A chemical attraction

05 December 2019 | Story Sue Segar. Photo Je'nine May. Read time >10 min.
 Chemistry Professor Kelly Chibale is founder and director of Africa’s first integrated drug discovery centre.
Chemistry Professor Kelly Chibale is founder and director of Africa’s first integrated drug discovery centre.

“I see molecules everywhere – in hair, in clothes, in everything. It  fascinates me that you can look at a molecule’s chemical structure and modify the bonds and structures to modify the properties of molecules. Then those new structures can be used for something terrible, like bombs, or for something wonderful, like foods and medicines.”

Sitting in his office at the University of Cape Town (UCT), Chemistry Professor Kelly Chibale, founder and director of Africa’s first integrated drug discovery centre, UCT’s Holistic Drug Discovery and Development Centre (H3D), spoke about his love for organic chemistry, which started during his childhood in Zambia.

“I simply fell in love with it. It was just like the way I fell in love with my wife Bertha. When you fall in love, you don’t plan!”

He related how, despite his background of extreme poverty in Zambia – and some serious setbacks in childhood – he was exposed to an excellent education system which made all the difference to his life.

 

“When I look back, I know I was born to be a chemist.”

“At high school we had an excellent chemistry teacher. The government of Kenneth Kaunda brought great teachers from countries like the UK and India, really educated people. They became role models.

“When I look back, I know I was born to be a chemist.”

Nearly ten years ago Chibale founded UCT’s H3D, which hosts more than 60 people, including staff and post-doctoral scientists. It is effectively run like an innovative pharmaceutical company albeit within an academic environment. In 2017 it became the first African centre to lead an international team that discovered and put an antimalarial drug into Phase II human clinical trials. This drug is being watched closely globally as it has the potential to cure, block transmission and protect from malaria in a single dose.

Today, Chibale is a member of the Royal Society of Chemistry; he holds an A rating by the SA National Research Foundation which means he’s recognised internationally as a leading scholar in his field; in 2018 he was named by Fortune as one of the top 50 World’s Greatest Leaders.

But he believes his most significant achievement to date lies in efforts to establish the H3D African Drug Metabolism and Disposition Project – otherwise known as the African Liver and Microbiome Project – which was launched earlier this year. Anticipated as a game-changer in African medicine, the project aims to lead to tailor-made medicines and more appropriate drug dosages and dosage intervals for different African populations.

Growing up in Zambia

In our interview, Zambian-born Chibale described his childhood as the son of a single mother raised in extreme poverty. He spoke about his determination to overcome the hardships of his youth; his conviction that drug discovery in Africa can, apart from finding medical solutions, create thousands of jobs; and about his commitment to confront Afro-pessimism.

Opening up about his faith, Chibane quoted the words of the French biologist, microbiologist and chemist Louis Pasteur, one of his role models and a believer in God: “A little science takes you away from God; more of it takes you closer to God. The deeper you go into science and medicine the more amazed you are at the work of the Creator. Science can explain something that cannot be explained,” Pasteur wrote.

 

“Nobody has a monopoly on suffering.”

Chibale, who has been at UCT for 23 years, also discussed his role as warden of student residence Smuts Hall, a position he was awarded in 2015 at the height of the Fees Must Fall movement. (He lives with his family in the warden’s lodge, not far from his office.)

"I guess God saw it fit that I was the right guy for the job.”

He spoke of his connection with the students – and about the recent developments on campus relating to gender-based violence. “Many students can relate to my under-privileged background once they find out about it. My message for them is that if they want things to change in their own lives and in the institutions they inhabit, they must get involved – don’t lash out – and focus on the opportunities. Nobody has a monopoly on suffering.

“The recent developments highlight the appalling rate of gender-based violence (GBV) in South Africa and on university campuses. I’ve seen male students and staff appraising their attitudes and actions – a new unity, solidarity among female students, resulting in more women students having the courage to bring their concerns to the fore.”

