supporting the military objectives and the responsibility to cater to patients and treat every patient⁵.

Military healthcare professionals are usually specially trained by their medical body and Army officers to be resilient, empathic, and physically fit to provide care under such diverse and sometimes harsh conditions.

They must also have a strong ethical compass to guide them in their duties as a military healthcare professional; you can get deployed anywhere, on the battlefield, on naval bases, or even in remote areas, which is why one of the critical skills is adaptability³. Requirements for joining the army include a basic physical fitness assessment, an age requirement of 17 to 35 years, basic military training and a bachelor's degree in your field; for example, for a Biomedical scientist, you would require a degree in Biomedical science and be registered with relevant bodies.

This rigorous training prepares them for the psychological and physical challenges of treating both civilians and soldiers. Some of the training includes emergency medical procedures, trauma care, and the use of other medical technologies. Also, military healthcare professionals must be adaptable to different cultures, traditions, customs, beliefs, and medical needs of the population they are deployed to serve; this is part of military training and is designed to maintain the integrity and core elements of medical military professionals².

Medical personnel must follow a different set of rules and ethics. This is very different from being a civilian healthcare professional because of the different circumstances and modes of operations in the military.

The ethics of doctors and healthcare professionals are summed in the dictum, “First do no harm, so they do their best to save every sick and injured person that comes their way. In military ethics, the soldier is loyal only to his country and must fight the war to protect national security. The role combines both the military physician and the healthcare professional.

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The military physician is expected to be both a patriotic soldier and a human physician. A military physician is expected to bridge these professions and blend into one.

Military medical personnel are faced with diverse challenges, especially on the field¹.

Their roles as military healthcare professionals may be termed complicated as they may face different challenges. For example, confidentiality cannot be breached; they must keep every patient's information confidential. These healthcare professionals find themselves in a dilemma whether to keep the information of a soldier struggling with alcohol dependency from the military commanders⁷.

Also, in a war situation, the healthcare professional may face challenges making difficult decisions urgently, deciding who receives treatment on the severity of injuries and survival likelihood. This may be a heartbreaking decision to make for the healthcare professional and others⁴.

The Geneva Convention states, "Each belligerent must treat his fallen adversaries as he would the wounded of his own army. It means that medical healthcare professionals must treat all injured and sick soldiers regardless of whether they are the enemy or not. This would mean two things: upholding the mission of winning the war and keeping the Hippocratic oath⁶. Assaults and injuries are a standard part of the war, so medical aid must be provided solely for medical needs regardless of sex, race, nationality, religion or political opinions. The wounded and sick must not be left without medical assistance, and treatment should be based on urgency. It is also important to note that following the Geneva Conventions, Military medical healthcare professionals are to be regarded as non-combatants and are forbidden to engage in war, so they have a special status, and they are not to be captured and they are immune from attacks⁸.

Being a military healthcare professional is beyond duty; it is more of a calling because you are responsible for many lives, including your own. You can decide who gets urgent attention and who can wait with limited resources. These tough choices are part of what moulds the military healthcare professional¹.

It is, however, very rewarding to serve and to be able to help save the lives of others.

If eligible and fit to be a military healthcare professional, you will undergo several training sessions to prepare for your roles and guide you in your ethical duties and responsibilities. Aside from the generic training that would need to be undertaken by every personnel in the military, some other institutions have developed training, such as the ICMM Centre of Reference for Education on International Humanitarian Law and Ethics, the U.S. DoD Medical Ethics Centre (DMEC), and the King’s College London Centre for Military Ethics (KCME). These trainings and workshops are usually done annually on Military Medical ethics and are solely to support military healthcare professionals to make legal and ethical decisions in the military context⁵.

Navigating the ethical challenges of a military healthcare professional requires a solid ethical and moral compass.

Military healthcare professionals are primarily responsible for their patients and must ensure they give their best care to their patients, whether civilians or soldiers.

They are also responsible for the resources allocated to them, whether limited or abundant, ensuring the most crucial needs are met. They must find the balance between their military obligations and medical duty. It is, however, the most rewarding position, and their commitment and resilience help to save lives and uphold the core values of both the medical and military professions.

References

1.

Bricknell, M., & Story, R. (2022). An Overview to Military Medical Ethics. Journal of Military and Veterans' Health, 30. https://jmvh.org/article/an-overview-to-military-medical-ethics/ 2.

Brintz, C. E., Miller, S., Olmsted, K. R., Bartoszek, M., Cartwright, J., Kizakevich, P. N., Butler, M., Asefnia, N., Buben, A., & Gaylord, S. A. (2020). Adapting Mindfulness Training for Military Service Members With Chronic Pain. Mil Med, 185(3-4), 385-393. https://doi.org/10.1093/milmed/usz312 3.

Finnegan, A., Finnegan, S., McKenna, H., McGhee, S., Ricketts, L., McCourt, K., Warren, J., & Thomas, M. (2016).

Characteristics and values of a British military nurse.

International implications of War Zone qualitative research.

Nurse Education Today, 36, 86-95. https://doi.org/https://doi.org/10.1016/j.nedt.2015.07.030 4. Hines, L. A., Gribble, R., Wessely, S., Dandeker, C., & Fear, N. T. (2014). Are the Armed Forces Understood and Supported by the Public? A View from the United Kingdom. Armed Forces & Society, 41(4), 688-713. https://doi.org/10.1177/0095327X14559975 5.

Lin, C.-Y., Bricknell, M. C. M., Brockie, A. F., & Kelly, J. C. (2022). Military Healthcare Ethics: Making It Relevant to the Whole Military Care Team. Military Medicine, 188(1-2), 21-24. https://doi.org/10.1093/milmed/usac321 6.

Meyer, H. S., Bader-Larsen, K. S., Artino, A., & Varpio, L. (2021). Ethical Bearing Is About Our Conduct: Ethics as an Essential Component of Military Interprofessional Healthcare Teams.

