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Harden: We would like to begin this interview by having you tell us a little about your background, where you grew up, your undergraduate education and medical training and how you became interested in the problem of AIDS.

Macher: I was born in a refugee camp in Stuttgart, Germany, following World War II. My family was lucky enough to have a family sponsor them to come to the United States and guarantee that they had a job waiting for them. I was educated in New York. I went to Queens College, which is part of the City University of New York. In the summertime, I worked in the Department of State in Washington, D.C., in the laboratory of the Foreign Service Medical Division as a laboratory technician. That is when I became interested in medicine, especially in infectious diseases, because at the Department of State Foreign Service Medical Division every parasite coming back from overseas in Peace Corps volunteers, Foreign Service people, and ambassadors is seen.

Harden: How did you get that job?

Macher: I came to Washington, D.C., because I originally thought I wanted to be a lawyer and work in politics. I actually served as an intern for one of the congressmen. It was a congressman from Pennsylvania, Congressman Moorehead, I believe, and I worked on Capitol Hill for half of a summer.

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In fact, what we were looking at under the microscope was Gram-positive dotted material. It looked like debris. It did not look like an organism. Organisms are either round or bacillary and I was looking at dots under the microscope. Dr. Bennett said to the technician, “Let’s do a second stain.” He told the technician to do what is called a modified acid-fast stain. We put this second specimen under the microscope and all of a sudden these dots were glowing pink. I had never seen anything like this before. The reason my six-year-old boy with leukemia was not getting any better on conventional antibiotics was because he had a very unconventional organism called Nocardia.

Harden: Nocardia?

Macher: Asteroides, which was not responsive to the antibiotics we had the patient on. When we put the patient on the right medication, literally within days he was afebrile, and the pneumonia, three weeks later, had cleared. I was so impressed, because I had never seen anybody who had been able to do this before, that I asked Dr. Bennett–he had come by every day to see the patient–if I could come over to his laboratory at NIH to see what he did. I told him how impressed I was.

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But then, in the late 1970s, we started to hear about an even stranger phenomenon of young people who were coming down with Pneumocystis pneumonia and cryptococcal meningitis. At that time I was taking calls for Dr. Bennett from physicians who would call into the NIH to get consultations on difficult cases. That was our expertise, difficult febrile cases. Since Dr. Bennett was letting me take all these phone calls, I was on the phones at the very time when the first calls came in to the NIH about this new syndrome. I had a diary that I would keep of cases, of 23- year olds, 27-year olds, 19-year olds, 35-year olds, with Pneumocystis pneumonia and cryptococcal meningitis. By 1980-1981, I had lots of these cases on file. As you know, in the middle of 1981 the CDC [Centers for Disease Control] announced that there was a new syndrome as the cases from Los Angeles and New York were published. We actually brought in the first case into NIH from New York in April of 1981.

Harden: Tell me about that case.

Macher: The first case at NIH came in from New York in April of 1981.

Harden: This was the one that came into [Dr. Thomas] Tom Waldmann's immunology service?

Macher: Correct. On the immunology service. He was a young man who had been to Haiti. In the New York gay newspapers, it had been advertised that a person could go to Haiti, pick up young men for ten dollars, and have sex with them for weekends or weeks, or whatever, so he told us. We found out that two of his consorts in Haiti had died of some terrible infection.

He, himself, had Pneumocystis pneumonia, Cytomegalovirus pneumonia, and Mycobacterium avium. In fact, to this day, he is the classic case. He is the best teaching case there is.

Harden: Your curriculum vitae indicates that you moved from internal medicine more into pathology. Is that correct?

Macher: I did that because Dr. Bennett was always getting biopsy slides of very difficult cases. I was the person who would take the slides, go to Pathology, get under the double-headed microscope and analyze these cases. I enjoyed looking at these cases so much from a histopathological perspective that I thought that I should get some training in pathology.

For one year, 1978 to 1979, I went to the Armed Forces Institute of Pathology to do what is called a fellowship in Infectious Diseases Pathology. I enjoyed that so much that I actually went back to the NIH and did the two-year Clinical Pathology Residency, the two-year Microbiology Fellowship, and a two-year Surgical Pathology Residency.

Harden: And that is where you were when this first patient came in? I would like to pursue this.

Macher: In 1981, I was just finishing the second year of my Clinical Pathology Residency.

Harden: I would like to ask you about a couple of your papers related to the first patient at NIH–and maybe some of the other early patients. I just have a few questions.

Macher: In fact, the first case is in some of those early papers.

Harden: That is one of the things I wanted to know. You have a paper written with people from the National Eye Institute on Cytomegalovirus retinitis, and then, one with Dr. Henry Masur, Dr. Anthony Fauci, I think, and Dr. Clifford Lane. But I am looking at the autopsy pathology paper done with [Dr.] Cheryl Reichert.

