This article is part of “Innovations In: Sickle Cell Disease,” an editorially independent special report that was produced with financial support from Vertex Pharmaceuticals.
Sickle cell disease was first described in the scientific literature more than 100 years ago and affects more than seven million people. Cystic fibrosis was first described about 85 years ago and affects fewer than 175,000 people. Sickle cell results from a single mutation, whereas cystic fibrosis can be caused by nearly 2,000 different mutations, making it far more complex to diagnose and study. Yet cystic fibrosis has received considerably more attention, funding and research.
Those affected by sickle cell disease tend to be less affluent, live in places with fewer resources and mostly have darker skin. Despite the broad reach of the disease, it receives little attention in policy priority, medical research investment, advocacy and clinical-care funding. Such limited investments, relative to those for diseases such as cystic fibrosis that affect primarily lighter-skinned people in wealthier countries, are probably a consequence of the well-documented racism in society and in science over the past few centuries.
In 2021 sickle cell disease was one of the top three causes of death for children under the age of five in Portugal, Jamaica, Libya, Oman and San Marino. Researchers estimate that between 50 and 90 percent of children with the illness in Africa die before they turn five. In 2021 more than half a million babies worldwide were born with sickle cell disease, and more than 77 percent of them were in sub-Saharan Africa. According to those statistics, as many as 450,000 of those children will die. With better testing, treatments, and other resources, most of their deaths could have been prevented.
I was born in Cameroon and grew up witnessing the pain, challenges, social stigma, disability and early death caused by sickle cell disease among classmates, colleagues and family friends. This experience, coupled with the lack of health care and medications for those affected, led me to choose genetic medicine very early in my medical education, and I developed a strong commitment to researching the illness because I viewed it as a way to meet the greatest need of millions of people and have the greatest impact, particularly in Africa.
I introduced the idea of genetics-based prenatal diagnosis for early detection of sickle cell disease in Cameroon and South Africa in 2007 and 2010, respectively. Over the past 15 years I have published numerous papers on genetic variants associated with disease complications and longer survival in Africa. In 2017 I established the Sickle Africa Data Coordinating Center at the University of Cape Town, South Africa, which I continue to direct. The project is funded by the U.S. National Institutes of Health and aims to build significant infrastructure to support research activities in Africa within the Sickle in Africa consortium. A well-coordinated, multicenter, prospective longitudinal cohort study of sickle cell disease in Africa will improve our understanding of the pathophysiology, outcomes and determinants of the illness.
Sickle cell has so much to offer as a model disease for both science and medicine. But fully unlocking its potential and its treatments will take a concerted effort from high-, middle- and low-income nations alike. I believe there are three main areas where investment could accelerate equitable development of care and therapies.
One crucial area is newborn screening and comprehensive care. In high-income countries, treatments for newly diagnosed infants include penicillin to prevent pneumococcal infections and sepsis (the main causes of death in children under age five with sickle cell), hydroxyurea to increase fetal hemoglobin and reduce inflammation and vaso-occlusive episodes, and blood transfusions to treat anemia and prevent stroke. These interventions have reduced childhood mortality from sickle cell to nearly zero in countries where they are available.
In Africa, however, newborn screening has yet to become standard practice. It has been piloted in only a dozen countries across the continent, despite sickle cell’s ever increasing numbers. A 2013 study in PLoS Medicine predicted that by 2050 the number of affected newborns would increase globally by about 100,000. That number was surpassed by 2021, almost 30 years earlier than expected, with the large majority of those babies born in sub-Saharan Africa.
Investment in sickle cell disease warrants critical support from international agencies. The effort to implement universal neonatal screening and comprehensive care in African nations should ideally be led primarily by those countries’ governments. But the sums involved can be daunting: some studies have estimated that managing one person with sickle cell disease until age 50 could cost as much as $8 million. Four sickle cell drugs have been approved by the U.S. Food and Drug Administration, but they are not widely available, particularly in Africa.
We must establish sustainable global funding programs to improve care and longevity for people with the illness. Such investment would also benefit countries without large populations of sickle cell patients because the disease can be used to investigate how environmental factors modify a widespread, single-mutation illness and how other mutations affect complications such as stroke, cardiac problems and kidney disease. The research might reveal new targets for treatment not only in people with sickle cell but in the general population.
