Jay Levy is a physician, professor, and cancer researcher in the School of Medicine at the University of California, San Francisco (UCSF). His lab was one of the first three groups (along with Luc Montagnier and Françoise Barré-Sinoussi, Institut Pasteur, and Robert Gallo at the National Institutes of Health) to isolate the virus eventually confirmed as the cause of AIDS. We asked Dr. Levy about his work and the exciting discoveries of the early 1980s in which he participated.
Q. At what point in your life did you realize that you wanted to make a career of studying the human body? Why virology and oncology?
A. I grew up in the countryside in a suburb of Wilmington, Delaware and very much enjoyed looking at wildlife and animals in the streams and woods. When I was at Wesleyan University in Connecticut, majoring in biology, I came upon an article in a 1958 cancer journal about the possibility of viruses staying hidden in cells and their products causing cancer. I was fascinated by that idea, called bacterial virus lysogeny, and in medical school I conducted research on it. This work led me to explore the possibility that mammalian viruses might cause cancer by the same process. So I went to Uganda in 1964 to study the possible viral cause of Burkitt's lymphoma.
Q. Burkitt’s lymphoma, a cancer of the lymph nodes that causes tumors in the jaw, was described in children in Uganda in 1958 and was the first human malignancy associated with a virus. What did you learn from your work in Uganda that helped in understanding HIV?
A. My work with Burkitt’s lymphoma emphasized the fact that a virus could be closely associated with cancer and that it might not be a direct cause of cell transformation but could promote the cancer process. In terms of HIV research, this experience enabled me to appreciate the role of the immune system in enhancing the cancer process and in giving rise to the immune abnormalities in HIV infection. In both situations, a hyper- response of the immune system may be the cause of the disease process.
Q. How did you get your HIV samples in the early years?
A. There was very good communication and collaboration in the San Francisco scientific and medical community. The HIV samples came from San Francisco General Hospital and other hospitals in the Bay area in the early years. They were provided by Paul Volberding (one of my former postdocs) and other physicians in the city. Since doctors at the University California knew that our group was attempting to find the cause of AIDS, they called and either delivered blood samples to my laboratory or referred patients to my laboratory. We would then take a blood sample from the patients and use that in attempts to find a causative agent. At first the samples came from people who suffered from AIDS. Because of limited resources, we could only study perhaps two or three patients a week. Later we examined individuals who thought they had a risk for AIDS to look for the virus that we had by then isolated.
Q. How did you know where to look for the causal agent?
A. We began by looking at the possible viral cause of Kaposi's sarcoma, the cancer that's associated with AIDS. Within a few months it became known that the immune system was suppressed in patients with this cancer. We then began looking in the white cells (the immune system) from AIDS patients for the causative agent.
Q. What was the first solid piece of the puzzle to fall into place?
A. At first we were only able to look at cells grown from Kaposi's sarcoma for a replicating virus and found none at that time. We were also injecting blood from AIDS patients into a variety of animals to look for induction of disease and had outlined an algorithm to find a new infectious agent in animals and in cell culture. This algorithm included all the procedures current at the time for detecting viruses in culture (e.g. red blood agglutination, cytopathic changes, immunofluorescent testing for viral proteins in inoculated cells) as well as approaches for studies in animals. Our first solid piece of evidence came when we detected several fluids from white blood cell cultures that contained a protein, reverse transcriptase(RT), associated with retroviruses. We then had to take the RT- containing fluids and determine if we could induce this type of protein in white blood cells cultured from normal individuals.
Q. What actually does it mean to isolate a virus?
A. Isolation of a virus means that you can take a specimen containing the putative agent, filter it to remove cells and cell debris, and inoculate this material into normal cells and show that you can find evidence of this virus either because of alterations in the cells inoculated or because of proteins produced after the infection takes place. The important question then becomes whether this agent has clinical relevance for the disease being considered. When we isolated the virus from AIDS patients we knew about a retrovirus isolated at the Pasteur Institute. However, we were uncertain if this was the cause of AIDS or the result of a virus growing in an immune compromised person. Importantly, we needed to be certain that a retrovirus could survive all the procedures involved in passing an infectious agent to people with AIDS. One of the most notable questions was to know if it could be present in preparations of blood clotting factors, factor VIII and factor IX. They were made by procedures that we thought could inactivate a retrovirus. We began studies soon after we had isolated retroviruses from the blood of AIDS patients and completed those studies in early 1984. We found that a retrovirus could survive procedures for clotting factor preparation and thus recognized that this virus could be the cause of AIDS.
Q. What are the hurdles in developing an HIV vaccine?
A. We need to think of novel approaches to develop an HIV vaccine. A major challenge, not fully appreciated is the fact that this AIDS virus can be passed by virus-infected cells in genital fluids and blood not only by free virus. The virus also can mutate readily and various subtypes can exist and be resistant to immunologic responses induced by a vaccine.
Q. What did you do to relieve your stress while the intense work was going on?
A. The most stressful part of the early days was the time it took to determine if the virus we found was actually the cause of this devastating disease that was affecting so many people. Moreover, some people at the University were concerned about having this type of research conducted here. They thought the fear of AIDS might cause patients and students to avoid coming to UCSF. The mood in the lab, which in the early days was composed of only four or five people, was very uplifting and dedicated to finding the cause. I went to the gym and still work out almost every day. Also I find that I am greatly relaxed when spending time with my wife Sharon and friends.
Q. What vivid memories do you have of the early 1980s and your work in HIV science?
A. The most vivid memories of the early 1980s are of the young men who were so sick with no real hope of surviving. Our first patient was Dan Turner whose sarcoma lesions we cultured in the laboratory. Dan became a regular visitor to the lab and like so many we’ve been following for over 30 years became a “member” of the lab. He would share insights into the spirit and activities of the gay community in San Francisco and together we would discuss ways that we hoped would influence progress towards therapy and preventing transmission. It is unfortunate that Dan passed away just a couple of years before the current antiretroviral therapies became available. It was gratifying at the same time to be part of a small group of researchers in San Francisco who stuck together and gave each other support in our efforts to find the cause and a solution to AIDS. Among those was Marc Conant who helped me in the very beginning to get my equipment updated to look for the cause of AIDS.
Another vivid memory of the early days was the meeting in Los Angeles requested in early 1983 by the then State of California Speaker of the House, Willie Brown. He recognized the importance that AIDS held for communities in California and had a small group of us outline a program of research and care that could be supported by the state. He was able to obtain funds for us at a time when money was not available from the government. Those funds helped my group find the AIDS virus which I feel we could have done earlier if the money was available.