Curiosity Issue 16 by Curiosity

ISSUE 16

Research . Rethink . Relearn

CONTENTS 6

The future of medicine

FEATURE Leading the way to an HIV cure

Obesity: A new treatment frontier

14 Alternatives to traditional cancer treatments 16 Vitamin and nutritional supplements: Jagged little pills or panacea for health? 18

The daily drugs in our diet

20 Inside the mushroom bubble: Psychedelics as therapeutics 22

Cheers to SA’s most pervasive drug

24 Q&A: Getting into that natural study rhythm 26

Your drug questions answered by experts

FEATURE Turning green grass into gold

32 Beating the ‘pharmaceutical arms race’ in sports 2

CONTENTS

Hooked on games and the silver screen

Blocking the opioid pipeline

Antibiotics: too much of a good thing?

The antibiotic bully in your beef

Mosquitoes on birth control

PROFILE 44 Down the rabbit hole to bring back some words 46

Motivational messaging for medicine

Printing 3D patches to heal wounds

Sucking the venom out the bite

52 From ancient apothecary to modern medicine COLUMN 54 Seeing through the haze of the cigarette tax smokescreen 56

COLUMN Put a pill in it!

HISTORY 58 Doobee or not doobee? Unravelling Shakespeare’s green quill

2023 56

EDITORIAL

DRUGS!

The word ‘drugs’ evokes a range of reactions – from the hopes of ‘miracle’ cures to the sadness of addiction and social harm. As a virologist, drugs are an important part of my profession and I am continuously amazed by the ingenuity in this field.

enicillin, first discovered in 1928, revolutionised medicine and highlighted the serendipitous nature of research. When Alexander Fleming, an astute researcher with a sloppy laboratory technique noticed there were no bacteria growing near the mould that had contaminated his petri dish, he immediately understood that a diffusible compound with anti-bacterial properties was responsible. It took another 12 years of research before penicillin was available, saving millions of lives. I am familiar with this story having done my doctoral studies in the Oxford laboratory where Howard Florey and Ernst Chain first isolated and purified penicillin, and for which they and Fleming won the Nobel Prize in 1945. It also demonstrates the role that such discoveries have in solving public health crises. Advancements in biochemistry, molecular biology, and

Curios.ty is a print and digital magazine that aims to make the research at Wits University accessible to multiple publics. It tells Wits’ research stories through the voices of its academics and postgraduate students. Curios.ty is published twice a year, the first time in 2017. Each issue is thematic and explores research across faculties that relate to the theme. Issue 16 is themed #DRUGS. Our feature stories delve into advances in HIV drugs and the economic potential of cannabis respectively. We reveal innovations in drug delivery, drug adherence, psychedelic therapeutics, and what horses have to do with snake venom, and birth control with mosquitoes. We explore alternatives to traditional cancer treatments, consider antibiotics and their corollary antimicrobial resistance, and how plants could mitigate this World Health Organization-identified threat. Alongside lifesaving legal drugs, we interrogate the dark side of drugs in research stories about addiction, doping in sport, and how those legal but lethal drugs – alcohol and cigarettes – permeate our lives as do ‘fixes’ in food and the modern proclivity to ‘pop pills’ for obesity or for nutritional supplementation. We cover when and how drugs began, how they manifest in literature, where medicine is headed, and Wits experts answer your drugrelated questions.

genetics have led to rational drug design and the rise of ‘big pharma’ making enormous contributions to developing lifesaving drugs. By understanding the structure and function of target molecules, researchers are able to reverse engineer drugs for higher specificity, fewer side effects and improved therapeutic outcomes. Personalised medicine, enabled by the completion of the human genome project, advances in robotics and automation, and data analysis through AI have led to major advances in drug discovery. However, it still takes years of research and clinical testing before new drugs can be used in humans. The Covid-19 pandemic changed that. The availability of highly effective mRNA vaccines within a year of the discovery of SARS-CoV-2 was unprecedented, even unexpected. It was achieved by conducting testing, approvals, and manufacturing in parallel, which under normal circumstances would be too risky, especially for a new modality. Now, with this breakthrough, if a new virus with pandemic potential was identified, it’s estimated a vaccine could be ready within 100 days. That’s why it’s critical that we develop our own mRNA manufacturing capability, which we are doing through initiatives including the mRNA WHO Tech Transfer Hub, in which Wits scientists are playing a leading role. HIV is another devastating public health crisis where Wits researchers play a prominent role. For decades, Wits has been leading the way in diagnosing, treating and documenting the epidemiology and genetic diversity of HIV. Studies conducted in South Africa on long-acting antiretroviral therapies, novel drug combinations, monoclonal antibodies, experimental vaccines, and microbicides have all led to significant findings, providing evidence-based guidance on when to initiate treatment, which drugs to use, and how to monitor and support individuals living with HIV. An emphasis on community engagement and implementation science ensures that HIV treatment programmes are locally relevant and effective. This edition of Curios.ty highlights the diversity, scope, and multi-dimensional nature of drug-related research at Wits. It spans experimental laboratory studies, clinical applications, community impact as well as social and behavioural aspects. Multidisciplinary drug research will ensure that our work positively impacts current and future diseases. Our collaboration with other academic institutions, research organisations, government agencies and pharmaceutical companies helps to accelerate the pace of drug discovery and increase its impact. Professor Lynn Morris Deputy Vice-Chancellor: Research and Innovation

Professor Lynn Morris Deputy Vice-Chancellor: Research and Innovation

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Dr Robin Drennan Director: Research and Development

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Shirona Patel Head of Communications

COVER DESIGN Nadette Hartzenberg

Schalk Mouton Senior Communications Officer and Curios.ty Editor

LAYOUT AND DESIGN Nadette Hartzenberg

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PHONE: +27 (0) 11 717 1025 EMAIL: Curiosity@wits.ac.za WEB: www.wits.ac.za/curiosity/ All material in this publication is copyrighted and all rights are reserved. Reproduction of any part of the publication is permitted only with the express written permission of Shirona Patel, the Head of Communications at the University of the Witwatersrand, Johannesburg. The views expressed in this publication are not necessarily the views of the University, nor its management or governance structures. © 2023

FEATURED

RESEARCHERS LEIGH CRYMBLE

Leigh Crymble is a doctoral student at the Wits Business School, specialising in behavioural communication, i.e., using language to drive ethical behavioural change. As part of her research, Crymble has developed a new communications framework to encourage decision-making across the healthcare, retail, and financial services industries. Her current focus is prohealth behaviour, ranging from healthier living, doing preventive screenings, getting vaccinated, and adhering to chronic medication. This won her business Best Behavioural Communications Consultancy at the 2023 Global Healthcare and Pharmaceutical Awards.

JOEL FRANCIS

Dr Joel Francis, medical doctor and epidemiologist, is a Senior Researcher in the Wits School of Clinical Medicine. He is a National Research Foundation-C2 rated researcher. He is a member of the International AIDS Society and a Board member of the International Confederation of ATOD Research Associations (ICARA – International Confederation of Alcohol, Tobacco, and other Drug Research Associations). He is Deputy Editor-in-Chief of Health Promotion International. He holds an MD and MSc in Epidemiology from Harvard and a PhD in Epidemiology from London School of Hygiene and Tropical Medicine.

F. XAVIER GÓMEZ-OLIVÉ

Associate Professor F. Xavier GómezOlivé, PhD, is the Associate Director of the Medical Research Council Wits Rural Public Health and Health Transition Research Unit (Agincourt), School of Public Health. He is a medical doctor, epidemiologist, and specialist in public health and preventive medicine. An author of over 250 publications, his research interests include health systems research and the health and wellbeing of older populations, particularly regarding sleep disorders, multimorbidity, non-communicable diseases, disability and frailty, HIV, and migration and health. He has supervised master’s, doctoral and postdoctoral students to completion.

GLENDA GRAY

Professor Glenda Gray is a National Research Foundation A1-rated scientist, world-renowned for her research in HIV

vaccines and interventions to prevent mother-to-child transmission of HIV. She studied medicine and paediatrics at Wits University where she remains a Research Professor in the School of Clinical Medicine. She co-founded the renowned Perinatal HIV Research Unit at the Chris Hani Baragwanath Hospital and is co-Principal Investigator of the National Institutes of Health-funded HIV Vaccine Trials Network. She is President and CEO of the South African Medical Research Council, a role from which she steps down in 2024 to focus here on research at Wits.

LEIGH CRYMBLE

JOEL FRANCIS

F. XAVIER GÓMEZ-OLIVÉ

GLENDA GRAY

COLLEN MASIMIREMBWA

JURGEN MEEKEL

NEELAVENI PADAYACHEE

JON PATRICIOS

COLLEN MASIMIREMBWA

Collen Masimirembwa is a Distinguished Professor at the Sydney Brenner Institute for Molecular Bioscience at Wits. His research focus is clinical pharmacogenetics and preclinical drug metabolism and pharmacokinetics. In clinical pharmacogenetics, his work aims to evaluate the feasibility and effectiveness of implementing pharmacogeneticsguided precision medicine. This research is expected to uncover novel African population specific genetic variation to explain observed drug responses. He is currently researching the pharmacogenetics of tamoxifen in breast cancer treatment in women of African ancestry, as well as the pharmacogenetics of anti-hypertensives in black South Africans.

JURGEN MEEKEL

Jurgen Meekel is a Lecturer in Television and Film in the Wits School of Arts. He works on contemporary art installation pieces, sculpture, and audio-visual art. His interests extend to motion-graphic design, animations, camera and sound works, videocompositing, visual effects, editing, and music scoring in bordering applied artistic fields. Currently, he collaborates with pianist Jill Richards and artist Dr BJ Engelbrecht in the playgroup art collective, which focuses on sound in the city space investigating auditory ambiances when moving from one space to the next.

NEELAVENI PADAYACHEE

Associate Professor Neelaveni Padayachee is a Senior Lecturer in the Department of Pharmacy and Pharmacology. Her research expertise lies in pharmacovigilance and health systems strengthening, with a keen interest in adverse drug reactions, counterfeit medicines, and rational medicine

use. Her goal is to raise awareness on the risks associated with adverse drug reactions (ADRs) by empowering individuals to report on any ADRs that they may encounter.

JON PATRICIOS

Professor Jonathan Patricios leads the Wits Sport and Health (WiSH) Research Group in the Faculty of Health Sciences. He is founder and Director of Sports Concussion South Africa, Co-chair of the scientific committee for the International Consensus Conference on Concussion in Sport, and co-lead author of the 2023 International Consensus Statement on Concussion in Sport. He is an editor of the British Journal of Sports Medicine and the author of over 120 peer-reviewed scientific publications. His research interests are sport-related concussion and the health benefits of physical activity.

THE FUTURE OF MEDICINE Imagine a world where medicines can be guided to the exact place that they are needed in the body, where treatment is designed around the individual’s genetic makeup, and where spinal cord injuries can be repaired through a simple implant. It sounds like science fiction, but that world might be closer than you think, writes Delia du Toit.

or centuries, smallpox ravaged humankind. During the 18th Century, 400 000 people died every year in Europe from the viral disease. The earliest evidence of skin lesions resembling those of smallpox was found on the faces of mummies from the Egyptian dynasties as early as 1570 to 1085 BC. Thanks to the development of a vaccine in the late 1800s, smallpox has since been wiped from the face of the earth. Such is the nature of medical innovation. Once a viable solution to a problem has been found, a disease can become part of the history books. It is not such a big reach, then, to assume that some of today’s biggest medical challenges such as hypertension, various cancers, and even certain forms of paralysis could be more easily treatable in the coming years. DEVELOPMENTS IN DRUG DELIVERY Professor Yahya Choonara, Chair and Head of Pharmacy and Pharmacology in the Faculty of Health Sciences as well as Principal Researcher and Co-Director of the Wits Advanced Drug Delivery Platform (WADDP), is one of the experts leading the charge in advances in drug delivery. The WADDP, he explains, focuses on three broad areas: advanced drug delivery that delivers medicine to specific sites in the body; nanomedicine, which reduces formulations to a nano scale for better targeting; and tissue engineering and regeneration, which includes such marvels as the 3D bioprinting of human tissue. “Advanced drug delivery is the science of developing 21st Century therapeutic interventions that ensure drugs can reach their target site of action in the body. This is beneficial because it improves the absorption and effect of medicines and significantly reduces side-effects. Some examples of targeted drug delivery technologies and nanomedicines include stimuli-responsive biomaterials, self-assembling molecules, ultrafast or extendedrelease delivery systems, and multilayered tablets that can be taken once but absorbed at different rates, and even the use of magnets to guide drugs to certain parts of the body.” The focus of current projects at the WADDP is on infectious diseases such as HIV and TB, targeted anti-cancer therapeutics, 3D-bioprinted wound healing systems, bio-inspired tissue engineering, and oral insulin systems. THRIVING TISSUE REGENERATION Merging nanomedicine with tissue engineering is changing the face of regenerative medicine. One such exciting development from the WADDP is the work

An antimicrobial foam: The foam in this image has antimicrobial properties and has been designed for use in the oral cavity for periodontal diseases. of Dr Poornima Ramburrun, a researcher in biomaterial design and tissue regeneration, who designed a biodegradable hydrogel conduit used to repair peripheral nerve injuries. Currently, treatment for such cases involves taking nerves from another site in the patient’s body, creating two compromised sites. Alternatively, cadaveric donor tissues are used, which are sometimes rejected by the patient's body. This new device offers a better alternative, and a patent has already been granted in South Africa, Europe, the USA, and China. “Where nerves have been severed due to traumatic injuries such as vehicle accidents, or stab or gunshot wounds, the nerves have limited capacity and need assistance to regrow. This conduit acts as a bridge across that gap and protects growing nerves from the surrounding inflammatory environment, while releasing drugs to help the nerve fibres to regenerate. The device looks similar to the clear ink tube inside a pen, and it is sutured by a surgeon to either side of the damaged nerve,” she explains. Another very promising project is that of Dr Gillian Mahumane, who has developed a nano-reinforced hydro filled 3D scaffold for neural tissue engineering in the brain. She explains: “Brain tissue has a hard time repairing itself, sometimes causing a loss of function. So, if, for example, a small tumour is surgically removed, leaving a cavity, the brain tries to heal that tissue very quickly to restore the communication network, forming a scar that can block neurons. “This device mimics healthy tissue to trick the brain into not

responding immediately to repairing it, and instead carrying on with its normal daily cleaning and regeneration at the site, as if this was healthy tissue, eventually rebuilding healthy tissue at the injured site. Nerve signals travel across the scaffolding, which is biodegradable so that the body can break it down when its job is done.” JUMPS IN GENETICS In tandem with these innovations, advances in genetics research make ‘personalised’ medicine a very real possibility. Professor Michèle Ramsay, Director of the Sydney Brenner Institute for Molecular Bioscience (SBIMB), explains: “At the moment, the most broadly effective drug for any given condition is usually prescribed to most patients. So, if there are five drugs available for a condition, doctors prescribe the one that usually works for the majority. But people are very different – some will respond well, others will see little effect, and others could suffer serious side effects.” The results could be disastrous. One 2015 study of four South African hospitals, for example, showed that 16% of hospital deaths are related to adverse drug reactions. Pharmacogenomics aims to take the guesswork out of prescribing, by looking at genetic variants that determine how a person will metabolise and respond to a drug. This is especially important locally, adds Ramsay. “We need more data to apply precision medicine in African populations. There’s a lot of data available on European and Asian populations, but these studies wouldn’t necessarily be relevant in an African context.” Available studies confirm this. Collen Masimirembwa, Distinguished Professor at the SBIMB, showed that side effects of the HIV drug Efavirenz (EFV), which include rashes, depression, and even suicidal tendencies, are more commonly observed in African patients on a standard dose of 600mg/day. Many people in Zimbabwe and Botswana also have a gene variant that increases the metabolism of EFV and renders the standard dose toxic when it is administered. Following this discovery, lower doses led to increased compliance and better viral control. In Botswana, too, genomic studies showed that about 13.5% of the population would be unable to effectively utilise EFV-based therapies, leading to a change in the country’s HIV management policy in favour of dolutegravir. Masimirembwa is currently also working on similar studies to look at the effects in African populations of the breast cancer drug Tamoxifen as well as certain tuberculosis and malaria drugs. Ramsay hopes that the practical application of some of this research could be as close as two or three years away. Kuda Nyamupa, a PhD candidate at the SBIMB, is also working on a new pharmacogenetics-guided treatment algorithm for hypertension in black South Africans. His research involves 600 patients from Soweto and the goal is to develop a guide for health practitioners to discern what medications and dosages to use for these patients. This decision is not only influenced by genes, he says, but also by other factors such as age, body mass, activity levels and alcohol use. “We don’t apply the term ‘one size fits all’ to most facets of our lives and yet we take this approach with medication. In the future, this will change. As genetic testing becomes more common and readily available, especially in Africa, medicine will become personalised and much more effective,” says Nyamupa. C

Dissolvable wafer: The wafer in this image dissolves in seconds and can be used to deliver drugs through the cheek or under the tongue. This can be very useful when giving medicines to infants and children.

Mini-donut tablet: This mini-donut tablet is an implantable tablet for administration within the eye. The tablet releases over a few months and can be used for serious infections in the eye that are difficult to treat using conventional tablets and injections.

Nerve conduit: This conduit has been developed for peripheral nerve injury and can be used to replace or regenerate damaged peripheral nerves, allowing for feeling and movement to be returned in some conditions.

