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Harden: In your book Virus Hunting, you said that you learned, first about molecular biology, and then about skepticism in science, from Sidney Pestka. Would you expand on your comments about him and explain what you meant by that statement?
Gallo: Yes. I learned a number of things from Sidney Pestka. I have commented on Sy Perry and Ted Breitman, my first training in enzymology, and in basic science, more or less. What I did in erythropoietin as a medical student could be called basic science, but my first real biochemistry was with Breitman, and with new kinds of tools that I was not used to.
With Sidney [Pestka], I was extremely “professionalistic” and probably a little compulsive, too. What I remember best is that he never believed anything. A situation occurred which I described in the book and which I can never forget, because I wondered if I would be killed in the process. Sidney did not believe that the isotopes that were sent to us were necessarily what they were supposed to be. If New England Nuclear said, “This is labeled ‘tritiated leucine,'” Sidney said, “Go prove it.” We always had to do high-voltage electrophoresis on the isotopes. I had never done high-voltage electrophoresis before and I think that I am lucky that I did not end up staying in that group permanently as a mummy after doing high-voltage electrophoresis.
But one day I came to Sidney with some water. I said, “Sidney, how do we know this is water?" Because he was always saying we had to reidentify everything that we received. But, if you start thinking that way, you could never do any science, because you have to believe something at the beginning.
But I think Sidney's approach resulted from his experience in Marshall Nirenberg's laboratory where it was very important that they remove any traces of contaminating amino acids. They always subjected the substances that they were sent by some of the companies to such analyses.
Rodrigues: One question that always comes to mind when I talk to people who have worked in a laboratory and who, at a later point in their career, move into an administrative, or a coordinating role, is how do they feel about the transition? What did you feel when you moved out of the laboratory and were no longer working at the bench?
Gallo: The transition was gradual. Let me phrase my thoughts a little better. In moving from working full-time in the laboratory to not working there day-to-day, I cannot say that there was a specific moment when there was an emotion about it, because the transition occurred in multiple steps. It was not an all-or-nothing phenomenon. It occurred little by little until I finally had technicians or postdoctoral fellows joking with me, “Please don't use the equipment because you are not going to do it right.” Then I started realizing that I was not spending my time best by being in the laboratory; it was better that I spend it talking to the postdoctoral fellows because they could do things better than I could. Of course, in time in a laboratory young people come in with new techniques that you have never done. When this occurs, the word that describes my feeling about this is insecurity.
It is not a good feeling when a young postdoctoral fellow has been well trained in a good laboratory in a technique that you have never seen done and that you need to know about. Then he or she becomes your mentor in learning such a technique, so that is not easy. This happens increasingly when technology changes as fast as it does in modern biology. There are always new techniques and there is always a young person bringing something new to the laboratory, so you have to become accustomed to it. After a while this insecurity passes and you try to give back what you are receiving. There are so many new things to learn from incoming people.
I would say that I did not have any traumatic emotions about going outside the laboratory and taking on a director's role. I do not like to call it managing. I hope to call it leadership. I think there is a difference. I have read the book by Stephen Covey [The Seven Habits of Highly Effective People] that is a best-seller. It said managers push people up the ladder, but a leader has to know that the ladder is on the right wall. I think that a laboratory chief at NIH, if he is not working all the time in the laboratory, should be making sure that the ladder is leaning against the right wall.
I have to say that I was never overwhelmed with the need to pipette. I think there are people who need it for the serenity of it all. I am not one who feels that this is necessarily a great pleasure. I like seeing the results when they first come out when they do that.
Rodrigues: In 1972, when you were made Chief of the Human Tumor Cell Biology Branch, you renamed it the Laboratory of Tumor Cell Biology. This, in NIH's designation, indicated that there was a shift from a clinical to a basic science focus. Would you elaborate on your decision to emphasize basic science, and yet to emphasize studies that were closely related to disease problems?
Gallo: Yes. I changed the name of the unit. Of course, we were the administrative unit on it. The change from Human Tumor Cell Biology Branch to the Laboratory of Tumor Cell Biology was appropriate, because the laboratory was moving more towards basic science and away from day-to-day clinical involvement.
I felt–and I guess this happened to many people–that science was becoming more and more complicated. There was more and more technology, and it was becoming increasingly difficult to be good at this, and to be good at that, as well. I did not believe that I had to be good at everything. I just could not keep up with it. I did not think that I could be a good clinician and continue having patients and all the responsibility of that in Building 10, and also be able to do productive research that I felt was useful and exciting, and important and fun. You try to put all those things together and do it well, and, in addition, say, “I am also going to be on the wards.” But, at a certain point, I did not feel that I could handle it all, so I had to make a choice.
On the other hand, I try not to forget my origins and the advantages that I have. I think the advantages M.D.s have over Ph.D.s, if I may say this, is that they have a broader knowledge of biology related to medicine. I try to continue that. I thought that the NIH was the best place in the world to be at that time, because there was no doubt in my mind that it was unique in that scientists were able to do research that could be applied to clinical medicine.
