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Harden: At that point?
Klein: At that point.
Harden: A virus we did not know anything about?
Klein: That is right. Do not forget, we had not seen a new virus in the blood supply in thirty years, and retroviruses did not cause human disease, we thought, with the possible exception of T-cell leukemia. So these were all disturbingly new concepts. A disease with an incubation period of ten years, or seven years at the time, whatever was believed. A retrovirus. A disease that was transmitted by blood, but was not seen in these other situations. I think it was hard to be convinced earlier than early 1984. Good luck to the people who were absolutely convinced earlier than that. There were some who fervently believed it was transmitted. One of the regional public health officers fervently believed it, but he thought it was the hepatitis B virus that was causing it. Many people who had many theories were only partially right. I think the officer was as wrong as the people who did not think it was caused by a virus, because hepatitis B did not have anything to do with it.
I can tell you that since we were able to collect biologic materials from these patients, a number of very well-respected scientists at NIH came down to talk to me about the work that they were doing for which they would like to get biologic materials, if we could help them, and the theories which I thought were very plausible had nothing to do with infectious disease. It was immune suppression from antigens on spermatozoa crossing the mucosal barrier in the rectum. All kinds of theories that today appear ludicrous, but, in 1982 and 1983, appeared very plausible.
Harden: One of the great critiques of the AIDS activist groups and the publications that have come out is that Government scientists did not pursue this research as vigorously as they might have because they were homophobic. Did you see any of that in the Clinical Center, and could you characterize the patients, or the interaction between patients and physicians?
Klein: As far as I am concerned, that is absolutely wrong. First of all, by the time we realized that there were more than three or four cases in the United States–this may sound cold–and that scientifically these were very interesting cases, people were rushing to study this disease in the Intramural Program. It was going to make for publications and fame, which I think, without any question, is what drives many of the scientists at NIH.
One of the first patients here was actually a woman from Chicago, but, as you might guess, the large majority of patients were gay men. I never saw any indication that people were reluctant to study these men because they were homophobic. Perhaps that existed somewhere in the Intramural Program, but not here. It never crossed the mind of anyone I talked with. But then the people in my circle–Cliff (Lane) and (Tony) Fauci, Dr. Henry Masur, and Dr. Harvey Alter–became very interested in this disease, because it smelled a lot like hepatitis. Alter did the first studies in chimpanzees along with Henry Masur. No, I never saw that attitude. If we could have gotten more patients, more money, and more resources, we would have done more. But again, this was a fairly unusual disease compared to cancer, let us say.
Rodrigues: In the chronology of things, at the time when you were convinced that this was a viral-borne disease and there was still an absence of any test, another one of your immediate concerns might have been the problems that your department was going to have in attempting to ensure the safety of the blood that was being used in the Clinical Center. Could you talk a little about that problem, and what thoughts people had on other types of surrogate markers that could possibly be used as indicators?
Klein: First, let me go back a bit. This may be of some interest to you. Bob Gallo wrote a letter to the New England Journal of Medicine in 1982, I think–it might have been early 1983–indicating that he had found a retrovirus in buffy coats from the NIH Clinical Center Blood Bank. This caused an uproar. Dr. Paul Holland, who was the Chief of the Blood Bank at the time, almost got into a fist fight with Gallo. Betty Colbert may have some letters about this that she can give you. Paul, first of all, said that Gallo, in his publication, suggested that the Blood Bank was working collaboratively with him, which we were not, and that we endorsed his letter, which we did not. We were not signatories.
The second thing Paul Holland said was that Gallo’s publication might inflame the concern about blood transfusion because it might suggest that these retroviruses would be deleterious to human beings and there was not a shred of proof that they were. Finally, the buffy coats that we had given out to Gallo and to everyone else were strictly for research purposes. Trying to find the donors who had given these in order to study them was simply not cricket. Of course, it was not, and is not. One of the donors–I think this was HTLV-I that Gallo found actually, not HTLV-III–but it raised the issue of retroviruses going into human beings and causing disease. One of the buffy coats actually came from a Japanese researcher who was back in Japan and HTLV-I is endemic in Southwest Japan.