FEATURE

LEADING THE WAY TO AN HIV CURE The battle to save millions of HIV positive lives bears fruit in unexpected ways, writes Deryn Graham.

hen the business, commerce, and manufacturing sectors in South Africa were all forced to ‘pivot’ during the Covid-19 pandemic and find new ways to ensure their business sustainability, so too were our health scientists, who took time off of their decades-long intensive research into HIV, immunology and virology, to tackle the latest health threat. But while their focus shifted from what was once South Africa’s leading causes of death, it was just these expertise, from some of the world’s leading specialists in the field, that helped the country become one of the leaders in the fight against the Covid-19 pandemic. “The labs, expertise and knowledge that we have developed in South Africa in our work on HIV was invaluable in our preparedness for the pandemic,” says Glenda Gray, Research Professor in the School of Clinical Medicine at Wits (pictured above and next page). “Without the clinical infrastructure and the work on neutralisation that our researchers have been doing around HIV, South Africa would not have been able to run the vaccine trials and respond in the way that we did.” Now, however, the HIV focus is back on track, and the work that the country’s specialists are doing is paying off directly in fighting the human immunodeficiency virus at which it is directed. The tide in the thirty-year battle against HIV has finally turned in South Africa. From a country that was once simply “the one with the largest population of HIV infected people in the world”, through the denialism years in 1999 to 2008, to rolling out the most extensive treatment programme globally, we have finally taken matters into our own hands. “South Africa is taking the lead in HIV vaccine trials, implementation science, and different ways to deliver antiretroviral drugs,” says Professor Lynn Morris, Deputy Vice-Chancellor: Research and Innovation at Wits, whose work Gray cites as part of the Covid-19 pivot. TREATMENT VS CURE Local money is being put into the search for a ‘cure’ for HIV and into finding a vaccine for a virus that Gray describes as one of the most difficult to crack. A functional cure has in fact been demonstrated in a number of patients worldwide, with Wits

“South Africa is taking the lead in HIV vaccine trials, implementation science, and different ways to deliver antiretroviral drugs.” scientists being deeply involved in the study group of international researchers who were responsible for the third patient that was cured of HIV. The so-called ‘Düsseldorf patient’ followed successes in Berlin and London. What the patients had in common apart from being HIV positive, was that all three had leukaemia [blood cancer]. They each underwent a stem cell transplant from a donor known to have a genome mutation in the HIV-1 co-receptor, CCR5 that makes cells resistant to HIV. After receiving the transplant, patients remained for a time on antiretrovirals (ARVs) but after a period that differed in each case, were finally taken off this medication and the HIV remained supressed and undetectable. The goal of a functional cure is to render HIV unable to replicate so that the carrier no longer transmits the virus to others, and this is what was achieved in each of these cases. At the International Aids Society Conference on HIV Science held in July 2023 in Brisbane, a new patient, the so-called ‘Geneva patient’ was revealed to have been ‘cured’ in the same way, but this time by a donor who did not have the CCR5 mutation. “While these results are exciting, they do not represent a scalable cure for people with HIV,” says Dr Annemarie Wensing of Ezintsha, a division of the Wits Health Consortium, who, along with her colleague Dr Monique Nijhuis from the HIV Pathogenesis Research Unit at Wits was part of the Düsseldorf study. “Stem cell transplants leave patients extremely vulnerable with no immunity whatsoever for a period of time, making the procedure very dangerous,” says Wensing. But in terms of HIV treatment, much the same as with cancer,

putting patients into remission is almost as good as a cure. For now, the ARV drugs on the market are also able to achieve this. FINDING A VACCINE “Staying ahead of a virus that mutates at an incredible rate like HIV is a major challenge,” says Morris. “It means vaccines needs to keep changing too.” Another major obstacle is that HIV integrates itself into the DNA of our T-cells, so vaccines need to block every single virus particle from infecting a cell by making sure that they stimulate the right kinds of immune responses. “Traditional vaccines that produce antibodies to fight off a disease have proven ineffectual against HIV. So far, all the efficacy trials of HIV vaccines have been disappointing,” she says. “One of the biggest challenges of our times is how to make a vaccine

The first cases of HIV/AIDS were reported in

1981 10

that produces neutralising antibodies against the HIV envelope protein, but there are some encouraging new approaches including mRNA [messenger RNA] that proved so successful with Covid-19.” PREVENTION BETTER THAN CURE The adage ‘prevention is better than cure’ has never been truer than with HIV. Behaviour amongst young, sexually active females continues to pose a risk of exposure to HIV, but if government is able to ramp up its 95/95/95 by 2025 programme, which lost some ground during the Covid-19 pandemic, we may be able to slow the rate of new infections down. The 95/95/95 programme targets seek to ensure that 95% of people living with HIV know their status and that, of these, 95% receive ARVs. Of those on treatment, the aim is to achieve a

An estimated

40 million people worldwide have died of HIV/AIDSrelated diseases

Almost the same number of people are living with HIV around the world today

Free antiretrovirals (ARVs) were introduced into the South African public health system in

2004

“There is an entire cohort of people living with HIV and who are on ARVs. They are living long and healthy lives.”

level of 95% with an undetectable viral load, reducing the risk of transmission to zero. Currently we are sitting on 94/77/92. Morris believes that what ARVs have already achieved in South Africa is remarkable. “The fact is there is an entire cohort of people living with HIV and who are on ARVs. They are living long and healthy lives. Indeed, they are living longer and healthier than many other people, as they have learned to take better care of themselves,” she says. New drug regimens have been shown to prevent HIV infection, including daily pills for pre-exposure prophylaxis (PrEP), the use of neutralising antibodies as passive immunity, and a bi-monthly injection of a long-acting ARV, CAB-LA, have all been trialled in South Africa. SYSTEMIC FRAGILITY There are local investors and financial and medical resources at our disposal in South Africa, but in terms of commercial viability, Morris believes that we need more incentives for pharmaceutical companies specifically. In business, these are known as ‘off-take agreements’ – pre-orders or commitments to purchase – but

2019 HIV/AIDS was the fourth leading cause of death in Africa

In 2020

68%

of new HIV infections in southern Africa fell outside the traditionally defined key risk groups

it appears that government has neither the budget nor political will in this case. The country’s inadequate public health system remains a barrier to achieving better results in dealing with HIV. Both Gray and Morris are excited for the future of HIV research and the eventual eradication of the virus through vaccination, immunotherapy treatment or a possible cure, but they are cautious about the South African health system’s capacity to implement potential new protocols. “Our health system is fragile, and we saw a number of slippages as a result of Covid-19,” says Gray. However, there is certainly a great deal to be hopeful about in the search for a solution to HIV. Gray says, “South Africa has some of the world’s leading medical researchers in HIV. The country – and Wits – are open for business when it comes to investment in new technologies, new medicines, and new treatments for the virus.” Any work done on HIV can also benefit research on other viruses, which may or may not already exist as was shown with Covid-19. Gray underlines the importance of the work that Wits is doing on HIV for other medical fields, including cancer research. Every victory against HIV, every step forward in the search for more effective treatments and preventative medicines, takes us closer to discoveries in other fields. “Any investment in HIV and immunology research is an investment into the future health of the country,” says Gray. C

The prevalence of HIV in the South African population according to the 2022 census is

13.9%

This figure rises to almost 20% in 15-49-year-olds in South Africa

OBESITY: A NEW TREATMENT FRONTIER Obesity affects millions of South Africans but remains low on government’s list of priorities. Current treatments are complex and expensive but new studies reveal that obesity medication could be the answer to this epidemic. In order for the wider population to benefit, it needs to be produced and managed affordably. LEM CHETTY

hat is the biggest threat to the lives of most people in the world today? You would be wrong if you imagined natural disasters, war, crime, or famine. The global pandemic that far outweighs any other is associated with lifestyle related diseases such as diabetes, hypertension, and heart disease, among other ‘preventable’ illnesses. Obesity is a driver and co-condition of these illnesses. Wits researchers say that obesity is a real yet ignored global pandemic. In southern Africa, 41% of women and 11% of men over the age of 15 years are affected. This ‘obesogenic environment’ features “a rapidly changing diet driven by an aggressive processed food industry and a genetic hand that predisposes one to obesity.” New research shows that there could be a cost-effective pharmaceutical treatment that could help solve obesity. So why aren’t we giving it to people who so desperately need it? LESSONS FROM HIV HIV researchers Dr Nomathemba Chandiwana and Dr Simiso Sokhela in the Faculty of Health Sciences, and Professor Francois Venter of Ezintsha, a division of the Wits Health Consortium, have taken up the challenge of fighting for access to lifesaving medication that tackles obesity, that something they have done

previously with great success with antiretrovirals (ARVs). In their article, Tackling obesity with medication: New hope and real challenges, the researchers write about their successful use of medication to treat patients battling obesity – but these drugs are expensive and need to be carefully monitored, including by an endocrinologist. “[The] results [of using obesity medication] are pretty predictable and amazing! Every person that we have treated who tolerated the drugs, including lots of people who do not have HIV, have shown between 7% to as much as 20% weight loss in just over a year. Regrettably, if you stop the medication, weight steadily comes back … so people with obesity may be on some form of these drugs permanently,” says Venter. The team had explored traditional weight loss interventions in both HIV patients and HIV negative people who had unexpectedly gained weight. For both groups, lifestyle and dietary changes proved ineffective. “We learned that exercise and dieting only occasionally achieve sustainable weight loss. Although eating properly and being active is very, very important for good health, for the majority of people it won’t make you lose weight, except in the very short term,” says Venter.

OBESITY DRUG HURDLES Venter and the team’s secondary focus into obesity research emerged from their 2019 study, ADVANCE, which sought to compare new ARVs to historic ones. While weight gain initially was thought to be a side effect of certain ARVs, it now seems rather linked to genetics, access to healthy food, or the obesogenic environment. Intrigued, the HIV researchers found that “a new world of weight physiology, exciting new treatments, and even new non-stigmatising language around obesity emerged,” says Chandiwana. While the results of the obesity treatment trial are remarkable, it also showed that access will be the main barrier for the general population. A 2023 Lancet paper in the journal Obesity, titled Pharmacotherapy of obesity: an update on the available medications and drugs under investigation, showed that it is possible for patients to access obesity drugs and keep pharmaceutical companies profitable at the same time – but South Africa is way off being able to access these obesity drugs, other than in the private sector. While there may be some similarities to the hurdles faced with ARVs, the obesity epidemic is “killing us more slowly” and is indirectly and directly responsible for earlier death. The issue of obesity lacks prioritisation and a coordinated civil society response. “Obesity does not receive the same level of attention and funding as other health issues, which impedes progress,” says Chandiwana. There are also significant gaps in the pharmaceutical supply chain, from research and development, through regulatory processes, to affordability and accessibility. “Ensuring that antiobesity medication is affordable and accessible to everyone living with obesity, including those with limited resources, is a significant challenge,” she says. PRIORITISE BEATING OBESITY Chandiwana outlines her wish list for tackling obesity in South Africa: • The first step is the acknowledgement and prioritisation of obesity as a chronic disease and pressing public health issue by government, healthcare systems, and society. • Then, comprehensive prevention efforts, including promoting healthier food, simple and honest food labelling, and creating supportive and safe environments for physical activity and nutritious eating.

“Obesity does not receive the same level of attention and funding as other health issues.”

• Next, treatment options need to be accessible and scaled up in primary healthcare clinics for greater impact. • Finally, health equity – ensuring that interventions and resources reach all segments of the population, particularly those most vulnerable to obesity, including black women and children. “It is going to take multidisciplinary collaboration between researchers, healthcare professionals, policymakers, community organisations, and individuals affected by obesity to address the multifaceted nature of the epidemic,” says Chandiwana. Venter concludes that it will be a “long time” coming before new medicines to tackle obesity are widely available unless more urgency and attention is paid to the issue. “First, the Department of Health needs to be more proactive about classifying obesity as something it actively wants to do something about.” C

10 REASONS TO IMPROVE YOUR LIFESTYLE BEFORE POPPING OBESITY PILLS While drugs like semaglutide are a valuable tool in treating obesity and diabetes, they can’t replace the benefits that lifestyle changes provide, however challenging! Professor Shane Norris, Director of the Developmental Pathways for Health Research Unit explains the benefits: 1. Holistic benefits: Beyond weight loss, diet and exercise improve cardiovascular health, mental wellbeing, bone density, and reduce the risk of certain cancers. 2. Sustainability: Medication may result in rapid weight loss, but without lifestyle changes, weight often returns once the medication is stopped. 3. Side-effects: All medications have potential side effects.

5 HEALTHY LIFESTYLE TIPS

4. Accessibility: The cost, insurance limitations, or availability of drugs may restrict access.

Dr Gudani Mukoma, Director of the African Centre for Obesity Prevention, shares these non-pharmaceutical tips to help prevent and manage obesity:

5. Individual variation: While drugs like semaglutide are generally effective, individual responses vary. Lifestyle interventions are more widely beneficial.

1. Exercise. Increasing your heart rate for 30 minutes a day is beneficial.

6. Psychological benefits: Research proves that physical activity and a balanced diet positively affect mental health, reducing symptoms of depression and anxiety which medication may not achieve.

2. Sleep. Adults typically require seven to nine hours per night. 3. Move. Be less sedentary. Move briskly every 30 minutes. Stand up more and consider a standing desk if you’re a ‘desk-jockey’. 4. Eat better. Improve food choices including whole grains, fruits, vegetables, healthy fats, protein and drink eight glasses of water daily. Fibre fills you for longer. Eat smaller portions. Limit refined grains, sweets, processed meats, and sugary drinks. 5. Cook smarter. Steam, boil or grill, rather than frying.

7. Co-morbidities: Lifestyle changes can help manage or even reverse other conditions like Type 2 diabetes, hypertension, and dyslipidemia. 8. Prevention: Drugs may treat obesity, but lifestyle behaviours can prevent it. 9. Empowerment: Take control of your own health.

10. Comprehensive treatment: Most healthcare professionals advocate a multi-faceted approach to managing obesity but lifestyle changes can complement the effects of medication, leading to better outcomes.

ALTERNATIVES TO TRADITIONAL CANCER TREATMENT

Opinions around cancer treatment options can be highly divisive, but many patients don’t have the luxury of choice. No matter how advanced the science, it’s the results that matter more. UFRIEDA HO

he harm versus benefit argument around cancer treatment is complex and not easily resolved. But more harmful than any drug is not getting a diagnosis, or one early enough, to give more people the luxury of choice. Razeeya Khan, Lecturer in the Department of Pharmacy whose special interest is oncology pharmacy, says we cannot argue harm or benefit without acknowledging the lack of cancer awareness and patient education in the country, or the shortage of oncology specialists. “The problem is about more than who can access hospital treatment. It’s also empowering people to recognise the signs and symptoms of cancer and getting them to go for check-ups or a referral, coupled with seamless care through the health system,” she says. “We are not talking just about availability and access to care, but also the need for better patient advocacy and initiatives to close the gap between private and public sector healthcare.” TREATMENT INEQUALITY There are also divides between access to new therapies and advances in cancer treatment in developed countries versus availability and affordability in less-resourced countries like South Africa. Research and development imbalances result in skewed resources, with less funding and fewer opportunities in the Global South. And yet Africa is facing an increased cancer burden. The World Health Organization (WHO) in February 2023 reported that an estimated 1.1 million new cases of cancer are reported in Africa each year, resulting in about 700 000 deaths annually. The WHO estimates that by 2030, this number will be closer to one million. In developed countries, Khan says, cancer treatments are moving toward precision medicine; using targeted therapies to manage some cancers as chronic illnesses. These therapies target the proteins that control how cancer cells grow, divide, and spread. Khan says: “The aim is to reduce the size of the tumour to stop it from spreading. The cancer is kept in check by targeting specific cycles of its cell growth. There are also immunotherapies that enhance the patient’s immune system to fight the cancer.” In South Africa we are far from being able to offer these therapies, but scientists and researchers are nonetheless pushing ahead.

AN ALTERNATIVE 3-STEP TREATMENT PhD student Alisha Badal in the School of Molecular and Cell Biology has made advances with her award-winning research which hones in on the treatment of triple negative breast cancer through a three-step method using advanced gene editing to manipulate a tumour suppressor gene. Triple negative refers to cancer cells without oestrogen, progesterone or HER2 (human epidermal growth factor receptor2) receptors, making them more complex to treat. “This is the most difficult type of breast cancer to treat because it is associated with higher proliferation and recurrence rates compared to other types, but for now treatment options are limited mainly to chemotherapy, which has adverse side effects and can, over time, become less effective as cancer cells become resistant,” Badal says. “We have devised an alternative three-step treatment. Firstly, we aim to increase the expression of the GAS5 gene using advanced molecular CRISPR-CAS9 technology. In healthy cells, GAS5 is produced in sufficient quantities to identify defective or damaged cells, triggering programmed cell death. In cancer cells,

“There are still a lot of unknowns about how cannabis works in cancer treatment. We need more legislative reform so that we can do more research.” GAS5 is produced in very small quantities, allowing cancer to grow and form tumours,” Badal says. These altered cancer cells are then exposed to two drugs that are both inexpensive and highly efficient. One is UJ3 and the other is a US Food and Drug Administration approved PARP inhibitor. UJ3 has shown to be 10 times more effective than the conventional chemotherapeutic drug Cisplatin while the PARP inhibitor works to stop the process of cell repair and renewal, causing cancer cells to die. PARP, poly-ADP ribose polymerasea, is a protein (enzyme) found in our cells, which helps damaged cells to repair themselves. “It is the first time using this approach. Advancements in immunology and endocrine therapy for treating cancer are important because in Africa we are at a major disadvantage. Many drugs are unavailable, and screening resources and awareness programmes are limited, so many cancers are detected late resulting in limited treatment options,” she says. HOMEGROWN TREATMENT Leveraging locally available and appropriate science may be part of the answer. For Associate Professor in Anatomical Sciences, Tanya Augustine, one area of opportunity for cancer management lies in compounds derived from cannabis. The region is ideally suited to growing cannabis and its decriminalisation for personal use for adults in 2018 opened the door for more research. Although research is in its very early stages, cannabis has long been used by cancer sufferers and those undergoing chemotherapy to relieve pain and nausea and to stimulate appetite. An Associate Professor in the School of Anatomical Sciences, Augustine’s research looks at how cancer subverts the immune and coagulation system to procreate. “We need to do more research to understand cannabis’s utility better so that it doesn’t remain forever in the realm of complementary medicine,” Augustine says. She adds: “One of the biggest effects of cannabis on the endocannabinoid system is in helping pain reduction. Some of the receptors for these phytocannabinoids are concentrated in the central nervous system, that’s why they work so well in relieving pain. Cannabinoids bind to the receptors, preventing the release of certain neurotransmitters associated with pain. Very early in vitro studies are showing that some of the compounds in cannabis may enhance the effects of one of breast cancer’s gold standard drugs.” Augustine adds: “There are still a lot of unknowns about how cannabis works in cancer treatment – such as what it’s doing to immune cells, if it’s anti- or pro-inflammatory and how the interactions might switch certain transmitters and receptors on or off. We need more legislative reform so we can do more research. For every question, there are five more, it’s like a rabbit hole,” she says. It’s a rabbit hole that researchers want to explore for an opportunity to change the landscape of cancer cure and care – and not a moment too soon. C

JAGGED LITTLE PILLS OR PANACEA FOR HEALTH?

