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There was an amazing amount of understanding in the public from the very earliest time. I felt there was a lot of responsible reporting about AIDS very early on. Almost weekly we had somebody in the office talking about AIDS, ranging from people at the U.S. television networks to those from newspapers. The vast majority of the reporting was very responsibly done. It is amazing how much good information comes out over the TV and in the press when the media deal with this subject. This responsible reporting has led the majority of the population to understand this particular disease, what is going on and the need for all kinds of research, not just treatment trials.
The people who are afflicted have bombarded the press with the need for instant cures, instant answers, instant vaccines, and immediate access to drugs that have not been proven yet. The afflicted are the ones who are really driving for things that cannot be done. They are driving for answers that we do not have. They are driving for drugs to be used that are not available or have not even been adequately tested for safety. It is understandable to do that if you have a disease that's 100 percent fatal. When people with cancer get to a stage that's 100 percent fatal, they do the same thing, just perhaps not so vocally. It is understandable. But I think that the general public understands the disease reasonably well, although it always bothers me when I see kids being ostracized in school because of ignorance in some families. At the same time I see many school districts turning around and welcoming those kids into their schools. Many parents and various school officials do understand. There are always a few misguided [people], but the understanding of the disease is pretty remarkable.
Harden: Following up on your comments about drugs, I recall a reporter asking me whether scientists were trying to hold up the release of potential therapeutic drugs from people with AIDS. I replied that I thought it was a regulatory question, that the Congress had decided that the U.S. would not permit people to market drugs without testing for safety and efficacy. Clinical trials, of course, take a long time. Is there any other way rather than having a proper clinical trial to tell if a drug is working?
Sell: Even when you have a proper clinical trial it is often difficult to know what value any particular drug is. I don't think any scientist is holding up anything. The regulatory agency [Food and Drug Administration] wants to be shown that one drug is better than another. It is the safety of the public that is important. There is also a huge financial burden. Take a look at what the federal government has paid for AZT [3'-Azido-2',3'-dideooxythymidine]. If we didn't have some data indicating it really did some good, it would be an incredible rip-off of society, of people dying with AIDS.
The primary concern about drugs is the safety of the individual. Even if people with AIDS are dying, that does not mean we should hasten their death or make their existence more unbearable. Even AZT has a huge problem with bone marrow depression and the need for blood transfusions. It is not an innocuous drug, and yet we are talking about using drugs that are more toxic but that we don't know much about. There is tremendous pressure from those who are dying to try anything, and there is pressure from the regulatory agency saying we cannot approve everything. We have to have at least some modicum of knowledge about the drug before we let the public use it. I don't think any scientist has held anything back in terms of treatment of patients. In fact, the doctors and the scientists are pushing on the patients' side. They are willing to try almost anything they can get their hands on to help the patients, because they feel just as helpless as the patients do.
Harden: Now that you have been at Emory for three and a half years, how is the academic approach to AIDS different from that of the NIH? What do you see happening here?
Sell: AIDS in Atlanta developed over the three years or so since I have been here. Although it was a problem, it was not as big a problem as it was in New York and San Francisco. The infectious disease physicians, and to some extent the oncologists, took care of those patients. There was not very much to offer them and interestingly, the local physicians were not very interested. This was different from almost all the other centers around the country, which were participating in the clinical treatment programs that were being funded out of NIAID.
The first year there was around $20 million in funds for a large number of centers for new drugs. The physicians here at Emory were not very interested in that because they could not see any new drugs of great interest for the community here. They felt the need was much more in the area of education, in dealing with partners and individuals who were exposed, and in trying to deal with the infection. It was more important to deal with the economics of this situation for the patients who were involved, the tremendously devastating effect on the families and the devastating effect it had on the hospital personnel when it moved from a few cases to ten or twenty on the floor. They were much more concerned about all of these problems. The university research division was much more concerned about precise evaluation of the mechanisms of the disease and not with treatment trials.
Here at Emory, we have a Yerkes Primate Center, and we tumbled into one of the best models for AIDS virus infection in the sooty mangabey monkey. It has an SIV virus which is homologous to HIV-2. It infects these monkeys, but they never get ill. They live with this virus without problems, and yet when you take blood out of that monkey, the mangabey, and put it into Asian monkeys like the macaques, they exhibit features of the AIDS-related complex (ARC), they develop a full-blown disease like AIDS, and they die of opportunistic infections. This provides us a model to study that is better than a human model. We don't have to inflict our studies on humans, and we can follow in a programmed and planned way a primate model. We had a virus that was living happily and not destroying a group of monkeys. This may have been the situation in Africa with HIV-1, which then moved to man. It was in this area that we submitted most of our research grants. We now have quite a few millions of dollars to study that primate model, so basic research can be done much more precisely, much more planned. The research is quite fascinating, although one disturbing thing has come out of it. One variant of this SIV retrovirus, when put into macaques, is now thought to kill them in a matter of weeks. If, in fact, this is substantiated, then it would suggest that this virus may under some circumstances be modified to become a acutely lethal virus. That is one of things we are currently studying.
It has also allowed us to develop what we think is the first understanding of cellmediated immunity in AIDS. It is difficult to measure cellular immunity in AIDS. There have been various attempts, more or less satisfactory, using this system to explore many different approaches. We now have what we think is a sensitive and specific cell-mediated immune assay that allows us to replicate it, so that we can take a look at this and other infections in the same animals–cytomegalovirus and other infections–to show specificity. So this model may, in the long run, provide more understanding of the whole AIDS process.
Now in our human populations, of course, we have been impressed, like everybody else has, that there is a tremendous neurological component to AIDS. It may be the first component of AIDS that appears in many of the patients. A lot of our attention has been directed that way. The most recent observation, moreover, is that more and more AIDS cases are occurring in drug addicts. We just happen to have had a program here to look at the effect of drugs on the immune system. We have shown clearly that surface receptors on T lymphocytes are modified by drugs. You can cause them to appear or disappear with various of amounts of cocaine or heroin. In fact, one of our graduate students just did his thesis on that subject in our department. So we are now concerned with drug usage and its effect on the susceptibility of progression of AIDS.
Harden: Thank you, Dr. Sell.
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