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Harden: I remember Dr. James Wyngaarden used to talk about needing either M.D.s or M.D./Ph.D.s to provide the interface between the laboratory and the clinic. Maybe you could comment on what a physician brings to laboratory research that a scientist without a medical training does not?
Gallo: What a physician brings to laboratory research that a non-M.D. does not is becoming more blurred now, and I think it is less remarkable. Jim Wyngaarden's book with John Stanbury and Donald Fredrickson, Genetic Inborn Errors of Metabolism, which was a book I used to carry around in medical school, was the frontier of medical science at the time. Clearly, in this area, M.D.s had contributed to, in fact, they had dominated, that kind of research. Before you could get ideas that were important in the field at the time, you had to understand the metabolism and all of the pathophysiology. So, that kind of research was dominated by M.D.s Not only did they contribute, they were absolutely essential to it. A Ph.D. could not think about such phenomena in the same way at all.
But, as science has progressed, medical science has passed this meta stage, and today there is much more blurring of the difference between an M.D. doing basic research and a Ph.D. doing basic research. Indeed, many Ph.D.s have now become more sophisticated in their knowledge of medicine. They have gotten more into applications. The new molecular biology brought this about, and I think we are at the stage of being able to apply many of the developments from basic molecular biology to clinical medicine. The Ph.D.s are well aware of this and their minds are open to learning more in medicine, whereas in the earlier period I think most Ph.D.s did not want to hear about the medical aspects. Now many cannot get enough of it, and so they start learning more broadly this way.
Meanwhile, an M.D., to survive in basic science, even basic science that has an implication for clinical medicine, has to have the tools of basic science. But I still think that an M.D., in general, has an advantage, with his or her greater breadth in medical biology, and the ability to see things from this perspective. The disadvantage is that sometimes, by temperament and by training, the M.D. has less experience in technology, and less experience in analyzing and criticizing data. I think that those are things that M.D.s have either to learn on their own or when they are in training in science. But an M.D. is not trained as fully or as rigorously as a Ph.D.
Harden: I have one or two more background questions before we get into more specific questions. I want to return to the question of the style of managing or leading a laboratory at NIH. I wondered whether there is any person, or idea, that particularly shaped your leadership style. I would also like you to speak about the fact that your laboratory is relatively large compared to many others. Many people prefer smaller, tighter laboratories, but you have a large one. How does this relate to your vision of research?
Gallo: When you ask about style, or about running either a large or a small laboratory, or about which model do I follow in my laboratory, I cannot point to an example. I look up to hundreds of scientists, but I do not think that there is one on whom I have modeled myself. I think perhaps that the person I tend to be most like, although he had a smaller laboratory–not because he wanted a smaller laboratory, but that was the way it was–is Alan Erslev. He was the man who discovered erythropoietin, and I spent some time with him in my summer years in medical school. I would say that his temperament, his personality–probably I was at a stage to be readily influenced by him–may have influenced me more than anything else in these matters. But, in the end, you are a product of your genes and your total environment, of your own will, imagination, and conscience, so all of those characteristics combine to affect your style.
I was also influenced by Sy Perry, by Ted Breitman, and by Sidney Pestka. There was also influence from a distance–it was more than admiration, perhaps the right word is hero worship–from Marshall Nirenberg and a few other people like that. So you do imitate a little. Then I had contact with [Dr. Solomon] Sol Spiegelman outside of NIH. He was an enormous competitor, and certainly increased my competitive instincts and spirit. There was also Bob Huebner with his breadth of vision in virology. You cannot help but be influenced by him when you hear him talk and when you meet him. Things are registering in your neurons–you do not even know it.
Often the other person never gets credit for influencing you because you do not even know it is happening. Sometimes when I have lectured and it has gone well, I hope that some younger people, or maybe even some older people, will be influenced and not even know it. All of the people and experiences combined together to affect me, but I cannot point to one man or woman who overwhelmingly influenced me. I suspect, because of my age and because I think my style is like his, that Alan Erslev may have had the most influence on me. Working with him was my first real job and the first time I had ever done research in a laboratory, so it had a serious effect on me.
Regarding size of laboratory, I think it is a mistake, and sometimes it is not well thought out, for people to argue this way or that way as if they have an answer as to what size is better. A case can be made either way. There is something that the average person, I believe, is always drawn to when you think and talk small. It is “Oh, isn't that nice,” whereas, if you are big, it is not so nice. But I believe that is poppycock. People do what they do according to the limits of their talent or what suits them best. There is no science that is better because it is small, or science that is better because it is big. There is no simple answer, actually.
I believe that the greatest scientist in my field in my time, the greatest man I have ever known, was the late [Dr.] Howard Temin. Howard was very different from me, but we were extremely close friends in many different ways, especially during the last decade, and, in that period, especially in the last five years or so. It is interesting, but in time I think we both came to appreciate the opposite point of view. I do not think that Howard, by temperament, by personality, or by his biology, could have run a large laboratory well. Not by brains, but because he just would not have been happy.
I think I would be lonely in a small laboratory, and I think by temperament, by style, and by my need for flexibility, I do better with a significantly sized group. Also, if the research is public-health-related, if it is medically related, you need flexibility. I think it is wrong for an NIH director now, and it was in the past, to try to pose questions about what the size of a laboratory should be. Individuals have different needs according to the nature of the problem they are investigating and according to their own temperament. Let productivity be the judge, and discovery and review. That is the way I see it.
