Charles Rotimi, PhD, the newly minted scientific director of the National Human Genome Research Institute (NHGRI), has two passions: genomics and fighting health inequity. He has spent his career working to make medical research—genomics research, specifically—a global enterprise that benefits all human populations—“not just the rich ones.”
Born in Nigeria, Rotimi came to the United States in the 1980s to continue his education. Twenty years ago, when the Human Genome Project was taking the world by storm, he dreamt of a program that would engage African scientists in the genomic revolution. He had concerns that, without one, the gains genomics was making in understanding biology and medicine would not benefit populations across the African continent.
With this in mind, Rotimi founded the African Society of Human Genetics. When the society started, as an “African Genome Project” of sorts, its organizers did not know where they would find financial support. “We were just dreaming,” Rotimi recalls. But their dream started to come into focus when the group engaged the Wellcome Trust and the National Institutes of Health (NIH).
Rotimi eventually got the attention of Francis Collins, MD, PhD, the director of the NHGRI at the time. In 2007, Rotimi invited Collins to give the keynote at the Annual Meeting for the African Society for Human Genetics. To Rotimi’s surprise, Collins agreed, and traveled to Cairo, Egypt, to attend the meeting. Collins was more than receptive to Rotimi’s ideas. He quickly became the program’s champion.
To those who knew Collins, his interest in buoying science in Africa came as no surprise. Earlier in his career, Collins practiced medicine in Nigeria, creating a connection to the continent and developing a commitment to increasing its access to medical care and science.
Collins returned from the meeting in Cairo with a fervent interest in the program. He sought out allies, including Eric Green, MD, PhD, current director of the NHGRI who was, at that time, the Institute’s scientific director. Others jumped on board and became enthusiastic supporters, including Sir Jeremy James Farrar OBE FRCP FRS FMedSci, director of the Wellcome Trust, as well as Mark Guyer, PhD, and Jane Peterson, PhD, both now retired from the NHGRI. There were many discussions and meetings, Green says, but the program couldn’t get traction because of the scale of what was needed.
Rotimi didn’t know, at that time, the stroke of luck that was about to come his way. Two years after the meeting in Cairo, the biggest supporter of his vision would be appointed director of the NIH. With that one move, Collins was given the podium and the bank account that were needed to get the Human Heredity and Health in Africa (H3Africa) program off the ground.
“H3Africa is a testament to how transcontinental partnerships can foster scientific infrastructure and greatly expand our understanding of human genetic variation and its implications for health and disease,” Collins tells GEN. Over the past decade, he adds, this initiative has nurtured a new generation of African scientists. Today, these scientists are working together to generate data on genomic diversity across the continent—data that can be used globally to improve human health.
One of the program’s successes is the creation of infrastructure that allows African scientists to compete globally while staying in their environment. A revolutionary aspect of the program, according to Jennifer Troyer, PhD, program director at H3Africa, is that the funding goes directly to the African institutions. And African principal investigators decide if they would like to engage collaborators elsewhere in the world, such as in the United States. This balance of power shift, notes Troyer, has been important.
In addition, African scientists have been empowered to ask the questions that they believe are most important, instead of questions that would be about “following the money.” Another hallmark of the program is the focus on training young scientists to take the reins and continue to grow the work.
Many of H3Africa’s projects (roughly three dozen overall) fall under the umbrella of capacity building. They include establishing collaborative research centers; biorepositories; a coordinating center; ethical, legal, and social implications (ELSI) research projects; an informatics network; and bioinformatics training programs. They also include individual research projects.
H3Africa has been a major enabler for the research of Michele Ramsay, PhD, professor in the Division of Human Genetics at the National Health Laboratory Service, University of the Witwatersrand in Johannesburg. The program has provided funding for capacity development and for the work of doctoral students, bioinformaticians, project managers, data and laboratory scientists, and field workers.
In addition, in one of her projects, the Africa Wits-INDEPTH Partnership for Genomics Research (AWI-Gen), the funding supported a large transcontinental study on genetic and environmental contributions to cardiometabolic diseases and traits in Ghana, Burkina Faso, Kenya, and South Africa. The research has benefitted from building an African and international network of genome scientists who are all focused on understanding the genetics of diseases in people living in Africa.
H3Africa has also supported the headline-generating work of Christian T. Happi, PhD, a professor of molecular biology and genomics and the director of the World Bank–funded African Center of Excellence for Genomics of Infectious Diseases (ACEGID) at Redeemer’s University in Ede, Nigeria. Happi’s laboratory, which focuses on viral surveillance, started studying Lassa fever and Ebola, but quickly pivoted to COVID-19 during the pandemic.
H3Africa has created three regional biorepositories (in Uganda, Nigeria, and South Africa) that store samples across Africa. In addition, the program has created a bioinformatics network of close to 30 countries across Africa that trains bioinformaticians for data analysis.