Vitamin and nutritional supplements are big business, widely available, and easily accessible, but are they effective or just a waste of money – or even dangerous? LEM CHETTY

ROFHIWA MASHAU

here was something oddly familiar about a recent superfood trend. Matcha is a green tea from East Asia, similar in taste to spirulina, and found everywhere from coffee to confectionery. Both are powerful antioxidants, but are these and other nutritional supplements formulas for longevity and vitality or just expensive snake oils? ENERGY, YOUTH, BEAUTY FOR ALL IN A BOTTLE Associate Professor Neelaveni Padayachee, in Clinical Pharmacy and Pharmacy Practice at Wits, says that the vitamins and supplements industry is growing. “Demand escalated during the pandemic because people believed they reduce the risk of Covid19-related complications… which, as a matter of fact, is yet to be proven,” says Padayachee. The South African health supplements industry is worth more than R2 billion. But who is consuming these products? The answer is everyone from students on Omega-3 supplements, to athletes looking to increase performance, middle-aged adults to preserve youth, and older people seeking alternative nutrition options. BUT DO THEY WORK? The disclaimer on supplements is standard: Always ask advice from a healthcare professional and consider the scientific evidence before you try something new, particularly in conjunction with chronic, acute, and over-the-counter medicines. Padayachee adds that people should not replace seeking professional healthcare advice with supplements which they believe will cure them. “Health benefits are also based on what supplements are taken and in what quantities. Here, the concept of ‘less is more’ applies. For instance, high doses of vitamin C and B6 can lead to kidney stones and toxicity respectively,” she says. Padayachee believes that administered correctly, some supplements do work. Omega-3 fatty acids, such as fish oil, have been proven to be effective in reducing inflammation, supporting heart health, and improving cognitive function. Supplements are commonly recommended for vitamin D deficiency, as this is important for bone health, immune function, and overall well-being. CoQ10 is involved in cellular energy production and acts as an antioxidant. It may be beneficial for individuals with heart conditions, migraines, and certain neurological disorders. But there are many others that don’t work and/or are downright dangerous: Ephedra, also known as ma huang, was used for weight loss and athletic performance enhancement but due to cardiovascular events and fatalities, was banned in many countries. St. John’s Wort is used to manage mild to moderate depression, but it can interact with medications including antidepressants, birth control pills, and anticoagulants, reducing their effectiveness. Vitamin E can be dangerous especially for people taking bloodthinners. Despite its being an essential nutrient with antioxidant

properties, excessive intake through supplements may increase the risk of bleeding and haemorrhagic stroke. MELAMINE IN PROTEIN SHAKES The work of Dr Gary Gabriels in the Department of Pharmacology and PhD student Mandisi Sithole has highlighted the use of harmful substances in protein supplements, including melamine, a chemical compound used in products including cabinets and countertops. Gabriels’ 2015 paper reads: “These supplements may contain adulterated substances that may potentially have harmful shortand long-term health consequences to the consumer. ‘Scrap Melamine’ is such an example, which has been implicated in the kidney failure and death of animals.” Sithole says, “My additional research in 2022 found two other compounds, cyanuric acid and uric acid, both related to melamine, present in protein supplements. Research has shown these substances to be more toxic to the kidneys when found in combination with melamine, which was the case in most of the supplements that were studied.”

“The aim isn,t to demonise the products. The purpose is to regulate them instead.” Melamine is rich in nitrogen and can artificially and inexpensively enhance the protein content of protein supplements. While the additive may be banned in one country, it could appear in animal feed elsewhere, reaching the consumer in other ways. Gabriels’ advice is to be cautious as these products could have health consequences later on. “We’ve seen this in athletes who use supplements during the peak of their careers and only feel the negative effects decades later,” says Gabriels. He also suggests that consumers read labels. “A shake will say ‘100% protein’ and is often a lie. If you cannot understand the ingredients, phone the manufacturer and ask for an explanation.” Padayachee says that there’s a regulatory deficit between vitamins and supplements, and scheduled medicines. “Medicines are regulated for safety, quality, and effectiveness by the South African Health Products Regulatory Authority (SAHPRA) – unlike complementary and alternative medicines (CAMS) including vitamins and supplements. However, in 2017, after amendments to the General Regulations of the Medicines and Related substances Act 101 of 1965, SAHPRA has been making strides in regulating the CAMS sector.” Gabriels concludes: “The aim isn’t to demonise the products. The purpose is to regulate them instead. If we don’t control the environment, we will be dealing with the consequences.” C

THE DAILY DRUGS IN OUR DIET Regular and accessible stimulants like caffeine and nicotine feature daily in the lives of millions, while what we consume, and the marketing of some of these food products, also pose a threat to public health. LEANNE RENCKEN

arlier this year, community WhatsApp groups and social media lit up with parents desperately looking for a fix. Under pressure from their social media savvy children who’d landed on YouTube viral content, it seemed consumers would do and pay anything to score some Prime, splurging upwards of R400 for 500ml of the American energy drink, and parents were left scrambling. If you weren’t part of the Prime frenzy, think about the overinflated prices people were prepared to pay for cigarettes and pouch tobacco during the most stringent Covid-19 lockdowns, and about the brewing of hazardous homemade concoctions to bootleg or top-up the booze cabinet. It seems we are all prepared, in one way or another, to go the extra mile for ‘our daily drugs’ – those seemingly benign items we consume regularly without thinking too much about their impact on our health. And these daily drugs including caffeine, nicotine, alcohol and ultra-processed foods are readily available, aggressively marketed, promoted by influencers, and glamourised in the media. DANGEROUSLY TRANSFORMED FOOD Professor Susan Goldstein is the Deputy Director and COO at the South African Medical Research Council (SAMRC)/Wits Centre for Health Economics and Decision Science (PRICELESS SA). She’s a public health medicine specialist in a multidisciplinary team focusing on non-communicable diseases (NCDs) in South Africa. She says that specific foods constitute a potential daily drug and are therefore “an important area to look at, as a lot of the food we eat every day is highly processed”. She says that, although it hasn’t always been the case, these days we’re shopping for convenience foods; ready-to-eat that doesn’t require any preparation but which “can be very harmful”. The excess fat, sugar and salt contained in these foods has resulted in a sharp increase in NCDs like diabetes, hypertension, cardiovascular disease, and some cancers. COMMERCIAL DETERMINANTS OF HEALTH One of the reasons we like to eat so much of these foods is because the additives with which they are filled make them taste good. Big industries have developed around these products to make them more competitive in the marketplace – think about the cartoon characters, games, and movies affiliated with children’s food. This is what’s known as a ‘commercial determinant of health’. “We don’t even know what we’re eating. A big part of the problem is that it’s all hidden,” says Goldstein. Children’s cereals are a clear example. They are filled with sugar, so kids are tempted to eat them, which results in a sweet tooth, potentially leading to obesity. Historically, sugar was considered a condiment and used sparingly. Today, however (although some of it still exists in its most familiar form), ingredients like ‘corn sugar’ and ‘glucose’ on packaging are not recognisable to us as sugar. These are added to food in huge quantities and labelled using terminology with which we’re unfamiliar. LEGISLATING LABELLING This is where food labelling becomes important. The South African Department of Health is on the threshold of introducing policy that will see a big change in food packaging requiring labels to be a certain size, and if the product contains more than the recommended amount of sugar, fat and salt, or non-nutrient sweeteners, the label needs to be placed on the front of the product. “If you have these on the front of the pack, it means that at least people have an idea of what’s in there. It doesn’t necessarily mean that they are not going to buy it or eat it, but at least it will

guide people’s understanding of what’s healthy and what isn’t”, Goldstein explains. Furthermore, if products fall into the category requiring front labels, advertisers won’t be allowed to market them to children, and product owners will have to adapt the fonts, colours, illustrations, design and affiliations that make them so appealing to youngsters. SMOKE BREAKS AND CAFFEINE FIXES While food is clearly problematic, Goldstein says caffeine, in moderation, is probably okay. But when it comes to electronic cigarettes (e-cigarettes) or vaping, she believes these are just as dangerous and carcinogenic as any other tobacco product, including snuff and regular cigarettes. “The tobacco industry wants us to think [e-cigarettes and vaping] help people stop smoking, but it seems like it’s the opposite. Studies are now showing that young people who use electronic cigarettes and get addicted, often then move on to smoking tobacco.” Her other concern is that e-cigarettes are available to youngsters and with their bright colours and over 50 flavours, including bubblegum, they’re specifically marketed to appeal to the youth. Research by Guy Richards, a pulmonologist and Emeritus Professor of Critical Medicine at Wits, confirms the health hazards of e-cigarette vapours. His paper, published in the European Respiratory Journal (ERJ Open Research) in August 2023, compared the effects of e-cigarette vapours and tobacco smoke extracts on human neutrophils (a type of white blood cell that acts as your immune system’s first line of defence). The study found that e-cigarette vapours, exactly in the same way as cigarette smoke, “adversely affect the innate immune system”. Richards says, “These findings indicate that while e-cigarettes may be less harmful than cigarettes in some respects, they are still harmful and have the potential to predispose to pulmonary infections”.

“We need to create an environment for people where the healthy choice is the easier choice.” STEP-UP FOR A HEALTHIER ENVIRONMENT It’s clear that our daily drugs are far from benign, but how do we steer clear of them? Goldstein says, “The way we look at it from a public health perspective is that we need to create an environment for people where the healthy choice is the easier choice – where it’s easier to choose a healthy food than a processed food, easier to walk somewhere than go by car”. She concedes that in some cases this is difficult to apply, given many people’s environment and financial constraints. Those who are living in poverty frequently have no means or space to cook, have no refrigeration, and limited access to shops offering fresh and healthier products. People who do have choices should lobby government to ensure that products are labelled correctly, Goldstein says, and as consumers we should demand food that is healthier, cheaper, and more readily available to everyone. Highly processed foods are feeding our addiction to salt, sugar and sugar derivatives and yet we remain oblivious to the harm they are doing. C

T INSIDE THE MUSHROOM BUBBLE Psychedelic substances are the latest thing being discussed for the treatment of conditions such as depression and post-traumatic stress disorder. Are they the magic bullet some would claim they are? BETH AMATO

he colourful, spiralling land where people can supposedly hear colours, taste shapes and confront the traumas of their past seems to have captured the world's imagination. Psychedelic drug acolytes have been known to spend their life savings travelling to these Dali-esque cure-all mindscapes from the earthly comfort of their luxury accommodation in the Amazon jungle. In fairness, the quest to slay hungry psychic ghosts and finally get to grips with the human condition is understandable and, perhaps, necessary. Psychedelics, which alter the state of consciousness bringing purported mental and emotional benefits, include ayahuasca, psilocybin (magic mushrooms), San Pedro (mescaline), toad venom, MDMA (Ecstasy), peyote, and ketamine and indeed are part of post-capitalism's lexicon. Now, you too can get rich off psychedelic stocks because hallucinogenic start-ups are (ahem), mushrooming. Before hallucinogens hit the mainstream, making appearances in swanky sweat lodges from Sao Paolo to Swellendam, they had been used for thousands of years for ritual, medicinal, cultural and trade purposes in indigenous societies. This raises many concerns, chief among which include the economic exploitation of indigenous knowledge and resources, and of course, the overall safety and oversight of the psychedelic industry. So promising are psychedelics’ treatment of complex post-traumatic stress disorder and intractable depression, that Australia became the first country to allow doctors to prescribe MDMA and psilocybin to patients. Many developed countries have embraced the zeitgeist, with several US states such as Colorado and Oregon making psychedelic use legal. WHATEVER HAPPENED TO THE WAR ON DRUGS? Ironically, it is these countries that were staunch proponents of the so-called "war on drugs" that pushed psychedelic and traditional healing medicines to the margins. But the Global North is very good at spotting and exploiting monetary opportunities. Cue health entrepreneurs with immense wealth to set the wheels of production in motion. Eventually, pharmaceutical companies will be able to sell their psychedelics (heavily marketed as the ultimate medical magic bullet) back to the people who have been custodians of these products and systems for generations. In South Africa, mind-altering substances and rituals were regulated by draconian colonial laws. Cannabis, which can have psychoactive components, has a long history of indigenous use in South Africa. The practice of using cannabis to induce a trance-like state in 'rituals of rapture' has been embedded in Khoisan culture for over 600 years. Notably, cannabis performed a critical role

Sandra Maytham-Bailey.

ourselves up to receive messages. We want our ancestors to show us the path," she explains. These plant medicines hold a central place in many cultures in which people and plants are mostly seen to have a reciprocal relationship rather than one of extraction, expedience, and exploitation of the one by the other.

Sandra Maytham-Bailey.

Traditional muti stored in a dried calabash pod.

Traditional muti displayed on the floor of an ndumba in Mpumalanga, South Africa.

in the pre-colonial exchange economy until the British sought to outlaw it. They believed that cannabis caused mental instability, insanity, crime and delinquent behaviour. The government under Jan Smuts officially prohibited cannabis in 1922. Professor Catherine Burns, a medical and health historian, and the Educational Developer at the Wits Health Sciences Teaching and Learning Office, says that historically, people have always used the fruits of the land, particularly in the northern parts of the country. "People have used plants to aid in childbirth, to connect with ancestors, to suppress hunger, assist with aches and pains, and alleviate nausea," she says. Burns notes that many South Africans continue to use a variety of healing modalities, despite the dominance of the western medical model in hospitals and clinics, and the fact that so-called alternative medicines have been marginalised. Nevertheless, she still laments the split between ethno-pharmacology and chemical pharmacology. The latter is deemed robust and has a strong tradition in South Africa with its range of clinical trials and its leadership at the height of the HIV/AIDS pandemic. Dr Sinethemba Makanya, a Lecturer of Medical Humanities in the Department of Family Medicine and Primary Care at Wits University, explains that while there is no specific name for psychedelics in African traditional medicine, substances are used to bring one closer to spiritual guides. Makanya, who is also an inyanga, calls it dream medicine. "We ingest it so we open

BIO-PIRACY AND CULTURAL APPROPRIATION Hoodia, a well-known appetite suppressant cultivated initially by the Khoisan, was the subject of a landmark "bio-piracy" case. When the Council for Scientific and Industrial Research (CSIR) patented 'P57', derived from the Hoodia cactus, and granted development rights to UK pharmaceutical firm Phytopharm, the San community was not informed but ultimately won the legal case and is now part of a 'benefit-sharing' agreement with the CSIR. This case highlights issues of cultural appropriation relevant to the use of indigenous hallucinogens, and the brazen profiting from ancient healing practices. "It's tricky territory," says Makanya. "What does compensation mean? And what makes it meaningful?" She believes that we need to consider using others' practices as tools to incorporate into one's repertoire. "It is the energy you approach it with. We can't have a purist notion of healing … It's about incorporating different therapies into the canon of your work." Makanya is concerned with issues of access and the continuation of systemic injustice in the healthcare system. "I came to San Pedro and psilocybin through well-connected people and with access to technology. It was from a privileged place. If these medicines are indeed important for healing, then we need to make them available to everyone," she says. SAFETY FIRST Makanya explains that there are strict guidelines for taking traditional African dream medicines. Clients must perform cleansing rituals to prepare the body mentally and physically. "I think this kind of oversight is really important, because we are talking about people's psychological wellbeing." In Australia, they have experienced some pushback due to the psychedelic hype outpacing safety and ethical considerations. Psychedelics are still illegal in South Africa and are classified as Schedule 7 drugs, along with heroin. Meanwhile, adults are allowed to possess, use and grow cannabis for their own personal consumption. This was a landmark Constitutional Court ruling, and while beset with flaws in its application, it has inspired South African advocates to push for legalising psychedelics. The burden of mental illness means wider treatment options should be available Burns says that we must guard against believing psilocybin, for example, is a silver bullet to treat mental health isues. This reductionist view doesn't account for the range of ways and combinations of modalities often required in a treatment plan. Nevertheless, the available treatment options for mental illness could be expanded. A paper by the South African Medical Research Council Developmental Pathways for Health Research Unit shows that more than a quarter of South Africans suffer from probable depression and anxiety. This is significantly higher than in other countries. Sadly, only a quarter of those with mental illness seek treatment. “With our high burden of disease, the time is now to consider broadening treatment modalities”, says Burns. C

CHEERS TO SA’S MOST PERVASIVE DRUG The social lubricant that is alcohol is so ubiquitous and its marketing so pernicious that there’s a tendency to underestimate its impact on public health. That begs the question: Why do we drink? SHOKS MNISI MZOLO

ool and hip youngsters glowing with good health and living the high life grace a billboard at Johannesburg’s Maponya Mall. The thirst-inducing billboard extols some recently introduced ‘extra smooth’ beer. Of the 28 billboards with prime locations along a 10-minute drive on the M1, five sell beer, whiskey, and brandy. Further, about 10 alcohol adverts per hour are beamed to SA households during primetime TV, united in their silence on its toxicity and other harms.

DANGEROUS DAILY SUNDOWNERS

The World Health Organization (WHO) warns that alcohol is a toxic, psychoactive, and dependence-producing substance and that any beverage containing alcohol, regardless of its price and quality exposes drinkers to cancer. Drinking alcohol daily is toxic and considered a public health red flag. Broadly, tolerable maximum units equate to 10-14 per week. For context, the 750ml bottle of wine (with 14% alcohol by volume) equals 10.5 units of alcohol, while a 440ml beer can (5% alcohol by volume) totals 2.2 units. Thus, the ceiling – to keep harm minimal – is somewhere around a dozen cans of beer or a bottle of wine per week. Expect a dizzying 35 units from a 750ml bottle of brandy. But nobody walks around with a calculator to keep track of units taken. Alcohol is the most pervasive drug in South Africa – and its abuse is alarmingly clear.

BRUISE CRUISE

Alcohol abuse abounds and is at the heart of gender-based violence and sexually transmitted infections (STIs), notably when judgment is impaired, argues Mafuno Grace Mpinganjira, a Research Assistant in the South African Medical Research Council Wits Rural Public Health and Health Transitions Research Unit (Agincourt) in the School of Public Health. Mpinganjira blames this scourge, in part, on easy access. The sight of intoxicated people and fights breaking out on weekends at taverns, pubs and clubs is common. This underscores Mpinganjira’s assertion that alcohol consumption impairs judgment and triggers an invincibility complex. “Drinking opens a lot of problems. As with any drug, it is hard to self-regulate. The ground is fertile in South Africa because of the country’s socio-economics set-up,” Mpinganjira says, adding history and socialisation.