But if you are looking at something such as, let us say, very basic research that has an implication for clinical medicine, sometimes you have to be able to move people from one direction in research to another direction fast. I never can do it by ordering somebody. My style is never to tell a postdoctoral fellow what to do ever. In fact, I have had a few who worked completely outside the main area of research of the laboratory. They did not do well. But the most I can do is to try to influence postdoctoral fellows. The way I could influence them is that I had them talk to everybody in the laboratory, including myself. I would try to convince them that subjects A and B were very important, because I knew where help was needed, but they had to make the decision on what they would work because you take away their excitement if you decide for them. At least that is my opinion.
There are laboratories where research is much more regulated, basic science laboratories and small laboratories, where, when a postdoctoral fellow comes in, he is told exactly what to do. “You are going to make this codon,” or something similar, if you were working in Nirenberg's laboratory at X period of time. But my statement is, “I have a biological problem. Here it is. This is where we are. This is what we are trying to do. These are our long-range ultimate objectives, and these are the people working in the laboratory.” I talk to every single one of the postdoctoral fellows. We have staff, section, and unit meetings regularly, and I go to as many of them as I can. I have meetings in my office to try to influence the postdoctoral fellows or the visitor to work in an area that I believe is important and where help is needed. But I think I personally thrive on the flexibility of being able to shift.
We have senior tenured people working independently of me in this laboratory and publishing independently of me. But, in some cases, our origins go back to a similar period of time. For example, let us take [Dr. Genoveffa] Veffa Franchini or [Dr.] Marvin Reitz, who have been here for a long time. They are both section heads. They publish independently. But we overlap in our research, cooperate frequently, and often publish, all three of us, together. We have never had a problem where one or other of them would say, “This is way out. I have no interest in it, because our interests are overlapping. It is natural. It happens without any arguments or fights, and just by virtue of the fact that our interests overlap and there is natural collaboration. I find it enormously beneficial to have that kind of inter-laboratory environment.
If your goal is to work on one enzyme well, you can do good science doing that and it is important. For instance, I know someone in Boston, at Harvard, who worked on an enzyme of herpes virus for his whole career. I do not think it takes a very large laboratory to do that, however. And you are happy. You are happy with your grant of $100,000, or $200,000, and you characterize that enzyme and study its function and biology for a decade or two decades. That can be very good science. It is the kind of science in which I do not think there should be any mistakes, or not too many mistakes. On the other hand, if your goal is–whether it is too large I do not know–to find the cause of a disease, to develop better therapy for that disease, and to understand its pathogenesis to the best of your ability, you had certainly better have a reasonably sizeable laboratory.
I hate the notion that there is a scientific style. I think it is just such hypocrisy and such nonsense. Or this notion of a scientific personality. People think of the more withdrawn person, the shy one, as the scientific personality. If you read books about making the atomic bomb, you find that [Dr.] J. J. Thompson, the man who discovered the electron, fits this personality perfectly. Then, in the same book, you read about Lord Rutherford who is always arguing and telling jokes, sometimes apparently with some color to them. I do not know [Dr. Francis] Crick, but from the stories I hear–I have met him once–if you compare Crick's style to that of J. J. Thompson, they are opposites.
Read [Dr.] François Jacob's book, The Statue Within, and you will see all the different styles of scientists. In this [book] Jacob admits that if it was not for [Dr.] Elie Waldman he would have been trapped many times in being wrong because when he would predict an answer–not to say that it is the method that everybody thinks that you follow.... I found out literally by reading Jacob's book that I do not follow the scientific method most of the time. You go by a certain intuition or a certain belief, or you think that this is how it is going to be and you go after it. Yes, you have to be objective enough to attack your own hypothesis, but you often start with a premise. To return to Jacob, he writes in his book, that often he would get there with one approach, and then he would become bored and go on to something else. But Waldman wanted to see the point that we really wanted proven from twenty directions. Thank God there are different personality styles in science.
Rodrigues: I want to follow up on that. Would you say that your decision to look for a human retrovirus was guided more by analytical thought or was it, as you have indicated, more of an instinctive feeling that this was something to go after?
Gallo: The latter. I think my decision to look for a human retrovirus at the worst time, when people were feeling strongly that one could not exist for multiple reasons, only some of which I put in my book, was certainly more of–I do not know what the right word is–an intuition, a belief, that, yes, there had to be a human retrovirus. The arguments that I was hearing that there was not a human retrovirus had, in my mind–maybe this is the analytical side–little holes in them. There could not be a human retrovirus because so many people had looked for one for so many decades and had not found one. Now, when there is a retrovirus, it replicates a lot and special techniques are not needed to find it. But then my mind was telling me, yes, but it is only the animal model that has been studied, and this was done for the reason that it was easy, because there was a lot of virus. What about the giraffe and the chipmunk in which a retrovirus has not yet been found? Maybe retroviruses are there and causing disease, but their mechanisms of doing so are not by overwhelming viremia. You would never study them because it is difficult and you do not even know that the virus is there. So the models that have been selected are the models in which you know there is a lot of virus. It is easier.
Then the next idea that came along was that in human serum there was the presence of a complement lysing system that could lyse mouse leukemia virus, that could lyse cat leukemia virus, and that could lyse and destroy gibbon ape leukemia virus. Therefore humans cannot be infected by a retrovirus because we have a complement lysing system that destroys retroviruses. Yes, that is true, but only in the few that have been tested. But, I knew that if humans got infected by a retrovirus, it would be one that had evolved to avoid destruction. So, for each argument I was hearing I could think of a counter argument. I had a strong feeling that retroviruses would be found in humans and it became, in time, maybe as much a belief as it was science, so I guess it was more what you would call an intuitive idea than a careful analysis of the problem.
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