Dr Dolphin – Winter 2024

DR D LPHIN INTUITION

PR E

ION CIS

E V ID

ENCE BASED

PAST PRESENT FUTURE OF MEDICINE

Cover By: Enara Faes

Welcome to the 2024 Winter Edition of Dr Dolphin!

In this issue, we traverse the evolving landscape of medicine—reflecting on breakthroughs that have shaped its past, exploring the current frontiers of innovation, and envisioning a future where cuttingedge advancements redefine the boundaries of healthcare. Join us on this journey through time and progress in the ever-evolving field of biomedicine.

We have made the decision to select the theme of 'The Past, Present and Future of Medicine” as it encompasses a myriad of remarkable facets within the realm of medical science. We hope you enjoy reading all the wonderfully written articles, and playing the crosswords, word searches, and connections!

-Senior Dr Dolphin Team1

Dr Dolphin - Winter Edition Table of Contents

Page Number 1 2 3-5 6 7 8 9 10 11-12 13 14 15-16 17 18

Contents Editors’ message Table of contents Importance of the Apothecary Game 1 One Man, One Frog A brief history of radiofluorine tracers in PET scanners Game 2 Game 3 Past, Present and Future of the NHS Game 4 Build-a-pill Climate Change’s impact on public health Game 5 Game 6

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The Importance of The Apothecary Georgina Heckels Apothecaries have always had a very important role in society. But what exactly did they do?

The apothecary was a medical profession where the main role was to formulate and dispense medicines and herbal remedies to physicians, surgeons, and patients. Plants were not just used for the making of medicines, but also for strewing (scenting rooms), cooking, dyeing fabrics, and brewing. A particular plant could have several uses. For example, lavender could be used to scent rooms, to keep moths out of clothes, flavor food, and as an anti-inflammatory. In order to create these remedies the apothecaries needed a space to work. An apothecary's workshop would have included things like mortar and pestle, scales to weigh products, an alembic to distill medicine, manual pill-makers, containers to store medicine and cork-making stoppers, among other contraptions.

Apothecaries used pestles and mortars for pounding, mashing, and grinding ingredients down so that they could be added to medicines for patients. An apothecary would have had a range of mortars in different sizes and materials, for different purposes and ingredients. Mortars made from brass, bronze, and iron were used for harder materials, such as resins, firm spices, or bark, and for grinding ingredients into smaller particles.

Mortars made from bell metal were also used when ingredients needed to be heated in fire. Bell-metal mortars were often made in bell foundries, and, when used, the metal rings with a bell-like sound.

An example of an apothecary’s workshop that you can still visit today is the garret (or attic) of St Thomas’ Church. Throughout most of the 18th century, until Old St Thomas' Hospital vacated Southwark in 1862, the apothecary lived and worked in what is now 15 St Thomas Street. As a permanent resident, he was not permitted to marry or to practice medicine outside the Hospital.

In Old St Thomas' Hospital, the daily care of patients was the responsibility of the apothecary and the medical students. It is very likely that the use of the garret of St Thomas’ Church was for the hospital apothecary to dry, cure, and store herbs and dates back to 1703, when the Church was constructed. Hooks, ropes, and nail holes in the roof and dried "opium" poppy heads discovered under the floorboards in the 1970s are evidence of its former use. At Old St Thomas’ Hospital, large quantities of herbs were purchased from a visiting herb woman. Moreover, the Hospital had its own botanic garden and an apothecary's shop sited within its grounds. The apothecary was the chief resident medical officer of the Hospital and besides formulating medicines, he was responsible for prescriptions for surgical cases and, in the absence of the physician, for dispensing medicines to all the Hospital's patients. Before the development of the chemical industry in the late 19th and early 20th century, medicinal compounds were made from minerals, animals, and plants. Even today, the majority of medicines originate from these sources.

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An example of one of these books is De Materia Medica, which is a pharmacopeia of medicinal plants and the medicines that can be obtained from them. It was written between 50-70 CE by the Greek physician Pedanius Dioscorides. It was widely read for more than 1,500 years until it was supplanted by revised herbals in the Renaissance, making it one of the longest-lasting of all natural history and pharmacology books.

