Kelly Chibale likens the search for new medicines to a long, patient fairy-tale quest—one in which progress comes slowly and surprises arrive unexpectedly. That metaphor guides the Holistic Drug Discovery and Development (H3D) Centre, which he founded at the University of Cape Town and now directs. H3D’s mission is straightforward: discover and develop treatments for malaria, tuberculosis and antimicrobial resistance—diseases that take a disproportionate toll on Africa.
Chibale, a Zambian chemist trained in the U.K. and U.S., fell in love with organic chemistry early and came to see drugs as molecules whose shapes and functions can be constructed and refined in the lab. After observing well-resourced drug-discovery pipelines abroad—and how those systems often set global priorities—he returned to Africa to prove that world-class discovery could be done on the continent. He joined UCT in 1996 and established H3D in 2010.
H3D is rare in Africa because it assembles the tools for end-to-end drug discovery under one roof. Its labs, spread along a chemistry-building floor, are equipped with fume hoods, flasks, automated dispensers and high-throughput screening instruments. The team sifts through enormous libraries of molecules—sometimes tens of thousands—using robotics to identify compounds that stop a pathogen or inhibit a target enzyme. Promising “hits” are then chemically optimized for potency and selectivity, prioritizing molecules that kill parasites while sparing normal human cells.
That model produced a milestone: an Africa-led candidate antimalarial that advanced into human clinical trials, first in South Africa and later in Ethiopia. Development was eventually halted after animal studies raised safety concerns: the compound targeted an enzyme found in both parasite and human host, and the team chose caution. Still, the project marked the first time a discovery initiated and led in Africa reached clinical testing.
H3D’s goals go beyond single compounds. The center seeks to build scientific capacity and retain talent on the continent. It employs more than 75 people and draws researchers from across Africa. Team members like Mathew Njoroge, originally from Kenya, say the center gives them optimism about what African drug discovery can become.
A crucial and sometimes overlooked part of development is understanding how drugs behave in different populations—how they are absorbed, metabolized and excreted—so doses are safe and effective. Mwila Mulubwa, a drug scientist at H3D who grew up in Zambia, points out that Africa’s extreme genetic diversity means metabolic differences between subpopulations are likely. Treating dosing as one-size-fits-all risks ineffectiveness or harm. Ideally, dosing strategies are informed by liver samples from the populations being treated, because the liver metabolizes most drugs.
Obtaining those samples is difficult in many African settings. Cultural beliefs about bodily integrity, historical mistrust of research and taboos around organ donation restrict access to donated tissues. H3D works with a limited number of liver samples and supplements them with computational models that simulate drug metabolism across African populations to predict safer, more effective dosing. These tools are part of a complex pipeline that moves a molecule from bench to bedside.
The center has attracted international attention. Philip Rosenthal, a malaria researcher at UCSF who has collaborated with Chibale, regards H3D as a world leader in comprehensive drug discovery for diseases of the developing world. Mohammad Shafiul Alam, a parasitologist at icddr,b in Bangladesh, finds H3D’s integrated model encouraging and potentially replicable in other parts of the Global South, and he hopes it will spur more cross-regional partnerships.
For Chibale the work is deeply personal: as a child he survived severe malaria. He remembers the chain of investment, scientific effort and volunteer trial participants that produced the medicine that saved him. That memory drives his commitment to bring discovery and development closer to patients in Africa—linking clinical needs back to the lab and translating research into locally relevant treatments.
Reporting for this story was supported by a grant from the Pulitzer Center.