ALCOHOLIC INFANTS

The contrast between communities hardest hit by alcohol abuse and the buoyant youth on the Maponya billboard is stark. In the Western Cape at wine farms, the ‘dop’ system of part payment of wages to workers (including pregnant women) in wine, prevailed until it was outlawed in 2003. As a result of the ‘dop’ system, the Western Cape is the world capital for foetal alcohol spectrum disorder (FASD), which took root in colonial times. It is a condition that condemns unborn children to stunted physical and mental growth. “Regardless of what the law says now, people are unable to just abandon drinking – it’s a behavioural issue,” says Dr Joel Francis, an epidemiologist in the Department of Family Medicine and Primary Care in the School of Clinical Medicine, who advocates that direct interventions extend to neonatal care and that alcohol intake be discouraged during pregnancy.

LABELS AND MIXED MESSAGES

While advertising bans and explicit warnings printed on cigarette packs make the dangers of smoking clear, government is ambivalent about alcohol-induced harm, argues Mpinganjira. “We’ve got to stop looking at alcohol consumption in isolation because its effects are extensive. There’s a link to the health side, to the economic side, to societal development,” she says. Aggravating the ambiguity are those messages that incorrectly but loudly claim that there are health benefits to moderate alcohol intake. Francis, who advocates appropriate labelling of alcoholic drinks, says, “Messaging with alcohol abuse is conflicting. This is a huge industry. It’s an oligopoly of seven companies pushing for aggressive marketing. We are in a place where commercial determinants lead to a conflict of messages.”

BIG LIQUOR VS PROMULGATION

Another source of conflicting messages is the stop-start-stop Liquor Amendment Bill, approved by Cabinet for public comment in 2016, now stuck in the pipeline. In the meantime, East London’s Enyobeni tavern tragedy in June 2022 – where 17 of the 21 youths who died were reportedly underage – demonstrates the urgency for stronger legislation. Liquor is big business. It sustains jobs in every community, from taverns to high-end clubs. The alcohol industry even has its own Association for Alcohol Responsibility and Education (AWARE)

“for promoting the responsible use of alcohol”, according to www.AWARE.org. AWARE claims to support “sober pregnancies” to staunch FASD and to fight “binge drinking”, which targets people aged 25 to 34. While acknowledging studies that suggest excessive alcohol indulgence affects people as young as 15-years-old, the industry continues to invest billions in sports sponsorships and mints a fortune in government taxes.

DRINKING DURING LOCKDOWN

Although promulgation on its own will be no panacea for alcoholinduced social ills, regulation could arguably tame some bad habits. A study by Dr Witness Mapanga, a postdoctoral researcher in the Centre of Excellence in Human Development, found that despite alcohol sale bans during lockdown in 2020, not only did many people polled find access to the bottle, but a third of those who drank “were classified as having a drinking problem that could be hazardous or harmful” and nearly a fifth “had severe alcohol use disorder during the Covid-19 lockdowns”. Mapanga reckons that short-term gains should not hurt long-term public health. “Surely reduced consumption will lead to a decrease in sales and that could mean job losses. The question that the industry should ask itself though is: what’s ideal? Are suppressed sales and better health outcomes less important than better sales and poor national health? When people drink and smoke excessively, outcomes include several problems,” he says. “Does the industry want healthy and fit customers or a damaged society?” A damaged society suffers multimorbidity (the presence of two or more long-term health conditions). Professor Xavier Gómez-Olivé, Associate Director at Agincourt, says alcohol use is associated with multimorbidity among adults. The risk of multimorbidity increases with age, and liquor compounds exposure to unprotected sex, multiple partners, and other forms of irresponsible behaviour. In rural areas, drinking alcohol increases the chances of multimorbidity by 5% (if HIV is included) and by 6% if HIV is excluded. This is according to a Wits study that involved 10 000 participants in South Africa, Burkina Faso, Ghana, and Kenya. The study found that, of the urban communities polled, the highest level of intake was in Soweto where about 71% of males polled drank.

“Does the industry want healthy and fit customers or a damaged society?” yet they still drink heavily. Others drink to get drunk. Let’s find out why people drink so much. There’s a lot of poverty and inequality here. In villages without structure, there seems to be higher consumption levels. As we saw with lockdown, forbidding or banning sales doesn’t stop consumption. South Africa is the most unequal country in the world. That brings us to a lot of problematic social issues or family matters.” Mapanga wants the subject probed further. “We need more research to establish why things are the way they are, to search for interventions. Let us understand the impact of drinking and smoking on adults.” C

RAISING THE BAR FOR PUBLIC HEALTH

One of the most effective ways to fight alcohol abuse should involve outlets for messaging and should focus on the youth – but not neglect the broader population, asserts Gómez-Olivé. “People know about car accidents, STIs and multimorbidity,

Q&A

GETTING INTO THAT NATURAL STUDY RHYTHM Study stress and academic pressure can lead to unhealthy choices such as medication cocktails, energy drinks and supplements, to help students cope. Ntando Hoza asks Shameen Naidu, a psychologist at the Counselling and Careers Development Unit about healthier ways to cope. How can students improve focus and concentration without resorting to drugs or substances? Start with an appropriate study environment that is preferably quiet and free from distractions. Establishing a study routine or timetable is crucial.

Regarding actual studying, there are many different individual styles and techniques. Students should identify what works best for them, whether it's visual, auditory, or another technique. In general, breaking up study material into smaller, manageable sections or tasks helps improve focus. One useful study method

“Sleep is incredibly important for maintaining energy, focus, and concentration.” is the Pomodoro Technique, which involves studying for a concentrated period, followed by a short break. Periods should be timed, and after completing several cycles, breaks can be extended. Breaking up the workload and adhering to a schedule is also useful in reducing the feeling of being overwhelmed, which creates unnecessary stress.

Sleep right, sleep tight

Sleep is incredibly important for maintaining energy, focus, and concentration. Students should ensure that they get seven to eight hours per night after studying, and before an exam. Practising good sleep hygiene is recommended to establish a good sleep pattern, including maintaining a calming bedtime routine, turning off electronics at least an hour before bed, and engaging in wind-down activities before going to sleep.

Get moving

In addition to rest, exercise and physical activity are also important. Regular breaks should incorporate exercise or a sport, which not only benefits mood but also contributes to brain health. Physical activity helps with the stress of academic work and enhances focus and concentration. Hobbies and maintaining social connections that help students relax and unwind are also beneficial.

How can students increase their energy levels and maintain mental alertness throughout the day? Physical activity, hydration (drinking enough water), and sleep!

Are mindfulness techniques or relaxation exercises an alternative to medication? Yes, practising stress management techniques, such as mindfulness, deep breathing exercises and meditation can be extremely helpful.

What coping mechanisms or strategies can students incorporate daily to cope with academia?

Students should prioritise what is important. Creating a schedule that accommodates academic obligations, rest, relaxation, as well as a healthy social life is necessary for a well-balanced life. C

YOUR DRUG QUESTIONS ANSWERED BY EXPERTS WHY IS ALCOHOL SOCIALLY ACCEPTABLE BUT NOT CANNABIS? One is legal and the other isn’t! Any drug in excess, including alcohol, is dangerous. More people are addicted to tobacco, nicotine, and alcohol, than to other drugs. Alcohol users are much more likely to develop dependence and build tolerance, making alcohol a major drug of addiction. Lenore Manderson, Distinguished Professor of Medical Anthropology and Public Health, School of Public Health

WHAT MAKES COCA-COLA ADDICTIVE? WHAT HAPPENS TO YOUR BODY WHEN YOU DRINK COCA-COLA? Coca-Cola's addictive qualities can be attributed to its high sugar content which triggers dopamine in the brain, creating a temporary sense of happiness and satisfaction. Caffeine provides the stimulating effect. This and other similar drinks’ excessive sugar content is a major cause of obesity, which is linked to heart disease, stroke, diabetes, and some cancers. Professor Susan Goldstein, Public Health Medicine Specialist, Centre for Health Economics and Decision Science - PRICELESS SA, School of Public Health

WHAT ARE THE LONG-TERM EFFECTS OF CAFFEINE? This is dependent on several factors including body weight, genetics, chronic health conditions (including medication) and the amount regularly consumed. Possible effects include insomnia, dehydration, gastric irritation, heart palpitations, tremors, nervousness and anxiety (including panic attacks). Two to three cups of coffee a day (200-300mg of caffeine) is regarded as moderate use unlikely to cause harm. Positive effects have also been ascribed to coffee due to the antioxidant and antiinflammatory properties of some of its other 1 000 constituents apart from caffeine. These include a reduced risk of type 2 diabetes, liver disease, Parkinson’s, Alzheimer’s, stroke, heart failure and colon cancer. Professor Jonathan Patricios, Sport and Exercise Medicine Physician, Faculty of Health Sciences Studies show that dopamine release in the brain is the specific neuropharmacological mechanism underlying the addictive potential of both caffeine and sugar and is also caused by other drugs of dependence, including amphetamines and cocaine. Professor Karen Hofman, Director Centre for Health Economics and Decision Science PRICELESS SA, School of Public Health. WHAT MAKES COUGH SYRUP AND BIOPLUS ADDICTIVE? Cough syrup and Bioplus are two different types of medications, and their potential for addiction and side effects can vary significantly. Cough syrups can be classified into those containing codeine or other opioids, and those without opioids. Cough syrups that contain opioids like codeine have a higher potential for addiction. Opioids are pain relievers and can cause feelings of euphoria, leading to their abuse. Prolonged use of these syrups can result in physical dependence, tolerance (needing more of the drug to achieve the same

effect), and addiction. Over-the-counter cough syrups that do not contain opioids are generally not considered addictive. Bioplus is a brand of energy supplement that typically contains caffeine whose potential side effects are answered in question 3. Dr Stephanie Leigh-de Rapper, Department of Pharmacy and Pharmacology WHAT ARE THE SIDE EFFECTS OF THE LONG-TERM USE OF PAINKILLERS? The long-term use of painkillers, especially opioids, can lead to several adverse effects, including tolerance, physical dependence, and withdrawal symptoms when stopped. Chronic use can lead to constipation, nausea, drowsiness, and impaired cognitive function. Additionally, opioids can depress respiratory function, posing a risk of overdose. Nonsteroidal antiinflammatory drugs may lead to gastrointestinal issues like ulcers and bleeding, as well as kidney problems. Paracetamol, in high doses, can cause liver damage. It's crucial to use painkillers under medical supervision and explore alternative pain management strategies for long-term relief. Maxine Turner (née Grose), PhD Candidate, Department of Pharmacy HOW DOES ADDICTION ACTUALLY WORK? IS IT A PSYCHOLOGICAL OR PHYSIOLOGICAL RESPONSE, OR A COMBINATION OF BOTH? More than 60% of individuals who experience early life trauma, including fear are considered to be at risk of developing an addiction to a substance. Fear impacts on the development of a normal stress response system and consequently dysregulates brain circuits. The circuits involved in addiction are the: 1. amygdala and hippocampus affected by fear, 2. nucleus accumbens and the ventral pallidum which respond to rewards that increase dopamine, 3. anterior cingulate gyrus and prefrontal cortex, responsible for cognitive control, downregulate control of the orbito-frontal cortex, and 4. Orbito-frontal cortex evaluates the value of rewards and the decision to use a substance is given. Dr Dee Muller, School of Physiology WHERE DOES COCAINE COME FROM? AND HOW DOES IT WORK? Cocaine is found in the leaves of the Erythroxylum coca plant and is indigenous to South America, Mexico, Indonesia, and the West Indies. Its use has been documented as early as the 1400s and remnants of coca leaves have been found in the remains of Peruvian mummies. In 1860, an active ingredient of the coca leaf he called cocaine was isolated by Albert Niemann whose colleague went on to develop its chemical formula. The two were credited with finding the effect of cocaine on mucous membranes although Peruvian

surgeon Moréno y Maïz subsequently conducted the first animal studies. In 1884 Carl Koller demonstrated the benefits of cocaine as an anaesthetic, sparking worldwide interest in the drug. William Halsted and Richard Hall later developed the nerve and regional blocking techniques of cocaine. Cocaine gained popularity among the medical fraternity for its clinical benefits, but this rapidly changed when it became a drug with potential for social abuse. Cocaine’s dopaminergic action affects the brain’s reward systems. High levels of dopamine produce intense feelings of energy and alertness inducing further cravings as well as increased tolerance levels. This can become dangerous and can lead to addiction and overdose. Furthermore, cocaine’s rapid absorption, delivery to the brain, short half-life, intense central and peripheral neural stimulation all contribute to its abuse potential. Medical cocaine administered in a controlled environment has reduced risks of adverse effects whereas unregulated recreational cocaine use is potentially highly dangerous. Cocaine is a scheduled drug and as per the Medicines and Related Substances Act 101 of 1965, drugs used for medicinal purposes should not be used for “satisfaction or relief of a habit or craving for the substance used or for any other such substance, except where the substance is administered or used in a hospital or similar institution maintained wholly or partly by the Government or a provincial government or approved for such purpose by the Minister”. Associate Professor Neelaveni Padayachee, Department of Pharmacy and Pharmacology IS IT BETTER TO VAPE RATHER THAN TO SMOKE CIGARETTES? Both cigarette smoke extract and e-cigarette extract inhibit neutrophil function. Neutrophils are a type of white blood cell that act as your immune system’s first line of defence. It’s important to note that this occurs whether or not the vaping liquid contains nicotine. Neutrophils also produce cell free DNA by exostosis in the form of NETS – Neutrophil extracellular traps. While this property is inhibited by cigarette smoke extract it is not by e-cigarette extract. These August 2023 study findings indicate that, while e-cigarettes may be less harmful than traditional cigarettes in some respects, they are still harmful and their use has the potential to result in pulmonary (lung) infection. Guy Richards, Emeritus Professor of Critical Care, School of Clinical Medicine C

FEATURE

Academia holds a uniquely advantageous position to pull together more pieces of the cannabis industry puzzle to show what a thriving sector in the country could be. Ufrieda Ho reports.

re-start for the Wits Cannabis Research Initiative this year is an opportunity to sharpen this academic focus on a plant and industry that holds wide-ranging promise, but which needs an appropriate framework and clearer direction for its potential to be realised. The research initiative got its start in January 2020 when a diverse collective of Wits researchers and academics came together to build stronger interdisciplinary research on cannabis. This emerged against the backdrop of a Constitutional Court ruling in 2018 decriminalising the use of cannabis for private use by adults. The ruling signalled a post-prohibition era in step with a global shift in attitudes to cannabis, but it also heralds unchartered waters for regulation and momentum has now stalled. The ambitions of the group were also abruptly snuffed out with the Covid-19 lockdown starting in March 2020. Professor Imhotep Alagidede, in the Wits Business School, says the work of the group continued but in more separate streams. In 2023 though, he says, the Wits Cannabis Research Initiative is regrouping and reorganising in the hope of becoming a fullyfledged research unit. RED TAPE SMOTHERS GROWING GREEN Academic backing and collaborative endeavour, he says, are essential because the legislative barriers and licensing red tape to work with cannabis are significant. Wits University currently has a Schedule 7 licence that allows for growing the plant, to conduct research on it, and for the creation of products and compounds focused on drug development. As at June 2023, there were only around 93 licences granted by the South African Health Products Regulatory Authority (SAHPRA), which oversees licensing when cannabis compounds are used in health products. Alagidede says private individuals trying to secure licences face prohibitively expensive costs associated with meeting the legal and security

“Beyond finding the best plants to farm in the different regions in South Africa we want to create new businesses.” requirements set down for licensing approval. Individuals also need to have established physical facilities even before licensing approval. The research group’s members were part of the conceptualisation phase of South Africa’s National Cannabis Master Plan that was released in 2021. The plan’s key focus is on integrating small growers into formal cannabis value chains and addresses licensing, technical and financial support. According to the master plan, the formal cannabis industry could be worth R28 billion and has the potential to create up to 25 000 jobs. “Beyond finding the best plants to farm in the different regions in South Africa we want to create new businesses. High unemployment rates mean we need to think about alternative ways of creating jobs and, by my own analysis, the sector has close to 250 different products associated with it – from applications in the industrial and construction industry, such as hempcrete, ropes and thread products, to fashion and medical applications,” Alagidede says. The next steps for the industry, he says, should include pushing for policy outlines to be relevant and specific for South Africa. He says they cannot be imported “copy and pastes” from North

American legislation and need to be focused on lowering barriers to entry and creating enabling spaces for entrepreneurs here. CURATIVE CANNABIS For Tanya Augustine, cell biologist and Associate Professor in the School of Anatomical Sciences, the therapeutic benefits of Cannabis sativa remain under-researched. This despite the fact, she says, that humans have cultivated the plant for thousands of years especially for cordage and textile manufacture. She adds: "The psychotropic effects of Cannabis sativa [how it affects a person's mental state] associated with religious rituals and medical applications were recorded as early as 5 000 years ago in ancient Chinese texts.” Augustine was a key lead of the research initiative in the years before the 2018 court ruling. She highlights the importance of understanding the compounds in cannabis as the plant is impacted by a range of conditions, including climate change, modes of harvesting extraction and drug delivery. For her, researching these complex variables is necessary to develop breakthrough drug therapies, and then to understand biological responses to such drugs. It’s also a boon for standardisation, which in turn is how small growers, who have always supplied the illicit market, can become more reliable suppliers, and carve out a bigger stake in any new cannabis value chain, she says.

“Legislation and policy frameworks can be tricky because there is no consistency. So that’s why we need to make it easier, especially administratively, to do more research. It’s also how science can better impact small scale cannabis growers, who should also be connected with those in the commercial space. We need to act fast enough so South Africa can have a foot in the door of global markets, but we can’t rush to commercialisation without the correct foundation in place either,” she says. DECRIMINALISATION DISEMPOWERS Prioritising inclusivity in this potential new economic sector is critical for Katrina Lehmann-Grube who is a researcher in the Wits Southern Centre for Inequality Studies. Before joining Wits, Lehmann-Grube worked at the Institute for Economic Justice where her research involved looking at inclusive development for the South African cannabis industry. She says the industry could look to models such as tiered licensing for small-scale growers and setting appropriate thresholds for maximum tetrahydrocannabinol levels for hemp classification that would protect small-scale growers. “You want barriers to entry to be low enough that traditional growers can enter the markets and benefit. You don't want to exclude the most marginal – who have been criminalised by the system before – and only make it a source of accumulation for the

because the route to decriminalisation in South Africa came through the narrow, and therefore limiting, channel of private rights of adults to use cannabis. “The pathway to decriminalisation through the privacy route was premised on the freedom for private use but should have been focused on more holistic approaches to social and economic justice,” she says.