Military Medicine, 186(Supplement_3), 23-28. https://doi.org/10.1093/milmed/usab197 7.

Noroozi, M., Zahedi, L., Bathaei, F. S., & Salari, P. (2018).

Challenges of Confidentiality in Clinical Settings: Compilation of an Ethical Guideline. Iran J Public Health, 47(6), 875-883.

8. Vaidya, R., & Bobdey, S. (2021). Medical ethics during armed conflicts: Dilemmas of a physician soldier. Med J Armed Forces India, 77(4), 377-381. https://doi.org/10.1016/j.mjafi.2021.08.013

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EXPLORE THE WORLD OF BIOMEDICINE WITH US...

Email | bioscientistmagazine@salford.ac.uk Instagram | @salfordbiosoc X | @salfordbiosoc

We are looking for passionate science enthusiasts to join our Magazine’s writers team for our upcoming issues!

Bioscientist is published on ISSUU and more recently Janeway for readers to supplement their lecture content and enjoy at leisure.

Bioscientist has been widely recognised by the IBMS and has had involvements from influential scientists and top-level executives from Universities and other national companies in all 6 issues produced so far. Hence, working on the magazine is a great CV boost and a fantastic talking point for interviews or casual conversations with friends.

For our writers, we are looking for Biomedicine Society members with strong writing skills, creativity, and willingness to contribute to the scientific community. A passion for science is desirable, but we are sure you’ll come to love it as you work on the magazine!

If you have any questions or would like to register your interest, please email the publication’s Editorial Team. Please send your email to: bioscientistmagazine@salford.ac.uk You may read our newly released and previous issues at issuu.com/bioscientistmagazine

Recruiting Now!

pg. 87 PROGRAMME LEADS ADDRESS The Biomedicine Programme Lead Team reflect on the academic year 2023-2024, highlighting the key achievements and events. They also welcome new and returning students to the University for a new year of learning.

pg. 89 COFFEE WITH CAROLINE Dr Caroline Topham discusses the neurobiology behind resilience and shares tips on how to bounce-back in tough times, whilst conversing with Ashleigh Bowskill.

pg. 91 MY PLACEMENT EXPERIENCE Biomedical Science placement student Heba talks about her placement at Wythenshawe Hospital and her experience working towards building her portfolio to achieve her IBMS Certificate of Competence.

pg. 92 BIOMEDICAL SCIENCE DAY 2024 Biomedical Science Day is an annual celebration of the work of Biomedical Scientists. The events that the University of Salford’s students got involved in are outlined in this piece, written by Salford Biomedicine ambassador, Sara.

pg. 94 MY JOURNEY TO SALFORD AS A DEGREE APPRENTICE Louise talks about her return to education as a biomedical science apprentice at the University of Salford. She mentions her work in Spire Healthcare as an Associate Practitioner and her transition to education.

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PROGRAMME LEADS ADDRESS

DR MATTHEW JONES Deputy PL (Biomedical Science), Directorate Head (Academic Quality) DR SARA NAMVAR PL (Biomedical Science), Directorate Lead (Student Experience) TAHMINA HUSSAIN PL (Biomedical Science Degree Apprenticeship), Directorate Lead (Staff EDI) DR PIKA MIKLAVC PL (Human Biology and Infectious Diseases)

We would like to begin by welcoming all of our new and returning students to the University of Salford, for the 2024/2025 academic year. For returning students, we hope that you are enjoying the new topics that you are studying and continue to engage well with your studies. For all of our new students and degree apprentices, we hope that you are adapting well to university studies and are enjoying the transition from learning in college to the much larger scale of university. We also hope that you are managing to interact with your fellow students and learners throughout your studies, to hopefully allow you to develop lifelong friendships and collaborations which last much longer than the time of your degree programme. We hope that you all take every opportunity the University of Salford can offer you, both timetabled and extracurricular to make you the best possible graduates, allowing you to achieve your dreams.

This previous year has been a busy year, with a series of major achievements and milestones for the Biomedicine suite of programmes. The Biomedical Science programmes were successfully reaccredited by the Institute of Biomedical Science (IBMS), confirming our accredited degree status until 2029. This was a monumental task led by Dr Sara Namvar but required significant input from the whole programme team to complete the submission and ensure it met the high standards the IBMS requires.

Our Biomedical Science degree apprenticeship provision was also inspected by OFSTED last year as a part of their wider university inspection, with us being awarded a good outcome. This is a great achievement with the inspectors highlighting numerous positives and areas of excellence within the programme and the team which deliver it. We would like to thank everyone involved in the inspection and the key members of the team who spent their evenings coordinating this successful inspection.

We are also delighted to have been awarded the IBMS Educational Institution of the Year at the IBMS Awards 2024. The IBMS said the following as the reasons for the award.

“Congratulations on being recognised as ‘Educational Institution of the Year’ at the 2024 IBMS Awards. Your commitment to excellence and innovation in biomedical science is truly exemplary.

Your degree apprenticeship program’s high pass rates and the successful transition of your graduates into biomedical scientist roles reflect the effectiveness of your educational strategies and robust support provided by your programme team. The curriculum innovations you’ve implemented such as the pathology specimen reception and blood transfusion simulations provide students with practical, real-world experiences that enhance their professional competencies.

Furthermore, the growth of your extracurricular career mentorship groups and the success of your portfolio club in aligning university studies with HCPC standards demonstrate your proactive approach to student development and career readiness. Your institution’s efforts to adapt to the needs of the workplace and continuously improve the educational experience have set a high benchmark in the field. This award is a testament to your dedication to developing skilled professionals who are well-prepared to contribute to the biomedical science profession. Congratulations once again on your outstanding achievements and contributions to the field”.