The term De Materia Medica (on medical material) was also used to describe raw medicinal plants. In the 19th century, a medical student studying to become an apothecary would have to memorize the identification of these raw medical materials by using a box containing a collection of specimens, which would have been grown in herb gardens by religious orders, and later in some pre-20th century hospitals, to meet their needs. Each box came with a booklet that matched the numbers on the box with the associated text The student had to be able to identify the Latin name and medical use and value of these essential medicinal plants in a formal examination to qualify as an apothecary.

There were a range of ways that plants were prepared for medicine, in order to extract the relevant ingredients. These included steeping in liquid, boiling, and dissolving in alcohol. Learning to prepare plants in these ways was also an important part of an apothecary's training.

The apothecaries were viewed as very important in preventing the spread of disease. The plague doctor figure was common throughout Europe since the Middle Age. In the 17th century, a famous French doctor, Charles de L'Orme, perfected the plague doctor mask, giving it the look we recognize today. It was, in fact, a mask with a purpose. In the past it was believed that diseases such as cholera and the Black Death were caused by a noxious form of bad air.

Rotting organic matter was supposedly its origin and the fumes it produced were the main cause of contagious epidemics. This was known as Miasma Theory. Plague Doctors' masks had a distinctive beak to fill with aromatic herbs which were meant to protect the physician from these fumes.

This is also the reason why some people in the past carried pomanders. Hippocrates advanced this theory in the 4th century BC by saying that inhaling “bad air” upset the balance of the humors. This theory was widely used in Europe until it was replaced by the Germ Theory of Disease after the 1880s.

Hippocrates' theory of the four humors, which influenced medical thinking until the late 19th century, basically states that the human body is made up of four substances. The theory refers to these substances as "humors." The four humors were blood, phlegm, black bile, and yellow bile. They were thought to control the health and temperament of every individual in a holistic way. For ideal health, they had to be in perfect balance. When this balance was lost, it was believed that it led to sickness.

By the 16th century, apothecaries were becoming more organised into guilds and had an extensive education.

Starting in the 18th century, some apothecary shops began to be attached to hospitals and other medical places. This was the beginning of a shift from apothecaries functioning as both doctors and pharmacists to more of a pharmacist-only role as we see them today.

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Herb

Use

Basil

Native to India, it is a sacred plant used todisinfect ‘malarious’ air and so protect thefamily home. Internationally, it was alsoused commonly against cold and fever and nervous disorders

Sage

Sage was once highly valued in fightingagainst typhoid, lung haemorrhage,measles and palsy

Thyme

Thyme contains chemicals that may helpbacterial and fungal infections. As well as this, it also might help relieve coughing and have antioxidant effects.

Bearberry

Traditionally, the leaves were soaked in thespirit of wine or brandy and used as asurgical dressing for lithotomy. It was alsoused against diarrhoea, for urinary andbladder bacterial infections, and to promote a speedy recovery after childbirth

Meadowsweet

Some doctors believed that meadowsweetcould be used to dry the body out, stopbleeding, vomiting, diarrhoea andexcessive menstruation. It was alsoElizabeth I’s favourite strewing herb andalso acted as a ‘pain reliever’

Lavender

Lavender was used to scent rooms, to keep moths out of clothes, flavour food, and as an anti-inflammatory. Aromatherapists use lavender in inhalation therapy to treat headaches, nervous disorders, and exhaustion.

Herbalists treat skin ailments, such as fungal infections (like candidiasis), wounds, eczema, and acne, with lavender oil. It is also used in a healing bath for joint and muscle pain.

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One Man, One Frog Elena Maddocks

The Age of Enlightenment was a period that saw philosophical, scientific, and literary revolutions. It was an age that marked a shift from blind faith in religion to trust in reason and science within European society. However, certain distinctions became blurred as new knowledge was uncovered. Namely, the border between life and death.

It became common in 18th century England for drowned ‘corpses’ to miraculously spring back to life, the majority of times due to being in a comatose condition where it was difficult for doctors to feel their heartbeat and therefore declare them as dead, with a fair number of unfortunate people waking up 6 feet under in their own coffin. The hysteria over being buried alive founded the invention of patents for safety coffins, fitted with gadgets that would allow the person to breathe, alert others, and even escape their grave. In 1789 Italian scientist Luigi Galvani found, by accident, that a frog’s spinal cord carried an electric charge when experimenting with a frog’s corpse.