Macher: Yes, the first patient was in that paper too. One of ten of our first patients.

Harden: Nobody has talked to us much about what you were seeing at autopsy on these patients that helped to define AIDS as a syndrome. Can you talk about that for a little?

Macher: Again, in the beginning, especially with this first patient that came to Tom Waldmann’s service, until that patient came to NIH, we had just heard about these cases over the phone. They were in California mostly, in New York, and New Jersey, but we had actually never seen any of these patients. We were just telling them what doses of amphotericin, what doses of Bactrim–trimethoprim sulfamethoxazole–to use. We were helping out with medications–5-fluorocytosine–et cetera.

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Remember, an autopsy is very expensive and, to this day, the overall autopsy rate on patients who die in our nation’s hospitals is probably no more than 15 percent. So, for every hundred patients that die, only 15 are autopsied. The same thing was true for these patients. But we were so interested in defining the true pathology that we were recruiting the cases to the NIH.

Harden: Were you worried about your personal safety?

Macher: We were always worried. In fact, when I was medical resident in April 1975, we received a call from the Peace Corps. They were air evacuating a 26-year-old Peace Corps volunteer from Sierra Leone, an American woman, with a fever of 106, who was very sick. When she came to us she had defervesced, that means her fever had broken, and she was no longer hypotensive. Her blood pressure was normal. But we were taking care of her and examining her, trying to figure out what was happening. We could not figure it out. One day she was listening to her husband, who was apparently in Ohio or somewhere, on the phone. She turned to us and said she could not hear any more from her ear on one side.

Now you have to understand that 26-year-old women do not suddenly lose their hearing permanently. I had never seen anything like that, especially as an intern. So I called the infectious disease specialist at the State Department where I had worked as a college and medical student and he came over. His name was [Dr. Martin] Marty Wolfe, and he looked at the patient. She also had peripheral eosinophilia, many eosinophils in her blood. She has been to Sierra Leone. I said to Dr. Wolfe, “She cannot hear. I don’t know what is going on.” He looked at the patient, talked to her, and examined her. He came out and told me what she had without even doing a blood test. He eventually sent her blood out for confirmation of his diagnosis. Guess what she had?

Harden: What?

Macher: Lassa fever, one of the hemorrhagic viral diseases. It can kill the health care worker who takes care of people with this disease. Fortunately, none of us got sick. The patient had the highest titer at that time of anybody ever seen with Lassa fever and she was subsequently used as a donor of plasma to treat other people acutely who were very sick. You treat people with Lassa fever by giving them antibodies from people who survived.

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Many dangerous things happen in what we do. After the Lassa fever case, yes, I was scared, but did it prevent me from doing the work? No. But I admit that I was scared. There were residents who refused to do these autopsies and I do not blame them. There are some centers that will actually scold a resident for not doing such an autopsy, and I do not think that is right. I think it is an individual decision. It is a life threatening decision. But that is a philosophical point and that is another hour of discussion.

Harden: How long did the NIH continue to fly in the bodies of AIDS patients to try and get a picture of the disease?

Macher: For a very short time. Why? Because the autopsy service was a busy service in those days and here I was bringing in these cases and they had to pay for dieners to stay overtime to do my cases as well as the regular cases. Some days we had five autopsies, not just of people who had had AIDS, and we could only do so many in a day. So the period of time when we were bringing in the outside cases was very transient because it was not cost effective, but we learned a lot. I brought in one man from Ohio, I think from Akron, who was a Haitian and we had never seen a Haitian with AIDS. But we had heard about them. He turned out to be a fascinating case. He was bisexual, and we now understood, from that experience, that that was probably another mechanism for spread of AIDS to women and their children. Very early on, we suspected that this was not just a disease among male homosexuals and intravenous drug abusers, but probably bisexuals were giving it to women.

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We were studying the cases intensively. We were not satisfied just to say, “Oh yes, I see Pneumocystis in the lung. He died of Pneumocystis pneumonia.” We looked at every organ in the body with all of our special stains to find out what else was in that body. 

Harden: You were aware, I presume, in working with other groups like the Fauci group, of what Cliff Lane and Henry Masur were doing. Were you meeting with them?