This is a fantastic achievement, with the University of Salford now nationally recognised as one of the best universities in the country to study Biomedical Science. But this is only the beginning. We are continuing to invest in our department with the appointment of four new academic staff, to support and expand our Biomedical Science teaching team. We would like to welcome Dr Amy Morgan (Lecturer in Biomedical Science), Dr Samantha Borland (Lecturer in Biomedical Science) and Dr Willian A. da Silveira (Lecturer in Medical Genomics), with a fourth new lecturer to arrive in the coming months.

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Further to this, we are continuing to develop our teaching and learning provision to ensure our students have the best possible student experience, with the development and expansion of numerous initiatives including the development of collaborative online international learning (COIL) opportunities, based on the successful COIL event developed by Dr Matthew Jones and Dr Pika Miklavc with Wayne State University in Detroit. We are also designing and implementing digital escape rooms into selected modules to offer students a “playful” way to better understand key academic content related to numerous areas of biomedicine using the UoScape platform (https://uoscape.co.uk/) developed by Dr Nicky Morgan. We will also continue to deliver key events alongside our extracurricular societies including the nationally recognised IBMS portfolio club led by Tahmina Hussain, as well as journal clubs, lab tours, book clubs, plus the return of Bioart and PassionFlash. You will hear a lot more about these events in the coming months, so keep your eyes peeled for the advertisements on how to sign up soon.

We would like to end by taking the time to say thank you to all of our staff and students who have made these positive outcomes possible, and we look forward to welcoming our new students into the Salford Biomedicine family. We wish you luck with your upcoming academic year of studies.

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STUDENTS

Coffee With Caroline Resilience DR CAROLINE TOPHAM GIVES ADVICE TO STUDENTS ON RESILIENCE WHILST DISCUSSING THE THEME WITH ASHLEIGH BOWSKILL.

What is resilience, and why is it important?

The American Psychological Association defines resilience as “the process of adapting well in the face of adversity, trauma, tragedy, threats, or significant sources of stress”¹. The physiological capacity to adjust behaviourally, emotionally and mentally is a core feature of being resilient, as challenges present themselves throughout our lives, some bigger than others. How we respond to these challenges is crucial. Adapting is a fundamental aspect of resilience, as obstacles arise continuously throughout our lives, and our ability to adapt increases our likelihood of survival. Our ability to thrive in the world is directly influenced by how we react to these challenges, given that our very existence depends on our reactions. Reflection upon our ancestors shows the increasingly evident link between resilience and survival, as their capacity to obtain sustenance, maintain warmth, and protect themselves against harm daily was vital for continuing to live their lives in the face of tragedy and adversity. If they were incapable of this, they would not have survived. In contrast, the majority of modern-day individuals in the UK enjoy a higher level of security in terms of access to necessities such as food, water and shelter. This increased security reduces the immediate need for resilience for mere survival.

However, resilience remains essential for individuals to thrive and reach their maximum potential.

How does resilience work neurologically?

Aspects of our personalities are linked to our neurobiology, such as my habit of creating to-do lists and checking off tasks as I complete them.

Over the years, I have noticed that this action triggers a sense of satisfaction and a release of dopamine, which reinforces the behaviour. Our brains form and strengthen neural pathways through repetitive behaviours, making certain actions feel more natural to us. When we consider the reinforcement of neural pathways in terms of resilience, individuals may experience various positive or negative outcomes based on the choices they make in each situation. These outcomes can be random, and/or be influenced by specific circumstances,

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leading to the development of habits (reinforced neural pathways) based on the success of their decisions. This might explain why some people remain calm in difficult situations while others quickly become overwhelmed. It seems that we develop certain reactions and coping strategies that become automatic habits when we are under stress.

For example, individuals who have experienced trauma may feel anxious and fearful in situations that remind them of the traumatic event, even when there's no logical reason for these feelings in the present. This is known as Post-Traumatic Stress Disorder (PTSD), which occurs when neural pathways associated with fight/flight/freeze responses are reinforced by past traumatic experiences.

These pathways can be quickly activated in response to minor stressors, causing significant distress and impacting daily functioning.

Thankfully, psychotherapist or psychiatrist consultations can effectively treat this condition.

Are humans naturally resilient, and what makes some people more resilient than others?

The way each person responds to stress varies and can be influenced by factors such as the environment in which they were raised.

Additionally, there is evidence as stated earlier, that we differ phenotypically in terms of our neurobiology, regardless of environmental factors.

Roughly 20% of the population is born with a “highly sensitive” nervous system, and these individuals are referred to as Highly Sensitive People (HSPs) by psychologists. HSPs have also been termed “orchids” by psychologists in comparison to individuals with lower sensitivity, who are called “dandelions”².

Orchids generally thrive in a specific environment, while dandelions can adapt and thrive anywhere.

Although HSPS can absolutely be resilient, they may require different forms of support to cope effectively. If you are curious if you may be HSP, you can try this test out!

How does genetics play a role in resilience?

Researchers who have focused on the genetics of resilience concur that there is a genetic element to our stress-managing abilities. It is not surprising that genes associated with neurotransmitter systems are among the potential candidates, and developing a deeper understanding of these genetic connections could aid in the prevention of mental illnesses and the development of various pharmacological interventions. A 2019 review by Maul S, et. al. provides a comprehensive summary of several studies examining PTSD and depression, making it an excellent starting point for reading³.

Does technology and social media impact a person’s resiliency, and are these impacts beneficial or detrimental?

Technology and social media use can potentially influence an individual's resiliency in both positive and negative ways. On the positive side, social media platforms allow opportunities for individuals to make connections, obtain valuable resources, and seek support that may aid a person through adversity. These also allow means of selfexpression, creativity, and personal development, all of which contribute to enhancing resilience.

However, the use of technology and social media can also have adverse effects on an individual’s resilience. Excessive reliance on social media platforms can trigger feelings such as envy, loneliness, and the stress of trying to create a perfect and unrealistic image of themselves. These outcomes can significantly consume an individual’s selfconfidence, as well as their physiological and physical well-being, overall undermining their ability capacity to cope with life’s challenges.

