NA University

Making Medical History
Discovery of AIDS

"I did something in it," he admits, "but I have enough of a spiritual
background to know that it's something working through me. A lot of what
you're called to do in life is not something you initially choose to do.
I didn't want to go to Los Angeles -- it was the last place I wanted to
go."

So maybe there was a point to being there.

Making Medical History

Twenty Years Ago Today, Doctors First Warned the World of the Emergence
of a Deadly New Disease -- AIDS

By David Brown
Washington Post Staff Writer
Tuesday, June 5, 2001; Page C01

Michael S. Gottlieb remembers the day he discovered AIDS.

He was 33, a first-year assistant professor at UCLA Medical Center, specializing in immunology. It's a field of uncommon diseases, and sometimes you have to go looking for patients. So one day in January 1981, he asked the immunologist-in-training to prowl the wards for "teaching cases."

"I remember sitting in the basement office, and my fellow returning," Gottlieb recalled, sitting in a different Los Angeles office, this one spacious and above ground. "He said: 'The intern has this patient who is really kind of interesting.' "

The patient's name was Michael. He was a tall, handsome model with cheekbone implants. He'd moved to Los Angeles in part to be openly homosexual. He'd been hospitalized because of unexplained fevers and weight loss.

A blood test revealed he had a severely damaged immune system. He looked like a cancer patient recovering from a bruising round of chemotherapy. The trouble was, he didn't have cancer and hadn't undergone chemo. Until recently he'd been healthy.

He was a diagnostic enigma.

Gottlieb remembers another scene from that admission vividly.

Although the department's immunology team had not been formally consulted on the case, its members went to see Michael every day. One visit was interrupted by a telephone call. In a stage whisper, Michael said to the caller: "These doctors tell me that I am one sick queen."

The doctors chuckled uneasily. "We were not accustomed to some of the self-deprecating humor that gay men can use," Gottlieb recalls. Perhaps, though, what made the statement memorable is not its language but its truth.

Michael was discharged in about five days. He was back in a week. He was dead in less than a year. But before his mysterious downward spiral was over, he entered medical history.

Twenty years ago today, Michael appeared, nameless, as one of five patients in a brief report in the weekly newsletter published by the federal Centers for Disease Control. It described a strange disease that eventually would be named AIDS.

Nobody could have imagined that acquired immune deficiency syndrome would have killed more than 20 million people two decades later and become one of the worst epidemics in the history of mankind.

Historians of science sometimes debate which is more important to discovery, the person or the moment.

How long would the laws of classical mechanics have lain undiscovered if Isaac Newton had never been born? Charles Darwin and Alfred Russel Wallace each took long voyages to exotic places. In July 1858, they each propounded a theory of natural selection. Was that a coincidence of genius? Or was the idea lying in plain view?

With the discovery of AIDS, though, there isn't any debate.

Piecing Together Clues

In spring 1981, AIDS was waiting to be found. If Michael Gottlieb and several other Los Angeles doctors -- principally Joel Weisman and Wayne X. Shandera -- hadn't described unusual infections in gay men, someone somewhere would have within weeks.

At the other end of the country, someone was already on the trail. In July 1981, a New York City dermatologist would report an outbreak of Kaposi's sarcoma, a rare cancer, in gay men. It would be the sound of the other shoe dropping in what was to soon become a stampede of illness and death.

Gottlieb, Weisman and Shandera did not describe AIDS in detail. The many faces of the disease, in fact, wouldn't become visible for years. Nor did they discover its cause, human immunodeficiency virus (HIV), which was isolated in 1983.

What they did was notice a pattern of unusual illnesses in homosexual men who'd had no contact with each other. Their observation created a frame on which the edifice of AIDS knowledge could be built, piece by piece. That the pattern was in some sense "obvious" doesn't detract from their achievement, or from the work of a half-dozen other people involved in finding the original cases.

They saw it first -- and first always counts.

Soon after Gottlieb met Michael, he learned of two other patients who bore some resemblance to that strange case. They were brought to his attention by Weisman, a doctor with whom, superficially at least, Gottlieb had much in common.

They're roughly the same age. Both are Jewish, and both grew up in New Jersey, about 20 miles apart. Gottlieb's father was a high school gym teacher and coach who'd died when Michael was 16. Weisman's father was an elementary school principal who died when Joel was in medical school. Both men settled at the other end of the country to practice medicine.

The differences, though, were more important.

Gottlieb was an ambitious young man. One year out of a fellowship at Stanford University, he'd landed a tenure-track appointment at the UCLA School of Medicine. He'd published a couple of research papers, and was eager to get more into print. Weisman, by contrast, had gone to an osteopathic medical college in Missouri. He'd done no research. For a while he'd been in general practice with an uncle in New Jersey. He was in Los Angeles for a simple reason: In 1975 he left his three-year
marriage, acknowledged his homosexuality, and crossed the country to start a new life.

