Kelly Chibale compares the hunt for new medicines to a fairy-tale quest: long, patient work with occasional surprises. The goal at the Holistic Drug Discovery and Development (H3D) Centre, which he founded at the University of Cape Town and now directs, is exactly that—finding new treatments for malaria, tuberculosis and antimicrobial resistance, ailments that disproportionately affect Africa.
Chibale, a Zambian trained in the U.K. and U.S., fell in love with organic chemistry early on. He came to see drugs as molecules with structures that can be built and refined in the lab. After witnessing the robust drug-discovery pipelines in wealthier countries—and how those systems tended to set priorities for which diseases are addressed—he felt a calling to return to Africa and show that world-class research could be done there. He accepted a faculty position at UCT in 1996 and established H3D in 2010.
H3D is unusual on the continent: it assembles the tools needed for end-to-end drug discovery. Its labs, spread across a chemistry building floor, are filled with fume hoods, flasks, automated dispensers and machines used to screen and optimize compounds. The team screens enormous libraries of molecules—sometimes tens of thousands—using robots to test whether any compound can stop a pathogen or disable a key enzyme. Promising hits are chemically refined to improve potency and selectivity, focusing on molecules that kill parasites but spare normal mammalian cells.
That approach yielded a milestone: a candidate malaria drug discovered by an Africa-led effort moved into human clinical trials first in South Africa and then in Ethiopia. Ultimately development stopped after safety concerns arose in animal studies; the compound targeted an enzyme present in both the parasite and the human host, and the team halted work out of caution. Still, it marked the first time a project led from Africa had progressed from lab discovery to clinical testing.
Beyond discovering compounds, H3D aims to build capacity and retain scientific talent on the continent. The center employs more than 75 people and attracts researchers from across Africa. Mathew Njoroge, originally from Kenya, is part of that team. He says the center gives optimism about what drug discovery in Africa might become.
A critical part of development is understanding how drugs behave in different populations—how they are absorbed, metabolized and excreted—so dosing is safe and effective. Mwila Mulubwa, a drug scientist at H3D who grew up in Zambia, notes that Africa is the most genetically diverse continent. Different subpopulations can metabolize drugs differently, so assuming a one-size-fits-all dose risks ineffectiveness or harm. Ideally, dosing strategies use liver samples from the tested population, since the liver breaks down most drugs.
Collecting those samples is harder in much of Africa. Cultural beliefs about bodily integrity, historical mistrust of research and taboos around organ donation limit access to donated tissues. H3D works with a small number of available liver samples and supplements them with computer models that simulate metabolism in African populations to predict optimized doses. These approaches are part of a broader, complex pipeline needed to move a drug from discovery to the people who need it.
Colleagues abroad have taken notice. Philip Rosenthal, a malaria researcher at UCSF who collaborated with Chibale, calls H3D “the leading center in the world for comprehensive drug discovery and development for diseases of the developing world.” Mohammad Shafiul Alam, a parasitologist at icddr,b in Bangladesh, says H3D’s model is encouraging and potentially replicable in other parts of the Global South; he hopes to see more partnerships across Asia and Latin America.
For Chibale, the work is personal. As a child he survived a severe malaria infection and later reflected on the chain that led to his recovery: someone invested in discovering the medicine, and strangers who volunteered for clinical trials. That memory fuels his commitment to bring discovery and development closer to patients in Africa, emphasizing the two-way path between the clinic and the lab—patients informing research priorities and research delivering locally relevant treatments.
Reporting for this story was supported by a grant from the Pulitzer Center.