The impact of technology and social media on a person’s resilience is multi-faceted and complex, ultimately depending on the use of these tools and the underlying factors that influence their relationship with technology and social media⁵⁻⁶. Being mindful of the use of technology is important. Healthy habits and boundaries to ensure these tools contribute positively to resilience.

What are some of the most common factors for strengthening and maintaining resilience?

This is a hot topic in the mental health world, and there are hundreds of resources and numerous books to choose from based on this subject! Having an effective stress and emotion management method is essential for building resilience, however, these attributes and skills can work differently among individuals.

To get started I recommend checking out the helpful tips on the Mind website, which is an excellent guide for those embarking on the journey to enhance their resilience. One key aspect highlighted in their recommendations is the importance of self-care and building a good relationship with yourself and others in your life and community. As social beings, humans tend to fare better in managing stress when surrounded by supporting networks.

Seeking assistance from a counsellor or psychotherapist can also aid in the process of strengthening resilience⁴. .

Are there any misconceptions and downsides to resilience?

Resilience is often seen as a positive trait to acquire, but it is important to consider the potential downside of becoming overly dependent as a coping mechanism. This hyper-independence can develop from childhood as a coping mechanism, from childhood experiences where trust in people and the world around you was shattered and could not be relied upon to keep you safe and secure.

Those of us who have experienced abuse or neglect, including emotional neglect, may decide at an early age that only we can take care of ourselves, and find it hard to trust people and form connections later in life. While self-reliance can be a survival strategy, it may also result in depression, anxiety, and loneliness if we do not learn to trust others again. As stated earlier, animals are social beings who thrive on community and connections. Denying ourselves this due to hyper-independency, and not sharing our feelings and needs, can be very isolating. If you recognise this yourself, I encourage you to reflect on how you can start building trust in your relationships, perhaps with a friend, counsellor, mentor, or therapist who can help you to start rebuilding those connections. Remember, a problem shared is a problem halved!

References: 1. American Psychological Association. (2020). Building Your Resilience. Retrieved 30/09/2024 from https://www.apa.org/topics/resilience/building-your-resilience 2. Matthews, K. L. (2023). HSPs, Are You an Orchid, a Dandelion, or a Tulip? Sensitive Refuge. Retrieved 30/09/2024 from https://highlysensitiverefuge.com/are-you-an-orchid-dandelion-ortulip/ 3. Maul, S., Giegling, I., Fabbri, C., Corponi, F., Serretti, A., & Rujescu, D. (2020). Genetics of resilience: Implications from genome-wide association studies and candidate genes of the stress response system in posttraumatic stress disorder and depression. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics, 183(2), 77-94. https://doi.org/https://doi.org/10.1002/ajmg.b.32763 4. Mind. (2022). Managing stress and building resilience. Retrieved 30/09/2024 from https://www.mind.org.uk/informationsupport/types-of-mental-health- problems/stress/managing-stressand-building-resilience/ 5. Naslund, J. A., Bondre, A., Torous, J., & Aschbrenner, K. A. (2020).

Social Media and Mental Health: Benefits, Risks, and Opportunities for Research and Practice. Journal of Technology in Behavioral Science, 5(3), 245-257. https://doi.org/10.1007/s41347-020-00134-x 6. Ostic, D., Qalati, S. A., Barbosa, B., Shah, S. M. M., Galvan Vela, E., Herzallah, A. M., & Liu, F. (2021). Effects of Social Media Use on Psychological Well-Being: A Mediated Model [Original Research].

Frontiers in Psychology, 12. https://www.frontiersin.org/journals/psychology/articles/10.3389/fpsy g.2021.678766

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STUDENTS

My Exciting Journey in Biochemistry A Year at Wythenshawe Hospital HEBA TOUMEH Heba Toumeh, a Biomedical Science student on placement, is currently working towards her IBMS Certificate of Competence by building her portfolio. She talks about her time at Wythenshawe Hospital, a part of Manchester University NHS Foundation Trust. She provides an insight into what life is like as a placement student, looking at the day to day running of a Biochemistry lab as well as the challenges faced by Biomedical Scientists.

Hi, I am Heba Toumeh. I want to share my incredible experience as a Biomedical Scientist (BMS) trainee at Wythenshawe Hospital’s Biochemistry Department. This year has been a stimulating journey of growth, learning, and discovery.

As a beginner, I dove into biochemistry, working on various tests from osmolality to diabetes diagnostics with HbA1c samples. Each day, we start with a team huddle, setting the stage for collaboration and problem-solving. These meetings have been invaluable in sharpening my professional and communication skills (HCPC SoP 7.1, 7.7 and 7.9).

A crucial part of my training involved mastering pipetting techniques and ensuring our lab results are accurate with strict quality controls (QCs).

Pipetting is fundamental in a biochemical lab, crucial for precise measurement and transfer of liquids, and it directly impacts test reliability.

I became proficient with various pipettes, including positive displacement pipettes, which prevent air from entering and are ideal for viscous or volatile samples; multi-channel pipettes for efficient handling of multiple samples; and air displacement pipettes, which are typical for general use.

Quality controls (QCs) are integral to this process.

They involve using different control levels to validate testing accuracy and precision and identifying errors early to ensure reliable results (HCPC SoP 12.6). Adhering to the Westgard rules, which provide guidelines for detecting errors and ensuring consistent results, is essential. Regular calibration and maintenance of pipettes are also vital. These practices are crucial for maintaining the credibility of diagnostic processes and impacting patient care.

Corporate mandatory training, especially on Equality, Diversity, and Inclusion (EDI), has broadened my perspective on creating an inclusive workplace. This training was not just a checkbox but a transformative experience that underscored the importance of respect and inclusivity within the workplace (HCPC SoP 5.2).

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Of course, the journey was not without its obstacles.

