THE ONCE AND FUTURE GALLO

by Rebecca Kolberg

Most researchers enter and leave NIH without creating many ripples beyond their own small, scientific circles. Robert Gallo's arrival as yet another eager young physician attracted little attention at the Clinical Center in 1965. But his departure 30 years later is certainly making waves in Bethesda and beyond. This fall, Gallo, the longtime chief of NCI's Laboratory of Tumor Cell Biology, plans to take the helm of his very own institute: the Institute of Human Virology at the University of Maryland in Baltimore. Accompanying the pioneer in human retrovirology will be William Blattner, chief of NCI's Viral Epidemiology Branch; Joseph Bryant, chief of NIDR's Animal Care Unit; and Robert Redfield, an infectious disease expert at the Walter Reed Army Institute of Research in Washington, D.C. An as-yet unspecified number of other scientists will be joining them from NIH and elsewhere. Although Gallo is certainly looking ahead to his new challenges, in a reflective interview with The NIH Catalyst, he talked about the evolution of NIH over the past three decades, as well as his own evolution, or some might say trial by fire, as a scientist.

Robert Gallo

Q: How have you changed as a researcher since you started at NIH in 1965?

Gallo: Back then, I think I saw NIH, myself, and other people with more idealism. ... Maybe that's just the normal process of maturation, or maybe that is a change in biomedical research. ... When I came, there was no biotechnology industry. ... Now, I think biotechnology and the commercial side is a good thing because it catalyzes getting new therapies to the clinic. But on the other hand, like chemistry and physics before us, the age of innocence is lost for biomedical science. ... Another factor is that there were many more young medical doctors interested in basic research and coming to NIH with their eyes wide open--and their mouths wide open with awe. I don't see that as much now.

I think the way I've changed is that my first five years were really a time of desire for intensive training in the tools of laboratory research. ... In the next decade or so, I applied what I learned in those early years to basic types of research. As for where I stand now ... my change is actually a full circle. Coming from an early clinical background, I now want to go back to seeing clinical applications of what I do in the lab-- much more so than I've been able to do these past five or six years at NIH. ...

I was also much more in a hurry [as a young scientist]. Certainly, I had more spirit of competitiveness in those early years--more insecurity in a way, more desire to know everything. And then came the realization that you can't always know and do everything. I guess that's part of maturation.

Q: And how has the NIH intramural research program changed?

Gallo: There's certainly a higher percentage of people from abroad and significantly fewer young people from the United States. ... In the mid-'60s, early '70s, it was almost essential for an M.D. going into academic medicine to spend some time at NIH. That is no longer true. This also might be paralleled by a slight lessening of the number of the young M.D.s interested in academic medicine.

A second change is that there is perhaps a little less focus or priority on some of the clinical programs. ... Although there was obviously great basic research when I came to NIH, I think the visibility and focus was more on the health aspects of research. Is it better to emphasize the science, or is it better to emphasize the health? ... I submit we clearly need both sides. ... Ever since I've been here, there's always been a mixture of the two, but I think there's a tendency away from the "h" part of NIH, maybe more toward the National Institutes of Basic Biomedical Science. ... Personally, I want to be where I can have a more direct clinical outlet for our laboratory research.

Q: What advice do you have for young scientists just starting out at NIH today?

Gallo: I still think this is the best biomedical research institution in the world--the greatest combination of people with diverse talents, backgrounds, and technological expertise. ... I could not have done outside what I did here, I'm sure of that. ... Careerwise, I personally owe everything to NIH. So one of the things I would say to the younger people is that there is still plenty of opportunity at NIH. Although it helped build its own competition, it still is the place where you can have the most diversity of experience--have the greatest contact with the greatest number and variety of clinical and laboratory scientists of any place in the world. Take advantage of that. There is no place that gives you as many visiting scientists, as many people from abroad, as many people stopping through. Make as many contacts as you can.

Another thing to remember is that if you intend to be an experimental scientist ... begin to apply technology as soon as possible because you learn as you are applying. That's the way one really learns--plunge into the experiment, make some mistakes, and learn as you go along. ... And don't be afraid to seek contacts outside of your own laboratory even if your laboratory chief is a little possessive. ...

