Sickle cell disease, an inherited blood disorder that affects an estimated 90,000 to 100,000 Americans and millions of people worldwide, can result in a lifetime of acute and chronic pain, organ damage, stroke, frequent hospitalizations and premature death.
Dr. Griffin Rodgers of the National Institutes of Health (NIH), a preeminent researcher in the fight against sickle cell disease, discovered the first effective drug treatment in the 1990s that has eliminated much pain and suffering, and more recently developed a modified blood stem cell transplant regimen that cured the disease in 26 of 30 adults participating in a lengthy clinical trial.
Robert Balaban, the scientific director at NIH, said the medical breakthrough from the sickle cell clinical trial announced in July 2014 is “huge.” Based on the work of Rodgers and Dr. John Tisdale, the principal investigator and Rodgers’ collaborator on the sickle cell clinical trial, developments on the horizon could result in a cure for a broader segment of the afflicted population. Currently, there is no widely available cure for the disease.
Dr. Thomas Starzl, a physician and researcher who performed the world’s first liver transplant, described Rodgers’ work as “revolutionary,” while Dr. Michael M. Gottesman, the NIH deputy director for Intramural Research and chief of the Laboratory of Cell Biology, said Rodgers’ work has had a “profound impact on the treatment of patients with this disease.”
Sickle cell disease is a condition that arises from a genetic defect that alters the structure of hemoglobin, the oxygen-carrying protein found in red blood cells. The modified hemoglobin causes normally round red blood cells to become stiff, sticky and sickle-shaped, in many cases blocking blood flow and causing pain and organ damage.
In the United States, the disease predominantly affects African-Americans and to a lesser extent Hispanic-Americans. Worldwide, some 300,000 children are born with sickle-cell disease every year, mostly in sub-Saharan Africa.
Although Rodgers has spent most of his waking hours during the past eight years attending to his duties as director of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), he has managed to carve out time to continue his clinical and research work on sickle cell disease, a decades-long passion. Rodgers grew up in New Orleans where he had three high school friends with sickle cell disease. Two of those friends died in their teenage years and the third passed away a few years after high school, leaving a tremendous impression on Rodgers that spurred his quest for a cure.
Years before becoming the director of NIDDK, Rodgers was the principal investigator on an NIH clinical trial that demonstrated that a drug called hydroxyurea, which had been used in pre-leukemic patients to increase good hemoglobin, could effectively treat many of the serious symptoms of sickle cell disease.
About three-quarters of the patients using the drug in the NIH clinical trial that began in 1986 responded favorably. Subsequent trials repeated these observations as did a larger, multi-center trial sponsored by the NIH. In 1998, the FDA formally approved the drug for sickle cell disease in adults, leading to the need for fewer blood transfusions and less agonizing bone and joint pain for patients.
Last year, Rodgers and his collaborators reported on a modified blood stem cell transplant regimen that was highly effective in reversing sickle cell disease in adults, a major breakthrough that does not require extensive use of anti-rejection drugs. The 26 patients in the clinical study who experienced disease reversal had normalized red blood cells, fewer hospitalizations and lower use of narcotics to treat pain. These patients also did not experience graft-versus-host disease in which donor cells attack the recipient.
All of the stem cell donors were siblings of the patients in the clinical trial because their cells were an exact match. Further studies may seek to broaden the range of donors to the parents of patients, and to take a patient’s cells outside the body, correct the defect and infuse them back into the individual.
Dr. Francis Collins, the director of NIH, called the findings from the stem cell transplant trial “a major development,” and credited Rodgers as “the driving force” who put the team together and developed the “innovative approach” that is likely to lead to further important discoveries. “His bold efforts on the stem cell transplantation have yielded exciting results,” said Collins.
Rodgers said that during all of his work on sickle cell disease, he has moved slowly and cautiously “until we were certain we wouldn’t cause more harm than good.” He said it has been extremely gratifying to “see people live longer and better,” and to “alleviate suffering.”
Rodgers came to NIH in 1984, where he quickly began his research on sickle cell disease. As he made his mark in the laboratory and the clinical setting, Rodgers also progressed through the managerial ranks, heading NIDDK’s Molecular and Clinical Hematology Branch starting in 1998, becoming deputy director of NIDDK in 2001 and director of the institute in 2007.
In his role as head of NIDDK, Rodgers oversees 600 employees and a $2 billion annual budget, including grants to scientists, laboratory research and clinical trials on diseases that encompass some of the most common, severe and disabling conditions affecting Americans. These include diabetes and obesity, digestive diseases such as hepatitis, kidney and urologic diseases such as kidney failure and prostate enlargement, and blood diseases.
“I am passionate about medicine and scientific discovery,” said Rodgers. “And public service has been with me since early days. My father was a science and physical education instructor in high school and my mother was a public health nurse, so public service is in my DNA.”