“While their technology is focused on cannabis, it has at its heart engineering for efficient crop cultivation of virtually any kind.”

elite, which is essentially what we're doing now,” says LehmannGrube. She points out that decriminalisation has resulted in “the bottom completely dropping out of the market.” Traditional growers’ prices for cannabis have fallen sharply, which has meant decriminalisation has had the opposite effect of economically empowering those on the margins. Also, as a newly legalised industry, the cannabis industry doesn’t have the benefit of advocacy and awareness that comes with long-established union, trade associations and civil society organisation support. Lehmann-Grube adds that mindsets need to change too,

ENGINEERING EFFICIENT CROP CULTIVATION It means making more equitable room for multiple actors, those who have always been on the bottom rung but come from generations of growers, as well as the likes of emerging entrepreneurs who do not have access to capital. Two Wits Master’s students who fall into this category of entrepreneurs are Constant Beckerling, a chemical engineer, and Anlo van Wyk, a mechatronic engineer. Their multi award-winning designs of automated closed loop hydroponic cannabis cultivation systems with LED lighting led them to set up their company, AgriSmart Engineering, in March 2020. By 2022 they had built and designed a facility and had 255 commercial prototypes of the LED technology on three different cannabis farms in the country. Their continued success in innovative solutions has seen them work with several commercial partners in southern Africa. Beckerling says: “When you talk about cannabis in the pharmaceutical industry, it means that you need to have a very close reproducibility of the crop outcome. The only way to ensure this consistency in crop outcome is to monitor and standardise your production inputs very closely.” This is where their engineering advantage of technology and science helps fine-tune cultivators’ reproducibility of output needs by controlling every aspect of growing conditions, from light, to temperature, soil composition, and pest and disease control. They have also seen the potential of being able to use their grow solutions from the vast range of cultivation options – from small scale open fields to hybrid models to sophisticated grow houses. The key for anyone growing commercially at whatever scale, techniques, illicitly or legally, they believe, is to be efficient and to engineer for appropriate problem solving. Van Wyk says South Africa must maximise its regional advantages, which include high solar availability, arable land, and competitive labour rates, to develop new technologies and pioneer industry models that can set standards and be innovative in a nascent industry. He says: “We aim to develop technologies that are affordable and therefore accessible to more clients, and that will help South African products compete on a global stage that is growing all the time.” Beckerling says that while their technology is focused on cannabis, it has at its heart engineering for efficient crop cultivation of virtually any kind. It’s about the future of growing crops by being energy efficient, minimising carbon footprints, striving for climate resilience which results in the quality on which people want to spend their rands. “This has been our objective since we got started – it’s all or nothing,” says Beckerling. What’s coming for the cannabis industry could be huge and South Africa cannot be caught napping. “It’s just a matter of time before South Africa wakes up and decides to take this really seriously,” he says. C

BEATING THE ʻPHARMACEUTICAL ARMS RACE’ IN SPORTS Drugs in sport is eroding public credibility of many of our sports heroes’ superhuman performances. Is there a way to restore trust in sporting achievements? SIMNIKIWE XABANISA

HE scepticism with which the recent slew of field and track world records was greeted revealed the broken trust between athletes and their public. In the last few elite Diamond League athletics meetings, the women’s 1 500m and 5 000m times, and the men’s 3 000m steeplechase and two-mile milestones, have all been smashed. But praise for Kenya’s Faith Kipyegon, who broke both the women’s records, Ethiopia’s Lamecha Girma, who won the 3 000m steeplechase, and Norwegian Jakob Ingebrigtsen’s two-mile achievements was lacklustre, considering these were essentially superhuman feats. Kipyegon broke her records in successive weeks while Girma

and Ingebrigtsen’s marks were established after 19 and 25 years respectively, the Norwegian running two back-to-back sub-fourminute miles en route to his record. Renowned South African sports scientist Ross Tucker spoke for everyone on his podcast – The Real Science of Sport – speculating that the new records were the result of more than just the advances in sports science and shoe technology. TOUR DE FARCE? Ever since Marco Pantani, Jan Ullrich, Lance Armstrong and others turned the Tour de France into a pharmaceutical arms race on wheels, the sporting public has struggled to believe in the

authenticity of these jaw-dropping achievements. The suspicion is a pity, because past performances by Girma, Kipyegon and Ingebrigtsen suggested that they each had the capacity to break records. Former Lions’ team doctor and Wits University sport and exercise medicine physician, Professor Jon Patricios says that given athletics’ doping history our sense of disbelief is to be expected. “It’s a real issue and Ross is right to ask the question,” Patricios explains. “What he’s doing is comparing trends, and when they skyrocket, you’re entitled to be cynical. Athletes will argue that training techniques have improved but who knows? Once you see trends like these, our cynicism is not misplaced.” Ever since marathon runner Thomas Hicks nearly died from a cocktail of brandy and strychnine he’d taken in the hope of enhancing his performance in 1904, administrators and athletes have been locked in a high-stakes game of cat-and-mouse over the use of performance-enhancing drugs.

“Those who would use science to cheat also have technology at their disposal.” SCHOOL BOYS ON 'ROIDS Today, questions are still being asked. “It’s reasonable to ask if the cheats are still getting one up on the authorities,” says Patricios. “At high levels, including in rugby, where there’s regular and random testing in and out of competition, the testing protocols are quite tight,” he says. “But I fear that in less high-profile sports, at amateur and school level, we’re losing the battle. We can see this for example from the numbers that are coming through from tournaments like rugby’s Craven Week, where there were 10 positive tests last year. This is astronomically high and can be attributed to the lack of randomised testing and regulations of minors and the need for parental consent. I have no doubt that the use is more prevalent than we think.” Patricios’ concerns around the use of performance-enhancing drugs at school rugby level are supported by the revelation in a BBC article three years ago that 21 youngsters in South Africa tested positive for steroids between 2014 and 2018. One especially notorious case was that of former Afrikaanse Hoer Seunskool (Affies) student, Salmon van Huyssteen, who was handed a two-year ban after it was found that he was administered a Nandrolone injection by his mother in 2012. In the stampede to create test tube Springboks from a school system that borders on professional in its competitiveness (a number of coaches have left the professional ranks to coach at school level because it is more lucrative), the health risks of taking these drugs are all but ignored. “Steroids affect many systems in the body. Blood pressure, changes to the heart, sugar and cholesterol levels, potential infertility, damage to the liver and kidneys, as well as psychological damage. Almost every aspect of the user’s physiology can be adversely affected,” says Patricios.

“It's reasonable to ask if the cheats are still getting one up on the authorities.” It doesn’t help that drug bans in South Africa have only the “nuisance value” of speed humps on a racetrack. Van Huyssteen, for instance, made his return on the Blue Bulls’ under-19 bench the day after his ban expired. Former Springbok wing Aphiwe Dyantyi, who was banned in 2019 after testing positive for a bodybuilder’s cocktail of three banned drugs, Metandienone, Methyltestosterone and LGD-4033, was similarly greeted on his return from his four-year hiatus when his new contract with the Sharks was announced. Dyantyi’s ban only officially ended on August 13, but the deal was all but done a year ago. The prevailing public sentiment was to hail the return of an allconquering hero because of Dyanti’s exciting talent and because he always denied knowingly taking the drugs. However, to cynics, Dyantyi had an improbable rise from not even playing first team rugby at school to Springbok status and being voted World Rugby’s Breakthrough Player of the Year in 2018. His lack of physicality at school hinted to the fact he would have needed help to reach his 90kg weight at the time of his ban. The doping scourge has even implicated the Kenyans, whose incredible distance running exploits were always put down to living and training at high altitude, hard work and ugali, their staple version of mealie pap. In 2022, no fewer than 45 Kenyan athletes were sanctioned for the use of Erythropoietin (EPO), which increases red blood cell production. When you think about it, living at altitude, which also elevates your red blood cell count because of the thinner air, is great cover for EPO. BIOTECH FOR THE WIN The cat-and-mouse game between authorities and athletes is being fought along technological lines, with the establishment’s greatest strides being the introduction in 2009 of the biological passport – a baseline snapshot of an athlete’s physiological make-up which is used as a point of reference should there be deviation in future in biological markers. “But remember that technology isn’t one-sided,” warns Patricios. “It doesn’t just favour the testers. Those who would use science to cheat also have technology at their disposal.” A great example of the sophistication the authorities are up against was legendary American distance runner Alberto Salazars, when he was head coach of the Nike Oregon Project, which gave the world Mo Farah and Galen Rupp, among others. Salazar, who won the New York, Boston and Comrades marathons – was given a four-year ban in 2019 for trafficking testosterone, administering athletes prohibited IV infusions and encouraging them to take prescription medication such as the thyroid hormone whose side effects include enhanced performance. All we can do is marvel as sporting records are broken and hope that they have not been fuelled by performance improving drugs. C

HOOKED ON GAMES AND THE SILVER SCREEN What is it about TV and film that’s so compelling that we can’t resist immersing ourselves in celluloid? LEANNE RENCKEN

inge-watching series? Obsessed with Netflix’s latest blockbuster? Human beings have ardently consumed TV and film for decades, and it’s the storytelling behind the medium that gets us hooked. Remember Scheherazade? The character and storyteller in the Middle Eastern collection of tales known as the One Thousand and One Nights, in which the sultan takes a new wife each night and has her executed the next morning. Scheherazade survives by telling the Sultan stories every night. Her early adoption of the cliffhanger – a plot device in which a part of the story ends unresolved in a shocking or suspenseful way – saved her life. The same thing that kept the sultan entranced is what keeps us glued to our screens today; how the narrative of shows is crafted, and its delivery are as important as the plot. Similar rules apply, whether we’re watching TV and film, or playing a video game. CONNECTION AND ESCAPISM But there’s more to our screen addiction than good storytelling. Lecturer in the Film and Television Department at Wits, Jurgen Meekel, speaks about the duality of connection and escapism, and how the medium offers both. People can either watch the news via a plethora of 24-hour current affairs channels or use film and TV services to escape reality. This was especially true during the Covid-19 lockdown; Nielsen reported early in the pandemic that “home-bound consumers led to a 60% increase in the

amount of video content watched globally”. Kieran Reid, Head of Wits Digital Arts, expands on the notion of reality and escapism and how games allow for a semblance of control. He says, “Our goals in life are really complicated and not so clear cut; you have no idea if you have the right tools to do what you need to do, whereas a game gives you a clear way of engaging and a core set of rules, and those rules are the correct rules to help you achieve your goal.” In addition, Reid explains that people keep playing games because they are competitive. “Whether you are playing against yourself or an opponent, there’s a sense of achievement in success, which is rewarding.” Whether they are games that can be played socially with several people, or that are played solo on a mobile device, success in these games is a compelling reason to keep coming back to them. “As a department, we are very interested in understanding play and facilitating interactions, so the students are constantly designing ways in which people will engage with their product, and obviously, in some ways, that’s about manipulating them to stay longer, to enjoy themselves, and to make sure the interactions lead to more interactions, so that they keep coming back,” says Reid. MORE MEDIA THAT MIRRORS Unlike gaming, when it comes to film and television, the appeal

of the win does not apply. However, social media has brought in an added dynamic to our compulsion to watch a show or series. ‘Discovering’ new content from the ever-expanding pool, before it trends, and making good recommendations translates to solid social currency, whose reward is the potential to give someone influencer status. In this example, both the influencer and the influenced become keen followers of a particular programme. “There’s a huge difference in the way we consume broadcast media and games today, but also how we make film and TV. The audience has become more versed with the creation of media, they’ve become experts, so the creators have had to develop more intelligent stories, deepen their characters, and include multiple narrative arcs, which I think is most interesting,” says Meekel. He also notes the democratisation of the media, with more representation of audiences and their lives in programming. This has led to streaming services clamouring to create and broadcast ‘local’ content. Ideally this will lead to more opportunities for students in his department. HOW WE WATCH AND PLAY But it's not just the amount, or types of content that have increased – how we watch has also changed dramatically. Since its launch in South Africa in 1976, television has had mass appeal. Now, with 72% of the South African population connected to the internet, streaming media is easier than ever. Despite the high

“Whether you are playing against yourself or an opponent, there's a sense of achievement in success, which is rewarding.” cost of data, Google reports that YouTube ads, and by extension YouTube content, reached over 42% of the South African population in 2023. Streaming services including Netflix understand the appeal of Scheherazade style story telling in pulling in viewers. Pilots are no longer the hook for television series and for this reason, streaming platforms prefer the series dump, enabling us to become addicted to our favourite (or favourite hate) characters, which research shows is by around episode three or four, and binge watch until we’ve had our fix. C

MORE ON THIS RESEARCH: BLNK is a screening series where directors, writers and producers come to show work and discuss it with students. BLNK facilitates Film and TV Department Cinema screenings, which are occasionally open to the public. For details, email pervaiz.khan@wits.ac.za.

BLOCKING THE OPIOID PIPELINE BETH AMATO

Treating opioid addiction is a painful, time consuming and often frustrating process. New medication can help solve this problem.

he drug nyaope has ravaged poorer communities in South Africa, with youth among the overwhelming majority caught in this opioid dragon's talons. Nyaope is a highly psychologically and physiologically addictive drug, which makes it an enormously difficult habit to kick, once addicted. Severe illnesses (including collapsed and infected veins, damaged heart valves and the effects of diseases transmitted when using) and death are common. Nyaope, also known as pinch, sugars or whoonga, is made of low-grade ('black tar') heroin, marijuana and antiretrovirals. Often, dangerous substances such as rat poison and pool cleaner are cut in. It can be snorted, smoked or taken through "bluetoothing", where one addict shares their blood with another through a minor blood transfusion. One hit can cost as little as R20 and is enough to get you hooked. Its high lasts between 6 and 24 hours and if not ingested again, withdrawal symptoms include vomiting and body aches.

OPIOID USE DISORDER Part of the reason that so many struggle to escape nyaope's grip is that medical treatment for rehab is expensive, and therapeutics are cumbersome to administer and maintain. One of the current treatment drugs, Suboxone, is taken twice a day until the physical addiction is managed. An addict may claw their health back only through a long-term and multipronged approach. "With the current treatment options available, people living with opioid use disorder (OUD) have to take treatment drugs at frequent intervals, with which patients find difficult to comply. Furthermore, current drugs used to treat opioid addiction only last six hours. Even then, only 50 to 60% of the drug treatment is bioavailable to the patient," says Sarjan Patel, a Master's student at the Wits Advanced Drug Delivery Platform (WADDP). The drug treatment is available in tablet, intravenous drip (IV) and implant form. While the range of options has

improved, and with that better compliance, a long-term option is desperately needed. Without buprenorphine and suboxone (the main treatment options), a patient has intense cravings and unfortunately, the chance of relapse is extraordinarily high. A CHEAPER, QUICKER TREATMENT Patel has worked over the past 18 months under the supervision of Professor Yahya Choonara and Dr Mershen Govender to produce a targeted, sustained-release drug delivery system for OUD. He notes that the effective treatment of OUD requires a combination of drugs, which the delivery mechanism can offer. Patel explains that the drugs to treat OUD (which are few and far between) compete to bind to the opioid receptors in the patient’s body and block the release of dopamine, which ignites feelings of pleasure. Even if an addict takes a hit of opioids, it won't find "space" and is unable to bind on receptors and so it loses its effect. "It is an amazing 'blocking' system and one administration is equivalent to 14 tablets”. With the new treatment, the patient will only need a weekly dose. "We hope that this will reduce costs and become a longterm treatment for OUD," says Patel.

URGENT NEED FOR OPIOID SUBSTITUTION THERAPY IN SA Opioid use disorders, including heroin, which is widely available in South Africa, account for 70% of the global burden of drugrelated disease and disproportionately affect the poor. In addition, there is the concern around the link between injecting heroin, hepatitis C virus and HIV and the impact this has on communities and healthcare systems. Consequently, the inclusion of opioid substitution therapy (OST) in the 2018-2022 National Drug Master Plan is a welcome development. Before this, there was a dearth of treatment options and the high cost of methadone, a common OST treatment drug, remains an issue. The Sultan Bahu Centre in the Western Cape, which opened its doors as a pilot site for OST in 2015, was the first of its kind. Others have been established since, but too few to beat the pernicious opioid beast. This is why Patel's Master's research at the WADDP is so important. "What’s really notable is that the delivery system in development is flexible enough to deliver other drug treatments. We are testing it for OUD, but there is a lot more potential to deliver life-saving treatment drugs in a cost-effective and longer acting way,” says Patel. C

ANTIBIOTICS: TOO MUCH OF A GOOD THING? Over-prescribing antibiotics, which are drugs that treat bacterial infections, may render them less effective in the future, but the complicated doctor-patient dynamic requires managing expectations to protect both drug efficacy and public health. DERYN GRAHAM

ROFHIWA MASHAU

f your doctor prescribes a broad-spectrum antibiotic for your bacterial infection, there’s a good chance that it will hit the mark and make you feel better within a matter of days. Or not. It’s more likely you had a viral infection – a common cold, for example – and your body would rid itself of the virus. Antibiotic medication is just the doctor’s way of pacifying you. We have a complex relationship with our doctors in South Africa. At the affluent end of the market, our medical aid pays in part or in full for both a consultation and the prescription with which you leave the doctor’s rooms, so the pain we feel is not necessarily financial. At the other end of the scale of the doctor/patient relationship in South Africa is the person who lives far from any primary healthcare facility, takes public transport to a clinic, and stands (or sits, if they’re lucky) in a queue for many hours before they finally get to see a doctor. After going through all this, on top of feeling ill, they probably have as high an expectation of receiving treatment in the form of drugs as does the private patient – and so the doctor dispenses an antibiotic. DOCTOR ANTICIPATION, PATIENT EXPECTATION Lenore Manderson, Distinguished Professor of Public Health and Medical Anthropology in the Wits School of Public Health contends that this is not a medical strategy to cure the patient but to keep their life on track. “Getting sick adds to the many insurmountable socioeconomic challenges that poor South Africans face every day,” she says. According to Dr Duane Blaauw, Senior Researcher in the Wits Centre for Health Policy, surveys show that patients assume that doctors who prescribe medication are more qualified and more knowledgeable than those who send you away with instructions to rest and drink lots of fluids. And the more medication these doctors prescribe, the more their stock rises with patients. As far as our belief in the medical profession goes, ironically, the doctor who spends a little more time with the patient to explain the difference between a viral and a bacterial infection, and which treatment goes with what, is more knowledgeable (though of course not necessarily more qualified) than the one who dispenses somewhat injudiciously. “It’s the tension between patient expectation and doctor anticipation of that expectation, which results in many cases of over prescribing,” says Blaauw. “For example, when a doctor sees a child and is faced with parental anxiety, they may write a script, even if it’s unnecessary.” The consequences of over-prescribing medication – that is, prescribing without any medical evidence that a drug treats the symptoms or cause of infection – is that drugs become ineffective. They are rendered antimicrobial resistant.