The World Health Organization recognized sickle cell disease as a major public health issue in 2006, and in 2018 the U.S. Congress officially designated September as Sickle Cell Disease Awareness Month. Although this kind of recognition doesn’t provide money, it can raise awareness among governments and international organizations, leading to more policies and investments in prevention, care and research. In California, for instance, the 2024–2025 budget provides $5 million in funding to the state’s Networking California for Sickle Cell Care initiative. The money is dedicated to comprehensive care for adults with sickle cell disease, including pain management and behavioral health services, as part of a larger, federally funded collaborative program that includes 13 states.
Moreover, significant funding from the NIH has helped the Sickle in Africa consortium develop its Sickle Africa Data Coordinating Center, which compiled the world’s largest African registry of sickle cell patients. The consortium is also researching newborn screening with a pilot program in seven African nations (Tanzania, Nigeria, Mali, Uganda, Zimbabwe, Zambia and Ghana). Such initiatives are urgently needed in the continent’s 47 other countries.
Another important aim of sickle cell research should be better understanding of African genomes. In people with sickle cell disease, a protein in the blood called hemoglobin is abnormal and causes red blood cells to become distorted. Before birth a fetus with the disease has healthy red blood cells because fetal hemoglobin (HbF) is dominant at that point and is unaffected by the sickle cell mutation. After birth, adult hemoglobin progressively replaces HbF, and it typically makes up almost all circulating hemoglobin within four months. Some people, however, have variations in HbF-modulating genes, such as BCL11A, that allow them to continue producing that form of the protein at higher levels in adulthood. Sickle cell patients with these variations, who can have HbF levels above 8 percent, experience fewer disease complications and have longer life expectancies because they have enough HbF to prevent their mutant hemoglobin from sickling too many blood cells.
The main genetic mutation known to keep HbF levels higher after birth is within BCL11A, but that mutation accounts for only a small fraction of the genetic variation. Researchers estimate that in African populations, as many as 90 percent of such gene alterations are unknown. Only about 2.5 percent of all genome-wide association studies have been on people of African descent. By incorporating highly genetically diverse populations of African ancestry into genomic research, we could uncover HbF-promoting variants and provide new targets for drugs to enhance production of the protein.
The third key area for investment is research into the genomics of cardiovascular complications of the disease. Childhood mortality from sickle cell has decreased significantly in the U.S. over the past four decades, but adult mortality has not seen similar improvements. This is primarily because people who have lived with the disease for a long time experience acute and chronic cardiovascular complications—including stroke, heart failure, pulmonary hypertension and kidney disease. Genetic variations can increase the risk associated with these complications, but they are also therapeutic targets, so the better we understand them, the more effectively we can prevent and potentially cure the problems they cause.
As just one example, in people of African ancestry the gene APOL1 has evolved common variants that confer resistance to trypanosome infections, which cause “sleeping sickness.” But these variants are also frequently implicated in kidney disease in these same populations, including among people with sickle cell. Recent research has identified antisense oligonucleotide drugs that inhibit the protein produced by APOL1, and some of these drugs are now in preclinical or clinical phases of testing. Global medicine is already benefiting from sickle cell research.
To develop effective interventions and extend lifespans for people with sickle cell disease and to advance our understanding of cardiovascular complications both in sickle cell patients and in the general population, we must invest in multicenter, longitudinal, prospective studies in Africa and in wealthy countries, such as the U.S.
Given the extreme neglect of sickle cell disease to date, the sheer number of people affected and all we could learn by studying the illness, we urgently need a global initiative to advance research and clinical trials for sickle cell patients, particularly in low-income settings. Our recent success in developing and deploying COVID vaccines has convinced me that such an effort is feasible. It must bring together various stakeholders, including international agencies, industry, national governments, patient support groups, and more. Investing now in sickle cell research and patient care would create the first model for understanding all other genetic conditions and could provide a blueprint for developing treatments for other diseases as well. Now is the time for global research to expand sickle cell disease programs so we can improve the millions of lives affected by this and other ailments.