“So we talked about mucocutaneous candidiasis, or oral thrush, which this patient had also. He was also homosexual, which meant nothing at the time. And there was a resident on the case. He was a smart guy. He had interned at Harvard, and he was interested too. So, there was an immunologist at UCLA, not my chief, but he had a lab just next door to us in the basement. His name was John Fahey, and he had come from the NIH (National Institutes of Health), and his lab was looking at monoclonal antibodies targeting T-cell subsets. But in those days, you counted them by fluorescent microscopy, a microscope and a little counter. You could count the helper and suppressor T cells. So, I said, hey, let’s take a sample of this patient’s blood and see what his T-cells look like.”

Healthy T-cells guard against and prevent candida, or fungal infections. “And so we found that the CD4 cells (T-helper cells) were basically missing. And that was pretty shocking. Well, that looks like the root cause of this man’s immune deficiency,” and his subsequent fungal infection.

“So, he gets discharged, and comes back in with bilateral, symmetrical, pulmonary infiltrates (pneumonia) a week later. The same, very sharp resident admits him. Since he is immune deficient, the resident pushes the pulmonologists to do a bronchoscopy (a scope into the lungs to obtain tissue and/or cultures). And they diagnose pneumocystis pneumonia, which, of course, was something you didn’t see in community-acquired pneumonia. So, the plot thickens.”

Pneumocystis Carini is an opportunistic pathogen that is an important cause of pneumonia in immunocompromised hosts, particularly those with HIV infection, organ transplants, or hematologic malignancies and those receiving high-dose glucocorticoids (steroids) or certain immunosuppressive monoclonal antibodies. (Harrison’s textbook of Medicine, 21st edition, page 1691, McGraw-Hill).

Originally thought to be a protozoan, it is, in fact, a member of the fungus community. Since it cannot be cultured, it is typically diagnosed by utilizing an uncommon stain called methenamine silver, which is not routinely done. In this case, it was likely the resident, or the pulmonary fellows that astutely alerted the microbiology lab or the pathologist as to the patients immunocompromised state, thus utilizing the methenamine silver stain to surreptitiously make the diagnosis. It was laterrealized that 80-90% of patients with HIV/AIDS would eventually develop Pneumocystis (or PCP) pneumonia without the proper chemoprophylaxis or the typical antivirals used to treat AIDS. PCP typically infects the lungs, with an insidious onset, generally over weeks, consisting of dry cough and progressive shortness of breath, initially on exertion, and ultimately, with worsening severity, at rest. Fevers are typical. During 1981, however, unless you were undergoing chemotherapy or were known to be immunocompromised, the occurrence of PCP pneumonia was rare and unknown to most doctors.

“The lab was sharp in doing that (stain). And the pulmonologists were pushed. They said, “This is a case of community-acquired pneumonia, so why do a bronchoscopy?” But the resident pushed for it and said, “Because this is an immunocompromised host.” I, myself, had only seen one prior case.” I had never seen a case of Pneumocystis in my training. I remember we considered it at Rochester, where there was a patient with Hodkin’s Lymphoma, a young woman, and I remember we considered it in the differential diagnosis, but it turned out to be radiation pneumonitis instead (from receiving radiation treatment for the lymphoma).” The confusion would be typical as both disorders have insidious onset and similar pulmonary infiltrates, and in someone who would be considered immunocompromised.

“We were scratching our heads and then we got contacted by the chief of rheumatology who was moonlighting in the San Fernando Valley at Riverside Hospital, where a couple of gay physicians, osteopaths, (with a large gay practice) were hospitalizing their patients. The rheumatologist had heard about our cases. (The patients) were a number of men with an unknown syndrome. Fevers, weight loss, oral thrush (white patches of fungus in the oral cavity). All the things we now know are routine to find in AIDS. He arranged a meeting between myself and one of these (gay) physicians, Joel Weisman, at Riverside Hospital. We met at the Wadsworth VA. Weisman was originally from Woodbridge, New Jersey, so we had that in common. And he told me about a couple of these patients, and I said, you know, we would be happy to accept these patients and transfer them to UCLA and work them up. So they transferred two patients.”

“One had a horrible herpetic whitlow (herpes involving the finger)), which totally denuded the skin of the index finger. And another had CMV retinitis (another opportunistic infection you would only see in immunocompromised hosts that affects the retina of the eye).

“These patients came over and both turned out to also have Pneumocystis Pneumonia. Both went to the ICU and one survived and the other didn’t. At that point, we had three patients with Pneumocystis Pneumonia. We checked their T-cells and their CD4 (T-helper cells, which ward off infections) were essentially absent.” “This is 1981. In retrospect, the HIV virus was subsequently traced back to around 1977, based on retrospective analysis of old Red Cross blood samples that had been saved.” Dr. Gottlieb suggests the HIV virus may have been around in the 60’s, but not in the gay male population. He states the typical time from HIV infection to AIDS, untreated, was eleven years.“At that point, I made a call to the New England Journal of Medicine, whose editor, was Arnold “Bud” Relman, a nephrologist by training. I reached the assistant editor, Joe Elia, and told Joe the story. He said, “Let me put you through to Dr. Relman, which he did, and I told him the same story. He said, You know, Dr. Gottlieb, this sounds very interesting. We’d like you to (write it up) and send us the article. But if you think this has public health import, have you called the CDC (Centers for Disease Control), as the lag time from contact to publication is typically six months here at the Journal.”

