Kelly Chibale founded the Holistic Drug Discovery and Development (H3D) Centre at the University of Cape Town to hunt for new medicines for malaria, tuberculosis and antimicrobial resistance — ailments that hit Africa particularly hard. A Zambian by birth who trained and worked in the U.K. and U.S., Chibale says the search for drugs is like a fairy-tale quest: “You have to kiss many frogs before you meet the prince.” He returned to Cape Town in 1996 driven by a sense of calling to show that world-class research can be done from Africa, and he launched H3D in 2010.
H3D is unusual on the continent: it houses the chemistry, biology and drug-development capabilities needed to take early discoveries toward clinical testing. Chibale’s lab fills much of the seventh floor of the chemistry building, stocked with fume hoods, flasks, reagents and machines. Their approach is classic drug discovery at scale: screen enormous libraries of molecules — sometimes tens of thousands — using robots to dispense compounds and test whether any block a pathogen or disable a key enzyme. Promising hits are then optimized through medicinal chemistry to improve potency and selectivity, keeping an eye on killing the parasite without harming mammalian cells.
A little more than a decade ago, that process produced a promising malaria candidate that entered human clinical trials in South Africa and Ethiopia. Tests in rats later raised safety concerns because the drug’s mechanism targeted an enzyme also present in humans, so development was halted out of caution. The episode demonstrated both the potential and the challenges of drug discovery.
Beyond finding molecules, Chibale’s mission is to build capacity so Africa can develop and keep scientific talent. H3D now employs more than 75 people from across the continent, including Mathew Njoroge from Kenya and Mwila Mulubwa from Zambia. Njoroge helps determine appropriate dosing by studying how drugs are absorbed, metabolized and excreted — crucial work because Africa is the most genetically diverse continent and populations can process drugs differently. That diversity means dosing and safety profiles derived elsewhere may not translate directly to African populations.
Practical obstacles complicate this work. In many Western countries, donated human livers are used to test metabolism before trials; across much of Africa organ donation is less common for cultural and historical reasons. H3D therefore works with a limited number of liver samples already collected and relies on computer models to simulate metabolism across African subpopulations and predict optimized doses. These steps are part of the elaborate pipeline needed to move a drug from the bench to patients.
International colleagues praise H3D’s scope and ambition. Philip Rosenthal, a malaria researcher at UCSF, calls it “the leading center in the world for comprehensive drug discovery and development for diseases of the developing world.” Mohammad Shafiul Alam of icddr,b in Bangladesh says the center’s model could be replicated across the Global South and urges more partnerships with groups in Asia and Latin America. Given that Africa bears the bulk of global malaria cases and deaths, regional institutions leading drug discovery are particularly important.
Chibale’s personal history reinforces the center’s purpose: as a child he survived a severe malaria infection that left a lasting impression. He recalls later recognizing that his recovery depended on medicines developed by others and on volunteer clinical trial participants. Now he aims to be part of that cycle — discovering medicines that will save lives in his region.
H3D’s work combines technical rigor with a broader goal: to make drug discovery relevant to African health priorities and to create opportunities that keep researchers on the continent. The center’s integrated facilities, multinational staff and collaborations show a path for locally led science to contribute directly to combating diseases that disproportionately affect the Global South.
Reporting for this story was supported by a grant from the Pulitzer Center.