Green highlights H3Africa’s investments in computational facilities and data infrastructure. He suggests that in addition to facilitating communications, these investments support a data sharing ethos among African researchers. To complement these investments, H3Africa has developed an ethical framework for conducting biomedical and genomic research across national boundaries in Africa—research that would involve scientists within and beyond H3Africa programs.
Another metric of success, for Green, is the increase in the number of talks given by African scientists at meetings such as the American Society of Human Genetics (ASHG) meeting.
Ramsay describes working in Africa, on key research questions affecting the health and lives of the people on the continent, as both exciting and rewarding. It is a treasure trove for discovery. “Every time we sequence another African human genome,” she says, “we discover new genetic variants not yet documented in any databases.” It is part of a global puzzle that may help us understand the links between genotypes and phenotypes and our environments.
Genomics has a diversity problem, notes Green. And in the United States, many who are underrepresented are more recent African descendants. So, a better understanding of genomic variation in Africa, he says, will teach us a tremendous amount about genomic variation in the underrepresented groups in the United States and how this variation affects health.
Not an easy road
H3Africa was “a grand experiment,” Green declares. Like all experiments, it has bumped up against multiple challenges. Rotimi notes that while many challenges have been overcome, others have remained “quite stubborn.” One of the most stubborn is the inability to engage African governments and private funders within the continent to take ownership of the program. The governments, Rotimi adds, need to realize the potential and momentum that the program has created, and to move the program forward in a powerful way.
Another hurdle is to make the data that H3Africa generates available, globally, for free. Because of the uniqueness of African genomes, not making those data available results in the inability to fully understand biology and human migration and history. The sharing must be done while allowing the scientists to publish their work and ensuring that they do not become data collectors for other people’s discoveries.
Because much of the work requires African people to give their genomic information, H3Africa has emphasized community engagement and ESLI projects. For example, local languages have been analyzed for words that could be used to explain genomics. And in Botswana, the Collaborative African Genomics Network, which studies the progression of HIV and HIV-TB infection in youth, developed a series of comic books called “The Genome Adventures” with stories of locally relevant superheroes who participated in a genomic study.
The next step
H3Africa, as currently configured and funded, is coming to an end. NIH Common Fund projects have a strict expiration after 10 years. What happens next, beyond H3Africa, is a question mark, Green says. Despite the uncertainty, there is hope that the projects started by H3Africa will take root.
Troyer tells GEN that many of the principal investigators have received additional funding based on their preliminary data. Green had hoped that the African governments would recognize the economic and health benefits of supporting this work. Without the government support, the scientists will be cobbling together multiple arms of support, which is not sustainable in the long run. It’s too “herky jerky,” Green complains. The scientists need a more stable stream of funding.
Nonetheless, Rotimi is confident that the gains realized by H3Africa are “not going anywhere.” Indeed, despite preparing to end his tenure as director by the end of the year, Collins continues to hold meetings to discuss the next phase of H3Africa’s work.
Ramsay agrees, noting that the legacy of H3Africa will continue far beyond its formal end in June 2022. It has built a strong foundation for new research projects and collaborations. The data and samples will be used for many decades as there is much work to be done on the resources that are part of H3Africa.
One area of support that will fill some of the gaps left by H3Africa will come from a new program announced in late October that will focus on data science. The $74.5 million program will again be pulled from the Common Fund—sometimes called the Director’s Fund—which Collins can use to drive science from his own perspective. Collins realizes the momentum that has been created and needs to be built upon.
Part of that momentum, Rotimi notes, is the comfort level that H3Africa created in funding research across Africa. There has been a realization, he emphasizes, that our limited engagement of scientists in Africa is not due to a lack talent there. Rather, the problem is funding the competent and capable scientists across Africa that can do this work.
The money will be used over five years to advance data science, catalyze innovation, and spur health discoveries across Africa. The new program, Harnessing Data Science for Health Discovery and Innovation in Africa, will issue 19 awards to support research and training activities. They will continue to develop data sharing and computation biology software and procedures to allow for mining of the data.
Troyer notes that right now, there is a huge focus in health and genomics to address inequities and disparities. Companies such as Illumina, Regeneron, and others have shown interest in African genomics. She sees opportunities there now that were not there a decade ago.
This interest is, according to Rotimi, based on the success of H3Africa. He sees H3Africa as having set the foundation upon which other programs will build in the future. Back when Rotimi was dreaming of support for African scientists, he says he “could not have imagined” H3Africa. But now that H3Africa has been so successful, Rotimi is already dreaming new dreams.
What are his dreams for the next decade? He is quick to answer. First, he wants everyone to recognize that when human genome sequencing began, it was a mistake to overlook engagement with African countries or African people. Second, he hopes that we can build on H3Africa’s work and strengthen our engagement with Africa going forward. He adds that people should not see this work as anything exotic, and that they should, instead, feel comfortable that there are capable scientists and laboratories across the African continent. And the African people, who have been very generous in participating in genomic research, will benefit from their participation.