Office of NIH History
In Their Own Words: NIH Researchers Recall the Early Years of AIDS
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Gay: The centers are unique in that the NIH built the buildings, but each had its own emphasis and organizational structure. The New England center, like everything in New England was dominated by Harvard [University] and was built by them out in the country. It was a freestanding operation for both New World and Old World–that is, Asian–primates.

In the case of the center in Atlanta, Emory University proposed to the NIH that they would create the Yerkes Center. It would be based on the primate colony formed by Professor [Robert] Yerkes at Yale in about 1928. The facility was almost as old as the Russian Center. Emory brought the Yale chimpanzees to Atlanta from Orange Park, because Yale was anxious to close the facility, which was old and deteriorating. In the late 1950s, a number of Georgians were associated with the NIH, including [Drs.] Ernest Allen and Boisfeuillet Jones. They were delighted to put a center at Emory. It has been a very successful center.

Another center was located at Tulane. Since George Burch from Tulane had been a key person in establishing the primate centers, Tulane had to have one. The Oregon people, who already had a small center outside of Portland, came in with an excellent application, as did Wisconsin with [Dr.] Harry Harlow, the behavioral scientist who conducted the famous terry-cloth mother experiment. California also came in with an excellent proposal for Davis [University of California at Davis]. In the beginning, each of the centers tended to have rhesus macaques somewhere. But two of them, Tulane and Atlanta, had chimpanzees. A number of them had New World monkeys and the people in Oregon had some lemurs–these beautiful animals with the raccoon-like tail from Madagascar. The people at Tulane also worked hard at having New World monkeys, so, to some extent, they had different types of animals.

Now, what kind of research did the centers do? Yerkes, having chimpanzees, worked a great deal in the behavioral science area. The studies that I remember best coming out of Yerkes were the language studies. Are you familiar with the efforts to teach the chimpanzees to communicate? The scientists teach the chimpanzees with symbols, such as a symbol for “go for a walk”; a symbol for “food treats”; a symbol for “walk in the woods”; and a symbol for “visit with Sally, the chimp next door.” Once the chimpanzees had learned the symbols, the scientists wanted to see if they could communicate with one another. Sure enough, they could. That is a marvelous basic science principle. What could one do with it? Suddenly, somebody thought of a way to use the information. They taught retarded children the symbols, and added a voice synthesizer to the symbol board. Using the various symbols, a retarded child could be more independent–he or she could take the bus to school, for example.

The center at Tulane was interested in infectious diseases. The people there have done a lot of good infectious disease work, mainly virology. The center in New England is the only one that has been associated with the Nobel Prize. [Dr. Torsten] Weisel and his colleague, Dr. David Hubel, were very interested in vision. They studied children who did not use one eye or had other vision problems. Drs. Weisel and Hubel showed that if the developing eye does not get visual input, the part of the brain associated with the interpretation of vision does not develop. That probably applies to many other things, as well. They won a Nobel Prize for this work.

The people at the Wisconsin center also worked largely with behavior. This was where Dr. Harry Harlow studied mothering and the development of behavior. Dr. [Theodore] Ted Ruch at Seattle was interested in physiology. That turned out to be a great thing, because Washington had the best bioengineering operation. When I was at NIGMS, and later at NIAID, the Washington center had the best bioengineering operation available. These men could rig up a primate with a little box so that the animals could walk around and they could still transmit all kinds of physiological data.

Each center developed according to the way their institution wanted them to. At Oregon, there was a fair bit of behavior research; there was a lot of comparative anatomy; and there was some nutrition research. I am sorry but I do not remember anything about other research at the California center. AIDS came to dominate research at California so much in my memory. The center did quite a bit of environmental toxicology.

Harden: One of the things we have noted is that AIDS thrust these centers into the limelight and led to a dramatic increase in their funding. In your notebook on the history of the centers' role in AIDS you implied that, before AIDS, funding had been very tight and that people did not always realize the importance of these centers. Could you elaborate on this?

Gay: When I prepared the history, I had just finished being the bureaucrat who had the primate centers as one of his responsibilities, trying to get them a little more money each year. That probably influenced my text somewhat. Frankly, I do not think the centers were ever grossly underfunded. There were, just as for other parts of the NIH research community, opportunities to which they could not respond because of limited resources. But the centers always remained ready to move on to something new, and they had just enough backlog of resources to be able to do so. That was the nice thing for an investigator who could go to one of the centers with a few bucks, because they could assist with a new initiative very quickly. So, I would have to say in all fairness that I am not sure they were ever grossly underfunded.

