Charles Rotimi: Powering up African genetics research
Charles Rotimi - Image courtesy of Charles Rotimi and the National Human Genome Research Institute
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Kat: Charles Rotimi is the director of the Centre for Genomics and Global Health within the NIH National Human Genome Research Institute at Bethesda, Maryland in the US, and a distinguished NIH investigator. He’s also the founder of the African Society of Human Genetics and the driving force behind a major genomics project called Human Heredity and Health in Africa, or H3Africa, which he helped to establish ten years ago and is now wrapping up.
Kat: He’s certainly come a long way from his birthplace in Benin City in Nigeria, where he grew up as a curious child with a long-standing interest in science. Charles studied biochemistry at the University in his home town, but quickly realised that if he wanted to pursue his scientific training, he’d have to go further afield. He ended up in the US getting a PhD in epidemiology, including what was at the time the nascent field of genomics. From there, he ended up getting interested in a project called HapMap - a spin-off from the Human Genome Project, which allowed researchers to start teasing out the associations between genes and health.
Charles: My development from there in terms of genomics really started in my first participation in the HapMap project, where I engaged the African community, three African communities specifically, for the international HapMap project. That is the Yoruba community in Nigeria, and the Maasai community in Kenya and also the Luhya community in Kenya. And I think since then you can see that I was bitten by the genomic bug and it's been a wonderful journey since then. Yeah.
Kat: So tell me about the founding of the H3Africa. What made you realise that there was a project of this kind of scale and scope that needed to happen to understand the diversity of genomes in Africa? We say Africa, it's not a country, it's a continent. It's incredibly diverse. What was the drive and the impetus that started that project?
Charles: I think again, I'll take us back a little bit to the HapMap. During the HapMap projects, for me, I was extremely conscious of the fact that I was one or two or maximum three persons of African ancestry who were present in those discussions. So to me, that stopped with me and I did not, want that to continue. I wanted to create opportunity for African ancestry individuals to be a player in the genomic world. And also I was quite concerned that the genomic revolution may not benefit Africa if African scientists and the community members do not adequately participate in genomics. So that led us to the formation of the African society of human genetics, which actually created for the first time the forum for geneticists across Africa, and also non geneticists but interested in doing research in Africa, to come together and to create a forum for that discussion. So under the Africa study of human genetics we started, um thinking about what can we do to make sure that the genomic revolution did not fly over Africa physically. So we started thinking about doing an African genome project which subsequently developed into what we call H3Africa today.
Kat: So tell me a bit more about some of the work that was being done under H3Africa and some of the insights that came out of it. What did you actually discover along the way?
Charles: So we all know that we all, as human beings, if we trace our roots far back enough we all end up in Africa, so again, that contributed to the scope, wide scope of human genetic variation across Africa. So recently, as a result of sequencing over 18 ethno-linguistic group across Africa, especially among those populations that have not been a part of HapMap, and also thousand genome projects, we were able to make discoveries of 3 million new variants that is currently not in public databases. So again, just highlighting the critical importance of the systematic sampling of African genomes to fully understand human genetic variation. One of the things that enabled us to make this kind of discovery is that when humans migrated out of Africa about a hundred thousand years ago, that small group of humans that migrated, only took a subset or the variation that excited on the African continent.
Charles: So there are part of our human genetic inheritance that can only be studied in Africa populations, again just because of that evolutionary history. So we also make a discovery in terms of the part of our genome that has been under selection as a result of our ability to adapt to different environment. And we make discoveries about selective protective mechanisms in our genome. It gives things like viral infection, nematodes, infections, and even autoimmune response and pigmentation. So those were all very, very novel signs that H3Africa was indeed delivering on this Initiative. The medical aspects is going to come very soon because we have now genotype close to 60,000 individuals. And the analysis of that data set is ongoing for various diseases like kidney disease, sickle cell, stroke, uh, which is a major problem. So all of those are being analysed and we do hope that we'll make some novel discoveries that will really make us to understand how genetics interact with the environment to increase disease risk or resistance. Yeah.
Kat: Were there any things that were particularly surprising to you along this journey?
Charles: Yes, for me one of the main surprises, which was a very pleasant surprise, was the fact how ready African scientists were to take responsibility for this project. So I had suspected for some time, but it made it very clear that the issue is really not lack of training or lack of the ability to do this kind of work. It was really a issue of opportunity. And so the way African investigators rallied around this project and made it their own was absolutely a wonderful surprise for me. And a very good one because it really led to the success that it enjoys today.
Kat: So with all the information that's coming out, the insights that you're getting, the tools that you're being able to build to understand the genomes of all sorts of different African people. How do we turn all these insights into benefits, into better health? Because Africa is a very broad group of very different countries, including some of the very poorest communities on earth. And there are all sorts of health pressures there. You know, you have food scarcity, you have all sorts of diseases, you have war and conflict. And here in the in the UK, we're talking about genomics in the NHS and all these sort of very expensive, fancy tests and things like that. How do we really make genomics and all this research really useful for the public health benefit of people living in Africa.
Charles: I look at it as making incremental progress. I'll give you an example of where genomics has indeed helped quite in a very practical sense. And that is, if you remember the 2014 Ebola epidemic, there was a need to be able to sequence the pathogen in a timely manner. Part of the success story about the ability of African scientists to be able to do that work was the fact that H3Africa has indeed enabled laboratories to be set up that has genome sequencing capabilities. And again, with some additional funding from the world bank. So the scientist in Nigeria and other parts of Africa were able to do sequencing of the Ebola virus and able to track it as he was mutating and also as it was spreading across different parts.
Charles: So that was a very practical utilisation of genomics as a surveillance tool in a public health setting. Another major area is kidney, kidney disease. One of the devastating consequences of kidney disease in African ancestry populations is the APOL1 variant that is highly protective against African sleeping sickness (trypanosomiasis), but it is devastating to the kidney. But evolutionarily, you can see how that kind of variant rose to high-frequency because you would die first from African sleeping sickness before you die of kidney disease. Kidney disease, is a disease of old people or older people. Therefore it rose to high-frequency and now it's really putting people at increased risk of kidney failure. Since the African sleeping disease has been sort of taken care of quite significantly. So understanding that biology, what happens to make preventive strategies, and also perhaps develop some kind of therapeutics that will save a lot of Africans from getting kidney failure, because the possibility of putting people on dialysis is not a workable option because of just the cost.
Kat: So you set up H3Africa, 10 years ago, we're now in 2021, where would you like to see the field of African genomics in 2031? Just take a leap 10 years into the future. What's it like, what's your vision?
Charles: I would just, I would like to see it without boundaries. I just went to see it blow up and grow in any direction that is beneficial across Africa. I want it to be a part of the economic development. I want it to be a part of the scientific development infrastructure. I also would like Africa to be a part of the process of creating a global good, not just recipients of global good. You know, there is a lot about African genome that if we understand it well, it will benefit everybody, not just Africans, because again, that is the root of human evolutionary history. You know, so I will, I will say that in 2031 or something like that, I will be very, very happy that African scientists are indeed making wonderful strides that has benefited African people. But, perhaps just as important, is benefiting the global community because we are sharing insights into the genome, where the whole genome came from. Human beings have lived the longest on the African continent. And if we studied that very well, we know that that environment has shaped the genome that we see all over the world. How do we study that in a way that will make Novel discoveries.
Kat: Charles Rotimi, from the Centre for Genomics and Global Health within the NIH National Human Genome Research Institute.
Discover more about H3Africa: https://h3africa.org/
Sequence three million genomes across Africa - Ambroise Wonkam, Nature https://www.nature.com/articles/d41586-021-00313-7
