From an oral history interview with Dr. Robert Gallo by Dr. Victoria A. Harden and Dennis Rodrigues of the NIH Historical Office, Aug. 25, 1994, pages 25-30. Gallo's laboratory had suffered two mysterious power failures, including a pulled out power plug, which destroyed their work; and a contaminated culture that was reported first in public.
Rodrigues: In talking to other investigators, and based on our own research, one program that came up a number of times when we started talking about the [National] Cancer Institute and its research in the 1960s was the Special Virus Cancer Program that Dr. Robert Huebner and Dr. George Todaro ran. You stated in your book that you disagreed with Dr. Huebner's theories about endogenous retroviruses, yet you found the arguments in favor of them highly stimulating. Could you elaborate on this and on the larger value of keen scientific argumentation as a mechanism to stimulate precise thought?
Gallo: The Special Virus Cancer Program was actually not headed by Huebner and Todaro, but was first administered by [Dr. Frank] Rauscher and then by [Dr.] John Moloney. But Dr. Huebner and Dr. Todaro were the two most obvious, visible, and famous virologists that were funded by the program and also, in turn, funded other people by a contract program that was controversial at the time. That led to the Zinder Committee's evaluation of it...
Now, Bob Huebner and George Todaro had a famous theory called the virogene/oncogene theory. It is true that I did not believe in the literal aspects of that theory, and it is true that that theory was not correct. However, the catchy word "oncogene" certainly produced some thoughts about going after a particular gene, or genes. Huebner and Todaro thought it would be one gene originally, or maybe a couple, and it turned out to be a very large number. Their knowledge and ideas that cancer had to involve something in the gene, something in the DNA, were already there, so that was not novel. But when you started to speak about it as a specific gene, or a few genes, I think that, in itself, helped to crystallize peoples' ideas on looking for such genes. But I could not imagine that the theory they were proposing, that virtually all of cancer, if not all cancers, was simply an activation of a set of endogenous retroviruses which included within them an oncogene, was the way cancer developed for many reasons. One reason was that all kinds of activation of endogenous retroviruses in animals were not associated with anything, except publication of papers. You would have it, you did not know what it meant, and there it was.
Also, I was impressed by the lack of evidence, after an intensive amount of work, that such viruses were ever playing a role in cancer. I was more impressed by the people -- such as [Dr.] William Jarrett in Glasgow who had discovered feline leukemia virus -- who pointed out that, when there was a clearcut viral cause of malignancy in an animal, it came from without.
But Huebner, in retrospect rightly, countered my argument, and not bashfully either, by saying that it was crazy to think of cancer being catching. You will raise the issue of catching. Well, the more I looked, the more I saw, and the more I thought of models that, increasingly, were showing an acquired virus. Bovine leukemia retrovirus came along in the early 1970s. There was not much virus replication. Maybe humans had the same kind of retrovirus. We did. And it was infective, maybe in utero, so it was not seen as a horizontal spread. That happens. We now know that happens in general infection. Quite frankly, I suspect more things happen congenitally in the causes of diseases that we do not have etiologies for right now than we know. I should rephrase that. I think we will see more diseases for which we do not now have etiologies that will be shown ultimately to be due to congenital causes...
Harden: When you related the story of working on HTLV-1 in your book, you talked about losing the cell line that was on a freezer plate and probably carried HTLV-1. This was before the Hershey meeting.
Gallo: Yes. Actually, a slight correction is needed. That mistake is often made because I put them too close in the chapter. It was not HTLV-1, it was just before HTLV-1.
Gallo: It would have been HTLV-1.
Harden: Yes. That was my point. You did not quite know what you had. It probably would have been HTLV-1.
Harden: We have heard many stories from scientists about freezer failures, yet, supposedly, the NIH has a very good back-up system to prevent this from happening. What happened in your case?
