Opinionista

Africa is the most genetically diverse continent, and yet it is ignored in new drug research

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Dr Clinton Veale is a Royal Society-African Academy of Sciences FLAIR Research Fellow and Senior Lecturer in Organic Chemistry at the University of KwaZulu-Natal. His research focuses on the application of synthetic organic and biophysical chemistry methods for the design of new biologically active compounds. Prof Adrienne Edkins is South African Research Chair (SARChI) in Molecular and Cellular Biology of the Eukaryotic Stress Response, Newton Advanced Fellow of the Royal Academy of Medical Sciences, and Associate Professor of Biochemistry at Rhodes University, South Africa. She is a fellow of the African Academy of Sciences and a member of the Academy of Science of South Africa. Her research is focused on understanding the molecular basis of differences in stress responses in healthy and diseased cells.

Despite Africa representing the most human genetically diverse region on the planet, only 2% of genetic material used in medical research comes from the continent. Furthermore, Africa hosts very few clinical trials, which together means that clinical data used in the improvement of drug therapies largely excludes African populations.

Most of us will at one time or another, take medicine when we are not feeling well. But how much do we understand about how these medicines come about? Or how they produce the desired response? They don’t magically appear on the shelf of the clinic, but rather are developed over many years by teams of scientists from disciplines including chemistry, biochemistry, and biotechnology. The overall process is known as “drug discovery”, and it can take many forms.

Modern drug discovery often starts with an understanding of the biological processes that drive disease. It uses an understanding of the shapes and functions of molecules in our bodies to develop targeted medicines that recognise only those disease-associated molecules.

Traditionally, the approach has been a one-size-fits-all in the development of a new medicine. However, we are individuals, and so is our response to medicines. This individuality is driven at the level of the genetic blueprint coded in our DNA, known as our genome. The DNA in our cells is read like a recipe book and contains all the information required to make a human being.

The fact that individual humans have DNA that is 99.9% identical to each other is a testament to the fact that small genetic changes can make a big difference. While this may be obvious to us in terms of appearance, it is also true of the responses we may have to medicines. This is because most medicines, whether it is aspirin to treat a headache, or chemotherapy to treat cancer, have specific chemical shapes designed to be complementary to the shapes of disease-related molecules in our body in a lock-and-key manner.

Small genetic variations in the shape of the biological lock may mean that the key (or medicine) changes its effect, becoming either less effective or more toxic. The technological advances of the post-genomic era have allowed us to understand the links between genes and disease better than ever before, and to determine which genes we need to block to treat certain diseases.

It has also increased our appreciation that genetic differences influence individual responses to medicines, and a universal therapeutic approach may not be the most effective. Consequently, contemporary approaches to medicine, particularly the development of treatments for major health threats for like cancer and diabetes, are now aimed at personalisation based on an individual’s specific genetic background.

Infectious diseases, such as malaria, tuberculosis and HIV, are commonly perceived as the major health concerns in sub-Saharan Africa. However, rapid growth in the burden of non-infectious disease (also known as non-communicable diseases or NCDs for short) over the last two decades, means that NCDs are poised to become the leading causes of death in sub-Saharan Africa by 2030.

The complexity of drug discovery economics has traditionally been seen as a disincentive to develop medicines for populations of low and low-middle income countries who cannot afford expensive long term therapies.

Unfortunately, despite Africa representing the most human genetically diverse region on the planet, only 2% of genetic material used in medical research comes from Africa. Furthermore, Africa hosts very few clinical trials, which together means that clinical data used in the improvement of drug therapies largely excludes African populations.

Accordingly, this blatant lack of Afrocentricity means that the data used in the production of new therapies largely excludes a detailed consideration of genetic backgrounds from African populations, resulting in medicines which may have increased adverse effects, or reduced drug effectiveness.

NCDs also have far-reaching implications for regional economic growth. Between 2006 and 2015 in South Africa alone, diabetes, stroke and coronary heart disease resulted in an estimated GDP loss of $1.88-billion.

While research into NCD therapies globally is allocated far greater resources in comparison to infectious disease, given the Eurocentric focus in the development of personalised therapies, African NCDs are still very much neglected diseases. Therefore, there is an urgent need to consider a wider diversity of genetic backgrounds during development of targeted medicines.

Large-scale initiatives have been launched to document and understand genetic diversity in African populations, and these data can be used to support an Afrocentric outlook toward NCDs. While currently this is being used as a means of optimising treatment regimens of currently available therapies, from an Afrocentric perspective, this information should also be used with the aim of developing and fine tuning new, effective therapies, designed specifically for the genetic backgrounds of African populations.

This, we hope, will not only translate into new medicines tailored to be the most effective for African patients, but also begin the process of embedding Afrocentricity into mainstream drug discovery.

The complexity of drug discovery economics has traditionally been seen as a disincentive to develop medicines for populations of low and low-middle income countries who cannot afford expensive long term therapies.

However, given growing affluence, and the fact that the African population is expected to increase from the current 17% of the world’s population to 40% by 2100, Africa represents a targeted medicine market that the pharmaceutical industry can no longer afford to ignore. DM

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