The Johns Hopkins geneticist on what the data shows, what it lacks, and who has been left behind
The disease that shaped a career
Ambroise Wonkam did not choose sickle cell disease at random. The condition chose him. Born in Cameroon, trained across three continents, and now leading genetic medicine at Johns Hopkins University, Wonkam has spent decades studying a disease that carries one of the heaviest burdens in global health — and one of the smallest shares of research investment.
Sickle cell disease has been known to medicine for more than 114 years. Yet it remains catastrophically undertreated in the regions where it is most prevalent. In Nigeria alone, half of all children born with the condition may not reach their fifth birthday, not because treatment does not exist, but because universal newborn screening and consistent access to basic interventions like penicillin prophylaxis and hydroxyurea are simply not available. Wonkam has framed this not as a medical failure but as a moral one.
Why the human genome is incomplete without Africa
At the center of Wonkam’s work is a fundamental scientific argument. Africa is where humanity began. Human beings evolved on the African continent approximately 300,000 years ago and did not begin migrating to Europe and Asia until roughly 50,000 to 70,000 years ago. That means the vast majority of genetic variation that influences human health never left Africa. Yet today, less than 2% of the genomic variation in major medical databases comes from people of African ancestry.
The implications are significant. Genetic medicine as currently practiced cannot serve African children equitably because the genomic variation underlying many of the diseases those children face has never been fully studied. For Wonkam, this is both a scientific problem and a justice problem, and his research center GeneMAP, which stands for Genetics Medicine of African Populations, exists specifically to address it.
The breakthrough hiding in the genome
One of Wonkam’s most striking research contributions involves what geneticists call modifiers. These are genetic variants that do not cause a disease but significantly influence how severe it becomes. He used a vivid example to explain why they matter. Two siblings from the same family, both diagnosed with sickle cell disease, can have radically different health outcomes. One may live without major complications. The other may develop kidney failure before age 20. Same mutation. Same environment. The difference may come down to a single genomic variation that protects one and not the other.
A long-term American study tracking sickle cell patients over 40 years found that those with higher levels of fetal hemoglobin, above 8%, lived significantly longer. Those hemoglobin levels were later found to be influenced by genetic factors. One gene in particular, BCL11A, is now the target of the first FDA-approved gene editing treatment for sickle cell disease. That breakthrough was made possible by understanding modifiers.
Wonkam’s own team published research in Nature Communications identifying a variant in a gene called FLT1 that may one day be modified to increase fetal hemoglobin as a treatment strategy. A separate finding from nearly 15 years ago showed that sickle cell patients who also carry a mutation called alpha thalassemia live significantly longer and are protected against kidney disease, stroke, and anemia. Some specialists now believe every sickle cell patient should be screened for alpha thalassemia, and that treatment should be more aggressive in those who do not carry it.
What he wants patients to hold onto
Wonkam is clear-eyed about the present but genuinely hopeful about the future. Stem cell transplantation and gene editing work. They are not yet accessible to most of the patients who need them most, but Wonkam believes that within the next decade it may be possible to treat sickle cell disease with a single injection. Until that day arrives, early detection, penicillin prophylaxis, and hydroxyurea remain the standard of care that saves lives. He urged patients and families to stay engaged with research and to hold onto hope as a form of participation in the future being built for them.