Macher: In fact, we had a weekly session–I believe it was on Wednesdays at eleven o'clock in the morning–which actually went on for about a year, or a year and a half. But it was excellent because at that point we had dozens of patients. In order to keep all the information straight, we had somebody from Radiology, somebody from Pathology–myself–somebody from the Virology laboratories, somebody from Henry Masur’s group, somebody from the National Cancer Institute, all meeting once a week for an hour and a half at a time to go over every case in detail so we could manage the patients’ care. It was very complicated care because, in those days, we were not getting in people in the early stages of HIV infection. We only got the tip of the iceberg; we got people dying. They were very sick. In order to give them coordinated care, you had to have an entire team from

Pathology, from Radiology, going over every case in detail once a week That system broke down because apparently one of the subgroups took some of the data that we were working on together and wrote up an abstract, or a paper, and published it. The rest of the group was angry that the subgroup took some of the data. But who cares, because we were doing it this for clinical reasons, for patient care. The meetings were stopped after that because of the disagreement. But they were excellent meetings for as long as they lasted because we gave coordinated care.

Now, Henry Masur runs the program and he is the best there is. There is nobody like him for being able to take people, put them together, and get a product out of the group. In fact, for the recent task force on Mycobacterium avium, Henry Masur brought in people from all over the country for two days. We reviewed everything on Mycobacterium avium, microbiologically, pathologically, and clinically, and at the end of two days, Masur had a consensus document. There is nobody else that I know of who can take all these different people from all over the country and get a product in two days. If anybody needs to interviewed, it is Henry Masur. He is just incredible. He has endless energy, and his ability to coordinate people to work together is fascinating. He was responsible for bringing the initial working group together at the NIH. The only reason it broke down was because people were angry that somebody took a segment of the information that was yet to be published and published it themselves. But Henry is a mastermind at getting people together.

Harden: We have talked with him. Dennis, do you have questions that you want to ask?

Rodrigues: I noticed in your curriculum vitae that there was one paper in which you discussed working on developing a stain for Pneumocystis. Could you expand on that? Was there a problem in diagnosing Pneumocystis?

Macher: It is very interesting. Early on, when we first started seeing lots of these patients, the Microbiology Laboratory was inundated with specimens. In fact, there is a three-day conference that is run by pathologists, this weekend, starting tomorrow, sponsored by George Washington University Hospital, which I will be attending. The chief topic will be the effect of HIV disease and AIDS on workloads, because microbiology and pathology laboratories around the world now are suddenly being inundated with specimens. When a patient gets sick, laboratories receive specimens of sputum, bone marrow, urine, stool, aspirations, and whatever from all parts of the body for just one patient. The laboratory has to do bacterial, viral, mycobacterial, and fungal cultures, and look for parasites.

So this is overwhelming the laboratory, and very early on, we were looking for different and more rapid methods to detect these different organism in these specimens.

I like to tinker and I was tinkering with these different stains. I am glad you brought this topic up because that was an interesting time in my life.

There I was in a laboratory mixing different solutions and trying to find organisms that I knew were there, but I wanted to bring them out so that they were easy to see. In those early days we realized that what looked like a background of ghost-like material–it did not stain very well–was actually the Pneumocystis on some of these early stains. We brought the Pneumocystis out using methylene blue and other techniques just to highlight the organisms. Now, as it turns out, monoclonal antibodies are available that are even better for detecting Pneumocystis and other organisms. But early on we were very interested in helping microbiologists and technologists find these organisms rather rapidly and easily. That is what we became involved in. Again, those were very exciting days because we were literally mixing solutions just like you see on television. You mix blue and green and pink. We were trying to make the best solution possible to bring out these organism.

Harden: What finally convinced you that AIDS was a communicable disease and when, if you can remember?

Macher: That is a good question. I think fairly early on when Waldmann's patient gave us the information that two of his consorts in Haiti had died recently of terrible illnesses; even back then we thought that there was something that was being communicated, at least homosexually. Then, when we started to see the intravenous drug abusers, we suspected that this was just like hepatitis-B and the communication goes both ways. Then we started hearing about the bisexual men and eventually about the children. So very early on, we were concerned that this disease was being transmitted heterosexually, homosexually, and parenterally, and then, eventually, vertically from the mother to the child.

When we saw the hemophiliacs–in fact, the first hemophiliac that I saw was in Ohio. I was asked to give a lecture out there and the people there happened to have a hemophiliac on the ward. He was just 19 years old, and I sat down and talked to him for a long time. He told me that he had never had any homosexual activity, and it was very straightforward. The main thing we learned early on was not to be judgmental, to be very casual and open in our discussions. Even though when I came back to Washington, some people thought that this hemophiliac might be a closet homosexual, I did not think so. Then, when I heard of more and more hemophiliacs who were getting sick, I thought it was probably from factor concentrates.

I remember the first meetings in Washington when that was brought up. There was great consternation amongst the blood bank people and the factor concentrate people because they would have to start preparing their concentrates in a different way, which meant money. It would cost more.

