An Interview with Robert Gallo
Robert C. Gallo, MD, Director of the Institute of Human Virology (IHV) at the University of Maryland School of Medicine and International Scientific Director of the Global Virus Network (GVN). Since 1996, Dr. Robert C. Gallo has been Director of the Institute of Human Virology (IHV) and Professor of Medicine at the University of Maryland School of Medicine. He is also the Homer & Martha Gudelsky Distinguished Professor in Medicine and Co-Founder and International Scientific Director of the Global Virus Network (GVN). Previously (for 30 years) he was at the National Cancer Institute (NCI) in Bethesda, MD. While at NCI, he and his co-workers discovered interleukin-2 (Il-2) in 1976.
Il-2 was one of the first cytokines (“messenger” molecules that allow cells to communicate and alter one another’s function) and proved to be a major tool not only for immunology but also for the discovery of all human retroviruses. Gallo and his colleagues then opened and pioneered the field of human retrovirology with the discovery of the first human retrovirus (HTLV-1) and along with Japanese investigators showed it was a cause of a particular form of human leukemia. A year later he and his group discovered the second known human retrovirus (HTLV-2). Dr. Gallo and his colleagues also independently discovered HIV, and provided the first results to show that HIV was the cause of AIDS. They also developed the life-saving HIV blood test. In 1986 he and his co-workers discovered human herpes virus-6 (HHV-6), the first new herpes virus found in more than 25 years and as workers in Japan discovered is the cause of Roseola. In 1995 he and his colleagues discovered the first endogenous inhibitors of HIV, namely some of the beta chemokines. This discovery helped in the later discovery of the HIV co-receptor, CCR5, and opened up entire new approaches to treatment of HIV disease.
Dr. Gallo has been awarded 32 honorary doctorates, is a member of the U.S. National Academy of Sciences and Institute of Medicine, and a member of the National Inventors Hall of Fame. He is also the recipient of numerous scientific honors and awards. Dr. Gallo was the most cited scientist in the world 1980-1990, according to the Institute for Scientific Information, and he was ranked third in the world for scientific impact for the period 1983-2002. He has published close to 1,300 papers.
Do you think that HIV-1 eradication can be achieved one day and why?
This question could be taken two ways: the first meaning the eradication of the virus from an infected individual, and the other meaning eradication of the virus from the planet. Ironically, I do believe we can eradicate the virus from the planet, but I do not think one can fully eradicate the virus from an already infected individual.
Let’s start with the idea of eradication of the virus from an infected person. Really, of course, this is only a guess because no one knows the answer to this question. My best guess is that it is very unlikely, and to prove it would require a post-mortem examination because we have seen many times that in monkey models we thought no virus was left until post-mortem found some viral sequences in some lymph node tissues. We can also question the logic of making this a monumental pursuit at the expense of some other areas that might be more pressing and more practical – like reaching out to communities at high risk by testing and earlier treatment. I recall that the U.S. Centers for Disease Control and Prevention (CDC) estimates 20% of those infected in the U.S. are unaware they are infected.
As for interpreting the question of eradication another way, such as can the HIV epidemic be ended and ultimately eradicated? I do believe this is possible by lowering the virus substantially in the bulk of currently infected people so that the epidemic cannot be sustained.
Do you think that HIV-1 functional cure can be achieved one day and why?
Yes, I think a functional cure is possible. In fact, we are really reaching that stage when we have drugs that allow people to live a reasonably normal life and with the lack of the profound suffering that used to occur prior to therapy. But I know the question really means can we have patients never again needing therapy, and yes, once again, I do believe that is a possibility. The approach that I would think best would be continued research on long-acting, safe, non-toxic drugs. Some of the new integrase inhibitors may fit that requirement. Perhaps these integrase inhibitors coupled with some of the more powerful broad neutralizing monoclonal antibodies might make a serious difference. My concern about the use of the monoclonal neutralizing antibodies is their longevity. They may not last very long and this may alter the dynamics of the antibody virus interactions as the monoclonals are needed to be used again and again over a period of time. Nonetheless, I do believe that we could reach a situation where we will have safe, long-lasting therapies that allow people to withdraw from drug therapy.
In terms of therapeutic vaccine, is there some hope?
I don’t think so. I don’t think therapeutic vaccines are likely to do very much. There have been many trials of therapeutic vaccines and they haven’t done much of anything. And even with the best ideas we have today, one can see reasons why they would not be a panacea.
In terms of preventive vaccine where are we and where do we go?
As you may know, I just wrote with my colleagues, George Lewis and Tony DeVico, a perspective in the U.S. Proceedings of the National Academy of Sciences. In this perspective, we pointed out that our thinking is that we must target the gp120 component of the HIV envelope, and since it is hyper-variable we have to target conserved regions which are hard to get at. We also believe there are approaches to do that. We believe that the variation of HIV is not the most serious problem rather that it is the longevity of the antibodies that target gp120. For unclear reasons, they do not last very long, usually ending in months. This is not unique – there are other antigens that induce antibodies that are short-lived. We feel that we must find the answer to that because continued boosting is neither feasible, practical nor without risk, and likely in the end would fail as the quality of the immune response will change after repetitive boosting. This is a basic immunology science question and we think there are approaches to find answer to it and indeed our Institute is very much involved in such research. There is however an additional problem and that is that we know we need T cell help to make antibodies, and when we pursue agents that give higher antibody titer and possibly longer lasting antibodies in monkey experiments we find that these approaches reactivate too many T cells which provide new targets for HIV infection and thus we can lose the efficacy of the vaccine. Consequently, we need to find the right balance between inducing the right titer and longevity of antibodies and the T cell response. Again, I think this is doable but will require additional basic research.
Now there are some other claims of success that are different than targeting gp120. For example, Dr. Morgane Bomsel from France has targeted gp41 (the other component of the HIV envelope), specifically the gp41 region called MPER, and she has very interesting and positive results. I have heard her present it at our Annual IHV International Meeting on a few occasions. I think this is exciting but must be confirmed. There are many people in the field that have not paid much attention to it because approaching that region of gp41 by others has not worked well. We will see in the next year if this data is confirmed and if positive it will certainly move the field in a different direction.
There is also another work from France by Jean Marie Andrieu and his collaborators in China which is very unorthodox with astoundingly positive results in Chinese macaques. This involves inducing tolerance to the virus. Certainly a unique pathway, and one again that has not been pursued by others and felt to be controversial but which is now being studied by independent groups such as Dr. Guido Silvestri and his colleagues at Emory. That answer as to whether this approach is confirmed should be available very shortly, within the next few months if not even earlier. If this is confirmed it will also change the direction of the field substantially. I cannot predict either way.
Key words: HIV cure, HIV persistence, HIV reservoirs, HIV vaccine, Robert Gallo, interview