Q&A with Harvey Alter

An award-winning alumnus targets invaders in the blood

Harvey J. Alter, M.D., M.A.C.P., graduated in 1960 from the University of Rochester School of Medicine and Dentistry. He has spent most of his research career at the National Institutes of Health. He is currently a Distinguished NIH Investigator and serves as chief of clinical studies and associate director for research in the Department of Transfusion Medicine. He is co-discoverer of the Australia antigen that proved to be the hepatitis B virus and was principal investigator in studies that identified non-A, non-B hepatitis, defined its chronic sequela and later showed its link to the hepatitis C virus. His prospective studies of transfusion-associated hepatitis demonstrated how different donor interventions reduced hepatitis incidence from 30 percent in 1970 to near zero in 1997. For these studies, Alter has received many honors, including the U.S. Public Health Service Distinguished Service Medal, the Landsteiner Prize, which is the highest scientific award of the American Association of Blood Banks, the Presidential Award of the International Society of Blood Transfusion, the James Blundell Award of the British Blood Transfusion Society, and the Inserm Medal from France. He was elected to fellowship in the American Association of Physicians. For his contributions to the discovery of the non-A, non-B/hepatitis C virus and for his vital role in reducing hepatitis risk and improving the safety of the blood supply, Alter was the co-recipient of the Clinical Lasker Award in 2000. He was elected to the National Academy of Sciences and the Institute of Medicine and was made a Master of the American College of Physicians. 

How did you get involved in transfusion medicine?

I was an undergraduate at Rochester, a graduate of the medical school and I did my internship there. I was drawn to internal medicine. I loved the medical program. I might still be in Rochester if I had not been drafted out of my residency. They were taking first-year residents, at the time considering them expendable. I had been accepted to NIH but I had not been commissioned. I did a lot of scrambling. Scott Swisher, who was then head of hematology at Rochester, had a connection with the organization that is now the FDA. He helped get a position for me in what was called the Division of Biologic Standards that ran the blood bank. That’s how I got into transfusion medicine.

In August, you were the senior author of an article in The Proceedings of the National Academy of Sciences that reported findingmurine leukemia virus (MLV)-related gene sequences in cells from patients with chronic fatigue syndrome (CFS) and from some healthy blood donors. That caused quite a stir. How did you get interested in chronic fatigue?

The abiding theme through most of my career has been transfusion-transmitted disease. The report in Science that came out last October linking chronic fatigue syndrome to the retrovirus XRMV didn’t prove the link but raised the possibility of blood transmission. One of my collaborators had samples in hand from well-pedigreed chronic fatigue patients. We had stored blood donor samples. We wanted to look at XMRV DNA in those peripheral blood mononuclear cells. We did not expect what we found: a strong association of MLV-related virus with chronic fatigue patients. The virus is also present in normal donors, but the differential was great. We found mouse leukemia (MLV)-related gene sequences in 86 percent of chronic fatigue syndrome patients and in approximately 7 percent of healthy volunteer blood donors. This raises the possibility that chronic fatigue could be due to a virus and transmitted by transfusions. We have not proven the virus causes chronic fatigue, but we have proven that the virus is there. If it does cause chronic fatigue, it opens the possibility of treatment. Viruses have a way of finding me, instead of my finding them. If this chronic fatigue link pans out, there are years of work in that. Unfortunately, I don’t have many years left. There is a lot about this that remains unanswered. I think chronic fatigue will prove to have a whole spectrum of causes. Some will be viral and some won’t be. I am convinced this is a real disease for some people. I get letters from these patients and they are so desperate. Their lives have been totally disrupted. If a treatment could come out of this research, it would be a great.

 What other targets do you have for your research?

We are looking for everything, any agents that threaten the blood supply—malaria, dengue, West Nile virus. We also are interested now in developing gene chips that would enable you to look for 20 or 30 agents at one time using a relatively small amount of blood. This technology is just emerging. An ultimate goal is to inactivate viruses. There are technologies out there that try to do that but it is not clear they will pan out. There always seem to be another agent that is a threat and interests me. This work is still so interesting and fun, even after all these years. I’m in a very nice setting. NIH is a spectacular place. I have a good boss who lets me do what I want. I may have to quit someday, but I am reluctant to give up. The journals pile up on the floor. There are so many interesting things, not only in viruses, but in all of medicine. I’ve kept myself in a narrow field, hematology and now hepatology. Hematology was so strong at Rochester that it was very influential in which direction I took my career. Liver and blood have overlapped with infectious disease for me. I work a lot in fields where I have not been trained, but I learn by osmosis.

What concerns you about research today?

It is very hard for a young guy starting out. I have a son who is beginning his research career. He has his first grant but it is a constant battle to get funding. Everything now is so sophisticated that it makes research very costly. It has been touch and go for many people in academia. Rochester has done very well in funding. The faculty have an admirable record in getting grants. It was and is a great medical school.

What is the one nemesis or problem you would like to solve before you retire?

How to save enough money to retire! Besides that I would like to find a way to inactivate pathogens in blood rather than having to test for them. This would not only increase the safety of the blood supply since there are many agents we can’t test for, but also would provide a preemptive strike against a totally new lethal agent, such as the next HIV-like agent, that might devastate the blood supply. Unfortunately, my chance of achieving this in the time I have left is very slim, but younger and smarter people are waiting in the wings.