I always thought that a good function of a laboratory at NIH–it does not have to be–was to have a theme, whether it was protein chemistry like Anfinsen, or the genetic code like Nirenberg. It is not exactly like a university department, but a branch or a laboratory at NIH is a sort of department with some independent investigators. The difference is that NIH laboratories have a theme, whereas a university department that has to teach all kinds of things does not necessarily have one.
I believed that the study of the biology of blood cells and their normal growth and differentiation would have ramifications for the understanding of the abnormal, for leukemias and for lymphomas, or for lack of production of blood cells–aplasias–or for deficiencies, like the immunodeficiencies that we find, like AIDS ultimately.
To this day, in my laboratory we study AIDS and we study leukemia and lymphomas. Sometimes we have branched out a little from those themes. We now do some research in breast cancer and obviously in Kaposi's sarcoma, but basically AIDS and leukemias and lyphomas still receive the emphasis in this laboratory. I believed that we could make our greatest impact by doing basic science, making our results known, publishing and presenting them, and hoping that they will get picked up for use in the clinic.
Sometimes this works well, and sometimes it does not. Let me give you an example. In 1993, the General Motors Award went to individuals from France, I think, and China for the retinoic acid treatment for acute promyelocytic leukemia. But I bet that very few people know where the first observation on this was made. It was made in this laboratory a decade earlier. So the discovery did not get picked up very fast. We established a cell line called HL-60. It was the first of the cell lines ever to be established–and there are only a few such cell lines today–of the granulocytic, or myeloid, leukemias. The cell line was established from a patient with a promyelocytic leukemia, and it was done by a postdoctoral fellow of mine named [Dr.] Steven Collins, who is now at the University of Washington in Seattle. We were deliberately trying to grow these cells and one immortalized, and that was unique.
Then Ted Breitman, who, as you will remember, was my mentor, but ironically, when I was a Branch Chief, he worked for two years, in this branch. Breitman discovered that retinoic acid would induce the cell line to differentiate normal cells, stop its growth, and terminally differentiate it. The research was published in a visible journal, but it stayed there rather dormant. Somehow, a decade later, we hear that people are getting dramatic remissions from promyelocytic leukemia with retinoic acid. That is an example maybe of where the transfer of knowledge from the laboratory to the clinic did not work very well. This discovery should have reached the clinic earlier, I think, from the observations we had made and, if I had had a clinic, it would have.
But now I will give you an example of a transfer that did work well. As is described in my book, partly by accident in my laboratory we made the discovery of what today is called interleukin-2. I knew that I was not going to see, nor was anyone with me, the ramifications of this for the clinic. We were using it purely as a practical means for growing human T cells for virological studies and cell biology. But I knew that there were clinical immunologists in the Cancer Institute [NCI] who could possibly make use of interleukin-2. While the paper was in press, I discussed the results of our work with [Dr. Steven] Steve Rosenberg here at NCI, and with [Dr. Ronald] Ron Herberman, who is now the Director of the Cancer Center at the University of Pittsburgh. Indeed, we began seeing applications of interleukin-2 ultimately into the clinic. That happened very rapidly.
Harden: We will come back to a number of these items.
Gallo: The other question that you did not ask me is what it is like when an M.D. without much–or with little–training in science comes to the NIH. I have described the feeling of awe, but what about when the M.D. gets into a laboratory and does not know anything about equipment and so on? That is an interesting question.
Harden: Let me ask you that question.
Gallo: It gives you a horribly insecure feeling.
Harden: Does it really?
Gallo: Yes. I was very uptight about this, because one of the first things that I saw when I came to NIH was the analytical ultracentrifuge. When I saw it, I said, “I am never going to learn how to use these things.” It was a nightmare. All those buttons. I thought, “I will never remember.”
Rodrigues: It sounds as though in medical school you had had no contact with such equipment.
Gallo: No, of course not. Analytical ultracentrifuges and things like that? A medical student gets a little exposure to equipment in a biochemistry laboratory, or a physiology laboratory, but not to anything like an analytical ultracentrifuge. I worked in a biology laboratory run by [Dr.] Alan Erslev, where there were rats and mice and partial purification was done of some things, but it was very crude analysis. And bioassays. We had never seen some of the modern equipment that I came into contact with on my first day in the laboratory at NIH.
Harden: Let me ask you then. As a physician, when you were thrust into a basic science laboratory, what was your reaction?
Gallo: My dominant reaction at the beginning, other than the actual curiosity about it all and the desire to do well, was fear. It was a fear that I would not be good enough, and a fear of all this equipment, some of it looking terribly complicated.
I remember a friend from the University of Chicago who was working with Donald Chudee and who ultimately died of malignant melanoma. One of the first pieces of equipment that he introduced me to, as I was trying to pick up some things for my own research, was the analytical ultracentrifuge. I looked at all the buttons and all the other gizmos on that machine and said, “I am never going to learn how to do modern science, how to use all this equipment.” When I first met Dr. [Arnold] Beckman–I had to give a lecture in his honor once about six to eight years ago–I said, “You saved me, because, like other M.D.s, I could always bank on the Beckman pH meter. I just pressed a button and took a pH.” I said, “It gives us a little confidence.”
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