Also, at 35, I tended to report what I saw objectively. At 45, when we had a string of successes after some difficult years, those successes led to perhaps some overconfidence. ... So, for example, I hypothesized in '82 that AIDS would be caused by a retrovirus that targeted T cells. ... I certainly, absolutely assumed and predicted it would be a variant of HTLV [human T cell leukemia virus]. ... The reality of it, of course, was that Mother Nature plays interesting games. It would be a retrovirus, it would be a retrovirus that targets T cells, but it would not be a variant or recombinant of HTLV. It was a whole new family of retroviruses--my god! It took me too long to acknowledge that the data was going in that direction. ... That's a lesson. It's very hard to retain the freshness of the beginner with [the] knowledge and confidence of the more mature scientist. So, to translate this into concrete advice: have your hypotheses, but don't try too hard to put Mother Nature in her place.

Q: Why did you decide at this point in your career to enter the academic research setting?>

Gallo: There are a number of reasons, but the most important one by far was the desire to bring the 30 years of lab research more into the clinic, which I can definitely do better outside [NIH] than inside, coupled with the fact of the timing--my 30th year ... when I'm eligible for retirement.

The reason I can do more clinical research outside [NIH] is because ... I'll be in administrative control over such decisions and I will have my own clinical program. At NIH, I chose to be head of a lab or branch that is nonclinical, but in the past five years, I sort of wished ... that I had a clinical outlet and could more prioritize what I wanted to move from the lab to the clinic. Instead, my position at NIH is dependent upon the interests of members of the large pharmaceutical industry with whom I might have CRADAs ... or on higher [NIH] administrators' perception of the value of this or that ... .

Since the early `80s, I have had a vague dream that if I left NIH, I would like an Institute of Human Virology. ... I want to leave a legacy. ... NIH laboratories tend to be reshuffled and very often, there will be nothing left a year or two after you're gone. I'd like to see something specific left behind when I retire, if I ever totally retire.

Q: Why did you opt for academia rather than private industry?

Gallo: Because I can do everything I want in an academic setting and it's a less traumatic change, less of a psychological change. ... No, it doesn't pay the same amount of money. But I'll be fine, and that's what I want to do. I want the interaction with the academic circles. I want to be able to infiltrate, if you will, the pathology department, the medicine department, the cancer center at the University of Maryland. I want to be able to have closer collaborations with people at [Johns] Hopkins. I want to maintain close collaborations with people at NIH. I think if you are an officer in a company, these things are more difficult.

A 1966 photo of the NIH Clinical Associates finds an eager, young physician named Robert Gallo standing in the back row.

Q: Whom are you taking along from NIH? What criteria will you use for assembling your team at the University of Maryland, and what will its primary research goals be?

Gallo: I'll take the best people I can take from anywhere to build the best possible little piece of NIH that I can build. ... It also depends on what I can afford and who will follow. I can't give you specific numbers, but I can tell you that when the information came out that I was leaving, a very large number of people at NIH did write to me, including some lab chiefs. My goal would not be to make this new institute 100% ex-NIH people. I'm looking for some kind of balance in the science that is there. Some clinical, some epidemiology, some very good basic researchers. Everybody is not going to be a virtuoso ... because we are going to be practically oriented to solve a problem. ... And [the Institute of Human Virology is] not going to get big fast; it's going to grow in steps. ... If this institute is as successful as we strive for, in three to five years, it will be around 300 people. ... Our primary scientific goals will be [to study] chronic viral diseases clinically and in the laboratory and to develop better therapies for them and to have some role in preventive vaccine development, as well. The focus will be on AIDS, but ... there will be studies of some herpes viruses--some of which are relevant to AIDS, some of which aren't; the leukemia viruses, HTLV-1 and -2; and in time, we are hoping, some hepatitis viruses and some papilloma viruses.

Q: What do you consider to be your biggest achievement at NIH?