But that was a little footnote to the blood problem, because we were all very sensitive at that point about whether or not AIDS was being transmitted from an agent that went through blood. In fact, the meeting at the CDC in January of 1983 was the first big meeting to try and address what looked as though it was going to be a major issue. I am not going to say a major public health threat, because I think most of the scientists, did not think it was, or were not sure. But in fairness, several of the epidemiologists at the CDC, including Dr. Donald Francis, probably Bruce Evatt, I think, and several others, felt that there was enough data that something needed to be done. The scientists from NIH–Dr. Amoz Chernoff was the one from NHLBI, and Dr. Kenneth (Ken) Sell–I think were sort of neutral. Then there were some blood bankers who were concerned about the issue of being able to supply enough blood to the United States. Supply was always an issue. A large concern was that if you put in any kind of screening device that took out large numbers of donors without pretty good proof that you were helping the blood supply, you might, in fact, end up with people dying because there was not enough blood available.
Amongst the kinds of indicators that were suggested at the time, the first were surrogate tests. The CDC had a list of a dozen or so surrogate tests that might be beneficial. Actually, we had begun using a surrogate test for hepatitis in 1981. We were the first blood center in the United States to use a surrogate test for hepatitis by about four to five years, and we were roundly criticized for doing it. We did it because our population studies by Harvey Alter demonstrated that we could cut down on post-transfusion hepatitis by about a third in our population in the Clinical Center, and so we felt obligated, based on those data, to do that.
The TTV Study subsequently showed that the same surrogate test was effective in the multicenter study. Surrogate tests were therefore nothing new for us, and we put them in very early for hepatitis.
None of us had seen the data presented by the CDC. That was a closed meeting. In fact, the sheets and graphs that were passed out were collected before the end of the meeting, so they were not widely available. I have seen them subsequently, and I can tell you that I would not have introduced one of those surrogate tests based on the data that they had. So I do not criticize those people who said, “What you are going to do is eliminate an awful lot of normal individuals and threaten the availability of the blood supply while you are not going to improve its safety.” I think that that, based on what I know now, was a reasonable criticism.
On the other hand, some things were becoming clear. One seemed to be that gay men with numerous sexual contracts were a risk. We knew that already from hepatitis and we probably should have been thinking about getting heterosexuals with multiple sexual contacts as well as gay men out of the blood donor supply, but the transfusion community had not done that. At that point is seemed that if there was a clear association, we ought to do that.
There was an issue about Haitians. The disease seemed somehow to be endemic in Haiti for whatever reason. Let us then prohibit Haitians from being blood donors. That would not have eliminated many American blood donors. It might have done some good. Again, it did not seem an unreasonable thing to do, even if you alienated some people who were born in Haiti.
Hemophiliacs seemed like a risk group. Later we defined this as risk behavior. Hemophiliacs were not really donating blood anyway, but we put them down as well.
Drug users were another group that were now being looked at. We had always kept them out of the donor group. If a person used intravenous drugs he or she was not allowed to donate blood. But we would emphasize that.
And then we said sexual contacts of any of those people.
It was the four H’s: the hemophiliacs, the homosexuals, the Haitians, and the heroin addicts, and their sexual contacts. The American Association of Blood Banks, the Council of Community Blood Centers, and the American Red Cross, the three major collectors in the United States, put out a joint statement saying that we should try and eliminate these individuals from donating blood.
Harden: What date was this?
Klein: I think they framed the statement in January of 1983. It might have come out then, but I believe it came out in March of 1983.
Harden: I know there was a meeting in Washington, two days, I believe, after the Atlanta meeting.
Klein: Yes. I was not a party to that.
Harden: But then DHHS Secretary (Margaret) Heckler, did something in March?
Klein: That is correct. A statement came out over Dr. Edward Brandt’s signature, I think. Heckler had a news conference and I have actually seen the transcript of it. She had a news conference, and Brandt put out a Public Health Service position. The position was essentially the same position as the joint statement.