AIDS made a big difference, however, because the centers were in the front line of a very major health problem. Many of the people there realized what a health problem they were up against. There is a man who ought to be more famous around NIH than he is named [Dr. Robert] Bob Huebner. If you talk with Dr. Murray Gardner you can understand why. Murray is always so enthused. Have you ever watched the Boston Pops with Arthur Fiedler? I call Dr. Murray Gardner the Arthur Fiedler of American pathology, because he is always so enthused. He seldom talks about the history of AIDS without getting enthused about Bob Huebner. Bob did a lot with retroviruses in mice. Bob Gallo profited tremendously from being closely associated with everything that Bob Huebner ever did in retrovirology

Harden: Could you elaborate on the nature of the 1981 outbreak of Simian AIDS? It seems strange to me that it suddenly popped up. The centers had been there all these years. Were they just recognizing it for the first time or was it something really new?

Gay: All of the above. The Washington center reported a problem with retroperitoneal fibromatosis–it was not called AIDS. By 1983 it had been haunting those people for three years. A tumorous lymphadenopathy had also been troubling people in Washington, as well as in California. It had been spreading through their outdoor corrals where the monkeys could get close to one another through the fence. They knew that they were going to have to partition the monkeys off from each other. This disease had been bothering the Washington center since 1979 at least, and they probably did some autopsies on similar cases before that. Fortunately, the California center had saved lymphatic material and sera from the animals since 1976, so they have been able to trace the infection to that year.

Harden: Was the virus that caused the tumorous lymphadenopathy the Simian Immunodeficiency Virus (SIV), or was it one of the other viruses uncovered in the early 1980s?

Gay: Yes, it was SIV. There were two other centers, whose primates also had a Simian retrovirus, but they did not realize it. Their viruses did not become known as SIV because they did not look exactly like the human one. They were not as closely related in their genetic material.

Harden: So SIV was defined through cloning and comparing it with HIV [Human Immunodeficiency Virus].

Gay: Yes. It was pretty close to 1984 before they could do that. Some people's reputations were hurt as they tried to identify an etiological agent for this disease. The pathologist at Oregon really took a bath. He could not get to the bottom of the problem. He could not find any antibodies to anything for which he had an antigen, and there were not any inclusion bodies in any of the cells. That poor man really took a drubbing. The man at Washington had a bad time, too. For some reason, California knew that they had an infectious disease. They were a little more statesmen-like in not blaming each other for it. But there were a lot of personnel problems and infighting over what this disease was; whose fault it was; and what it had done.

A new and unknown infectious agent is always a trauma to the staff responsible for the health of a colony. It was a research tragedy, because they were losing some animals that had been on experiment for years. The primate centers tended to house their animals together because they knew it was better for the animals' behavior, for their development, and for their physical condition. Of course, I can remember getting a lecture at our first meeting on Simian AIDS from [Dr.] Ruth Kirschstein: “I never had any trouble like that with my monkeys; I kept them all in single cages.”

Harden: Were all of these outbreaks traced to African monkeys that had been imported? The argument was that HIV and SIV must have originated in Africa. Then some importations of Chinese and Indonesian macaques were also infected. How did they get infected?

Gay: I do not know.

Harden: Is it still the consensus that SIV originated in Africa?

Gay: It is still the consensus that it originated in Africa. Many animals have also been imported from China–I think White Sands has brought in quite a few. They have been tested and SIV positives found in them. Who knows where they came from? The Chinese may have accumulated a variety of monkeys for breeding. They might have brought them out of Africa, taken them to China, and ended up breeding them there. It is hard to say, the Chinese are great traders. [Dr. Myron] Max Essex at the Harvard School of Public Health and [Dr.] Preston Marx at the Primate Research Laboratory in New Mexico State at Holloman are the two researchers who have done the most work in determining where the virus came from. They are of the opinion that it came from Africa. I find their evidence and views convincing.

An interesting curiosity in all of this is that the chimpanzee is not susceptible to SIV. It can be infected with HIV, and it will reproduce in them. If you infect an Asian ape, like the Gibbon, with SIV, they get pretty sick, although none of them have died from it. It is not unusual that an African virus that has very limited effect on the African green monkey is very destructive for the Asian macaque. I do not have any trouble with that idea at all.

Harden: This raises the question: Will humans adapt to HIV as they did to a number of other infectious diseases like syphilis, which was very virulent in Europe in the sixteenth century? Adaptation of the host would not eliminate morbidity, but it would reduce mortality.