So there was great consternation. “Are you telling us that this might be in the blood supply or in the pooled products?” And yes, it was.

But it is interesting that you asked, and I guess that it was with our first case that we worried about that.

Harden: Even that early? We have seen that somewhere in mid-1982, when the epidemiological data finally started to build up, the people concerned with the blood supply took a very conservative approach to the whole thing. It was not just the money, I think, although that certainly was a major factor, but when a great structure is in place as to how something is done and when it starts to be altered, you need to make sure you know what you are doing before you do it. That was the basic argument that they were making.

Macher: You can see what happened in France. In France, the law suits are ongoing until today because, as you say, it was a tremendous effort to switch from the process that was being used to heat treat a product. It took years in some places to institute that. The amazing thing about this disease is how much was learned very early on, especially if you look at the history of medicine. Look how long it took to figure out tuberculosis.

It was hundreds of years. It is amazing how quickly information on AIDS was pulled together.

Harden: We came across a very sad thing in some memos to the NIH in the fall of 1982 from the mother of a hemophiliac. Bob [Dr. Robert] Gordon answered them. “Is my child in danger? We have struggled so.” That must have been wrenching for a physician dealing with the patients to handle that part of it at the same time as he or she was trying to figure out the science.

Macher: Yes, I think there were some very tough moments in those days. When you were in medical school, you had learned how to deal with cancer, diabetes, and heart disease, but AIDS was different. Even though at the NIH we were doing consultations on the cancer floors all the time, there was something different about this new disease. Psychosocially, for some reason, AIDS made a much greater impact on most of the people with whom I was working. We were seeing people die very quickly.

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two months earlier; he got it in the 1970s.

Harden: When did you start thinking of AIDS as a chronic disease?

Macher: When we first did the longitudinal studies. As you know there are cohort

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general internal medicine people, that they can take care of these patients

for many years.

Harden: That is very interesting.

Macher: This is a major effort because when somebody goes into practice and has a

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that consultation service. As they get about thirty phone calls per day,

they are very busy.

Harden: Is this for primary care physicians who are treating AIDS patients to call

in and consult?

Macher: Yes. For instance, they call me in on the difficult cases and we talk about

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clinical pharmacologists.

Harden: That is a project of the Health Resources and Services Administration?

Macher: Yes. I can give you literature on that as well. It is an exciting project

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diagnosis. We would cut the specimen, and stain it, to make a diagnosis.

Harden: I want to come back to this topic, but I wanted to ask Dennis if he had any

other questions he wanted to ask before we move on.

Rodrigues: You indicated that very early in your career you had an interest in politics

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was raging about the disease?

Macher: That is a very interesting question, but we were so inundated, seven days a

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were taking care of the patients. We never felt that they were angry at us.

Harden: On a personal level though, if I can take this one more step, a nurse to

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give it to them. Did you have any personal repercussions in your family or

elsewhere?

Macher: No, I was never in a situation where either friends or family said, “That is

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doing the work. I think the bureaucrats were taking most of the firestorm.

Harden: I wanted to talk a little more about your time at AFIP [Armed Forces

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that and get out of the situation at NIH where you were doing so much

direct patient care.

Macher: NIH works on a pyramid system and after you finish a residency or

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putting them in one place.

Harden: What does a registry mean? Could you explain that a little more.

Macher: For instance, there is a registry at the Armed Forces Institute of Pathology

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lead and steel for feet at a time, and I was in one such part of the building.

Harden: I am trying to recall just when it happened. Were you there when you

were the consultant on the AIDS exhibit that the museum developed?

Macher: Dr. [Mark] Micozzi put together a plan to have an AIDS exhibit. I put up

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them up pathologically. I guess that was the first AIDS exhibit they had

ever put together.

Harden: That was a good exhibit.

Macher: Thank you. Much credit should go to the people at AFIP because they had

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memories. We are so busy that we do not really have time to recollect on

things like this.

Harden: In the course of this interview, if you think of additional things you would

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that you think it is important that we record.

Macher: What I have been doing for the past four years is to serve as the medical

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know about HIV disease and tuberculosis.

Harden: Now I want to ask a speculative question. I have this notion in my head

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Who is going to be interested in AIDS? What will happen at that point?

Macher: Yes, the inner city Hispanics, African Americans, whoever is in the inner

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care. It is a dilemma and almost an oxymoron.

Harden: Is there anything else that you would like to say before we end the interview? Is there anything that we have missed or that you think is important to get on the record.

Macher: No, I think we have covered a lot of issues and I thought you did the interview very well. You brought up a lot of provocative points and I found it very interesting myself.

Harden: We thank you very much.

Macher: The first case at NIH came in from New York in April of 1981.