ANTIMICROBIAL RESISTANCE Muhammed Vally is a Lecturer in Clinical Pharmacy at Wits. He says that overcrowding and poor infection control in hospitals exacerbate the spread of infection. When the first, second, and third lines of attack against infection – via antibiotics – have been knocked out due to overuse, patients may be left

“We need to protect our drugs against overuse, because before long there will be nothing left in the doctors’ arsenal with which to treat genuine cases.” vulnerable from virulent infections that do not respond to available drugs. That’s when we start to see deaths because of antimicrobial resistance. “If doctors tested for certain conditions, they would find that antibiotics are not required, but they don’t send samples to labs because of costs and the risk of overburdening the system. However, the flip side of that is that prescribing antibiotics unnecessarily is also costly to the public health system,” says Vally. The World Health Organization (WHO) defines antimicrobial resistance (AMR) as occurring when bacteria, viruses, fungi, and parasites change over time and no longer respond to medicines, making infections harder to treat and increasing the risk of disease spread, severe illness and death. As a result of drug resistance, antibiotics and other antimicrobial medicines become ineffective and infections become increasingly difficult or impossible to treat. The WHO has declared AMR one of the top 10 global public health threats facing humanity. Manderson says, “Pathogens are always mutating and therefore different variants of a virus, bacteria, or fungus become resistant to certain drugs. We need to protect our drugs against overuse, because before long there will be nothing left in the doctors’ arsenal with which to treat genuine cases.” ‘ANTIBIOTIC GUARDIANS’ It’s all about the judicious use of antibiotics. For some infections, an antibiotic is absolutely the right thing to prevent complications. Manderson cites the prevalence of untreated urinary tract infections (UTIs), especially in the elderly, as an example. If the elderly lose their capacity to respond to antibiotics, UTIs can lead to much more serious symptoms, and then there is nothing left with which to treat the UTI,” she says. The Federation of Infectious Diseases Societies of Southern Africa supports the South African Antimicrobial Stewardship programme. A collaboration between the Department of Health and the Department of Agriculture, Forestry and Fisheries, the programme invites both human and animal healthcare professionals to pledge to become ‘antibiotic guardians’ committed to improving antibiotic prescription, to protecting patients from harm caused by unnecessary antibiotic use, and to combat antibiotic resistance. C

THE ANTIBIOTIC BULLY IN YOUR BEEF The use of antibiotics in livestock that is later consumed by humans threatens public health, the environment, and food security because antimicrobial resistance renders drugs ineffective in the treatment of disease. However, novel research in the School of Physiology explores plants as an alternative to synthetic antibiotics. SHAUN SMILLIE

ntimicrobial resistance (AMR) occurs where bacteria, viruses, fungi, and parasites no longer respond to medicines, making infections harder to treat. It’s a growing threat that’s on the radar of the World Health Organization (WHO). In 2019, 1.27 million people worldwide died from AMR, according to the US Centers for Disease Control and Prevention, while another five million deaths associated with AMR were caused, in part, by antibiotics fed to livestock that end up on the tables of consumers across the globe. AMR is set to claim even more lives in the future – by 2050, ten million fatalities annually are forecast, a figure higher than the 8.4 million deaths from cancer that occur every year. As AMR takes hold, common diseases that include respiratory tract infections, sexually transmitted diseases, and urinary tract illness will become untreatable. Furthermore, the WHO estimates that, by 2030, AMR will force up to 24 million people into extreme poverty and has warned that lifesaving medical procedures would become riskier, and food systems increasingly precarious. POTENTIALLY FATAL PRIORITY PATHOGENS To combat this plague, governments and health organisations have embarked on an ‘arms race’ to develop new antibiotics to fight antibiotic-resistant ‘priority pathogens.’ In 2017, the WHO published a list of these priority pathogens, which were given the acronym ESKAPE. They include Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species. These are the pathogens that represent the greatest threat to humans and whose rise is in part linked to the practice of using antibiotics in food production. Associate Professor Eliton Chivandi, Associate Professor Kennedy H. Erlwanger, and Dr Michael Madziva are researchers in the Endocrinology and Metabolism Research Laboratory in the Wits School of Physiology. They explain that low doses of antibiotics are given to livestock to suppress the growth of microbiota that use up nutrients meant for the animal. The problem with this practice is that these synthetic antibiotics are the same, or similar, to those used in humans. “Research has shown an explicit relationship between antimicrobial use and antimicrobial resistance in veterinary science,” says Chivandi. The use of these antibiotics has been found to cause kidney, liver and pancreatic toxicity in both livestock and in the humans that consumed those animal products. “Some of the antibiotics also cause allergic reactions, immunosuppression and reproductive failure,” adds Madziva. As more and more antibiotics are used in livestock and make their way into livestock products like eggs and meat, the greater the negative impact on consumer health. Furthermore, the continued use of antibiotics to promote growth in livestock increases the chances of the transfer of antibiotic resistant genes to humans, which will further exacerbate the challenge to public health in the future.

“The clarion call by consumers of livestock and poultry derived foods is to replace synthetic antibiotics with natural products that mimic the biological effects of synthetic antibiotics.” “Additionally, and most important, the antibiotics expelled in livestock waste contaminate the physical environment leading to even further development of antibiotic resistance in the environment,” says Erlwanger. However, there is potentially a safer alternative that these researchers are exploring: Phytochemicals. And humans have known about them for millennia. FIGHTING AMR WITH PHYTOCHEMICALS Phytochemicals are what plants use to protect themselves not only from browsing animals, but also from bacteria, protozoa, and viruses. They are known as metabolites and examples of these are tannins in tea, and flavonoids, a group of natural substances found in fruit and vegetables. Flavonoids are known for their anti-cancer, antioxidant, anti-inflammatory, and antiviral properties. For centuries humans have known that some phytochemicals have medicinal properties. A well-known example is salicin which, for at least 2400 years, has been used to treat headaches. Salicin is found in the bark of the white willow tree and the compound is known for its anti-inflammatory and pain-relieving properties. By the end of the 19th century, salicin was being synthetically produced and used in the manufacture of aspirin. It is only recently, however, that science has been studying purified phytochemicals to determine the efficacy and possible toxicity of the compounds. While much of the work on phytochemicals is still in the research phase, increasingly they are being seen as a safer alternative to antibiotics as growth promoters. “In recent years there has been a dramatic increase in the use of phytochemicals, nutraceuticals and other dietary products to support health and wellness and to treat illnesses,” says Erlwanger. Examples of these include coumarins, flavones, isoflavones and tannins, which are being used in food supplements to promote health. But the trio believe that more research is needed not only to evaluate the efficacy of phytochemicals but also to determine their safety when it comes to the health of consumers and farmed animals. Then comes the task of getting the agricultural industry to accept the use of phytochemicals. This can be done through educational campaigns and more research. “The clarion call by consumers of livestock and poultry derived foods is to replace synthetic antibiotics with natural products that mimic the biological effects of synthetic antibiotics,” concludes Chivandi. C

MOSQUITOES ON BIRTH CONTROL Eradicating malaria in South Africa is a national policy goal, but is easier said than done. But sterile insect technique could take the bite out of mosquitoes. BETH AMATO

n a north eastern corner of KwaZulu-Natal, the community of Jozini is at the centre of a groundbreaking trial to eradicate malaria. The innovation, known as the sterile insect technique (SIT), is essentially male mosquito birth control. These exclusively lab-reared male mosquitoes are sterilised before being released in infested areas. Male mosquitoes (referred to as “non-biters”) do not carry malaria and so when they mate with native female mosquitoes in malaria-infested areas, only “non-diseased” offspring are produced. This drastically reduces the resident mosquito population size. When a human contracts malaria, the body takes a hard knock. Usually, about 10-15 days after being bitten by an infected mosquito, a person will experience symptoms such as fever, nausea, vomiting and severe headaches which can result in seizures, susceptibility to bacterial infection, cognitive impairment and even death. If not treated, people can experience recurrences of the disease or act as carriers of the deadly malaria parasite. A recent study notes that despite exposure to malaria assisting in the build-up of immunity against the disease, not seeking treatment is dangerous. “The resultant chronic yet silent infection not only helps perpetuate malaria transmission but, over time, also contributes to serious health and developmental impairments,” the study reports. INTRODUCING THE SIT The SIT is a biological vector control technique based on the release of many laboratory-reared sterile insects in significantly higher numbers compared to the natural population. The technology has been applied successfully in agriculture, such as in the control of the screwworm. SIT for mosquitoes was conceived in 2010 to supplement existing malaria prevention techniques which include oral prophylaxis and indoor residual spraying (IRS). The former is only helpful once the diseased mosquito has bitten (and some of the pills have concerning side effects, including psychological). Malaria parasites may develop resistance to these drugs. Meanwhile, other mosquitoes have built resistance to the IRS insecticides. While IRA targets indoor feeding and resting mosquitoes, in South Africa, it has been less efficient in controlling Anopheles arabiensis, a mosquito species that sometimes feeds and rests outside, contributing to outdoor transmission. This is the most significant challenge in malaria-affected provinces. Dr Givemore Munhenga, Principal Medical Scientist at the National Institute for Communicable Diseases (NICD) and a Senior

Researcher at the Wits Research Institute for Malaria (WRIM), says that the SIT might be a game changer in addressing these challenges. SIT is highly effective in suppressing and eventually eliminating mosquito populations regardless of their biting and resting behaviour, or insecticide resistance status. The technique requires community buy-in in order for people to understand the process and its implications. In some cases, locals believed that the treated male mosquitoes represented a threat to their health, but as Dr Muhenga explains, “As only female mosquitoes bite their host, the release of non-biting sterilised males will have no negative effects on people in the area.” In order to dispel concerns about this potentially controversial public health intervention, intensive community dialogue and public engagement processes were undertaken in Jozini before the technology was piloted. Finally, in 2022, sterile male mosquitoes were released into the field site, the first time in such a large area targeting an African malaria vector. Already, there are positive signs of a mosquito population reduction. “The ultimate goal of the SIT project is to establish mass-rearing capabilities so that a good number of sterile male mosquitoes can support the efforts to eliminate malaria,” explains Munhenga. The next phase of the SIT project, funding permitting, is to test its suitability and affordability as a public health initiative. A CHANGING CLIMATE PORTENDS TREATMENT AND PREVENTION COMPLICATIONS As mosquitoes thrive in warmer environments, hotter temperatures generate more breeding grounds. Floods and droughts work in the mosquitoes’ favour as they breed in temporary pools when it rains and in permanent bodies of water in dryer periods. MALARIA ELIMINATION: A SOCIAL JUSTICE ISSUE Professor Lizette Koekemoer, the Co-Director at Wits Research Institute for Malaria, explains that 90% of the global annual malaria mortality cases emanate from Africa. Children under the age of five account for at least half a million deaths. “There are major repercussions when someone is infected with malaria. If a breadwinner, for example, becomes ill, then the family suffers. Often this is in a context where there is already widespread poverty. Yes, there have been gains on the treatment front, but it is expensive and follow up treatments are often not completed,” says Koekemoer. She notes that malaria reduction and elimination research

takes between five and 10 years. “We see that once we have identified drugs and screened the compounds, the parasites develop resistance very quickly.” This challenging task has been made easier by the combined expertise of multiple units from the University of Cape Town, the University of Pretoria, the NICD and Wits. Koekemoer says that elimination is an ambitious goal. This is because transmission is complex, involving 40 parasitic mosquito species behaving very differently. GLOBAL HEALTH PRIORITY BOXES TO DETERMINE WHICH VECTOR-CONTROL DRUGS WOULD WORK COVID-19 highlighted the critical importance of pandemic preparedness and a robust response to current and emerging public health threats. As crises breed innovation, new tools can rapidly be developed, particularly when barriers to collaboration are removed. One such tool, the Medicines for Malaria Venture Global Health Priority Box, has a collection of compounds acting against pathogens and vectors. Scientists can access this at no cost and build on each other’s work. The box provides scientists with confirmed starting points to further advance the development of treatments and insecticides to tackle drug resistance and communicable diseases. The WRIM’s Dr Ashley Burke, Ayesha Aswat, Nelius Venter and Erica Erlank are screening the Global Health Priority Box as part of a collaboration with the University of Pretoria. The components of the box include 80 compounds with confirmed activity against drug-resistant malaria, 80 compounds donated by the Bristol-Myers Squibb compound library for screening against neglected and zoonotic diseases, and 80 compounds tested for activity against various vector species from the Innovative Vector Control Consortium. The plate can be used to screen and develop compounds for vector control and transmission blocking medicines. The World Health Organization has certified 38 countries malaria-free. In southern Africa, South Africa and eight other countries have made malaria elimination a policy goal. While scientists have many hurdles to jump over, the WRIM is committed to developing new and innovative methods which can be implemented in the field. C

MALARIA – A HISTORY The World Health Organization describes malaria as an ancient disease. Indeed, there are inscriptions on bones, tortoise shells and bronzeware in China, dating back more than 3500 years. “The circular nature of transmission of the parasite, from human to mosquito and back to human, the ability of the parasites to form resistance to treatments and of the mosquitoes to form resistance to insecticides, and the complex lifecycle of the parasites makes malaria a tough disease to eliminate.” South Africa has a long history (about 120 years) of malaria control activities. This has led to a drastic reduction in malaria cases. Nevertheless, the country is still prone to epidemics: the 1999/2000 outbreak resulted in about 65 000 cases in malaria season. Before this, the cases were totalling around 11 000.

MORE ON THIS RESEARCH: Known as the Sterile Insect Technique for Malaria Mosquitoes in a South African Setting, the initiative is a multiple and global stakeholder initiative coordinated and operated under the auspices of the Nuclear Technologies in Medicine and the Biosciences Initiative.

PROFILE

DOWN THE RABBIT HOLE TO BRING BACK SOME WORDS A firm believer in art for art’s sake, Dr Eva Kowalska argues that drugs and addiction are not synonymous, as her research of drug literature and opioid biographies across time and space reveals.

ou wouldn’t expect to find a Polish person with a PhD in Drug Literature in the Wits Faculty of Engineering and the Built Environment. But that’s where Dr Eva Kowalska teaches first-year students English and academic literacy. Evidently, as is often the case with recreational drugs, things are not always what they seem. Kowalska is part of a multidisciplinary team in the Academic Development Unit (ADU), a role which is quite divorced from her research. “We don't really get to teach much of what our research is about, but we're allowed to pursue it in our own time,” says the 38-year-old Linden resident, whose thesis, in the English Department, was titled High Without Respite: A Study of Drug Literature.

THE “DRUG IDIOM”

“The focus of the PHD was the idea that drug texts are a kind of genre within themselves,” explains Kowalska. “The idea is that across contexts, they have enough in common with each other in terms of style, in terms of how substance use, or even addiction, opens boundaries and affects style or form in literature. So the idea was to trace a history of those things.” She’s in search of a “drug idiom” – an idiom being a phrase which cannot be understood simply by looking at the meaning of the individual words in the phrase – as is the case with the thesis title “high without respite”. This is a line from the work of Charles Baudelaire, the 19th Century French poet who experimented with hashish and alcohol and one of the writers that Kowalska studied in her PhD. Another author under her gaze is Hunter S. Thompson, whose novel Fear and Loathing in Las Vegas: A Savage Journey to the Heart of the American Dream (1971) was turned into a film in 1998, starring Johnny Depp. Kowalska also delves into the writing of Tom Wolfe, author of The Electric Kool-Aid Acid Test, about the counterculture Beat generation in the 1960s. They were amongst

DEBORAH MINORS the troupe of Merry Pranksters experimenting with psychedelics, whom Timothy Leary urged to “turn on, tune in, drop out”. Similarly, Kowalska read the writing of Irvine Welsh, author of the heroin-fuelled Trainspotting, which became a celluloid cult classic in the 1990s. These counter-cultural shifts from psychedelics to opioids emerge in literary style and form.

SPIRALLING, REPETITIVE … LOOPING

Across centuries and geographies, drug literature is created within “a specific social and sub-cultural setting.” In the early 1990s, South Africa was an explosive socio-political and cultural milieu on the cusp of democracy. It’s also the decade that Kowalska immigrated here as a child. The maelstrom of the Rainbow Nation in the New South Africa set the (modern) scene for her later research interest in drug literature. Kowalska says that the first real drug novel is Thomas De Quincey’s Confessions of an English Opium Eater. He was a Romantic poet in the 1800s who was drinking laudanum – a tincture of opium dissolved in a spirit. “[His writing] is very dense and of its time but I would argue that all writing about addiction follows that form. It’s very inwardlooking, it’s very looping and repetitive,” says Kowalska of De Quincey, whom she calls “the Godfather of the opiate novel”. This stream-of-consciousness writing is also an important part of modernism, she says, and “modernism in literature is a lot about isolation, and the stream-of-consciousness and the inward gaze, and formal innovations in terms of writing.”

MODERNISM, WAR AND PIECES

Fast-forward to the 20th Century, however, and the cultural context is vastly different. This era featured World Wars, flower-power, free love, Vietnam, apartheid, as well as tech and medical innovations. Kowalska says that many problems around substance abuse have a lot to do with people returning from those conflicts

addicted to drugs. Morphine, for example, is a powerful painkiller and a very good thing to have in a war situation, given that it’s small, easily stored and consumed, and palliative. “A lot of people came back addicted from the wars. Modernist writing is not separate from this,” says Kowalska. At the same time, there were two very important inventions: the portable typewriter and the invention of the hypodermic needle. “With these two inventions, things happen BANG BANG BANG – much faster and harder than the slow, laborious handwriting.” Unlike the Godfather of the opiate novel slow-sipping and immersed in his tincture, “the immediate hit of injecting morphine or heroin is an entirely different experience and it’s much more modern.” And the depiction of addiction in drug literature is a lot darker.

