Having grown up in the villages and townships of Zambia, Professor Kelly Chibale became well acquainted with the ravages of malaria at a young age. Now, inspired by a deep spirituality and a love of chemistry, his invaluable contribution to the ongoing battle against this disease – among others – has been awarded an A rating by the National Research Foundation.
“To know that peers in my field think so highly of me is humbling,” says Chibale, adding that “although this means a lot to me personally, the work on which my rating is based is not mine alone. It is a result of a collective effort … I share this A rating with all my collaborators. I could not have done it without God and them.”
With an academic background in chemistry, the main thrust of Chibale’s research in recent years can be described as drug discovery for communicable parasitic and bacterial diseases – the former including malaria and schistosomiasis (or bilharzia), the latter tuberculosis and other drug-resistant infections of bacterial origin.
Since Africa suffers a particularly heavy burden where these diseases are concerned, Chibale’s research and its implementation has benefited the continent greatly.
“Our use-inspired drug discovery basic science research has led to historical scientific breakthroughs and, in the process, advanced both basic and clinical sciences at several levels,” he says.
Using both genomic and proteomic approaches to clarify how new drugs work through the identification of their biological target, Chibale and his lab have contributed to fundamental understanding and basic scientific knowledge.
Within the context of malaria, these approaches led to the identification of the human malaria parasite enzyme known as PfPI4K as the target for MMV048, an antimalarial clinical drug candidate that was found to be effective against resistant strains and with activity across the entire parasite life cycle. It was also shown to have the potential to cure and protect in a single dose due to its inhibition of PfPI4K, which is involved in the correct membrane assembly around daughter parasites as they leave infected human red blood cells (RBCs) to infect other healthy RBCs. Inhibition of PfPI4K results in defects in the new plasma membrane.
Chibale and his team’s work around MMV048 has been significant for a number of reasons. It was the first time a chemical proteomics approach was used to identify a malaria drug target; MMV048 was the first and only molecule that reduces the activity of the PfPI4K enzyme to have progressed to Phase I human clinical studies and it is the first known malaria kinase inhibitor to enter the clinic. Lastly, the advancement of MMV048 marks the first time an Africa-led international drug development effort has taken a small molecule from screening through to human clinical trials, all through modern drug discovery techniques.
In 2016, H3D and its partners identified a second preclinical development candidate – UCT943 – which may be even more potent against the malaria parasite and easier to formulate.
Establishment of H3D
It is Chibale’s establishment of UCT’s Drug Discovery and Development Centre (H3D) – of which he is director – that has made much of this research possible.
Set up to bridge the gap between laboratory and patient, H3D integrates medicinal chemistry, biology, pharmacology as well as drug metabolism and pharmacokinetics studies. It is the first and only centre of its kind on the African continent and also one of the rare integrated drug discovery centres set up within an academic environment worldwide.
It is hardly surprising, then, that Chibale is an absolute believer in the power of partnership.
“I believe God created us to not only partner with him as our creator, but also partner with each other to tackle complex human challenges and contribute to alleviating human suffering,” Chibale explains, simultaneously offering insight into the deep-seated spirituality that drives his work.
H3D’s integrated approach has proven to be hugely beneficial in that the lab has no need to operate self-sufficiently, but can tap into a large network of partners.
Since its founding in 2010, H3D has also played a major role in changing perceptions around health innovation in Africa.
“It has been important to confront Afro-pessimism and debunk the myth that Africa is not, and cannot be, a source of health innovation, for example in the discovery new medicines. We have been working hard to prove that this continent has more to offer than the mere opportunity for human clinical trials,” Chibale explains.
He believes that it is vital for Africans to contribute to finding solutions for their continent’s health problems and, in the process, contribute to economic growth.
This connects strongly with Chibale’s future hope for stronger encouragement of entrepreneurship in science.
“There are large numbers of African scientists graduating, as well as a large number that forms part of the African diaspora; supporting scientific entrepreneurship can help move the continent forward,” he says.
Falling in love with chemistry
In order to get to this point in his academic career, Chibale has undertaken a journey with many stations – including the University of Cambridge where he completed his PhD, the University of Liverpool for a postdoctoral fellowship, as well as the Scripps Research Institute in the USA. It was the latter that truly sparked his interest in drug discovery and development, where his work with KC Nicolaou allowed him to help design and synthesise molecules that interfered with the growth and development of new blood vessels, triggered by cancer cells as a mechanism for their own growth and survival.
However, it was Chibale’s pure love for chemistry in high school and later organic chemistry as an undergraduate student at the University of Zambia that really helped him find his calling.
“I simply fell in love with organic chemistry and was drawn to it naturally. It was just like the way I fell in love with my wife Bertha. When you fall in love, you don’t plan. You simply fall in love."
As for his choice to pursue a career in academic research, Chibale cites creativity and freedom of thought as the main draw cards.
“There are three things I really enjoy about my job: firstly, the beauty of academic freedom – no one can stop me from thinking creatively! Secondly, with the patient at the centre of my research, there’s a sense of urgency about my work. Lastly, I have never stopped learning thanks to my colleagues and students.”
With the brand new A rating behind his name, Chibale looks forward to continuing his efforts to inspire and train the next generation of African drug developers, while also continuing to create the much needed science jobs.
Words of advice
Finally, Chibale has three pieces of advice for young African researchers. Firstly, make the most of every opportunity – you never know where each will lead. Secondly, be consistent and stick to what you believe. Lastly, “you will always have critics and naysayers – remember to run your own race because you were uniquely created by God to run your own race and not someone else’s.”
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