Every field has its detectives. In medicine, some of the most skilled professionals are physician-scientists: individuals trained in both medicine and research, caring for patients while investigating the biology behind their illnesses.
A physician treats. A scientist discovers. A physician-scientist operates in both worlds, identifying patterns in the clinic that can lead to breakthroughs in the lab, and then applying those discoveries to patient care. They don’t work alone — advancing against disease is always a team effort —but their training and expertise help them connect the dots.
One of the biggest medical mysteries of the past 50 years has been HIV. The story of our progress, and how close we are to a cure, shows why physician-scientists are vital.
The early days of HIV
When AIDS first emerged in the early 1980s, it was a frightening, deadly, and poorly understood disease. An early breakthrough occurred when physician-scientist Dr. Robert Gallo, M.D. (in the United States) and scientists Françoise Barré-Sinoussi, Ph.D., and Luc Montagnier, Ph.D. (in France) co-discovered HIV as the cause of AIDS.
At a hopeful 1984 press conference, the U.S. health secretary announced that a vaccine would be available “within two years.” But it never materialized. HIV proved to be different, and traditional vaccination methods continued to fail. Nevertheless, physicians, scientists, and physician-scientists persisted. By 1987, the first drug, AZT, and the development of combination antiretroviral therapies offered a lifeline. They changed HIV from nearly certain death to a manageable chronic condition. This was a triumph of biomedical research, but it was not a cure.
A genetic clue
The next twist came from a curious observation: Some people exposed to HIV never got sick, even after repeated exposure. Physician-scientist Dr. Paolo Lusso, M.D., Ph.D., helped uncover why. The key was a protein on the surface of immune cells called CCR5, the very door HIV used to enter and infect cells. Around the same time, scientist Stephen O’Brien, Ph.D., found that the people who appeared resistant to infection carried a rare mutation in CCR5 (CCR5-Δ32), which essentially locked the door shut to HIV. It was a detective story in real time — a mystery observed from patients in the clinic that was solved in the research laboratory. It hinted at a direction for a cure.
The first cures
The CCR5 breakthrough was a pivotal moment. In 2007, physician-scientist Dr. Gero Hütter met Timothy Ray Brown (the “Berlin Patient”), an individual with HIV who also had leukemia. Dr. Hütter recalled that the CCR5-Δ32 mutation was the key to HIV resistance. He and his team wondered: What if they treated Brown’s leukemia with a bone marrow transplant from a donor with the CCR5-Δ32 mutation? Could this also cure his HIV infection? The outcome was remarkable. Timothy Ray Brown was treated for his leukemia and was also cured of HIV.
This wasn’t a one-time event, however, as physician-scientist Dr. Ravindra Gupta, M.D., Ph.D., reported on a second patient, Adam Castillejo (the “London Patient”), cured of HIV through a similar procedure a decade later. Curing HIV with a bone marrow transplant using cells resistant to infection was crucial. Today, about 10 people have been “cured” this way.
What comes next
Although bone marrow transplants have been a breakthrough in curing HIV, they are risky, costly, and not a practical solution for the 39 million people worldwide living with HIV. The key question now is, exactly how did the donor CCR5 mutation, or the transplant itself, lead to the clearance and complete resistance to HIV?
At Oregon Health & Science University, scientist Jonah Sacha, Ph.D., and his team are working to answer that question. Supported by a new joint NIH grant, his team is studying these HIV-cured individuals to discover what truly happened inside their bodies, and how to replicate it into a safe, scalable cure. With the foundational knowledge and expertise from decades of observations, research, and clinical work by physicians and physician-scientists, the Sacha team is prepared for the next breakthrough.
The ongoing story of HIV and AIDS highlights how crucial physician-scientists were in connecting patients’ experiences to scientific advances and transforming clues into cures.
Medical mysteries still exist, and physician-scientists are here to solve them.