Kelly Chibale
South Africa has a strong reputation in the basic science and clinical studies of various diseases – but it has battled to translate this reputation into new medicines.
In fact, Africa as a whole lacks the modern skills in drug discovery that will allow the continent to address the increasing economic impact of its most prevalent diseases.
Those who do have such skills tend to look overseas for a living because of the limited job opportunities in pharmaceutical research and development in their home countries.
So it makes sense, in terms of economic and social development, capacity building and knowledge transfer, and medical need, to build a holistic centre to support and accelerate pharmaceutical research in South Africa. For these reasons, in April the University of Cape Town (UCT) launched the H3-D Drug Discovery and Development Centre.
H3-D (the H stands for holistic) aims to offer research infrastructure comparable in quality to that of overseas centres. With appropriate investment, it can play a significant role in creating jobs and stemming the brain drain of highly skilled Africans in the pharmaceutical field, while attracting expertise from other parts of the world.
Put simply, a drug discovery centre bridges the gap between the basic and clinical studies, integrating a number of scientific disciplines: biology, pharmacology, medicinal chemistry, synthetic chemistry, computational chemistry, as well as drug metabolism and pharmaco-kinetic studies.
These skills go towards designing molecules that contribute to the creation and delivery of new drugs.
H3-D will create a value chain and a skilled base of expertise and modern technology platforms to assist researchers in tackling the disease burden not only of Africa, but also other parts of the world. In doing so, H3-D will compete with similar initiatives in western and Asian countries – in many cases offering the same services and skills at a lower cost because of the exchange rate.
Strong drivers contributed to the establishment of H3-D. The local government adopted the National Biotechnology Strategy in 2001 and the National Research and Development Strategy in 2002.
The latter identified the creation of viable biopharmaceutical industries as priorities to help fight diseases prevalent in this country.
The South African Research Chairs Initiative (SARChI) – created by the Department of Science and Technology and administered through the National Research Foundation – was initiated to make South Africa competitive in the international knowledge economy.
As the founder of H3-D, I have the honour of holding the new SARChI chair in drug discovery, established to concentrate on the discovery and pre-clinical development of novel potential treatments for major communicable diseases in South Africa; the building of capacity and competency in the relevant areas of drug discovery; and the provision of leadership in medicinal chemistry.
The academic community also contributed to the founding of H3-D. In addition to UCT, other universities are producing research and graduates able to contribute to South Africa’s budding industry.
Stellenbosch University, Cambridge, other academic institutions and non-profit organisations (NGOs) will work closely with the centre.
Private industry is another driver. Pharmaceutical firms like Pfizer and Novartis became involved at the early stages of planning H3-D, as did NGOs such as Medicines for Malaria Venture (MMV) and the South African government-funded Technology Innovation Agency (TIA), in part to ensure that the facilities will be of a high international standard.
H3-D builds on a history of drug discovery and development in South Africa.
In 2009, the first SA Medical Research Council/UCT drug discovery and development unit was established to introduce technology platforms that would allow the exploration of the potential of African natural products from various biodiversity sources, including traditional medicines.
Funding for various initiatives was provided by Cape Biotech Trust, which is now part of the TIA, and by MMV, as well as the EU and the World Health Organisation Tropical Diseases Research.
African traditional medicines will be one of the research areas at H3-D from a safety point of view.
There are few studies of chronic safety data for most traditional medicines on the continent, and this lack raises concerns in the medical community.
It is both dangerous and irresponsible to promote the continued use of traditional medicines without rigorous scientific reassessment.
For example, the use of traditional medicines can interfere with the performance of conventional drugs when both are taken together. St John’s Wort (SJW) is a herbal remedy widely used for the treatment of depression.
Scientific studies have demonstrated that SJW extracts increase the metabolism and the premature clearance of various drugs, including antiretrovirals, oral contraceptives and cyclosporine, a drug used in hospitals for kidney and liver transplants.
Similarly, ginseng is known to reduce the anticoagulant effect of the drug warfarin, thus complicating the effectiveness of the drug.
Such interactions present an opportunity to bring modern drug discovery technologies to bear on African traditional medicines.
Drug discovery and development tools can allow us to reassess historical traditional medicines, evaluate potential new ones, and help identify treatment failure and toxicity related to interactions when patients use traditional medicines with conventional drugs.
But the discovery of drugs takes time and money; I compare it to a princess kissing many frogs before she finds the one that will turn into a prince.
The cost of producing one drug can be as high as $1 billion (R7bn) – and it takes a pharmaceutical company an average of 12 years to 14 years to successfully reach the market from inception. There are, of course, rare exceptions to this long timeframe.
Typically, a vast number of molecules are studied before one successful drug is identified; in the clinical phase a success rate of just one in 5 000 is not surprising.
The challenge is to shorten the time it takes to identify a preclinical drug candidate, to speed up its development and eventual marketing. That is the challenge H3-D is taking on.
Kelly Chibale is the founder and director of H3-D; a professor of organic chemistry at UCT, where he holds the SARChI chair in drug discovery; and the director of the SA Medical Research Council drug discovery and development research unit. He is also a full member of the UCT Institute of Infectious Disease and Molecular Medicine. His current research interests lie in the discovery of potential drugs that fight malaria, tuberculosis, cancer and cardiovascular disease.