WHEN WORDS GO AWRY

Kowalska’s study of the “opiate biography” is that part of drug literature that has to do with opiate addiction. Unlike the psychedelics, which are “fun”, Kowalska says “the heroin stuff is quite heavy, it’s not a happy space and it can be quite dark.” Kowalska cites the Godfather, De Quincey, followed by the advent of morphine and heroin, which inspired William Burrough’s Junky and Alexander Trocchi’s Cain’s Book. And what these opioid biographies have in common is the writing style; immersive, spiralling, but beautifully written texts that become a kind of interplay between addiction and writing. “[Writing and opioids] are both compulsions that these people have to play out, over and over. They start off exploring addiction, but they really end up exploring a liminal space,” says Kowalska. “It's both explicitly an exploration of addiction but also very much an exploration of writing.” Kowalska reckons that’s why, as a society, we find addiction so troubling. She says when people get addicted, “they go away from language, they go away from communication”, yet the opioid biographers were trying to reconcile the two. “I think addiction is when people get stuck on that boundary and they have to go over for some reason. They can’t quite reconcile it and that obviously becomes problematic.”

EVA, ADOLESCENCE, AND BOUNDARIES

The pervasion of addiction in drug literature begs the question: what’s the point? Kowalska’s PhD research questioned what draws these texts together? “I think it’s the drugs,” she says. And she doesn’t deny a personal earlier exploration of the usefulness of drugs. “As a younger person I had a healthy interest in experimentation. One dabbles in this and that growing up, and I think that’s healthy. One should consider what one does and not necessarily just say no.” However, this wasn’t the attitude of a draconian principal at Kowalska’s high school in Randburg in the ‘90s. Kowalska recalls the principal was “This ‘just say no’ religious anti-drugs crusader [who] would make us do little pee-in-a-cup drug tests. Just any mention of drugs was terrible, which is such a limited world view and so at odds when working with young people.” At that time, an adolescent Kowalska was expanding her mind listening to ‘60s music – the Rolling Stones, Led Zeppelin, Bob Dylan, Leonard Cohen – many of whose lyrics referenced the counterculture and Beat writers. “There was an intertextuality that became emergent to me,” she says. “When you start reading biographies, it makes you aware of interconnections between things and of broader cultures and sub-cultures around them. Where do those boundaries go?”

IN DEFENCE OF EXCESS

Kowalska’s research suggests that boundaries are fluid, and that excess is inspirational – at least in drug literature. The same can be said for society generally. Ever since the ancient Greeks’ Bacchanalia wine orgies, people have had a predilection to push boundaries and explore universal consciousness. “In society we sometimes need these excesses, these carnivals or these shamanistic practices or these binges, to release things and re-establish order, and I think the same is true individually,” says Kowalska. “It’s part of fully developing theory of mind, part of growing up, which is why young people tend to experiment more than older ones. One of the final things you have to ‘put right’ is that sort of boundary for yourself. And some people like to play with that boundary, and that I think is recreational drug use.”

TALISMANS, SPELLS, AND INCANTATIONS

As much as some people might not like it, drugs are an important part of culture and artistic practice, and have been for the longest time, Kowalska says. “Shamanistic practices all over the world often have to do with the ceremonial use of some sort of substance to see things, or to commune with the past, or the dream world.” Drugs not only facilitate these visions but relate to literature too, since they are often about interpreting a dream world, or narrating a spiritual journey. “Even though they weren’t written literatures, they had a storytelling element,” says Kowalska, adding that magic spells, for instance, are “a few words, an incantation, and there’s either a talisman or there’s a substance, a potion, or a leaf.” “That’s what drug literature does; it becomes that talisman. It almost becomes a sub-cultural object ‘to be seen reading’. They become symbolic in their own right.”

DRUG (IM)MORALITY

Kowalska doesn’t vilify drug literature writers for their use of drugs. “It’s difficult to say that any substance has a moral value – there’s no such thing – they’re just things. It’s what people do with them,” she says, adding that, illegality aside, the laws around drugs and substances are not fixed. For example, marijuana is legal now for some types of use, which it wasn’t when she was growing up. “Cigarettes are still legal and they’re horribly addictive. Drugs like nicotine and alcohol are taxed and are freely available, so the rules are arbitrary,” she says. “People tend to moralise substance use. Contemporary society is probably not familiar with recreational drug use; society tends to treat drugs and addiction as synonymous and they’re not.” Drugs, like guns, are devoid of intrinsic moral value, she asserts. “I suppose literature also doesn’t have a moral value – it just is. I’m a firm believer in art for art’s sake. It only has to answer to itself as far as I’m concerned, so if the text is worthwhile, well, then to me it’s worth it.”

DOWN THE RABBIT HOLE …

Kowalska shares an introduction written by William Burroughs for a book of poems by Alexander Trocchi: “Perhaps writers are actually readers from hidden books. These books are carefully concealed and surrounded by deadly snares. It’s a dangerous expedition to find these books and bring back a few words.” Kowalska concludes: “Isn’t that to some extent what this is? Going beyond to bring back a few words? Down the rabbit hole to bring back a few words for themselves and the rest of us?” And what a whorl of worldly words there are. C

MOTIVATIONAL MESSAGING FOR MEDICINE What’s best for us is often the exact opposite of what we humans choose to do. Odd, right? Enter Behavioural Linguistics, a new advanced area in healthcare that's especially critical to medication compliance and adherence. MAGDEL LOUW

n today’s world, where self-care is such a burning issue, and we are encouraged to take better care of our own bodies and minds, we often need a nudge in the right direction to find ways to help us make better medical and health decisions. As these decisions are not always easy, and, especially where we need to take daily regimens of a variety of drugs, we often opt for the easy way out, not taking our medication at all, where the benefits of taking it should be obvious. Leigh Crymble is a doctoral student in Behavioural Economics at the Wits Business School. Her research focus is on how we make the decisions that affect our daily lives.

“My research is all about how we make decisions. What makes us choose one thing over another? And how can language play a role in influencing these behaviours? At the core of my research is how the link between behavioural economics, psychology and linguistics can play an important role in shaping our decision making.” This fascinating field of study boils down to how information is delivered to us through language and communication. Many other elements come into play too, such as what the message is, when it is sent and who the messenger is. “They all play a significant role in whether the person receiving the message both

engages with the information and acts on it.” Behavioural Science in message framing is regularly tested and used globally, from getting people to eat better and exercise more, to saving money for retirement and taking out certain insurance products. “Post-pandemic, we saw the importance of taking a behavioural approach to health: starting with washing our hands, through to mask-wearing and then getting our vaccines,” Crymble points out. Enter Behavioural Linguistics, a new advanced area in healthcare that’s especially critical to medication compliance and adherence and which alleviates the need for preachy, know-it-all messaging that triggers our naturally rebellious behaviour.

GOOD BEHAVIOURAL MESSAGING BOOSTS MEDICATION ADHERENCE

Conservative estimates put the cost of people not taking their prescribed medicine, how and when they should, at more than $300 billion every year. Someone is considered “non-adherent” when they take less than 80% of medication prescribed to them, for example for diabetes, hypertension or high cholesterol. And the implications are huge. People who don’t manage their health conditions compromise themselves financially and their quality of life. In putting strain on healthcare resources, the broader economy is affected too. “One of the biggest behavioural blocks for people is the disconnect between the present and the future version of themselves – known as the ‘present bias’. Research on neuroimaging of the brain goes as far as suggesting we perceive a future version of ourselves in the same way as we think of a stranger. This makes it difficult for us to act in ways that are in our best future interests, especially if the action impacts us in the ‘now’, such as experiencing negative side effects,” Crymble explains.

A NUDGE IN A NUTSHELL

Fortunately, behavioural science research shows that a way to improve medication adherence is to deliver the right nudge to the right patient, at the right time and in the right way. Professors Richard Thaler, Nobel Prize laureate, and Cass Sunstein, American economist, support this very concept in Nudge: Improving Decisions about Health, Wealth, and Happiness: “A nudge is any aspect of the choice architecture that alters people’s behaviour in a predictable way without forbidding any options or significantly changing their economic incentives. To count as a mere nudge, the intervention must be easy and cheap to avoid. Nudges are not mandates. Putting fruit at eye level counts as a nudge. Banning junk food does not”. Part of Crymble’s PhD using behavioural linguistic theory was to develop a new communications framework to test how messages can be more effective across various industries. Right now, they are applying this specifically to test medication adherence messaging. Their research helps patients develop better health awareness and education in today’s technical, often intimidating, world. All people need is a small, friendly push, or “nudge” and so they are finding ways to encourage patients to take their medication in the right dose at the right time, and to make sure patients prioritise doctor appointments and health checks and collect and fulfil repeat medication scripts on time, she says. “Interestingly, these patterns of behaviour apply across demographics and often transcend languages, genders, ages, cultures, and other variable factors. This is particularly helpful in a

country as diverse as South Africa, where there are large numbers of people needing life-saving chronic medication.” Messages are tested across multiple communication platforms including SMS, in-app notifications (for patients with smartphones), print material and direct mailers - sent both to the patients themselves and to healthcare professionals. “A first in the country, we are also working with an innovative new company which prints ‘nudgey’ messages directly onto pill packs which are personalised to the individual patient,” she highlights. “In the end, crafting content in ways that are intrinsically linked to how people think and act means you are more likely to ultimately persuade them, which is crucial in helping to increase medication adherence,” Crymble says. “However, this discipline is heavily rooted in ethical action. People have full freedom of choice in what they decide to do and nothing is coerced, forced, banned, or used for ill-intent. Instead, the choice architecture we rely on is set up in ways to help nudge people in the direction that is in their best interests: to help reduce morbidity and mortality as a result of medicine non-adherence.” C

THE TEST FOR WHAT REALLY WORKS Crymble explains that five principles were developed for this research to test effectiveness and gain insight into the close link between language, decision-making and behaviour: • Incentives that motivate an individual to do something. Whether intrinsic (motivated internally by our sense of personal satisfaction) or extrinsic (motivated through getting a reward). Incentives are very effective in encouraging behavioural change. For example, testing the difference between receiving a free item or discount, and recognition messaging for being “a health superhero”. • The messenger effect for when we send messages through someone who is trusted, it boosts credibility and makes the message more persuasive. For medication adherence, this can be a doctor or pharmacist. They’re even testing preloaded messages from the patient (to themselves!) as well as messages from loved ones. • Social proofing as we are social beings heavily influenced by what those around us do and say, and often do what others do to fit in and ‘follow the herd’. Are patients more likely to fill scripts and take their medication correctly when told that “others like them” or “most South Africans” are doing this preferred behaviour? • Framing because how a message is positioned and structured, matters. You can highlight either the positive (gain) or negative (loss) aspects of the same decision. This is the difference between using a gain-frame message like “those who take their diabetes medication correctly can add five years to their life”, versus the loss-frame message of “those who don’t take their diabetes medication correctly can lose five years of their life”. • Timely reminders and cues which are simple methods to getting someone to act on time. This is a powerful tool for motivation and behavioural change. Language like “your medication is packed and ready”, “your meds are waiting for you” and “reserved for you” helps increase medication adherence.

New biotechnical treatments can fast-track recovery from traumatic injuries. MARCIA ZALI

CHANTÉ SCHATZ

esearchers at the Wits Advanced Drug Delivery Platform (WADDP) in the Department of Pharmacy and Pharmacology at Wits are on a mission to revolutionise the way we treat wounds. By using new technologies that target specific wounds, these treatments will eventually help the body heal itself. WADDP researcher and Lecturer in Pharmacy and Pharmacology, Dr Poornima Ramburrun and her colleagues are looking into ways of combining the use of conventional treatment methods, such as anti-inflammatories and painkillers with biotechnological innovations like implants and 3D printable material to heal wounds. “Tissue regeneration and wound healing is such a complex process; we have to combine all these systems to improve tissue regeneration. We can’t only focus on one element because all of these mechanisms come into play,” says Ramburrun. “Conventional drugs like anti-inflammatories, paracetamol and antibiotics remain critical in the healing process and are not likely to be replaced anytime soon.”

COMBINED TREATMENTS

As an example of how a combination of drugs and bioactive compounds can work together to become an effective tissue regeneration treatment, Rambarrun referred to one of her studies, which focuses on tissue regeneration of the peripheral nerve. In this study, she uses a bioactive growth factor that helps little nerves to sprout, combined with diclofenac sodium – a typical anti-inflammatory and pain medication – and an antioxidant to protect the newly regenerated tissues from any further injury or inflammation. “We are trying to reduce the dosage of medication that patients need to take by sending the drugs directly to the site where

they are needed,” says Ramburrun. “We know that the drugs are reaching the tissues that really need it and we are also using a much smaller quantity through the implant, because it will be implanted at the required site.” PhD student at the WADDP, Kate Da Silva, focuses on healing internal trauma to the liver caused by stabbings, gunshots, or car accidents. Instead of using the general approach of treating the entire organ, Da Silva focuses on the exact location of the wound in the liver.

3D PRINTING

“We use an injectable, 3D printed biodegradable material that will be absorbed by the body once healing is complete,” says Da Silva, adding that the aim is to only treat patients who suffered recent, acute trauma to the liver. “By using this treatment plan, we can cause the tissues to regenerate back to their original state while reducing the amount of medication patients need to take during recovery. We are using the body’s own regenerative hormones as a drug to cause native regeneration in the liver.” Sameera Khatib, a Master’s student in Pharmacy at the WAADP, like Ramburrun, also focuses on the peripheral nerve – aiming to create an artificial ‘bridge’ of the nerve when injury occurs. This conduit helps the nerves to heal themselves. “My research tries to expedite that regenerative step by making a conduit at the place of injury, which will trick your body into thinking that there is structural support and will begin the regenerative process,” says Khatib. The goal for both Rumburrun and Da Silva is that they are able to commercialise their research so that patients can benefit from treatment that ultimately improves the healing process, reduces side-effects, and further aids adherence to treatment. C

A 3D Bioplotter. This image shows the 3D Bioplotter which is capable of 3D printing cellular matrices for applications in tissue engineering. The design and cells used in this equipment allow for the printing of artificial/replacement/regenerative tissue and organs.

A pourable powder for wound healing applications. The powder in the right container can be placed onto open wounds that rapidly gels to seal the wound (gel on the left). The gel promotes wound healing and protects the wound against infection.

SUCKING THE VENOM OUT OF THE BITE Snakebites kills thousands of people every year, yet ways to treat snake bite victims remain antiquated. Hopefully a new way of creating antivenom can lead to a better solution. SHAUN SMILLIE

he fight against snakebites relies on a century old method that involves horses as a source for the treatment of the toxins. And while this technology is effective, it has done little to stem the estimated 138 000 deaths a year globally, most of whom are the poor who can't afford the treatment or make the journey to medical centres where the antivenom is kept. Besides the fatalities, hundreds of thousands of snakebite victims every year are left seriously maimed through the loss of limbs or eyes. In 2017, the World Health Organization officially recognised venomous snakebite as a neglected tropical disease, but to save more lives, health professionals believe antivenom needs to become cheaper, safer and easier to access. The answer could be in a new generation of antivenom serum that involves isolating monoclonal antibodies. It is a process that has proven success when it was used to develop the first Covid-19 therapeutics.

HORSES FOR COURSES

Here in South Africa, Dr Constantinos Kurt Wibmer is working on developing this new antivenom in his lab based at the National Institute for Communicable Diseases (NICD) in Sandringham, Johannesburg. The horses which are used in the current manufacture of antivenom, that has changed little since the late 19th Century, are kept not far away. “We are essentially using animal blood as a medicine. We basically immunise animals with snake venom and repeat the process, so you get better and better antibodies,” says Wibmer, who holds a joint appointment as a researcher in the Wits’ Faculty of Health Sciences. According to the African Snakebite Institute, the process takes up to nine months as only small quantities of snake venom are injected into the horse, which is not harmed, allowing the animal to build immunity. In the next step, the serum is removed from the horse’s blood and purified. In South Africa, a polyvalent antivenom is manufactured in which the venom of ten common South African venomous snakes, including the puff adder, Gaboon adder, rinkhals, green mamba, Jameson’s mamba, black mamba, cape cobra, forest cobra, snouted cobra and Mozambique spitting cobra, is used. South Africa has a reputation for producing high quality snakebite serum, but recently there have been shortages that have been blamed on the increase in power outages. “The problem with these antivenoms is that it is a very impure medicine. From batch to batch it is different, it is not like a drug made in a lab,” explains Wibmer.

THE HUNT FOR SUPER B CELLS IS ON

The discovery of this new antivenom still involves horses – for now. Among the horse’s blood B cells are what Wibmer refers to as “super B cells”, for which he is on the hunt.. These are the immune cells responsible for making extremely cross-reactive antibodies. “You find individual B cells that make spectacular antibodies so essentially we take the DNA out of those cells, clone it into a lab construct, and then we can reproduce those antibodies in the lab,” says Wibmer. The ultimate aim is to create an antivenom that is temperature stable, that will not need to be stored in a refrigerator and can be taken into the field. Aside from the storage issue, another problem with antivenom is the cost. When snake bite victims are treated, they often need several vials of antivenom, which, in South Africa, can cost as much as R100 000. Should Wibmer’s new

Monoclonal neutralising antibody drug.

antivenom be successful, it could be stored anywhere, and would require just a single vial. “We are looking forward to the next generation of antivenoms that are broader, safer, and generally applicable to whole general or even whole families of snakes,” explains Wibmer.

