Kelly Chibale says that the hunt for new drugs is kind of like a fairy-tale quest. And it takes a lot of time and patience. "It doesn't mean that there aren't surprises or miracles," he says. "They do happen, but you have to kiss many frogs before you meet the prince."
The "prince" might just be a new medicine to treat malaria or tuberculosis.
This search is what motivated Chibale to found the Holistic Drug Discovery and Development (H3D) Centre at the University of Cape Town in South Africa, where he currently serves as director.
The discovery of new medicines often takes place in North America, Europe and Asia. So that's where the agenda tends to be set for which diseases to treat and who benefits. But Chibale says H3D is a rare facility in Africa with everything needed to discover drugs for some of humanity's most intractable ailments.
For the 61-year-old Zambian, it's a natural outgrowth of his love of chemistry. When he was a student and started visualizing molecules and puzzling through how to transform one into another, he knew that he had found his cerebral soulmate.
Chibale grabs a chemistry book off the shelf in his office and riffles through a parade of molecules — each one like an old friend.
"Calicheamicin, zaragozic acid, taxol, brevetoxin B even — all of them are here!," he exclaims.
"It's a science, but it's also an art. And that's what really fascinates me about organic chemistry, and I fell in love. When you fall in love, you can't explain," he says with a laugh.
That love affair is what led Chibale to found his center so he and his team can go, in his words, drug hunting. "When you go hunting, you are hungry," he says.
And he's confident that this unrelenting hunt and hunger will pay off before long.
A return to Africa
Chibale moved to the U.K. and U.S. for graduate school and to work as a researcher. That's when he was struck by the connection between organic chemistry and the making of complex pharmaceuticals.
"What is a drug? It's a molecule. And a molecule has a chemical structure," he says. With effort, such a structure might just be built in the lab.
"So when you see these Mount Everest of molecules that have been made, it's incredible," says Chibale. "I mean, these things are just beautiful. There's no ugliness in molecules."
During the time that he was abroad, he also witnessed up close the powerful pipeline of drug discovery that exists in the wealthier countries of the Global North. He says, "I saw the pharmaceutical industry employing thousands and thousands of scientists working in research and development" — and tackling the health challenges relevant to those populations.
Chibale knew that this wasn't the case in Africa, a continent that struggles with its own afflictions, alongside limited funding, infrastructure and technical know-how.
As Chibale was wrapping up a stint in California, he considered jobs at Western pharmaceutical companies. Then he chanced upon a faculty positionat the University of Cape Town, and something stirred inside him.
"I just felt this calling," he remembers. "It wasn't from my head, it was from my spirit. I felt it. To come and inspire and show that it's possible to do world-class research out of Africa."
One of his mentors in the U.S. was stunned that he was even considering it. Chibale recalls him saying, "'Africa? You wanna go back to Africa?' He meant well, he was looking out for me."
Chibale came for an interview. "I didn't take long to accept the position," he says. "I knew this is where I needed to be.
That was 1996. Chibale founded the Holistic Drug Discovery and Development Centre in 2010.
"It doesn't matter who you are and where you are," he says. "If you create something that is valuable, people will come."
Focusing on molecules
Part of Chibale's laboratory fills a good portion of the seventh floor of the chemistry building at the University of Cape Town. He walks past fume hoods, flasks, numerous bottles of reagents, and all manner of machines that he and his team are using in their pursuit of new medicines to combat malaria, tuberculosis and antimicrobial resistance. "These diseases are very prevalent on my continent," he says.
Here's their approach: The researchers take enormous numbers of molecules (sometimes tens of thousands) and, using robots that precisely dispense those compounds, look to see whether any of them can thwart the pathogen in question or incapacitate one of its key enzymes.
"We focus on those molecules that selectively kill the parasite and not harm normal mammalian cells," Chibale explains.
Then his team tweaks the most promising molecules to see if they can make them even more potent until they have an ace in the hand. This was the approach that, a little more than a decade ago, surfaced a promising new kind of malaria drug that entered clinical trials first in South Africa and then in Ethiopia.