Gallo: The thing I'm proudest of is that we were the most referenced lab in all of science for the decade of the 1980s. ... As for specific sets of experiments, when outsiders introduce me, they often say I opened the interleukin field with interleukin-2 and [the] culturing of T cells. But that was not a planned experiment or an objective. Consequently, I would say it was breaking through to demonstrate that human retroviruses existed and ... that they could cause disease. ... In a practical sense, we've had things that have gone into the clinic, including interleukin 2 and the blood test for HTLV-1, which is now required [for blood donors] ... .

But obviously, the best feeling I have is to know that [the] development of the HIV antibody blood test was not only key to contributing to our knowledge and evidence and conclusion that HIV is the cause of AIDS, but that it saved a lot of lives. I'm proud that it moved fast, and I'm proud of the government role in that.

Q: What "hot" research leads are you currently pursuing, and will you be able to follow up on them in Baltimore?

Gallo: We will certainly be maintaining a heavy emphasis on Kaposi's sarcoma and HIV-associated Kaposi's sarcoma. We will be beginning an effort in HIV-associated B-cell lymphoma and continue exploring the mechanisms by which HTLV-1 causes leukemia and neurological disease. We will continue using antisense constructs to target HIV and also continue and expand gene-therapy work on HIV. We will continue and possibly expand vaccine efforts against HIV. We will continue, but not expand, work with the herpes viruses we discovered in the mid-'80s. ... We are getting increasing evidence [that] the human herpes virus 6 may play a catalytic role in HIV progression as well as being involved in harming bone marrow biology. We will look at biologic factors that regulate HIV replication and continue, but probably reduce, studies of cellular factors that HIV needs for replication. With FDA approval, we hope to initiate new clinical trials in some of these areas soon. ...

Q: Based on your experience with the HIV "discovery" controversy, how do you regard the handling of scientific-integrity issues by the government?

Gallo: I don't know where it's heading now, but obviously, it's massively improving because it's been reassessed. Before, it was nothing short of a farce. ... Nobody would realize or believe, so I don't really want to get into, the madness that was going on in that period of time. ... It was so bizarre, one could make a wonderful Broadway comedy out of it--or a tragedy.

Q: Do you consider yourself fortunate that your scientific career has survived such an ordeal?

Gallo: Most people say I am fortunate. But what did I do? ... Yeah, in one sense, I feel lucky, but on reflection, obviously, this was not the case. I lost six years, and my lab was blocked for six years, and we were harassed day and night for six years. I don't know what gods I should be thanking for that. And I don't feel lucky that much of the scientific community didn't engage itself adequately. ... How could you not feel that way when nothing was done wrong? ... It's a horror. You can't fight it. You can't control it. You certainly can't do anything about a writer [John Crewdson of the Chicago Tribune] who follows you day and night for seven years. You feel like Jodie Foster with [John] Hinckley. ... I think that a little more vigor was needed [within the NIH community] in evaluating what was going on and maybe a few people who truly understand what was happening and would be willing to stand up for me and my colleagues. ...

Q: What do you think NIH leaders and researchers can do to improve investigations of alleged scientific misconduct?

Gallo: It would help if the leaders as well as the scientists were more vocal about abuses by the "investigators." Organize something more nationwide where scientists couldcometogether who are fair-minded and who understand the field they are talking about. Avoid self-righteous know-it-alls. Never allow people from totally foreign fields to evaluate what they do not understand. ... Speak out when there is abuse of congressional power. Congress should be nowhere near this kind of stuff. ... And when [you] see Congress trying to control NIH through a planted person, react as strongly as possible and be willing to give up your job so this never happens again. It's not likely to happen any time soon again, but how did it ever happen in the United States in the first place?

Robert Gallo, left, at lab meeting.

NIH should have a strong director, which it has now, and the NIH director can have a committee to try to judge accusations rapidly. Someday somebody will cheat--that's inevitable. Minor data manipulation will sporadically occur, and sometimes will never be discovered. This hardly affects the flow of science and is not worth millions of dollars in effort and the blatant denigration and slander of innocent people. This has been the case. It is like putting the FBI, CIA, and KGB in charge of finding out who might have taken some candy from a grocery store and, in the end, finding out that no one did.


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