Gottlieb then notified the Los Angeles County Health Department first. He was connected to Wayne Shandera, an Epidemic Intelligence Service (EIS) officer, who Gottlieb had met when Shandera was a resident at Stanford. “I said, Wayne, are you aware of anything unusual going on in the gay male population? He said, “No, but I will look around.” I told him I think it has something to do with CMV (Cytomegalovirus), as all of our first three patients had CMV in the urine. So, he went down to Santa Monica Hospital and found a CMV culture isolated from the lab. He went and looked at the chart of the patient and, indeed, he was a gay man, but with Hodkin’s Lymphoma. He had a history of Hodkin’s disease, rather, treated, but nothing recently. He called me back and told me what he had found. So we met up and wrote these cases up and submitted them to MMWR (Morbidity and Mortality Weekly Report, a very well respected publication to keep physicians and county health departments aware of new developments or outbreaks of disease in certain communities so that doctors and health official can be on alert in their practices. Unfortunately, Wayne couldn’t get a byline on my paper because of EIS rules and regulations.” The EIS reports directly to the CDC, which publishes MMWR.

The MMWR article was published on June 5,1981. “The CDC published the article as the second article behind an article on Dengue Fever affecting American travelers to the Caribbean. In the article we postulated possibly a new CMV strain that was affecting the immune system, which was ultimately wrong. I was the lead author. We had six authors. More authors than patients. I was lucky though. The editor of the New England Journal says “Call the CDC, also.” That was good advice. I was also lucky to be able to get through to him. Some unknown first year professor calls the New England Journal and pitches a story and gets through to the editor. Describing a new syndrome and the beginning of a life in AIDS. I later found out it almost didn’t get published. One of the reviewers objected to something. Maybe it was the CMV hypothesis, I am not sure what. Of course, that unidentified causative agent turns out to be HIV, which is discovered two years later by the French. So, that paper gets published with two others, both from New York, one from Mount Sinai and the other from Cornell. Mount Sinai describes several cases of severe ulcerative perioral herpes and Cornell describes pneumocystis and other opportunistic infections in gay men, intravenous drug users (which transmits HIV by way of sharing used needles), and in some heterosexual women. But our paper identified the CD4 (helper T-cell deficiency), the other two papers didn’t. As it turns out, my paper is one of the most frequently cited papers in the medical literature. A few years ago, the New England Journal listed the most important papers it has published since the description of ether in 1915, and my paper makes the list.” Of note, in an editorial accompanying the NEJM article, DT Durack asserts that the CMV Gottlieb sited was more likely to be an opportunistic consequence of the immune deficiency, rather than itscause. This ultimately proved accurate. (Gottlieb and the identification of AIDS, by Fee and Brown, American Journal of Public Health, June 2006.).

Remarkably, Dr. Gottlieb and his cohort were able to, in one paper, not only identify a new syndrome of disease, but supply its pathogenic cause, which is an assault by an unknown agent, on the T4 helper lymphocyte subset of cells. “So the French took this information and looked at the CD4 cells as the target cells. They fed the virus to CD4 cells in cell cultures and identified the reverse transcriptase activity popping up in the cultures.” By identifying the CD4 immune deficiency, Dr. Gottlieb, and Dr. Fahey, who was not sighted on the article by omission, catapulted the progress of AIDS research infinitely faster had they just reported on the cases of Pneumocystis. The French team was awarded the Nobel Prize for the discovery, but Dr. Gottlieb feels politics at UCLA interfered with his sharing the award.

This scattered grapevine of random cases, coupled with deductive reasoning, allowed these highly intelligent physicians to make a critical connection. These men of science shared common traits: A strong foundational knowledge of medicine, an awareness and intellectual interest in cases- even those not their own- and a curiosity to try to understand and explain what they were seeing and hearing in the community. Without these unique, shared characteristics, a diagnosis, and the eventual treatment of AIDS, would likely have been significantly delayed, with an even higher death toll.

Gottlieb’s paper in MMWR set the groundwork for putting AIDS on the medical radar screen, but it wasn’t until Dr. Alvin Friedman-Kien published his paper, Disseminated Kaposi’s Sarcoma in young gay men in the Journal of the American Academy of Dermatology, did the national press pick up the story. Consequently, when Gottlieb’s article in the New England Journal of Medicine was published a few months after this, describing a “potentially transmissible immune deficiency,” it garnered enormous attention. (Michael Gottlieb and the identification of AIDS, by Fee and Brown, American Journal of Public Health, June 2006. After Gottlieb’s New England Journal of Medicine article, Pneumocystis Carinii Pneumonia and Mucosal Candidiasis in Previously Healthy homosexual men- evidence of a new Acquired Cellular Immunodeficiency, December 10, 1981, Dr. Gottlieb’s career took off. He started treating Rock Hudson, a handsome and charismatic Hollywood leading man, who was also gay and suffering from AIDS. He became outspoken in trying to put AIDS into the national dialogue and attract funding for more research. He became involved with Elizabeth Taylor, another famous Hollywood actress, who, due to the toll AIDS was taking on the entertainment industry, and her close relationship with megastar Rock Hudson, became an AIDS activist and founded the Elizabeth Taylor AIDS Foundation, its mission to help prevent discrimination against people with AIDS, who were seen as lepers of the community at the time. Due to the incurability of AIDS and a general lack of understanding on transmission, people with known or suspected AIDS were fired from their jobs and given a wide berth by society in general. They became isolated, shunned by friends and sometimes family alike. Gottlieb, gaining increasing notoriety with AIDS, developed the impression that UCLA, reflecting many in society, did not want to overly associate itself with AIDS, and he eventually left the institution and entered private practice, focusing on HIV and AIDS.