"It was the first time that an Africa-led international effort took a project from the lab and discovered a drug that entered human clinical trials — for any disease," Chibale says.
Safety concerns ultimately arose in rat studies so further testing stopped. "The decision to halt development was out of caution since we discovered a novel mechanism of killing the parasite by targeting an enzyme in the parasite that is also in the human host," says Chibale.
Keeping the talent
Chibale is searching for new medicines in Africa where he can focus on improving the health outcomes of Africans and staunching the bleeding of talent from the continent overseas. It's a trend that nearly made him decamp permanently to the West.
"If we can create this absorptive capacity in Africa to attract the talent, to develop it, to nurture it, we can keep the talent here," he says.
The center currently employs more than 75 people, including Mathew Njoroge, a scientist originally from Kenya. "It gives us all a lot of optimism about what the future of drug discovery in Africa might look like," he says.
Njoroge's job is to help calculate the appropriate dose of a drug to give to a patient by determining how it's absorbed by the body, processed or metabolized, and excreted. This is a crucial step in developing a new medicine because if it's tested in one group of people, it may not work in another population. It might even be dangerous. This is especially true in Africa, which Chibale says is "the most genetically diverse continent on planet Earth."
"We don't treat Africa as a homogeneous population like the way it is with Caucasians," says Mwila Mulubwa, a drug scientist at the center who grew up in Zambia. "There are a lot of distinct subpopulations who can metabolize a drug differently."
When testing a new medicine, the correct dose tends to be determined using liver samples that have been donated from the patient population in question. "The liver is the organ that breaks down most of the drugs," says Mulubwa.
In a country like the U.S., organ donation provides enough livers to test drugs on before they go to human trial. Such a practice is largely seen as taboo across Africa, however.
"There is that culture around the integrity of the body, so we might not feel comfortable donating organs," explains Njoroge. "But there is also a lack of trust sometimes of the scientific process" due, he says, in large part, to historical reasons.
So the team in Cape Town is working with a small number of liver samples that have already been collected while also running computer models to simulate the metabolism of African populations and predict an optimized dose. This is but one part of the elaborate process required to develop a drug and bring it to the people who need it.
"It's extraordinary"
Philip Rosenthal is a malaria researcher at UCSF who's followed Chibale's career and collaborated with him years ago. When he reflects on the H3D Centre in Cape Town, he's excited to see it playing on the same stage as other academic and pharmaceutical institutions in the Global North.
"It must be the leading center in the world for comprehensive drug discovery and development for diseases of the developing world," he says. "It's extraordinary. I know the rest of Africa pretty well and there's absolutely nothing like this."
"Their story is very encouraging," says Mohammad Shafiul Alam, a parasitologist working on malarial diagnostics and drugs at icddr,b, an international health research institute based in Dhaka, Bangladesh. And the model "should be replicable to other parts of the world, particularly in the Global South." As a first step, he hopes to see the center develop additional partnerships with research groups across Asia and Latin America.
Given that the African continent experiences the bulk of malaria cases and deaths worldwide, Alam says the work of the H3D Centre is critical. "So it's very important that the African countries and their institutions, they come forward to tackle this," he says, "in this challenging world when the funding is constrained."
Chibale agrees. "It's not just going from the lab to the patient, but it's also vice versa, from the patient back into the lab," he says.
In fact, when he was a child, Chibale was one of those patients, battling a particularly serious malaria infection. He recalls being wheeled into the hospital in Zambia, hearing of other children dying quickly from the same disease.
The doctors gave Chibale the medications he so desperately needed.
"And I took it for granted," he says. "Only much later in life did I realize two things. Number one, someone, somewhere in the world invested to discover and develop that medicine. The second thing was the fact that someone, somewhere, another human being I don't even know, volunteered to participate in a clinical trial for my benefit."
Chibale ended up making a full recovery. And now, he is that someone, committed to discovering new medicines to heal his neighbors.
Reporting for this story was supported by a grant from the Pulitzer Center.
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