He surmised that all animals must have an electric charge within them, dubbing the phenomenon ’animal electricity’, and the contraction of a muscle that is stimulated by an electric current, galvanism. After his death in 1798 his nephew, Giovanni Aldini, would continue his uncle’s work and perform a theatrical experiment on hanged man George Foster (accused of murdering his wife and children) using galvanism in 1803. Aldini showcased the effects of galvanism in front of a live audience within the Royal College of Surgeons in London, causing the corpse’s limbs to move haphazardly and it’s mouth twist into a grimace - as if it were alive. The spectacle was an instant source of craze within European society at the time, with the rumours snowballing into a tale of how Aldini brought a man back to life. Eventually it made its way to Geneva Switzerland, where Mary Godwin, Lord Byron and Percy Bysshe Shelly were enjoying a holiday.

The three were said to have enjoyed a late night talk on the then ‘fashionable’ scientific concept of galvanism, discussing topics such as the reanimation of corpses and the liminality between life and death, while also being under the additional influence of liquid opium. Lord Byron, who had been forced out of England due to scandals surrounding his incestual relationship with his half sister, proposed a ghost story competition that would later birth the concept of the modern vampire. That night, Mary Godwin (later known as Mary Shelley) would have the infamous nightmare that would become inspiration for the first science fiction novel in history: Frankenstein, a story of a scientist who used galvanism to reanimate a monster.

The novel was an instant success, prompting further research into the development of galvanism, as well as discussion around issues concerning medical and scientific ethics. Just 20 years after Frankenstein was published Carlo Matteucci proved that each heartbeat produces electrical activity. 1947 saw the first successful defibrillation of a human by Dr Claude Beck, who saved a 14 year boy with a homemade defibrillator made from just two silver spoons wired to an outlet.

The modern defibrillator works by discharging pre-programmed quantities of electricity through the heart to synchronously depolarise cardiac myocytes (a type of contractile muscle cell found in the myocardium of the heart) to return the heart to beating at its normal rhythm. Depolarisation is where the cells become less negative than when at rest and therefore contract. This technology was also transferred to pacemakers, where electrical impulses are sent when the sensors of the pacemaker detect a missed beat or if the heart has slowed down. Countless lives were saved using the galvanism-inspired technology, with the inventor of the wearable pacemaker (Earl Bakken) even stating he was fascinated when watching the movie Frankenstein and that it ‘inspired [him] to bring people back to life with electricity’ - proving that science and literature are capable of working hand in hand.

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A brief history of radiofluorine tracers in PET scanners Inaaya Laskar Positron Emission Tomography (PET) is a form of nuclear medical procedure that images tissues and organs by measuring the metabolic activity of the cells of body tissues. A common tracer used in PET scanning is a glucose molecule with radioactive fluorine attached to it. This tracer is known as fluorodeoxyglucose, with the fluorine nuclei undergoing beta decay, emitting a positron.

Fluorine-18 is the most used radioisotope in PET radiopharmaceuticals in both clinical and preclinical research. This is a result of its desirable physical and nuclear characteristics such as its 110-minute half-life, which is the time taken for half of its atoms to decay via the release of positrons (tiny particles with the same mass as an electron and an equal but opposite charge). Furthermore, fluorine-18 has high specific activity and is easy to mass produce. As the fluorine-18 decays, the positrons travel a few millimetres before they collide with an electron, producing two gamma-rays at 180 degrees to each other. These gamma rays can be detected by a camera, resulting in the 3D image of the target organ. The most widely used fluorine-18 molecule is ’18-FDG’ (Fluorodeoxyglucose).

The radiopharmaceutical 18-FDG consists of the fluorine-18 radionuclide (a nuclide that has excess nuclear energy making it unstable, a nuclide is a species of atom/nucleus characterised by number of protons, neutrons, and energy state). F-18 fluoride ion is created in a cyclotron (a type of particle accelerator) and then converted via an automated chemistry module into F-18 FDG. Specifically, F-18 FDG is produced through a nucleophilic substitution reaction (a negatively charged nucleophile attacks an electron-deficient atom, replacing one of its functional groups).