Managing my energy involved developing a consistent routine, prioritising self-care, and taking enough rest to maintain focus and productivity.

To overcome language barriers, I actively communicated with colleagues, sought help, and utilised scientific language resources to improve my vocabulary. Enhancing my time management skills required planning and the use of organisational tools, like schedules and to-do lists, to ensure all duties were completed efficiently. Each challenge made me stronger and more resilient, equipping me with valuable skills for my future career.

Reflecting on my year, I am deeply grateful for the support from my supervisors Susan Poni and Hetalika Banka, colleagues, and the University of Salford. Their guidance has been crucial to my development. This placement has increased my passion for biochemistry and prepared me for an interesting future.

Thank you for joining me on this journey!

References: Health & Care Professions Council. (2023). The Standards of Proficiency for Biomedical Scientists. https://www.hcpcRetrieved 28/01/2024 from uk.org/standards/standards-ofproficiency/biomedical-scientists/

STUDENTS

BIOMEDICAL SCIENCE DAY 2024 AT THE UNIVERSITY OF SALFORD SARA ALNASIR KASSAM Biomedicine Student Ambassador, Sara A Kassam, recounts the events that she helped organise and execute as part of Biomedical Science Day 2024. Working closely with Tahmina Hussain, Matthew Jones and several other ambassadors, events were run in tandem across two sixth form colleges and at NHSBT Manchester. Ambassadors and organisers share their thoughts on how the events went and what they gained from the experience.

Biomedical Science Day, an annual day of celebration highlighting the incredible contributions of Biomedical Scientists nationwide to the healthcare system, occurred this year on Thursday, 6th of June 2024. First established by the Institute of Biomedical Science in 2017, Biomedical Science Day is celebrated in several ways by all involved in the Biomedical Science field, whether working as Biomedical Scientists or students. Competitions are held to unleash the creativity of those who work at the heart of healthcare. This year, students from the University of Salford immersed themselves in the celebrations of this incredible day through three events that ran simultaneously. Level 4 and apprentice Biomedical Science students visited Manchester's NHS Blood and Transport Centre.

Additionally, a group of student ambassadors visited Connell Co-Op College, East Manchester, whilst another group visited Holy Cross College, Bury. Both groups delivered similar talks to students promoting Biomedical Science as a potential degree and career. Volunteers distributed merchandise to attendees who had the opportunity to ask questions about the Biomedical Science field and student life at the university.

The ambassadorial team that went to Holy Cross College was joined by practising biomedical scientist Waqas Hussain, from Manchester University NHS Foundation Trust.

He spoke of the role of a biomedical scientist on a daily and some of the equipment and tests they conduct within Biochemistry, sharing his professional experience with the college students.

The event was organised by Tahmina Hussain, with Manisha Mort being critical to its success.

Lloyd Mcleggon-Watkinson, a Biomedical Science Degree apprentice, accompanied Tahmina and a group of Level 4 students who tried their hand at virtual reality blood grouping, a groundbreaking training resource recently launched by NHSBT through their collaboration with Meta.

The organisers received positive feedback from attendees, participants, and Salford ambassadors.

Iqra, who was a Salford ambassador during the Connell Co-Op College Visit, stated: "I absolutely loved today's event. I would consider it a sudden breakthrough in my career and academic life as it demolished my idea of underestimating my confidence. I went from being a caterpillar to a butterfly spreading the beautiful colours of Biomedical Science to younger people."

Attendee Lloyd, who attended the NHSBT event, said: "My current work in Immunology doesn't expose me to all of the disciplines within healthcare science, so I seized the opportunity to view the NHSBT laboratory when it became available. And it was, coincidentally, on Biomedical Science Day… Without valuable donations, there would be no service to maintain blood products for patients in need.

What I have seen is a highly organised and complex service where laboratory staff, including biomedical scientists, can create products that contribute to maintaining the quality of life for patients with haemoglobinopathies (e.g., thalassaemia, sickle cell) or life-saving interventions in the event of a haemorrhage."

In an event running simultaneously, a visit to NHS BT Manchester was organised, based in South Manchester.

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STUDENTS

Dr Matthew Jones, who led the Holy Cross Event, reported that the event was highly commended by Holy Cross College & University Centre staff, with the staff invited back to attend an upcoming careers event and repeat this event again next year. The event was also very well received by students, with 98.4% of participants stating that they had a positive experience, and 96.8% of attendees said that they found the delivered activities fun and exciting. College students participating in the event found that it increased their knowledge of Biomedical Science. The day's events posed fantastic skill development opportunities for our ambassadors, some of whom took the brave step out of their comfort zones and volunteered to represent the University of Salford. Sanaria said: "I had a great time being able to educate and highlight the diversity of doing a biomedical science degree and the career paths. It was a great opportunity for me to network and help students with their future career prospects."

The events were all featured on the IBMS website. You may see the article by following https://www.ibms.org/resources/news/biomedic al-science-day-2024--ibms-manchester-branch/.

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STUDENTS

My Journey to Salford as a Degree Apprentice LOUISE ANNESLEY Louise is a Biomedical Science Degree Apprentice. Louise explains her journey involving her return to education, from unexpected opportunities to building confidence and competence to practice as a future biomedical scientist. She describes what her journey as a student has been like thus far.

My return to education at the University of Salford was really quite unexpected, as the COVID pandemic changed my life in a different way than it did for most. For a decade prior to 2020, I worked in the travel industry; however, it had started to feel increasingly monotonous, and I knew I wasn’t being challenged to my potential. The decade prior to that, I had worked in hospitality within the UK and overseas, gaining plenty of life experience along the way too.

When the first lockdown hit and I was furloughed indefinitely, I, along with millions of others across the world, was thrown into the unknown. I joined the admin team at a local hospital during my furlough to assist with their office archiving backlog on a temporary basis, and while I was there, the opportunity to apply for a full-time Medical Laboratory Assistant role in histology presented itself.

