This summer, 34-year-old Victoria Gray became the first person in the U.S. to have a gene editing therapy as treatment for sickle cell disease. “It’s a very big deal for me,” Gray said in a national media interview after learning the groundbreaking treatment was working. “It’s the change I’ve been waiting on my whole life.”
Gray, a Black wife and a mother of three from Mississippi, had been living with the complications of the inherited blood disorder that disproportionately affects African Americans for her entire life.
CRISPR is a new technique that involves cutting out a tiny piece of the mutation or defective gene that causes sickle cell disease in the hopes that the corrected gene will then work to make normal hemoglobin (a protein in red blood cells) instead of the sickle-shaped hemoglobin that gives the disease its name.
Dr. Emmanuelle Charpentier and Dr. Jennifer Doudna were awarded the Nobel Prize in chemistry in October for their work on the experimental gene therapy that made it possible for Gray to get the infusion. The technique has already “had a revolutionary impact on life sciences,” the Nobel Committee said, and for genetic diseases like sickle cell, it has the potential to “make the dream” of a cure “come true.”
But the hope for new treatments and a possible path to a cure for the mainly Black and Hispanic children and adults in the U.S. with sickle cell disease depends on their participation in clinical trials, says James G. Taylor, M.D., director of Howard University’s Center for Sickle Cell Disease in Washington, D.C. “Even if we get a cure today, we don’t have enough patients volunteering for clinical trial studies to implement it,” Taylor said at the center’s 2019 World Sickle Day conference.
Racism and a mistrust of the medical system dating back centuries remain an issue for many African Americans. Many cite the syphilis experiments the federal government conducted on about 600 Black men from Tuskegee, Alabama over a 40-year period starting in 1932. The men were promised free health care, but for decades, those with syphilis went untreated.
Today, as COVID-19 cases rage across the country and vaccine manufacturers race to the finish line, the level of trust from the Black community seems to have improved little. According to a September Pew Research Center report, Black people have been the most hesitant to volunteer for vaccine clinical trials and are the least likely to get a COVID-19 vaccine when one is available for use.
In his update about sickle cell disease a year ago, Taylor also spoke about what patients and caregivers need most, especially as people born with sickle cell are living longer: “more physicians trained to care for adult patients, more research investigators and greater research funding.” But “disparities in clinical care and research funding, and poor implementation of treatment” persist, he said.
Howard’s Center for Sickle Disease, which treats about 350 people in the Washington, D.C. metropolitan region, also has an international presence that includes two signed collaboration agreements with the Democratic Republic of Congo, which has the third highest concentration of people born with sickle cell in the world, behind Nigeria and India.
At Morehouse School of Medicine, an historically Black medical school in Atlanta, new sickle cell research is underway after the Centers for Disease Control and Prevention added sickle cell disease to the list of health problems that put people at higher risk of serious illness with COVID-19.
With backing from the UnitedHealth Group, Morehouse researchers are working to determine if there’s also a greater risk of contracting COVID-19 for those who carry the sickle cell trait, school officials said in a statement. Carriers represent a much larger group that includes about 8% of Black Americans.
“COVID can be seen as really kind of a stress test that has exposed these fault lines in American health and health care,” said Dr. Herman Taylor, a lead investigator on the study who also directs Morehouse’s Cardiovascular Research Institute.
The disease underdog
It’s been more than six decades since researchers discovered the mutation that causes sickle cell, but for the estimated 100,000 Black people in the United States born with the genetic disease there is still no cure, said Dr. Sohail Rana, a professor of pediatrics at Howard’s College of Medicine. Pain, he adds, remains sickle cell’s unpredictable and debilitating hallmark.
As a practicing physician and researcher, Rana has observed and welcomed experimental procedures now being hailed as breakthroughs, like the one that Gray said has already transformed her life and health. While a little older, bone marrow transplants are also a form of gene therapy with promise, Rana said. The mainstay drug hydroxyurea is also in his arsenal, and while it’s not new, Rana said it “works well and beautifully” to plump up and round sickled red blood cells that otherwise couldn’t bend or move easily through the body.
But the often frank, yet hopeful physician who’s spent 40 years at Howard treating some of the youngest patients with sickle cell and HIV/AIDS takes this view of what some call a cure:
“Sickle cell is a genetic disease, and it’s not going away, even as genes are mutated,” said Rana, whose patient focus has also meant tackling stigma around the disease. In 2010, working with colleagues in Howard’s School of Medicine, Rana launched an international conference on disease stigma that’s held annually on the Howard campus.
For Black sickle cell patients, not being believed or facing the “fear of being labeled drug users” keeps many from “filling their prescriptions for pain medication or seeking treatment for pain in the emergency room.” Such apprehension is common and steeped in a history of racism and myth that lingers, said Rana. For centuries, slave owners and White physicians justified violence against Black people by asserting they had a supposed greater tolerance for pain and thicker skin.
A new report by the National Academies of Sciences, Engineering, and Medicine, “Addressing Sickle Cell Disease: A Strategic Plan and Blueprint for Action,” is calling for an overhaul of how sickle cell patients are treated in the healthcare system, including putting an end to discrimination and stigma.
“Until we learn to treat people with health equity,” Rana said, “we have not made any progress in their care. And we are far from that.”
The National Academies of Sciences, Engineering, and Medicine report concluded, “Since its discovery in 1910, [sickle cell disease] has received relatively little attention and few resources from the scientific, clinical, and public health communities compared with other genetic disorders … Until December 2018 there was only one drug approved by the U.S. Food and Drug Administration (FDA) for the condition.”
On the ‘forefront’ of care
Rana was a medical resident at a Brooklyn, New York hospital when a Black baby boy with a raging fever and chills was rushed in. Medically trained in his native Pakistan, this was the first time that Rana had treated someone with sickle cell. His patient’s short life was fleeting, but for Rana, the baby’s trauma and his own sense of helplessness were transformative.
Rana, a pediatric blood doctor, “wanted to learn more about the disease and do more” for those born with sickle cell who faced barriers to care. It was the beginning of a medical journey, that, in 1980, led him to Howard and its Center for Sickle Cell Disease, one of the nation’s oldest. The center was led then by Dr. Roland Scott and Dr. Melvin Jenkins, whom Rana describes as being “on the forefront” of care, treatment, research and advocacy for sickle cell.
Scott, a Howard graduate, led the pediatrics department at Howard Hospital from 1949 to 1973. He was trained as an allergist but turned his attention to sickle cell anemia in the 1950s. In those early years, researchers had not discovered what caused the characteristic sickle-shaped blood cells to form, but what intrigued them more was that it was “apparently the only known disease completely confined to a single race,” the Journal of the American Medical Association reported in 1947.
Scott, who was renowned for his work on the blood disease, established Howard’s Center for Sickle Cell in 1972.
“The Howard center was possible only after he and other prominent doctors and activists lobbied Congress for passage of the Sickle Cell Anemia Control Act of 1971, which gave comprehensive federal funding to research centers nationwide,” center director Oswaldo Castro told The Washington Post in 2002. The legislation not only gave comprehensive federal funding to create research and treatment centers nationwide, it increased screenings for newborns to determine if they inherited the disease. Decades later, Rana credits the legislation with the advances in sickle cell research:
“This alone,” he said, “has led to improvements in lifespans and to standards of critical care” for those with sickle cell disease.
This article originally appeared in the November 26, 2020 edition of Diverse. You can find it here.