FDG activity reflects glucose metabolism. It is a very sensitive marker however it is not specific to cancer, infection, or inflammation. The molecule accumulates in several organs at once, thus lacking the selectivity and sensitivity needed for early disease detection. Professor Gill Reid, alongside her colleagues, are using metal compounds to help form stable radio fluorine tracer molecules. These new tracers should be effective at low concentrations to minimise the radiation dose needed. As well as this, the metal compounds allow a small peptide to be tethered to direct the radiotracer towards specific target areas, allowing far lower radioactive doses to be administered while giving higher imaging contrast. Her research explores macrocyclic complexes in which macrocyclic ligands are combined with metal ions.

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Past, Present and Future of the NHS

Anika Jha

The National Health Service stands as a cornerstone of healthcare in the United Kingdom. In its 75 year history, the NHS has undergone transformational phases which reflect societal changes and medical advancements. I had the privilege of interviewing my grandfather, Dr. Jha, who has dedicated over 40 years of his life to working in the NHS. Through his experiences, we can gain an understanding of how medicine in the UK has evolved, and may continue to develop in the years to come.

The NHS was established in 1948, by the newly elected labour party, as a part of a series of welfare reforms designed to guarantee basic levels of personal and social security. Its aim was to provide an integrated, state funded service. It was the first health system in any western society to offer free medical care to the entire population. This was revolutionary a step towards a more equal society, as basic healthcare would now be accessible to everyone, and with the right funding, this system could adapt relatively well to changes. However, this was not always the case.

In the first three decades of the NHS, the rise in costs could be matched by increases in funding, but by the 1970s and certainly the 1980s, healthcare cost inflation was outstripping politically acceptable levels of funding, with the result that services were being squeezed in the way that was most easily available to clinicians: waiting times and waiting lists grew ever longer, and delays in treatment began to be noticed by the general public By 1990, the NHS and Community Care act, which introduced an internal market to the healthcare system, directing local authorities to assess and arrange the care needs of elderly in-patients in hospitals. Moreover, the types of patients seen by doctors have definitely changed. Dr Jha, who has been working in Geriatrics since 1977, says ‘we now see more elderly patients than before. It is more common to see people aged 85+ now than 20 or 30 years ago’. This is due to increases in life expectancy, so more people are living longer.

An event which has undoubtedly changed the way the NHS operates was the COVID-19 pandemic. The pandemic has had a profound impact on the NHS. The surge in cases strained healthcare resources, leading to challenges in maintaining regular services. Hospitals faced increased loads, and frontline healthcare workers had to display remarkable resilience, especially when faced with unprecedented demands. For example, In November and December 2021, even before the Omicron variant peaked, the NHS was repeatedly described as under ‘record pressure’, with the average waiting times for primary care being 4-5 hours.

Furthermore, the pandemic accelerated digital transformation within the NHS, emphasising the importance of technology in healthcare delivery. When I spoke to Dr. Jha, he stated that ‘During the pandemic, I continued to work, however I switched to doing online consultations rather than in-person. Usually, the nurse would be sent for examinations and I would assign patients with physiotherapists who would carry out exercises at home. I had to adapt and use more technology during this time period.’

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Whilst we hope to never return to a state of completely remote working, the increasing use of technology is something that will only continue to develop, especially considering the prevalence of Artificial Intelligence in fields such as radiology and even surgery. Additionally, the rollout of mass vaccination campaigns showcased the NHS’ ability to mobilise swiftly. However, as successful as it may have been, it came with a host of challenges. Ensuring that everyone had full access to the vaccine was difficult, especially as high risk patients needed to be prioritised. Supply fluctuations, logistical complexities and vaccine hesitancy all posed as hurdles.

Despite these problems, the NHS continuously adjusted vaccination strategies in order to maximise the effectiveness of the campaign.