Gallo: I do not know. We had two disasters from freezer failures. I think we know the origin of one of them. You can get paranoid in the laboratory when things go wrong, and the person closest to the research gets the most paranoid. We found a plug not plugged in, and it was over... That was on one of these occasions. I always get them mixed. But twice we had freezer accidents that were very costly.
In one of the two times it was over a holiday. We came in and found the plug pulled out. People began thinking somebody was sabotaging the experiment, and that sort of thing. But sometimes it is due to the cleaning people. We did not have any back-up in that instance. I do not know what happened. But we lost everything in that freezer.
Harden: What happened at that first meeting at Hershey? You described the disappointment of finding out that your cell line had been contaminated.
Harden: What surprised us was reading that the scientist who reported the contaminations apparently waited to do this in public. Why did they not call you privately? Why were they so bitter? Was this a personal matter or was it related to broader currents in the field of viruses and cancer?
Gallo: No, I do not think it was only personal. It may have been a little of both. Personal, but not really personal, because he thought maybe of the competition and maybe that we were going too far too fast. It would be better to ask someone else who was there that question, like [Dr. Stuart] Stu Aaronson, [Dr. Takis S.] Papas, who is now in Charleston, or [Dr.] Ray Gilden who was there and who participated in that. But, there were plenty of people there. [Dr.] Jeff[rey] Schlom, who is still here, was there. Many people saw that. And [Dr.] Peter Fischinger at Charleston. I think it would be better to ask them. I mean, to put it briefly, it was really long. It was a very difficult time over a two-day period actually.
Yes, I learned from that. I should have given out the samples for everybody to analyze. I went in to the meeting knowing the nature of the problem from our own work, not conclusively -- I did not have as much data as they had -- but it was already becoming apparent that this was a laboratory contaminant. It was an extraordinary phenomenon. It had never happened before. It seems that there were three viruses, three different monkey viruses, in one culture. This is not something you want to say for the record, but I should say it because it is the truth. It looks awfully suspicious, having three different monkey viruses in one specimen, the thing that would deceive you the most. I spent a long time analyzing what happened. You wonder if somebody was crazy and did it on purpose.
[Dr.] Robin Weiss came from England to help us in that work and, as previously, there was failure for a month. We could not transmit anything. We had these particles, but we could not transmit them. We asked his help. He came and he could not transmit them either. Then all of a sudden every culture was positive. Then, as the year went by, there were three different monkey viruses in those cultures. Not one, not two, but three. I do not know how this happened, but it was a real disaster at Frederick and it put the field...
Yes, there were. When you asked me about whether it was a personal matter or was it the field, I think there was an aspect in which it was the field, because there was a big push to get rid of the Virus Cancer Program. There was a big push to go completely towards chemical carcinogenesis and just forget all the virus work. So these events coincided. There was a big push to say that there would not be any more retroviruses, and there were already some -- I would say in retrospect -- silly disasters. There was a virus announcement from the MD Anderson Cancer Center and they actually had no data that it was a human virus. It was announced as a human virus and it turned out to be a common mouse laboratory virus.1
Then Bob Huebner himself had a problem with the so-called RD-114, an endogenous retrovirus of cats. This is an example where knowing something hurt. They put human tumors in a cat, and the tumor came out with virus that was not feline leukemia virus. At that time the concept was ingrained, "one species, one virus, one retrovirus," and that is why you had these type-specific antigens tied to that species in a group across some species. If it was not feline leukemia virus, then it had to be a human virus. In fact, it was a new feline virus; it was the endogenous retrovirus of cats.
I was an author of a publication to say that. I was involved as one of five laboratories. But I really did not feel I had the data. I mean, we all knew and understood. It was not done in a meeting. But in our case, at Hershey, it was done rather dramatically for a whole day and a quarter by one person after another, about ten people in all. So I do not know what drove it the most. I had not had so much success at that time that you could argue that there was somebody jealous or something like that. I do not think there was much to be jealous of. I am not really sure. I want to be honest, so I am going to say I think there was a degree of mean-spiritedness to that show on that day. But I think the story is better told by other people than by me.