Chibale also spoke about his friendship with Neville Isdell, UCT alumnus and former chief executive and chairman of Coca-Cola, who last year donated about R18 million to H3D. The donation is being used to set up a five-year Neville Isdell Chair in African-centric Drug Discovery and Development at H3D. Chibale will hold the chair, which includes the directorship of H3D. His task is to provide leadership in establishing platforms that allow the customisation of medicines to the needs of the African patient population. 

 

“The medicines we have always used on this continent, which have gone through human clinical development, are never optimised for the African patient population.”

“The money will be pivotal to the discovery of new medicines in the centre,” said Chibale.

African-centric drug discovery

The work on the African Drug Metabolism and Disposition Project is even more important than its studies into malaria because this is “not even about the disease,” said Chibale.

“People talk about precision medicine, or personalised medicine but when you talk about Africans, the African in southern Africa is not the same African as in East Africa. Africans are probably the most genetically diverse population. South Africa alone is one of the most diverse countries from a genetic perspective. This is not about race but genetics and genetic differences.

“In general, when you compare the number of clinical trials that happen globally – when you test potential medicines in people to see whether they work and are safe – less than 2% of these happen in Africa. This means the African patient population does not contribute to the data because the medicines are not trialled properly on this population. It’s a neglected population from this perspective. As Africans we are not getting the full benefit of these trials. The bottom line is: What is the dose or dosing regimen that will be optimal for you as an individual and in this context as an African individual or African population?

“The medicines we have always used on this continent, which have gone through human clinical development, are never optimised for the African patient population.  Most medicines are studied in clinical trials in volunteers and patients in the global North – the dosing regimens (dosage and dosage intervals) are optimised there, and then the therapies are brought into Africa.”

The funding from Isdell for the African Liver Project will, importantly, look at the variability in the way African populations respond to medicine as a result of genetic differences in the different forms of the enzymes that metabolise the drugs in the liver. On the other hand, the African Microbiome Project focuses on the microorganisms in a particular environment (including the body or a part of it) in the African population.

“Humans depend on a vast army of microbes to stay alive: a microbiome that protects us against germs, breaks down food to release energy, and produces vitamins. Microbiome diversity impacts metabolism, efficacy and side-effect profiles of medicines.”

Chibale said he hopes the centre’s work could eventually lead to customised medicines and better drug dosage for various African populations. His work in this area, too, is attracting global attention. He paid warm tribute to Isdell, “my greatest CEO role model, who came out of retirement and saved the Coca-Cola company”. 

Isdell, who started his studies at UCT in 1961, became known as a formidable first-team rugby lock. For years he has been a patron of the UCT Rugby Football Club. (He is currently its 13th president.)

He and Isdell have become good friends, he says. “I met him in 2016. I’d read about him. We discovered we had lots in common when we first met. Neville was born in Ireland and, like me, came from humble beginnings. He moved to Zambia aged eight. He married and began his career with Coca-Cola in Zambia. So we both started our lives in Zambia. The second thing we have in common is Smuts Hall, where he was in residence as a student and where I am warden. Thirdly, Neville has a foundation aimed at eliminating malaria in the SADC countries, supporting the poorest of the poor and working with community leaders. His donation is going to make a massive difference. We are constantly in touch.”

During the interview, Chibale spoke about how, more than a decade ago, he had a vision for an integrated drug discovery centre. Highly aware that, as an academic, he was unprepared for such a large enterprise, he spent a mini-sabbatical at pharmaceutical company Pfizer in the UK, to learn how drug discovery and development works, before commissioning a business plan for H3D.

 

“There is huge potential to create jobs in science in Africa. We could create hundreds of thousands of jobs, depending on how we grow the industry.”

His dream was to create an infrastructure that had not existed before in Africa, an integrated platform, “because, discovering a medicine is not the end of the story”. He explained: “We can be trying to solve malaria one day and working on another disease another day – cancer, diabetes. For me, it’s about laying a foundation in terms of infrastructure, building the technologies and a critical mass of skilled scientists. 

