The problem. Tuberculosis (TB) is one of humankind’s deadliest diseases: Every minute, it kills four adults somewhere in the world. A disproportionate number of those people live in urban slum areas, which are home to approximately a billion people around the world. TB is only one of many infectious and non-infectious diseases that afflict them in greater proportion than in non-slum dwellers.
Exactly what makes those populations so vulnerable to diseases has been a relatively neglected area of medical research. Yes, poor sanitation is part of the problem, but it is not the whole story.
From East Asia to medicine. Lee Riley, MD, professor and chair of the Division of Infectious Diseases and Vaccinology at the University of California, Berkeley’s School of Public Health, was born in Japan in 1950. His father was an African-American civil servant who worked for the United States Air Force; his mother was Japanese. When Riley was 15 the family moved to Bangkok, Thailand. Later, as an undergraduate at Stanford University he majored in philosophy, but the idealism of the 1960s steered him toward medicine, where he felt he could make more of a contribution.
Riley earned his MD at the University of California, San Francisco, and completed an internship and residency in internal medicine at Columbia Presbyterian Hospital in New York City. He realized that as a practicing physician he might be able to help heal 100 patients a year, while the number of people he could potentially help as a researcher was far greater. “I wanted to do something that prevented thousands of people from having to seek health care in the first place,” he says.
A ticket to research freedom. After completing his residency, Riley accepted a position as an investigator in the Centers for Disease Control and Prevention’s Epidemic Intelligence Service. The job sent him to study disease outbreaks in several countries, including Brazil. A post-doctoral fellowship in infectious disease and medical microbiology at Stanford followed, and it was there that Riley learned of the Robert Wood Johnson Foundation’s Harold Amos Medical Faculty Development Program. The program provides four-year awards for postdoctoral research to physicians and dentists from historically underrepresented groups. (See the Program Results Report for more information.)
The grant money Riley received as a Harold Amos fellow beginning in 1986 gave him the freedom to continue his work on the problem he had first studied in Brazil: diarrhea, the most common cause of death in children worldwide at that time. For two years Riley studied the bacterium that causes infantile diarrhea, enteropathogenic E. coli (EPEC), trying to understand the mechanism by which it attaches itself to the inner wall of the human intestine. By exposing human cells to EPEC in laboratory cultures, Riley and his colleagues found that the bacterium generates extracellular material that allows it to attach to intestinal cells (Infection and Immunity, 1987, 55:2052‑56; Molecular Microbiology, 1990, 4:1661‑1666).
Riley calls the Harold Amos fellowship a seminal event in his development as a researcher. “It came at the right moment,” he says. “I was able to pursue a research question that I wanted to pursue,” he says.
The shift to TB. Riley interrupted his Amos fellowship in 1988 when he went to New Delhi to serve as a laboratory project manager for the World Health Organization’s India Biomedical Support Project. He returned to the United States in 1990 to join the faculty at Cornell University Medical College as assistant professor of medicine in the Division of International Medicine and Infectious Diseases. Riley resumed his Harold Amos fellowship, but with a new focus: tuberculosis, a disease he had seen far too much of in India.
Despite the differences between E. coli infection and tuberculosis—the TB bacterium invades cells, rather than attaches to them—Riley’s research methodology remained the same: Uncover the genetic properties that allow the bacterium to infect the human body. Mycobacterium tuberculosis is a remarkably pervasive organism. Up to a third of the world’s population is infected with it, but only about 10 percent of those infected will develop the active disease. Why some people do and some do not is one of the key questions Riley is trying to answer. How the bacterium manages to survive within the lungs for so long is another.
In the research funded by the Amos grant, Riley and his colleagues were able to identify two gene clusters in the DNA of Mycobacterium tuberculosis that are critical in the disease’s persistence. One cluster allows the organism to invade microphages, white blood cells that ordinarily are responsible for eliminating infectious agents from the system. The other cluster allows it to survive indefinitely within those cells (Science, 1993, 261:1454-1457 and 1390).
A commentary in the same issue of Science in which this research was published called it a “breakthrough” in understanding the etiology of TB. In 1993, Riley received two five-year RO1 grants from the National Institutes of Health (NIH) to continue his research—both of which were subsequently renewed for an additional five years. By then he’d moved from Cornell to the School of Public Health at the University of California, Berkeley, where he continues his research today. With other funding from NIH, Riley and colleagues have developed a vaccine for TB that works in mice, but many years of research are needed before it can be tested in people.
Healing the slums. Riley’s travels to investigate diseases around the world reinforced for him again and again the relationship between slum conditions and a whole range of diseases, including TB, leptospirosis, and rheumatic heart disease. Realizing that the root causes of these diseases remained largely unknown inspired him to become an early leader of a new medical discipline: molecular epidemiology.
Molecular epidemiology combines molecular biology, which studies the genetics of microbes; and epidemiology, which studies the distribution and determinates of disease in human populations (as defined in American Journal of Epidemiology, 2001, 153: 1135–41). In 2004, Riley wrote the field’s first textbook: Molecular Epidemiology of Infectious Diseases: Principles and Practices (ASM Press, Washington).
Passing it on. Even as he continues his own research, Riley now devotes considerable energy to bringing others into his campaigns against infectious disease and the dangers of slums. He is the principal investigator of an NIH-sponsored consortium of four institutions—University of California, Berkeley; Florida International University; Stanford University; and Yale University—that trains early-career researchers in many fields to address health problems in slum conditions around the world. Riley also travels to Brazil each year to teach a course on molecular epidemiology and mentors students in his laboratory.
As a member of the advisory board of the Harold Amos Medical Faculty Development Program, Riley helps identify and encourage scholars from minority backgrounds who have the potential to make contributions in medical research and practice. Certainly his own career stands as a testament to the program’s success. He has been a contributing author of more than 200 articles in medical journals and is an elected member of the American Academy of Microbiology and the American Association for the Advancement of Science. The many honors he has received include awards from the Pew Scholars Program in the Biomedical Sciences and the Ellis Foundation.
Riley is especially proud that the American Society of Microbiology included one of his research papers in a collection of 54 of the most significant publications in the 100 years since the society’s founding in 1899. Among those with whom Riley shares company in that collection is Alexander Fleming, the discoverer of penicillin.
RWJF perspective: The Harold Amos Medical Faculty Development Program is a four-year postdoctoral fellowship launched by RWJF in 1983. Its purpose is to increase the number of faculty from minority and other historically disadvantaged backgrounds who achieve senior rank in academic medicine and dentistry. A commitment to eliminating health disparities is among the selection criteria.
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.
Lee Riley is one of more than 180 Amos program alumni in academic medicine today. His 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,” says Krol.
Lee Riley, MD, wants to know why diseases like TB are more common in people who live in urban slums.