A Former Harold Amos Scholar Works to Bring the Best Research to the Greatest Number of Patients

    • April 22, 2014

The problem. Sickle cell disease is an inherited blood disorder that affects some 90,000 to 100,000 Americans, mostly African Americans. Red blood cells become crescent shaped, like a sickle, and block small blood vessels, resulting in damaged tissue, and often premature death—at least until recently.

Griffin Rodgers, MD, grew up in the 1960s and 1970s in New Orleans and recalls the horror of watching three high school friends become debilitated with sickle cell disease. Two of them died while still in high school and the third died several years later.

“They suffered unbearable, unimaginable pain, and I was helpless to do anything about it. When you’re a teenager, you’re not supposed to bury your friends. But that’s what sickle cell does. That’s the toll it takes.”

Other diseases also were taking their toll, Rodgers discovered as he accompanied his mother, a public health nurse, to low-income housing projects in New Orleans. “I saw that diabetes, obesity, and kidney disease hit African Americans harder than others,” he recalls. “This was my first exposure to the effects and interaction of genetics and the environment.”

A passion for research. These sobering realities stoked in Rodgers a passion for medicine, and in particular, hematology, the study of blood diseases. Having demonstrated an aptitude for science and math in high school, in 1972 Rodgers was accepted into an accelerated program at Brown University in Providence, R.I., where he could complete his undergraduate, graduate, and medical degrees in seven years.

During his clinical rotations, Rodgers met Charles McDonald, MD, the first chair of dermatology at Brown, who had pioneered the use of the chemotherapy drug methotrexate to treat patients with psoriasis, a skin disease that causes skin cells to grow too quickly.

Rodgers was intrigued by the possible parallels. “In the back of my mind, I thought, ‘Skin is a rapidly turning over cell type, and so are red blood cells. Maybe in the future we could consider a similar approach for sickle cell.’”

Discovering a new treatment. Rodgers would get the opportunity to find out in 1982, when he was asked to join a team of bench researchers at the National Institutes of Health (NIH) trying to understand the process thought to distort the red blood cells into their classic crescent shape. He gained additional support for that work a year later, as part of the first cohort of grant recipients in the Harold Amos Medical Faculty Development Program. The program provides four-year awards for postdoctoral research to physicians and dentists from historically underrepresented groups who are committed to developing careers in academic medicine and dentistry. (See Program Results Report for more information about the program.)

Rodgers’s research focused on understanding the cellular features that distinguish the severity of sickle cell disease. His research colleagues were some of the leading scientists at NIH, including a Nobel Prize winner.

“Based on our clinical work, it was clear that not everyone with the sickle cell mutation had similar severity in terms of complications or life expectancy,” Rodgers says.

One factor that modified the course of the disease was the presence of “fetal hemoglobin”—a type of hemoglobin that is abundant in red blood cells at birth that generally goes away in the first year of life. “That’s why infants with sickle cell don’t manifest their first symptoms till they are about nine months,” Rodgers says, “and why certain groups in the Middle East have almost symptom-free disease. They have a high expression of this fetal hemoglobin.”

The researchers knew that a drug called hydroxyurea had been used in pre-leukemic patients to increase fetal hemoglobin. Thinking of McDonald’s success in using chemotherapy drugs for psoriasis, Rodgers wondered, could hydroxyurea be used to treat a non-malignant condition like sickle cell disease?

In 1986, Rodgers and his research team initiated a clinical trial to test the theory. Of the first group of patients treated with hydroxyurea, about three-fourths responded favorably, seeing their fetal hemoglobin levels increase. Subsequent trials repeated these observations (see the New England Journal of Medicine article, April 12, 1990), 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.

Patients on hydroxyurea require fewer blood transfusions and suffer less agonizing bone and joint pain. “Mere words cannot describe how good it feels to see people live longer and better,” Rodgers says.

Rodgers and his research colleagues have continued to pursue new treatments for sickle cell disease. A bone marrow transplant can sometimes offer a cure in young children, but it is often highly toxic. His research team is experimenting with the wider use of a modified blood stem-cell transplant regimen, which has proven highly effective in reversing sickle cell disease in the first 10 patients in whom it has been tested, with relatively low toxicity (see the New England Journal of Medicine article, December 10, 2009).

Taking aim at chronic illnesses. In 2007 Rodgers was named director of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the same institute where he had begun his research career 27 years earlier. The fifth largest of NIH’s 27 institutes, NIDDK is charged with seeking cures and treatments for many of the most common chronic illnesses that plague Americans.

A key target of NIDDK’s research work today is diabetes—an illness on the rise in the United States, especially among minority groups. Twenty-six million Americans have the disease and another 79 million are pre-diabetic. The health care costs associated with diabetes are estimated at $245 billion annually.

“We are learning that prevention is better than treatment,” Rodgers says, citing results of an NIH trial published in a New England Journal of Medicine article (February 2, 2002) that found that modifying one’s diet together with exercise—30 minutes a day, five days a week—is effective in all age groups and all ethnic and racial groups for people who are at high risk for developing diabetes.

The preventive program had the best effect in people over 60, Rodgers says. That’s important as this age group will soon be entering the Medicare program, where treating diabetes makes up a big fraction of health care costs.

“We are measuring blood sugar and metabolism, but it is clear that if you could bottle whatever benefit you are getting from exercise and sell it as a pill, it has many, many additional health benefits,” Rodgers says. “When we talk about cost effectiveness, we know that we are preventing other conditions that we aren’t even accounting for. That is why changing behavior is so important.”

The importance of the Harold Amos award. Rodgers has been blessed with important mentors throughout his career, many of them cultivated through the Harold Amos program. He has returned the favor, serving for the last 10 years on the Harold Amos national advisory committee and mentoring young minority researchers through the NIH’s workplace diversity programs.

“It turns out that having differences in opinion and differences in experience enriches the entire enterprise,” Rodgers says. “Many of the diseases we are responsible for disproportionately affect racial and ethnic minorities. We try to make sure that in our clinical studies there is good representation of the patient populations at the highest risk.

“We have also found that retention in trials seems to be strengthened if some of the investigators or associate investigators are of the same racial or ethnic group,” he says. “We want to train the next generation of those investigators.”

RWJF perspective. The purpose of the Harold Amos Medical Faculty Development Program, launched by RWJF in 1983, is to increase the number of faculty from minority and other historically disadvantaged backgrounds who achieve senior rank in academic medicine and dentistry.

The program supports one of RWJF’s major objectives: to increase diversification of the medical and dental professions and, as a consequence, improve the health care received by the nation’s underserved populations.

Of Amos program scholars, RWJF senior program officer David M. Krol, MD, MPH, says:

Ultimately, we would like to see these individuals from disadvantaged backgrounds becoming full professors at prestigious institutions, putting out important, valuable work, looking at a variety of different issues—including how to decrease the disparities between rich and poor, majority and minority—while climbing the academic ladder.

Griffin Rodgers is one of more than 180 Amos program alumni in academic medicine today, and three (including Rodgers) direct institutes at the NIH. Rodgers’ career and research exemplify the academic achievement and professional contributions that the program was designed to stimulate.

“The measure of the success of the program is the success of the individuals who participate in it and how they impact the culture of health in the United States,” says Krol.

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Griffin Rodgers mentors young minority researchers who then draw more people of color into clinical trials.