Having not considered a career in healthcare prior to starting there, I jumped at the chance to learn something completely new. Starting this new role introduced me to the fast-paced world of histology, where I received first-hand training on the job, learning basic laboratory skills from my peers. This experience ignited a spark in me that had been lying dormant. As my confidence grew, I began taking on new tasks, and with each new skill-based competency signed off, I reached the limit of my practice as an Associate Practitioner without a science degree. We then entered a discussion about what to do next for me to continue progressing.

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Several avenues were explored to continue my progression, including online distance learning or potentially changing my role within the workplace; however, these options just didn’t feel like the right fit for me. When the discussion around doing an apprenticeship degree at Salford arose, it really piqued my interest because it was the perfect combination: I could continue doing the job I was really enjoying while completing the degree program on my study day (one day on campus per week) and integrating the registration portfolio into the apprenticeship. Getting that study day is such a vital tool to allow me to focus my time and energy to get the most out of all aspects of my working life. The combination of work-life, university-life, and life-life has so far turned out to be an intricate juggling act of prioritization, something which, thankfully, I excel at due to my experience in previous roles.

I never thought I would be going back into education at 36 years old, and some weeks are certainly more challenging than others, especially when life gets busy and the fear of falling behind strikes. However, I have found this first year to be incredibly rewarding, and the support received from both my tutors and my fellow apprentices has been beyond what I could have ever expected. That support network is such a blessing to have; knowing you can reach out to others who have gone through the challenges or are right in them with you has turned it into an incredible shared experience. Healthcare science is a fascinating, everdeveloping discipline, and I continue to be excited to learn more within this field on my personal journey to becoming an HCPC-registered Biomedical Scientist.

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PRESIDENT’S ROUND UP

BY TASFIA HAZARI Tasfia Hazari was the President of the Biomedicine Society during 2023-2024. She reflects upon the past year, recounting the events that were organised by the committee. Several achievements are also highlighted, some of which include the Biomedically Speaking Podcast as well as Biobites and the Passionflash and BioArt Competition Finals.

The sixth year of the Biomedicine Society has been a challenging year. I am Tasfia Hazari, the President of the Biomedicine Society for 2023-2024, and this is a reflection on the incredible journey we have had over the past year.

We kicked off the year with Freshers Week, where we met each other for the first time and introduced ourselves and the society to the new cohort of Level 4 HBID and Biomedical Science students. The following day, at the Freshers Fair, we attracted prospective members and welcomed back existing ones for another year. To create a more diverse cohort, we reached out to students from courses outside of Biomedicine and HBID. Our first social began that evening with a screening of Dr Arijit's documentary about glaucoma and his associated work.

Our initial events included weekly sports sessions and CV workshops delivered by our secretary, Mariam Yaqoob.

Alongside these, we organised a variety of activities such as charity stalls to raise money for aid in suffering countries, book club catchups, and a bowling event.

This year, we introduced three new initiatives: the Debate of Science, the Biomedically Speaking Podcast, and BioBites sector of the society. The scavenger hunt was a lot of fun, where the committee got to act, and members got to enjoy the creativity and solve clues like detectives. A memorable experience was the 12-hour live stream which helped our members, who joined in, to become closer; this was the most unique and engaging event we planned. We raised money for KidsCan through a boxing event where one of our BioSports Leads, Kayla Keza Millane, participated and gracefully won. Another highlight was the BiomedSoc Winter Dinner, where our academics joined us to relax and enjoy the end of the first trimester.

Additionally, we participated in the Morson Group’s Go Beyond Women in STEM Celebration, speaking about our society to many phenomenal women in STEM and recruiting new members. We also introduced our society in a GEMSPA event by inviting attendees to various events and promoting our society.

Our primary objective of this year was to help students in such a demanding course relax and enjoy university life while providing opportunities to build their portfolios, gain volunteering experience, and network with fellow students.

We achieved this by supporting and involving volunteers in every event possible, providing networking opportunities by collaborating with other societies and their members, and starting BioBites to create more opportunities.

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The year culminated on a high note with a grand masquerade gala, “The Final Show,” at the stunning Gorton Monastery. The event was an exquisite blend of classic elegance and modern flair. The soft, melodic tunes of a harpist welcomed us, setting a serene and elegant tone. The service from the Monastery team was impeccable, ensuring everything ran smoothly and adding to the evening's enjoyment. The food was delicious, offering a variety of dishes that pleased every palate. As the night progressed, the atmosphere became livelier and more vibrant.

We had the pleasure of meeting students from other universities who joined us, making the event even more special. The night culminated in dancing, with everyone hitting the dance floor and celebrating the end of an unforgettable year together.

This year, we introduced a delightful new mascot for the Biomedicine Society, created at the last minute but quickly becoming a beloved symbol of our community. The idea for the mascot emerged spontaneously during a fun and memorable moment in one of our group chats. At one point, everyone was trying to get my attention, and they started calling me a "host cell." Overwhelmed by the bombardment of messages, I humorously responded by addressing everyone as my viruses.

This playful exchange turned into a tiny inside joke within our group, which we felt perfectly captured the spirit of our society.

After a final voting for this new one of a kind member, the members of the Society decided to name it “Host Cell”. This mascot is a leaving memory from my committee and shall be embraced by the committees to come.

Reflecting on this journey as the President of the society, I am immensely proud of our strides and the positive impact we have had on our members. Leading such a vibrant and dedicated community has been an honour and a joy. While it is bittersweet to step down, I am filled with excitement and confidence as I hand over the reins to a deserving new committee.

Bio Debate.

SHOULD GENOMIC SEQUENCING BE MADE THE NORM?

BY AWEIYE OMUSI Students of the University of Salford came together on the afternoon of the 23rd of April 2024 to engage in a bold debate on the topic: “Everyone should get their genome sequenced”.