“In Africa to date we’ve had the two extremes: we do clinical trials because that’s where the patients are, and we do basic science research in a lab. There’s been nothing translational vis-à-vis innovative drug discovery, which is what we are doing here. My dream was to expand our capacity so that the skills and technologies are transferrable from disease to disease.

“It’s always been about being able to create the infrastructure so that we can do it again and again. For me it’s also about creating jobs. There is huge potential to create jobs in science in Africa. We could create hundreds of thousands of jobs, depending on how we grow the industry.”

The centre’s drug discovery for malaria started years ago with the task of identifying molecules that can kill the malaria parasites, starting with a library of about 35 000 molecules. The researchers moved from the test tube to testing which active molecules could kill malaria parasites in a living animal.

Fast forward to 2012 when a compound initially identified by Chibale’s team as a frontrunner – a molecule with the code MMV01007,  or the James Bond molecule, as they called it – had been optimised to be tested in humans, drawing widespread attention.

A cutting-edge pharmaceutical company

In 2014, Phase 1  trials began on the molecule now known as MMV390048 at UCT. In 2016, the first volunteer infection study in healthy subjects using the human malaria parasite induced blood stage malaria (IBSM) model was conducted in Australia (because of the lack of facilities in Africa). This is where a small number of healthy volunteers are infected with a strain of the malaria parasite that can be treated with established medicines and then treated with the trial drug. These studies found that the drug was well tolerated by people and that it treated malaria.

In 2017, a Phase 2 study of the new drug kicked off in Ethiopia. The results will determine whether the drug can be tested in larger groups of malaria patients in Phase 3. If this drug is able to treat malaria as well as existing treatments, it can be licensed for use, combined with other medicines.

Chibale’s pride in this development in particular relates to the fact that this is the first time an international team led by an African enterprise has taken a molecule from screening to clinical trials.

 

“We happen to be based at UCT but essentially we operate like an innovative, cutting-edge pharmaceutical company.”

The H3D centre also does research into drugs for tuberculosis, antibiotic-resistant microbial diseases and neglected tropical diseases exemplified by schistosomiasis (bilharzia) .

When it was established in 2010, the unit had five academic postdoctoral research scientists. Today it comprises more than 90 researchers, including staff, postdoctoral research scientists and postgraduate students, has an annual budget of around R70m and attracts experts in drug discovery from around the globe to its cutting-edge facilities. 

The unit has a range of partnerships, including with the Bill and Melinda Gates Foundation; Medicines for Malaria Venture; Celgene; Merck; Novartis; and the South African government. What Chibale is most excited about is that the H3D is training a new generation of African scientists specialising in a range of areas from chemistry to biology and pharmacokinetics.

“We happen to be based at UCT but essentially we operate like an innovative, cutting-edge pharmaceutical company. This is unusual, even by world standards. We don’t have an innovative pharmaceutical company on this continent.”

If H3D stays on track, Chibale believes it could mean the end of seeing Africa as a place just for conducting human clinical trials for Western researchers. “A centre of excellence like this, doing its own research, could spearhead a pharmaceutical industry focused on the needs of Africans.”

Chibale calls himself a Scientific Leader. His vision is for H3D to be the leading organisation for integrated drug discovery and development on the African continent. “It is high time Africans started doing it for themselves. As Africans we like to blame the politicians and others for everything (albeit blame needs to be apportioned) but who is stopping us from doing innovative things? This is the problem. What’s stopping us from seeking our own solutions.”

Chibale and his wife Bertha have three sons. Bertha runs a catering company in Cape Town called Hearts and Tarts. 

Chibale is a soccer and boxing fan. He supports Liverpool in the English Premier League and Barcelona in La Liga.

  • Next year, H3D will host the 4th H3D Symposium to be held in Africa, which will coincide with the 10th anniversary of the launch of H3D. Its theme will be “Celebrating a Decade of Infectious Diseases Drug Discovery and Development”. 
This article was originally published by Noseweek.

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