Harden: Let me just verify one point again. A number of the people who were criticizing you were NCI contractors and people inside the program?
Gallo: One hundred percent. People at the meeting were either within NCI, in the Special Virus Cancer Program, or contracted to the Special Virus Cancer Program. You see, I was not part of the Virus Cancer Program. I was in the Division of Cancer Treatment, of all things, at that time. I am now in the Cancer Etiology Biological Carcinogenesis Area, but then I was not. John Moloney, whom I knew very well, was the head of the Virus Cancer Program, and he gave me extra funds from that program. He transferred money from one division to another because he wondered whether we would maybe find a retrovirus and he thought it appropriate that we would be linked. So we were linked in that way. I suspect that some people in that program were not happy about that, so the attacks came from my competitor and -- in his last years of life -- friend, Sol Spiegelman from Columbia [University], who was under contract, and one or two people in his laboratory. It came from Ray Gilden, with whom I have worked and collaborated subsequently, who is out at Frederick. He had always been a contractor to Bob Huebner at that time. The criticism came from his associates and from several people who came from George Todaro's branch, in several of the talks, for instance. That was not the end of it, but it was all Virus Cancer Program people. It was relentless, talk after talk.1994 Gallo Oral History / National Institutes of Health (pdf, 37pp)
(Former NIH Director, emeritus board member of Research!America, and Washington Advisory Group principal James B. Wyngaarden is on the Board of Advisors of the IHV, which is almost exclusively concerned with HIV and AIDS research.)
1 The virus was identified in the labs of Leon Dmochowski of the MD Anderson Institute, a contractor of the Manaker section. Between 1965 and 1972, the Institute received about $2.7 million from the SVCP. In a 1965 letter to Paul D. Smith, Vice President and General Counsel of Philip Morris, Alexander Holtzmann describes how R. Lee Clark intimidated Dr. Leon Dmochowski out of testifying to Congress about the evidence that human cancers may be caused by viruses. "As to Dr. Dmochowski he observed that he was not raising any issues of academic or scientific freedom because he would not prevent him from appearing. But he repeated that it would be poor judgment on Dmochowski's part to agree to this. I told him that this attitude was tantamount to his prohibiting Dmochowski from cooperating since he must know that Dmochowski would not go ahead when informed how Clark felt about it. He let this pass without comment."Holtzmann letter, 1965 / UCSF (pdf, 5 pp)
"One of the first persons to proclaim success was Albert Sabin, who said he had found the virus shortly after he switched to cancer research in 1962. But what he found was not a virus after all, and talk about an exciting lead was quietly dropped. The latest person to proclaim success is also Sabin..." (Cancer Virus: Link to Disease in Man Reported Again, by Barbara J. Culliton. Science 1973 May 11, pp. 371-374.)Culliton, 1973 / UCSF (pdf, 3 pp)
Research News. Viral Carcinogenesis: Role of DNA viruses. By Jean L. Marx. Science 1974 Mar 15;183:1066-1070, 1112, page 14.Viral Carcinogenesis, Science 1974 / UCSF (pdf, 21 pp)
Viruses and cancers: Achievements, problems, prospects. Review of virus-cancer work by Guy de-Thé of the International Agency for Research on Cancer, Feb. 29, 1976. HPV was a suspected cause of cervical cancer but had not been studied, and EBV was a suspected cause of nasopharyngeal cancer and Burkitt's lymphoma. Work was conducted in part under Contract NOI CP 4-3296 within the Virus Cancer Program of the National Cancer Institute, NIH, PHS.de-Thé, 1976 / UCSF (pdf, 10 pp)
Big Dose of Research, But Still No Cure. By Frank Greve. The Miami Herald, April 23, 1978.Miami Herald, 1978 / UCSF (pdf, 3 pp)