The discussion involved three students on each side, all from the University’s Biomedicine programme, with one group arguing for the motion and the other against. The spirited debate was judged and assessed by Dr Arijit Mukhopadhyay along with members of the Biomedicine Society Committee.

The debate raised thought-provoking questions about the ethics and regulations around genome sequencing. The debate centred on the topic of genome sequencing and comes at a time when the topic has garnered the interest of many people who are interested in learning more about this rapidly developing scientific field.

The debate kicked off with the team in favour of the motion, who gave their opening statement and stated how genome sequencing would transform healthcare systems as we know it, especially for those with genetic diseases. They argued that it could improve health outcomes and enhance the quality of life of people globally by offering personalised treatments.

Following this argument, the team against the motion opened up their arguments for the debate by raising various concerns around practicality, safety, and morality of genome sequencing.

They noted that sequencing costs £6,625 per individual, making it impractical for widespread use.

They also highlighted consent and privacy issues, questioning who exactly would have access to information of individuals who took part in genome sequencing.

It was now the turn of the for side to give their response. One of the opposition’s key arguments was about data safety and who would have access to the data that is procured through the genetic screening. They argued that if personal information is removed and the data is encrypted, genome sequencing could actually be safe for everyone.

Additionally, by implementing the already existing regulations such as the Genetic International Data Guidelines this would make genome sequencing safe for everyone even on a global level.

The proposition rebutted that the cost of genome sequencing has dropped dramatically from $100 million to about $1,000 which contradicted the statement made by the opposition that the cost per person is £6,625. They stated that it makes it much more affordable and accessible to the wider community. The advocates pointed out that sequencing can not only save time but also money by reducing the need for countless consultations and endless blood tests to diagnose health conditions. They also highlighted how genome sequencing can help with more accurate medical care for each individual.

Understanding an individual’s genetic makeup can lead to more accurate prescriptions as well as dosages as a person need can vary based on their genetic makeup.

One student of the proposition noted that even though the cost has dropped significantly over time for genomic sequencing, the reason sequencing is still $1,000 which while still being out of budget for many, as it becomes more widespread, prices will likely decrease even further. As for the issue of data usage and consent for minors, they argued that receiving consent from a parent/guardian will suffice.

The debate continued with both the opposition and the proposition arguing valid and well researched points to make their arguments and articulated them in a cohesive manner.

The cross-examination portion of the debate had both sides fire quick fire questions at each other and gave them a chance to find cracks in the other team's arguments and also develop their arguments.

The judges asked questions to prompt further discussion between the teams.

After over an hour of lively debating from both the proposition and the opposition and more discussion of points from both parties, the judges took time to discuss and determine their winner. They determined that their winner was the proposition! The judges determined that their arguments were the most convincing in agreeing with the motion.

This concluded the exciting events of the first debate of the Salford Biomedicine Society brought to light the exciting yet controversial topic of genome sequencing. The proposition argued that it could revolutionise healthcare with personalised treatments.

Meanwhile, the opposition raised prominent issues about privacy, costs, and ethical concerns, questioning who would have access to the personal genetic data collected. This debate did not only inform students and peers about this interesting aspect of scientific research but also highlighted the need to balance new ideas and innovation with good ethical practice in the healthcare industry. The debate left everyone pondering how genomic medicine could influence the field of medicine and revolutionise modern treatment of disorders.

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Looking back on our role this year

BY ALI AL TAIE For the past year, our work as events managers was mainly focused on preparing the events, starting with brainstorming different ideas with the rest of the committee during our regular meetings. For the first event at Printworks, we were responsible for contacting Printworks management and arranging a time and date for the event.

We discussed the pricing and potential number of attendees. Post confirmation, we had our social media manager create an advertising post for the event, and we published it on all platforms, allowing members to book their tickets in advance.

At the event, we were responsible for regulating the event by ensuring everyone arrived safely and was satisfied with the atmosphere surrounding them. Post the event, we usually ask the members who attended to provide us with feedback so we can improve our upcoming events. We also allow the members to dictate the locations and activities of our potential events, ensuring they are tailored to our members' interests. These essential roles apply to most of our work, from educational and informative to fun and entertaining events.

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By Alvina Imran On the 16th of April, we successfully hosted our highly anticipated BioArt Competition, and it was an event to remember! As the BioArt leader, I was incredibly proud to see how science and art came together, creating a beautiful fusion of creativity and biology, all centred around the theme of "Sustainability”.

Participants truly embraced the theme, showcasing an incredible array of artworks that ranged from detailed depictions of microscopic organisms to breath-taking representations of entire ecosystems. It was inspiring to witness how artists interpreted sustainability, using their pieces to highlight the beauty, resilience, and complexity of the natural world. The diversity of ideas and styles made the competition a vibrant celebration of life and our connection to the environment.

The Event Atmosphere In keeping with the sustainability theme, the event featured a variety of goodies and refreshments that were thoughtfully selected to align with eco-friendly practices.

We provided organic, locally sourced snacks and sustainable packaging, ensuring that even the smallest details reflected our commitment to environmental consciousness.

The atmosphere was buzzing with excitement as participants and attendees mingled, exchanged ideas, and appreciated the artistic masterpieces on display.

Winners and Prizes We awarded prizes of up to £150 to those whose artwork stood out for their creativity, originality, and ability to convey the essence of sustainability. The winners demonstrated an exceptional understanding of the theme, and their works left a lasting impression on everyone who attended.

Collaboration and Decision-Making This event wouldn't have been the success it was without the collective efforts of the decision-making team. Alongside me, Harriet Burrow, Dr.Sara Namvar, Dr.Matthew Jones, and Dr.Niroshini Nirmalan played a pivotal role in planning and organising the competition. From selecting the theme to coordinating the logistics, their dedication ensured that the event ran smoothly and that we were able to create an unforgettable experience for all involved.