Gay: Syphilis, gonorrhea, tuberculosis, and other such diseases had survivors who could transmit their resistance. For that to happen with AIDS, there would have to be quite a lot of survivors who could transmit their resistance.

Harden: Do you think Simian AIDS would have remained a curiosity in primates if the human version of the disease had not appeared about at the same time?

Gay: No. I think it would have been such an interesting curiosity at California and such a threat to the colony that people like John Sever would have isolated the virus by 1984 or 1985. Retroviruses are not new, especially for the veterinary world. Swamp fever of horses–equine infectious anemia–is a retrovirus, for example. Dr. Leroy Coggins, now at the University of North Carolina, isolated the viral agent for this disease during the late 1950s. He developed the Coggins test. That virus was spread by veterinarians and trainers with needles. Because of the work of Huebner, of Coggins, and because the center in California was beginning to feel a major economic impact from the loss of animals, as was the one in Oregon, I am sure that it would have occurred to somebody before very long to look for a retrovirus.

Harden: DRR hosted a conference in March 1983 on AIDS in nonhuman primates. This conference addressed both the animal diseases and the disease as a possible animal model for AIDS. Who decided to hold the conference and who organized it?

Gay: Leo Whitehair and I. Leo was in charge of the primate centers. I was on a site visit with him in November 1983. Bob Gallo had not announced his test for AIDS yet. We were in the New England center when it came up. A number of people at the New England center were interested in comparing the pathology of what they were seeing at that time in New England with what the California group was seeing. They also wanted to compare the animal disease with the AIDS infection in humans. The epidemiology of the animal and human disease was so similar that it seemed to us that we had a likely animal model. We took our proposal for a conference to [Dr.] Betty Pickett, who sometimes was pretty strict and could be a stickler for detail like Dr. Kelsey. For some reason she had confidence in Leo and me, and she agreed to our proposal. So we organized the conference.

Like everything else related to AIDS, as soon as you mentioned AIDS in connection with a conference, there was immediately a great interest. In fact, there was more interest than we wanted. We had decided to hold the conference in Masur auditorium in the Clinical Center because the Building 31 conference rooms would only hold fifty or a hundred people. We were inviting people from the rest of the primate centers as well as other people. I think it was [Dr.] John Fahey's department in Los Angeles that first informed the CDC [Centers for Disease Control] about the conference. We invited people from both those places. We also had a former clinical director of NIAID, [Dr.] Sheldon Wolff from Tufts University, who was a big booster of the conference. His support was another thing that helped us get approval for it. He thought we were on to something.

The conference was held in early March. Unfortunately, the Masur auditorium holds a lot of people. Before we knew it, we also had fifty press people who wanted to attend. That created a problem. We also had many other people who came in. For example, there was a guy from Ohio with his homosexual pigs. This turned out to be a kind of a hoax. He wanted to participate, but I would not let him speak. He lied to John Sever, who was the chairman, telling him that I had approved it. I had to let him speak. It was a free-for-all. One woman wrote an article on the conference for The New Scientist, a British publication, in which she really roasted us for using it as a forum to “Budget Bust.” Let's face it. It was an attempt to improve the funding for this disease in the primate centers. We also thought of the conference as a public service, because we were announcing to the scientific community that an animal model for AIDS had been identified.

Once a virus had been announced as the cause of AIDS, research really took off, and we did make a difference. Leo and I agreed that the next year's conference was not going to be a circus like the one in 1983. We planned to hold our meeting in one of the conference rooms in Building 31 at NIH. We were going to have fifty people and no more. The following spring, a little later in the year than the first one, we had such a meeting. We invited the fifty people we thought we ought to have. But there were many scientists who said they just had to come, so we could not turn them all down. I remember being called on a Sunday morning in my hotel room in St. Louis. It was [Dr.] Raoul Benveniste, making his case for being allowed to come. We finally accepted 110 people to attend that highly restricted meeting. We just could not leave anybody out.

From then on the meetings became more formal and less restricted. Now they draw 200 to 300 people a year. Dr. Boris Lapin usually comes from the Russian primate center that was formerly in Sukhumi. I think he came last year. I guess he took up a collection as he went along, but he managed to come. Now there is a fundraiser for his center, because it got all the centers started. It is sponsored by the Washington center. I sent him a hundred dollars, and I suppose I will send him some more. They have raised $3,000 or $4,000 for Boris so far, which will help him a lot. It will probably support a dozen of his scientists for the year. People come from all over the world to the conference. The AIDS animal models' meeting is in Puerto Rico this year. It has become an international meeting.

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