The other thing we thought reasonable to do, as we now knew some of the signs and symptoms of AIDS–night sweats, unexplained fevers, unexplained diarrhea, shortness of breath, white spots in the mouth, candidiasis, thrush, Kaposi’s sarcoma–was to decide, “We will ask the blood donors these questions as well. If anyone says they have any of these conditions we will exclude them.” We did do some things but they were historical kinds of things and that we thought might not improve safety, but possibly might, and would not disrupt the system and therefore limit supply.
As it turns out, asking the questions about signs and symptoms probably did nothing because people with AIDS do not come in to donate blood. By that time in their disease they are not blood donors. The questions about risk behaviors clearly were important and remain so to this day.
Harden: Is that when you made up your first form with those questions on it for the blood donors at NIH?
Harden: I picked one up for the museum collection in 1987 or 1988.
Klein: We had a form in 1983. That was not the earliest form, but I am not sure that we would have had access to the earliest one. This one has the donor’s name on it. We would have to get rid of that.
Harden: You do not have to find it now. I just wondered.
Klein: We started asking in 1983 with a special form, because it takes time to print cards. Especially in the government it takes a lot of time to print cards. We did not actually redo our donor card until October or November of 1983, but clearly by April of 1983, and I think earlier than that, we were asking questions by giving donors a different printed sheet. On the donor card all we had in one of our blank spaces was something to the effect that these questions had been asked. The screening nurse had to check off that she had asked the donor these questions, but the questions themselves were not on the donor card until October or November 1983. They were on a different sheet. That was our approach to questioning the donors.
Harden: Maybe we can eventually try to get the earlier card, and then the series, to put in the archives.
Harden: That would be very good to have.
Klein: We were very concerned about the transmission of AIDS. We thought that there could have been a transmissible agent, but we were not concerned enough that we considered using surrogate tests which, by mid-1983, were being talked about but had not been published anywhere. In fact, the manuscript that came out of that January 1983 CDC meeting was rejected by the New England Journal of Medicine. I do not know why it was rejected. I was not one of the reviewers. But it was submitted to the New England Journal and rejected, I think in early 1984, and not in 1983. No one was using surrogate tests for AIDS, or HIV, or anything else that was associated with AIDS. No one ever did in the United States, with the exception of a few California blood banks who were doing it, so they say, one for a research protocol....
Harden: Was that the person at Stanford?
Klein: Stanford. Dr. Edgar Engleman was doing helper/suppressor ratios. Subsequent to that, Irwin Memorial Blood Bank was using core antibody tests which were later shown to correlate reasonably well in studies we did here at NIH actually with anti-HIV, or anti-HTLV-III, as it was then called. Then a couple of other California blood banks, one of which was a Red Cross blood bank, asked permission of the Red Cross to do this on an experimental basis to try and get some data. But there was a lot of pressure in California because there was real panic in the San Francisco area. In the Washington area, not only was there not panic, there wasn’t general acceptance that this was a transfusion-transmitted disease.
Rodrigues: You mentioned AIDS has perhaps some beneficial effects on certain clinical practices. Could you say a little bit about the overall impact of AIDS on other aspects of transfusions?
Klein: Yes. It was always very hard to convince clinicians that too much blood might be bad. In fact, I had a very prominent Boston physician, son of a Nobel prize winner, who told me he did not see post-transfusion hepatitis in Boston. In fact, if these people were infected six weeks to six months after the transfusion, and the original illness was relatively mild, they might not have reported it to their physician. So that information wouldn’t have gotten back to the blood bank. Or, they might have reported it to their physicians, who said well, it is a mild case of hepatitis, and might never have reported it to the blood bank. So the point was, he probably wasn’t seeing it, but it was there. So, people were using a lot of blood, a lot of times for the wrong reasons, a lot of times unnecessarily. Patients didn’t know the difference, there was no consumer advocacy. Patients didn’t say, “Wait a minute, don’t transfuse me until I really need it.” Patients weren't saying anything. They felt if your doctor felt you needed blood, you got blood.continued on Page 05
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