The COVID-19 pandemic has resulted in long lasting impacts on the NHS, which leads us to question its purpose in the future. The future of the NHS is likely to be shaped by various factors, including advancements in medical technology, demographic changes, evolving healthcare needs, and societal expectations. One key challenge is addressing the increasing demand for healthcare services due to an ageing population and the prevalence of chronic conditions. Efforts to integrate digital health technologies, such as telemedicine, electronic health records, and artificial intelligence, may play a significant role in improving efficiency and patient care.

Moreover, financial sustainability is another critical aspect of the NHS's future. Governments and policymakers may need to enhance cost-effectiveness to ensure the NHS’ sustainability. Moreover, emphasis on preventive care, personalised medicine, and community-based healthcare initiatives could become more pronounced. The NHS might increasingly focus on holistic approaches to health, promoting well-being and addressing social determinants of health. When I spoke to Dr Jha about his predictions for the future of the NHS, he said ‘‘A massive change has taken place in all faculties of medicine, and I think this sector will continue to develop.

Personally, I have found myself updating my knowledge every year, and constantly finding new ways to manage the care of elderly people. The use of new technology will definitely continue to grow.’

In conclusion, the NHS has been a vital institution in the UK for the past 75 years, adapting to societal changes and medical advancements. Through the insights of Dr Jha, we can witness the evolution of healthcare, from the beginnings to the profound impacts of the COVID-19 pandemic.

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Build-a-Pill Maia Massaro 3D printing is a growing area of technology which has recently been increasingly integral to various areas of biomedical research. From cartilage repair to applications within ophthalmology, it has the potential to be the vehicle for further steps forward in biomedical research. For the past half decade in Nottingham University, research has been done on pharmacological applications of high resolution 3D printing, with results indicating exciting new possibilities in this area of research. What the pharmacy and engineering departments at Nottingham University have been developing is a type of pill that can be engineered and personalised uniquely to each person and their requirements. For example, a pill might exist that releases the drug(s) it carries over a period of 3 months, releasing the multiple different drugs it has been charged with at different points. The huge benefit of a pill such as this is that it saves tens of boxes and plastic covers of pills per patient, hugely cutting down on waste. It also saves time by allowing the patient to take one pill and be covered for extended periods of time without needing to refill the prescription. Additionally, patients that may sometimes forget to take all their pills every morning, causing the effectiveness of the drug to be worsened no longer have to worry about this. The mechanism this pill uses to administer its payload is none other than little structures full of tiny pores and tubules containing the drug(s) within a larger structure resembling a pill. And the machinery used to create these microscopic mazes is high resolution 3D printing. However crafting a technology such as this comes with its challenges and it is no surprise it took the teams at Nottingham 5 years to develop this concept.First of all, the problem of finding the correct material for the non-drug part of the pill, or the “skeleton” of the pill. This material had to be edible, biocompatible, biodegradable, 3D printable (which meant having low viscosity but high molecular weight), and had to have no effect on the effectiveness of the drugs it was charged with. It took a team years to put together a library of possible materials with this particular set of attributes. Most of these materials were gels, as their properties often fit into these requirements. The method of production had to be addressed as well, as even high resolution printers would often leave bubbles in the finished products. This task meant modifying a 3D printer so that bubbles were minimised, print speed was maximised, and cost was kept reasonable. Eventually, a printer with multiple, smaller pipettes was built to allow this. The part of the challenge that crosses disciplines the most is the study of how the geometry of the skeleton affects the release profiles of the drugs (immediate, extended, delayed, pulsatile). One of the biggest challenges here was how to build a library of pill shapes that could accommodate any kind of payload variety and release profile. One was eventually put together through the use of computer simulations. This facet of the research is particularly interesting because it shows how maths can overlap with biology. .

This is just one of the applications involving 3D printing in medicine currently, and there are others including but not limited to the aforementioned cartilage repair and localised treatment of small, difficult to treat injuries in the eye. The research being done on customisable pills is however very significant as it is leading the way in terms of enabling future researchers to break further ground and find more applications of 3D printing in pharmacy.