The BioArt Competition was more than just an event—it was a celebration of how art and science can come together to inspire conversations about sustainability. We’re grateful to everyone who participated and contributed to making it such a memorable occasion. Thank you for joining us on this journey, and we look forward to even more creativity and innovation in the future!

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BY KAYLA KEZA MILLANE Before the first training session, I was filled with pure adrenaline and determination; between us, I thought this experience would be a walk in the park; little did I know that I was in for a rude awakening. The moment I stepped into the gym, the atmosphere was thick with the smell of sweat and a sense of tenacity. As I watched seasoned fighters spar in the ring, a shiver shot down my spine; I couldn't believe I was doing this.

The first week, aptly called Hell Week, was a wake-up call. The first session involved sweating and panting through countless drills. After what felt like a thousand drills, I lay on the soaking wet mat, looking up at the cloud of steam my peers and I had made, only to find that we were only 10 minutes in. I persevered through the session and somehow made it to the end, still alive. The pride I felt from making it through that first session was the fuel that powered me through every subsequent session.

I felt like I was becoming stronger and more skilled with each practice until I sparred for the first (and only) time. Initially, I was excited to spar, and honestly, I thought I would dominate until I saw the intense, fiery determination in my opponent's eyes. As the coach signalled for us to start, she swiftly moved towards me and hit me with a jab square in my face. The sparring was finally over after what felt like an eternity and a hell of a left hook. I knew I had my work cut out for me. I continued to work hard during the remaining training sessions and worked out in my spare time. During this period, I considered why I had decided to commit to this. After some contemplation, I realized that one of the main reasons I was competing was for the charity I was fighting for.

Kidscan is a charity that helps children with cancer and their families. These children are thrust into a battle that is a matter of life and death, and in all honesty, they're the real fighters.

So, when I needed that extra push, I thought of them and the responsibility to raise awareness about such a fantastic charity that offers muchneeded resources and care to those who need it.

After eight weeks of training, it was finally the day I was looking forward to Fight Night. As I entered the venue, a nervous energy permeated the atmosphere. At this point, only the fighters had arrived, as we needed medical clearance before the event began. The crowd started filling the venue, with over 1000 people cheering on their loved ones. I felt a cacophony of fear, excitement and a hint of pride.

Had I made it this far?

Would I be able to hold my own in front of the crowd?

Soon, it was my turn to fight. I boldly strolled from centre stage to the ring while Kanye's "All of the Lights" played in the background. The moment I stepped into the ring, everything else faded. My heartbeat was deafening as my focus narrowed down on my opponent. She looked as intense as she did during that first sparring session, with the same fiery determination. This time, I was ready. I raced towards her when the bell rang, eager to prove myself. The three rounds were a blur of punches and a constant reminder to keep my guard up. I had trained hard, but the reality of being in the ring was more demanding than any of my previous training. I felt fatigue set in early on, but somehow, I pushed through to the final bell. As the final bell rang, I felt relief wash over me. I had done it – I had fought my first boxing match. As we waited for the judge's decision, I held my head up because I had made myself proud regardless of the result.

I'm glad to say I won. However, that experience was about more than just a boxing match. It was about perseverance, discipline and self-belief. An Alex Hormozi quote says, "You don't become confident by shouting affirmations in the mirror, but by having a stack of undeniable proof that you are who you are. Outwork your self-doubt".

So, if you've read this far, I encourage you to have experiences that push you beyond your comfort zone and reveal the incredible person you are.

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Biosport

Hey guys, Keelan here!

As one of the two Sports Bees for the 23/24 Biomedicine Committee, I could not be prouder of the events we have achieved this year.

At the start of the year, we had badminton sessions. which were well attended and enjoyed by all! As a badminton player myself, it was great to see so many members getting involved regardless of ability, and even seeing some really good progression among members.

Following this, we had dodgeball sessions which were a blast. We could not have done it without Nafisa, our wonderful Sports Support Bee, who really brought energy and enthusiasm to the sessions and was lethal with a dodgeball! We managed to get male and female sessions running for the comfort of any student who wished to join in, and attendees really appreciated this consideration.

Finally, we had our basketball sessions toward the end of the academic year, where we saw a big increase in the activity of our members and even some interest in the Sports Bee position for the new committee.

Kayla, Nafisa and I are beyond grateful for the opportunity to work with the committee, and I wish the new committee well with the 24/25 year!

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BIO-BOOK CLUB 12HR STREAM

BY NAFISA ALI Nafisa Ali, our Sports Support Bee, reflects on the Biomedicine Society event called the ‘12-Hour Book Club Challenge’ and how it enriched the student experience by facilitating collaborative reading and bringing the members closer.

One of the highlights of my year with the Biomedicine Society was participating in the 12- Hour Book Club Challenge on behalf of the society's book club. This unique event involved all participants joining a Microsoft Teams call for 12 hours to study or read books, with a prize for whoever stayed on the call the longest.

Initially, we were all focused on being productive, diving into our studies or reading. We took breaks every half hour, relaxing for ten minutes before getting back to our tasks.

As time passed, however, our focus shifted, and we began to chat and relax together. Our conversations ranged from worldly matters, morals, and principles to fun topics like movies and childhood memories. These discussions were a fantastic way to get to know each other and understand different perspectives.

I met some incredible people during this challenge, many of whom are still my friends today. It was a great way to warm up to university life and connect with others, especially after the isolation of lockdown. The challenge started around 9 PM and ended at 10 AM the next day.

Initially, we thought it would be easy, but by 4 AM, the difficulty became apparent.

We started with about twelve participants, but by 5 AM, only four of us remained. The remaining participants were particularly engaged in discussions about politics and historical events. Given our diverse backgrounds, it was fascinating to learn about different cultures and beliefs. I truly enjoyed these conversations, even though I couldn't stay until the end of the challenge. The experience was enriching and a wonderful way to bond with fellow students, blending productivity with meaningful connections.

102 | BIOSCIENTIST MAGAZINE

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