WHEN TREATMENT IS WORSE THAN THE CAUSE

Another disadvantage of antivenoms currently on the market is their serious side effects that for some people can be as deadly as the snakebite. Wits herpetologist Professor Graham Alexander discovered this while conducting field research a number of years ago near Heidelberg in Gauteng. Alexander, from the School of Animal, Plant and Environment Sciences was handling a puff adder when it bit him on the leg. He was rushed to the nearby Heidelberg clinic where he was given antivenom. “Within 30 seconds I went into complete anaphylaxis,” he recalls. Alexander’s heart stopped and he had to be resuscitated. He was fortunately able to make a full recovery. However, if Alexander, who makes a living by researching venomous snakes was bitten again, doctors would be forced to treat him symptomatically and not give him antivenom. “It means I have to think twice when handling seriously venomous snakes like black mambas,” says Alexander. Wibmer’s new antivenom may be heaven-sent for people like Alexander, who have adverse reactions to the serum proteins that can act as immunogens. The new antivenom treatment will not have side effects such as Alexander’s allergic reaction. “I really think in the next couple of years we are going to see some major developments,” says Wibmer whose new technology might help save the lives of hundreds of thousands of people who for so long have been neglected. “Snakebite is not a reportable cause of death in South Africa, so who knows how many people could be saved by a new way of treating them?” says Alexander. C

FROM ANCIENT APOTHECARY TO MODERN MEDICINE How our early ancestors shaped our medicine use today. 52

Throughout history, humanity has used nature's pharmacy for healing. In exploring nature as a source of shelter and food, early humans fortuitously discovered the therapeutic properties of plants, with many of today's drugs having their roots in ancient knowledge. MARIETTE VAN DER WALT

ANCIENT SURVIVAL GUIDEBOOK

Adaptive memory, the ability to remember important information needed for survival, played an essential role in this process of discovery. After experimenting with various plants, our ancestors were able to remember which ones worked for their ailments and where to find them, giving them a remarkable edge in the game of survival. With each triumphant discovery of a plant with healing properties, their memory eagerly catalogued the plant's powers, creating a survival guidebook that would be passed down through the ages, forming the ultimate foundation for the development of modern medicine. One crucial plant discovery included the African yellow star (Hypoxis angustifolia). Widely distributed throughout southern Africa, it is also found in abundance around the Sterkfontein Cave, one of the important archaeological sites in the country. It is likely that our hominid ancestors in South Africa were the first to discover the nutritional and medicinal properties of the African yellow star. The herbaceous plants feature pretty, yellow flowers, sickle-shaped leaves and bulbous rhizomes that are good to eat once cooked. Wits University studies have shown that it was cooked and consumed as far back as 170 000 years ago. "It has small rhizomes with white flesh that is more edible than the bitter, orange flesh of rhizomes from the better known medicinal Hypoxis species which is incorrectly called African Potato. The part of the plant used for medicine is not a potato, which is a tuber, but a corm," says Dr Christine Sievers, an Archaeobotanist in the Wits School of Geography, Archaeology and Environmental Studies. “Plant remains are rarely wellpreserved and there is no direct evidence that people living around 170 000 years ago were aware of the medicinal properties of species such as Hypoxis hemerocallidea. There is, however, widespread evidence of animal self-medication. This is likely to be shared evolutionary behaviour and suggests that people had knowledge of the healing power

of plants at least during the Middle Stone Age (280 000 to about 50 000 years ago), and very likely much earlier in our evolution,” she says. DON’T LET THE BED BUGS BITE Once the healing properties of plants were discovered, early humans were extremely resourceful. With the discovery of the medicinal properties of plants came the realisation they could be used to keep pesky bugs away, evidenced by insect-repelling plants found in 77 000-year-old preserved bedding from a cave in South Africa. Today, communities continue to rely on many plants, including the Hypoxis species, for traditional medicine, treating various ailments. SAFEGUARDING THE FUTURE OF INDIGENOUS MEDICINAL PLANTS Scientists have recently delved into the use of ancient medicinal plants, collaborating with local communities to unveil their biochemical properties and potential applications. This interdisciplinary approach blends traditional knowledge with modern scientific techniques, opening exciting drug discovery and development avenues. However, the rising popularity and commercialisation of traditional medicine has led to the overexploitation and depletion of certain species. Alarming statistics from the South African Health Review report indicate that out of 2 062 plant species used for traditional medicine, approximately 32% have been recorded in traditional medicine markets, with 4% currently under threat. Unsustainable harvesting practices, habitat destruction, and the impacts of climate change further compound conservation issues, putting many medicinal plant species at risk of endangerment or even extinction. We need to safeguard not only the plants themselves but also the ecosystems that nurture them, the habitats that harbour them, and the cultural landscapes that shape our understanding and practices of healing. Recognising the historical, spiritual, and ecological significance of these environments is essential for preserving the integrity and resilience of traditional medicine systems. C

COLUMN

SEEING THROUGH THE HAZE OF THE CIGARETTE TAX SMOKESCREEN

The high taxes on cigarettes and tobacco products are counterproductive in decreasing smoking and only benefit the illegal cigarette trade – and its political masters. ALEX VAN DEN HEEVER

elling addictive substances as a commercial activity is always a winner. Demand is locked in, even if prices rise. Alcohol, narcotics, money, sex, gambling, and, of course, nicotine are where money grows on trees for suppliers. Addictions, however, become particularly harmful where they interfere with a person’s ability to pursue their normal daily activities – for instance, where family relationships, employment and social interactions are harmed. Physical harm can also result from addictive practices including smoking, the use of narcotics and excessive alcohol consumption. In the case of narcotics and alcohol abuse, harm can extend to non-users through acts of violence and direct and indirectly related criminality. Social controls have consequently been introduced for very dangerous substances where there are clear risks to individuals

and society – many with only limited success. Over time these controls have included blanket prohibitions, the criminalisation of the sale and distribution of certain products, stringent licensing conditions, the supervision of transactions and so called “sin” taxes or excise taxes. Such approaches have, however, been notoriously unsuccessful in controlling trade, distribution or consumption, and have typically succeeded only in driving these activities underground. Due to their very nature and the sustained demand for addictive substances, poorly designed control measures merely lead to the growth of well-funded criminal syndicates some in collaboration with corrupt elements within the state. While many addictive substances are extremely harmful, at a social level smoking falls into a category of harm that is sufficiently

mild to avoid more stringent and weighty control, yet sufficiently harmful to attract a degree of regulation. Any form of product control where a natural and sustained market exists, however, brings with it opportunities for corruption and patronage, with the risk that public health measures will be rendered futile.

IF THE PRICE IS RIGHT

A largely successful public interest lobby has existed in South Africa to reduce demand through the implementation of a consumption tax on cigarettes, in the form of a 40% ad valorem tax on top of VAT. Consequently, over 50% of the price of a legally traded packet of cigarettes goes to SARS. What might have been more effective is a specific tax with a fixed Rand value, rather than using the percentage levy. This means that legitimate manufacturers can, therefore, offset any drop in demand due to the ad valorem tax through price manipulation. Tobacco brands targeting price-sensitive (low income) segments of the market are discounted, with high prices reserved for the less price sensitive (high-income) smokers. Manufacturer strategies aside, smokers remain impervious to price fluctuations – precisely because the product is addictive. While there does appear to be some correlation between the effects on demand and tax increases on cigarettes in South Africa, there is, however, no studies to show the impact that non-financial penalties such as legislation around target marketing and smoking in public places, have had.

A FLOURISHING ILLICIT TRADE

Further confounding the picture is the growth of the illicit trade in cigarettes. Illegal manufacturers simply do not charge the excise tax, giving them a significant price advantage over legal manufacturers. Not surprisingly, the higher the prevailing tax, the greater their price advantage. Within South Africa there is also an apparent linkage between these illicit actors and parts of the political establishment with the result that investigations into illicit markets by, among others, the South African Revenue Services (SARS) appear to have been suppressed. The question now arises whether the calls for further public health interventions by government to control smoking have their origins in a legitimate concern for public health or are driven by players in the illicit market working through their political principals. The apparent demand-related effects of the various antismoking measures are also unclear as no data is available on the illicit trade. It is entirely plausible, therefore, that when the illicit trade is considered, overall demand for tobacco products is increasing and not decreasing. During COVID-19, the prohibition on the trade of cigarettes appeared to have no impact on demand whatsoever, with illegal trade filling the void left by the enforced withdrawal from the market of legal manufacturers. The fiscus consequently lost millions in tax revenue, with zero public health gains.

POLITICAL PATRONAGE

South Africa was the only country in the world that regarded this prohibition as an appropriate response to the pandemic. It appeared to many that the move in fact had very little to do with COVID-19, and a lot to do with political patronage in the illicit market.

“Smokers remain impervious to price fluctuations – precisely because the product is addictive.” The emergence of an illicit cigarette market with established links with government officials is, however, a predictable outcome of the very high excise taxes and VAT, coupled with an unwavering demand for an addictive substance. Exorbitant tax levels eventually become self-defeating, as illicit actors derive significant financial advantage from learning how to beat the system – including through corrupt relationships with the state. The more punitive the tax, the greater the incentive to circumvent it. The greater the incentive, the more likely that corruptible state officials will be drawn into the picture. As a result, the public health imperative becomes a smokescreen (pun intended) for the true motive – which is to divert demand away from taxed cigarettes to untaxed cigarettes, despite serious adverse implications for both public health and government revenue.

A NEW MODEL TO MANAGE TOBACCO IS NEEDED In conclusion, a more coherent model for regulating the tobacco industry is clearly called for. One that speaks to inter-related objectives – such as tax revenue maximisation and public health benefits. First, taxes could be reduced to a level that would allow for the maximisation of tax revenue without creating incentives for a persistent illicit market. A more moderate excise tax may yield better results in the reduction of smoking by being set high enough to disincentivise smoking in lower income groups and children, while generating an acceptable tax revenue but undermining what is an entrenched illicit market. Second, public health interventions should be diversified at the same time as being acknowledged for their inherent limitations. This includes the regulation of marketing, smoking in public spaces and measures to avoid the adoption of smoking by children. However, ultimately, it is arguable that in relation to smoking and the consumption of tobacco products, non-tax related measures are more likely to prove successful than excise levies in the achievement of public health objectives. C

Professor Alex van den Heever is the Chair: Social Security Systems Administration and Management Studies in the Wits School of Governance.

COLUMN

PUT A PILL IN IT! When it comes to health, we have grown into a society that is looking for a quick fix, rather than treating our lives holistically, writes Schalk Mouton.

ugust 2022. I am lying in bed. Suffering from cold night sweats, blinding headaches and extreme exhaustion. I am so tired that even opening my eyes is an effort. I have been sleeping for two days continuously, not even waking up to eat. The SMS with the test results just confirmed what I already knew. COVID. Through heavy eyelids I see a moving shadow. Sounds of drawers opening. Movement in the bathroom. The opening of packaging. Footsteps. Louder and louder. Closer. “Open your mouth.” It is my wife. I respond. Obediently. No will or energy to do otherwise. A huge syringe is stuck into my mouth. The plunger goes down and my mouth is filled with a gush of reddish brown, metallic gunk. Utterly defenceless, I have no other option but to swallow. I feel the thick, dirty brown muck as it enters, making its way down my oesophagus, and into my stomach. It courses through my body, doing … nothing. I open one of my eyes, look up at my wife questioningly. I hear a voice croak “ … Whaaat …?” and

realise it’s my own. “Ivermectin,” my wife says. Smiling. Lovingly, as always. “Horse medicine!” GAMBLING WITH HORSE MEDICINE A couple of weeks before I fell victim to the dreaded disease, a family member managed to sucker us into “investing” in two “Covid survival packs”. It contained various supplements, paraphernalia that you’d never use and the dreaded horse medicine. We reluctantly bought it, but for some reason, this survival pack was the drug of choice we reached for when Covid struck. There was no other option. Even the prescription that my brother, a doctor, sent me was gathering virtual dust, unopened, in my inbox. Granted, though, the horse medicine survival kit cost us something like R120, while the heap of tablets in my brother’s prescription would probably have cost thousands more, likely with exactly the same effect on my recovery from Covid. Two weeks later, I was out of bed. I was still weak, but feeling

“We have become too dependent on drugs. There is a drug for everything, and it is too easy to reach for the pill bottle.” better. Other than the one shot of Ivermectin, I had taken no other medicine. I just slept for two weeks solidly. Luckily the horse medicine had no noticeable side effects, other than the fact that I occasionally feel like the odd gallop around the house, and every now and then an involuntary whinny escapes from my mouth. I did notice, with interest, however, that when my wife also later got sick with Covid, there was not the slightest consideration given to the horse medicine in her Covid survival pack to help her get better. Growing up, I had a relaxed relationship with drugs. I got treated for just about any illness or injury with exactly the same medication by my GP. Whether I broke my leg, needed my appendix removed or had a common flu, the diagnosis from my GP was always that it was a “kiem in die lug” (a bug in the air), and I left the doctor’s rooms with a yellow pill packet filled with Tetrex antibiotics and Kantrexil for stomach cramps. DRUG NAÏVETÉ When it comes to any kind of recreational type of drug, I lived a completely sheltered life. The closest I came to taking any drugs was smoking a cigarette when I was in standard 8 (Grade 10). I immediately felt so sick that I vomited, and never touched a cigarette again. I couldn’t stand the taste of alcohol until varsity (and then, like everybody else, started to try and make up for all the drinks I missed). My first encounter with “real” drugs was at the OppieKoppie music festival one year, when I was offered a Daggakoekie – which I declined. The next time I came across any form of drugs was one night walking down Long Street in Cape Town with my wife. A smartly dressed dude approached me and asked “Do you want some Charlie?”. “Who the hell is Charlie?” I asked. My wife chuckled. I whinnied. I have absolutely no medical training. The closest I am to being a doctor is the fact that my wife is working on her PhD in financial journalism and my brother and father are both doctors, so I probably don’t have any right to say this. However, I do believe that we too often reach for a packet of pills as a quick fix for something that could, and should, be treated in a more holistic way, such as a change of lifestyle or diet, or just taking care of ourselves and each other. To be clear. I have nothing against conventional medicine. The work that the people in health sciences are doing with medicine is incredible, fascinating and lifesaving. There are many cases when medication or surgical treatment is the only option, but in most cases in daily life, small changes in our lifestyles can cure many more health issues that we think. THERE'S A PILL FOR THAT For instance, after coming home from a holiday in the Eastern Cape with my brother, braaiing every night, drinking vuil Coke and just overindulging in general, I came home with a terribly sore foot. It was one of the most excruciating pains I had ever

experienced, so I went to a doctor. It was gout. The doctor gave me an injection and the pain receded almost immediately. My brother prescribed chronic medication that I was to take daily, probably for the rest of my life. The pain from gout scared the life out of me, so, I took the pills daily for over two years. That was until my wife changed our diet – and no, it was not to a diet of oats and barley! Very soon after, I realised that I no longer needed the gout medication. Now, I very rarely experience gout attacks, and if I do, it is very mild and often goes away quickly. My point is that we have become too dependent on drugs. There is a drug for everything, and it is too easy to reach for the pill bottle. Whether it is obesity, smoking or a condition like gout, we too often reach for the pill bottle. Children get put on medication to treat things like depression and ADHD as quick fixes, rather than the doctor spending time and energy to find the root cause, and to fix it holistically. And again, yes, while I do understand that there are cases where medication is the only option, I believe we often treat things symptomatically. I had Covid again earlier this year. While we generally make a point of getting our flu jabs and Covid booster, this year we were busy and missed them. Before I knew it, I was knocked out, in bed. This time around, however, there was no horse medicine, and I declined my brother’s prescription. I just stayed in bed, and rested it out. It took me more than a frustrating month to recover properly, and I am determined not to get it again. So, next year, you’ll see me at the front of the Covid and flu vaccine lines, getting my jab. But now, it is time for a gallop. C

Frances Goodman, Happy Pills, 2023, Glazed Ceramics, 33 x 14 x 14cm. Image courtesy of SMAC Gallery, copyright Frances Goodman

HISTORY

DOOBEE OR NOT DOOBEE? Unravelling Shakespeare's Green Quill: Professor Francis Thackeray's quest for cannabis connection CHANTÉ SCHATZ

esides his fancy language and famous plays, a fascinating study first published in the South African Journal for Science (SAJS) suggests world-renowned playwright William Shakespeare might have had some knowledge of a mysterious plant called cannabis. The Bard's deep insights into the human condition have fuelled countless debates about the source of his inspiration. Leading this captivating research was a South African palaeoanthropologist and an Honorary Research Associate of the Evolutionary Studies Institute at Wits University, Professor Francis Thackeray. His regular academic journey took an unexpected turn when he delved into Shakespearean studies, a keen sideline interest. Armed with an insatiable curiosity and 154 sonnets, Thackeray set out to explore Shakespeare's works. "I decided in 1999 to read all his poetry, starting from the first one to the very last. It was when I reached Sonnet 76 that I had my Eureka moment," said Thackeray. The catalyst for the palaeoanthropologist's pursuit was found in lines 3-6 of the Sonnet: "Why with the time do I not glance aside/ To new-found methods, and to compounds strange?/ Why write I still all one, ever the same/ And keep invention in a noted weed". "He expresses a preference for a 'noted weed', turning away from 'compounds strange'. This can be interpreted to mean not only literary compounds but also strange drugs," said Thackeray. Thackeray then set out to test a few early 17th Century clay pipes found at the Bard's home in Stratford-upon-Avon in England and which he borrowed from the Shakespeare Birthplace Trust. Thackeray investigated this topic at a forensic lab owned by the South African Police Service. The team included Thackeray, archaeologist Professor Nicholas van der Merwe from the University of Cape Town, and Inspector Thomas van der Merwe. They used a scientific technique called gas chromatographymass spectrometry (GCMS) to examine the bowls and stems of old

pipes which had had been dug up from different places around Stratford-upon-Avon. "Interestingly, eight out of 24 pipes that we tested had signatures suggestive of cannabis. The chemical analysis pointed to the possibility that it was smoked as a kind of Indian tobacco or 'weed' from India," said Thackeray. “Astonishingly, evidence of Peruvian cocaine (a “strange drug”) was found in two pipes, although neither came from Shakespeare's property." The results do not definitively prove that Shakespeare used cannabis, but they do add a new layer of intrigue to his life and creative process. Some critics contend that ascribing Shakespeare's extraordinary brilliance to cannabis oversimplifies the nature of his artistic mastery. Additionally, they argue that the absence of definitive evidence of the presence of cannabis in pipes linked directly to Shakespeare himself makes the connection between his genius and use of cannabis even more tenuous. Thackeray himself remains cautious about drawing definitive conclusions. He acknowledges that while the evidence is compelling, it's crucial to approach the topic with critical analysis and avoid romanticising the potential link between Shakespeare and cannabis. "I was amazed by the degree of interest in this project. I have great respect for the academics who specialise in the study of Shakespeare’s work. We were extremely cautious in the research paper we published in the SAJS," said Thackeray, adding that despite the criticism, the theory remained strong based on the GCMS findings combined with literary analysis. Thackeray’s study has sparked a renewed interest in exploring the connection between historical figures and their potential use of mind-altering substances. The debate will undoubtedly continue, but one thing remains certain: the allure of Shakespeare's works and the mysteries surrounding his life will continue to captivate minds and confound students for generations to come. C

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