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Climate Change’s Impact on Public Health in the Future Leah Alemayehu Climate change presents a real threat to our ecosystems, and consequently public health. Climate change is caused by four main factors: the enhanced greenhouse effect, Milankovitch cycles, sunspots and volcanic eruptions. The enhanced greenhouse effect happens when less heat is able to escape the atmosphere, resulting in more short wave radiation from the sun passing through the atmosphere, so more heat is absorbed by the increased amount of greenhouse gases. This results in the climate of the globe warming, which has been unprecedented in the Earth’s recent history. This warming is set to wreak havoc on the planet, but most importantly, it is set to change the face of global public health forever for the worse.

The increase in temperature in conjunction with a lack of rain will result in diseases, primarily waterborne diseases such as cholera, being widespread, especially within developing countries which don’t have the resources or funds to provide preventative measures. With that, climate change is likely to alter the distribution of infectious diseases. The geographical range of certain vector borne diseases such as malaria are likely to expand as temperature and precipitation patterns change. This could result in new areas becoming suitable for disease vectors, exposing populations that were previously unaffected. Linking to that, disruption to ecosystems due to changes in temperature and precipitation could result in the resurgence of infectious diseases that were previously thought to be under control. This will require new strategies for disease surveillance, prevention and treatment. New and emerging technologies will likely play a huge role in the prevention of the spread of disease in the future.

Increased variability in the climate as a result of climate change will affect crop yields and the availability of water, leading to food and water insecurity being exacerbated in regions of the world where this is already prevalent, leading to droughts and famines. However, it will also result in regions that were previously unaffected by climate change to experience a severe decrease in crop yield, resulting in global food and water insecurities. Malnutrition and waterborne diseases will become more prevalent, requiring a more comprehensive approach to public health and healthcare delivery, which will partially be led by the World Health Organisation (WHO), but the rest will be fully reliant upon national governmental health organisations, such as the UK Health Security Agency (UKHSA) in the UK. Climate change will almost indefinitely increase the frequency and intensity of weather events, including heat waves and wildfires, which can contribute to the generation and dispersal of air pollutants, including particulate matter (PM2.5 and PM10), contributing to very poor air quality. This is linked with respiratory conditions, such as asthma, and more prominently, chronic obstructive pulmonary disease (COPD). Emphysema and chronic bronchitis are the two primary diseases associated with COPD. Chronic bronchitis occurs when there is inflammation and irritation of the bronchi, resulting in them narrowing, resulting in increased mucus production. The excess mucus blocks the airways, resulting in difficulty breathing and coughing. Emphysema occurs when there is an abnormal enlargement of the alveoli within the lungs. The destruction of the alveoli reduces the surface area:volume ratio, therefore decreasing its efficiency as a transport medium. This impairs the lung’s ability to effectively transfer oxygen into the bloodstream, and remove carbon dioxide from the bloodstream. An increasing proportion of the population with COPD will put more pressure on the healthcare system, because the condition necessitates ongoing medical management, including medication, pulmonary rehabilitation and supplemental oxygen therapy. This will increase demand for medical services, hospital stays and specialised care. Furthermore, a rise in COPD cases will lead to large financial burdens, such as those associated with direct medical expenses and reduced productivity at work. The dayto-day management of the disease will come with extra costs for things like

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medicine, hospital stays, and rehabilitation. The entire economy and healthcare budgets will be strained by all of this.

The effects of climate change on global health necessitate a multifaceted strategy, involving international collaboration, public health campaigns, and sustainable development methods. In order to protect the globe’s health in the years to come, it will be essential to modify and adapt healthcare systems to the changing environment and put policies in place to lessen its effects. To avoid the disastrous effects that climate change will have on other things as well as global health, I think it is best that we address the cause of the problem at its source.

So, should we be worried? Even while there are valid worries, it is crucial to remember that coordinated efforts to reduce the effects of climate change and adapt to it can help lessen some of its negative effects on health. If we each contribute individually towards protecting our climate, through reducing carbon footprints, supporting sustainable practices, and advocating for policies that address climate change, we can contribute towards the collective effort to protect global health. I think that it is also really important to stay well informed, as it will empower us to take steps in addressing this complex challenge.

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Connections: Past, Present and Future of Medicine Gene Editing

Hippocrates

Diagnosis

Bloodletting

Surgery

Ibuprofen

Arsenic

Osler

Aspirin

Snail Slime

Drug Development

Oxycodone

Lister

Nightingale

Hot Irons

Paracetamol

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