Dr. Harry Demopoulos, Associate Professor of Pathology at New York University Medical Center, woos the Synthetic Organic Chemicals Association, Inc., Oct. 4, 1979: "I was shocked and amazed back in 1975 when I came here to direct the Cancer Institute in New Jersey. The press and the Department of Environmental Protection in Trenton were literally tearing industry apart. I always thought that you fellows were rally hot stuff and would have answered back and I was surprised that industry was just laying back being beaten up. There was no response. I couldn't understand it." (Actually, this pussy response is the same as with the tobacco industry.) He offered them the false choice of lifestyle quackery against the pollution fear-mongers, while spreading outright lies against germ theory: "There is approximately 5 percent of cancers that are occupationally induced due to previous exposures 20, 30 and 40 years ago when even the best scientists did not know that many chemicals were capable of causing cancer. Recall that most university scientists and government scientists were engaged in chasing viruses and it's only recently that the blind-alley virus theory was proven invalid." (As a matter of fact, the main complaint of the Zinder Committee was that a select little clique of cronies was handing out money to each other. Furthermore, they scarcely glanced at the DNA viruses which were the leading suspects in humans.)Demopoulos, 1979 / UCSF (pdf, 10 pp)
"Richard Adamson, director of NCI's Div. of Cancer Cause & Prevention, has in the little more than a year since he took over that job established four new laboratories which reflect the division's shift in emphasis from viral carcinogenesis to a mixture of viral and chemical carcinogenesis. 'That was done without new positions or a budget increase, which shows what a good manager he is,' NCI Director Vincent DeVita commented to the National Cancer Advisory Board." The new lab directors included Curtis Harris, Human Carcinogenenesis. Elizabeth Weisburger, chief of the Carcinogen Metabolism lab (and the former wife of American Health Foundation Director John Weisburger) was appointed to assistant DCCP director for chemical carcinogenesis. (Four new DCCP labs established without new positions, more money. The Cancer Letter 1982 Jan 15;8(3):5-6.)Cancer Letter, 1982 / UCSF (pdf, 8 pp)
Unusual filterable agent isolated from horizontally transmitted Syrian hamster lymphomas. JH Coggin Jr., JE Oakes, RJ Huebner, R Gilden. Nature 1981 Mar 26;290(5804):336-338. "An outbreak of horizontally transmitted malignant lymphoma in an experimental hamster holding facility was previously reported. Retroviridae (oncornavirus) or other conventional oncogenic viruses (oncodnaviruses) could not be detected in these lymphomas by immunological methods, direct isolation procedures or electron microscopy but an infectious agent was clearly involved. The incidence of lymphomas during five recurrent epidemics ranged from 50 to 90% in young, inbred and random-bred Syrian golden hamster exposed. The agent seemed to be resistant to UV inactivation, formaldehyde vapour and other viricidal agents (chlorine and iodine), and stable for long periods in the absence of hamster hosts in the contaminated facility... We now report the successful, cell-free isolation of an unusual, filterable agent prepared in protamine sulphate buffer from primary and animal-passaged lymphomas, which produces lymphomas with good efficiency when injected subcutaneously (s.c.) into newborn Syrian inbred (LSH) and random-bred (LVG) hamster. The agent could be re-isolated from these induced lymphomas and injected into other hamsters to reproduce the neoplastic condition. It showed characteristics suggested for a mammalian viroid (a non-encapsulated, DNase-sensitive low-molecular-weight, disease-causing, self-replicating, naturally infectious nucleic acid).Coggin - Nature, 1981 / PubMed
Epilogue: Robert J. Huebner retired shortly afterward. When he died in 1998, it was said that he had suffered from Alzheimer's disease for 16 years, and had been a nursing home since 1991. (Research Pioneer Huebner Mourned. NIH Record, Nov. 3, 1998.)Huebner obituary / NIH Record