He was practicing in Sherman Oaks, a suburb north of Los Angeles. Nearly half his patients were gay men. It was a time when a few doctors had begun to recognize the particular health needs of that population, and Weisman was one of them.

Sexually transmitted diseases were on the upswing. Cytomegalovirus (CMV), a microbe that tends to cause illness only in people with compromised immune systems, was showing up in gay men. Hepatitis B was also common. The Gay and Lesbian Community Service Center in Los Angeles, where Weisman volunteered once a week, had been a place where researchers recruited people to test an experimental vaccine against that virus.

Against this backdrop of illness, Weisman had noticed some weird things.

In 1978 he had a patient with Kaposi's sarcoma, a cancer seen mostly in old Mediterranean men, according to the textbooks. His patient was a gay Anglo in his thirties. He saw several cases of shingles, also a disease of the old and infirm. He and another gay physician in the practice sent seven or eight men with persistent lymphadenopathy -- "swollen glands" -- for biopsies to make sure they didn't have lymphoma. None did.

He sensed something wasn't right. But no pattern jumped out and, in any case, the patients all seemed to respond to treatment.

In early 1981 Weisman and his medical partner each had a particularly puzzling patient. Both were homosexual men with CMV, yeast infections of the mouth (oral thrush) and persistent fevers. Unable to find an underlying cause for either man's problems, the doctors consulted a local rheumatologist named Peng Fan.

Neither patient had joint disease, but rheumatologists see many diseases of immunity, which often cause arthritis, and these men clearly had something wrong with their immunity.

Fan ordered various tests, looking for rare conditions such as zinc deficiency. He eventually concluded that he needed to learn more about their immune defects.

Gottlieb had reached the same conclusion after examining his patient Michael. He'd asked for help from another scientist in his department. Using a test available in only a few places in the country, that researcher had measured the patient's lymphocytes, the workhorse cells of the immune system. The results showed Michael had many more "suppressor" cells than "helper" cells, the reverse of the norm.

Fan called the UCLA department of immunology and inquired if anyone was working on the cell biology of immune-deficient patients. He doesn't remember whom he talked to, but the person directed him to Gottlieb. He called Gottlieb and told him about the two patients from Sherman Oaks. Gottlieb was interested, and Fan said he'd set up a meeting.

Sometime in February, Fan, Gottlieb, Weisman and Weisman's partner (who thereafter consciously took a back-seat role) gathered in the rheumatologist's office. They exchanged notes, and soon it was clear: Three cases had many features in common.

Three. It's a magic number that makes coincidence an unlikely explanation. A series.

"I know this is strange 20 years later, but I always had a feeling going into the meeting that what this represented was a tip of the iceberg," Weisman recalls. "My sense was that these people were sick -- and we had a lot of people that were potentially right behind them."

Soon after the meeting, both patients developed pneumonia caused by an unusual microbe called Pneumocystis carinii. Pneumocystis was an opportunist; as a rule it caused disease only in the immune-suppressed or malnourished. There had been numerous outbreaks ofPneumocystis carinii pneumonia (PCP) in postwar Eastern Europe, usually in nurseries or orphanages.

It was not an infection one expected to find in middle-class American men. It was sought in Weisman's patients only because it had been found in Gottlieb's patient Michael by a combination of luck and intelligence.

A week after his discharge in January, Michael returned with pneumonia in both lungs. He was assigned, by chance, to the same intern who'd helped care for him previously. That doctor knew Michael had deficient immunity. He also knew that such patients can die rapidly if the infecting microbe isn't identified and treated.

Michael wasn't coughing up phlegm, so the intern took the unusual step of requesting that a lung specialist get a sample through a procedure called bronchoscopy, in which a tube is put down the windpipe.

It found pneumocystis -- not a bug you'd ever have guessed in advance.

Things were falling into place in an ominous way. Gottlieb was convinced he'd found something public health authorities should know about. He also wanted to get a paper out of it.

He called the editor of the New England Journal of Medicine, the country's most prestigious medical periodical, and described his observations. The editor suggested that Morbidity and Mortality Weekly Report, the CDC's epidemiological newsletter, might be a better place for the findings. MMWR, as it's universally called, went to every health department in the country and thousands of private physicians. Publication there wouldn't preclude Gottlieb writing a fuller
description of the cases in the New England Journal later.

Gottlieb was relieved. Soon after, he made another important phone call. It was to Wayne Shandera.

Seek-and-Report Operation Shandera was with the Epidemiology Intelligence Service, a branch of the CDC. EIS officers are the medical equivalent of Green Berets. They go after trouble: disease outbreaks, reports of strange illness, pretty much anything of hazard to the public health.

Shandera's principal qualifications for the job were intelligence and conscientiousness. He'd gone to medical school at Johns Hopkins and done a residency in internal medicine at Stanford (where he'd gotten to know Gottlieb slightly). He'd done no graduate work in either epidemiology or public health.

His training consisted of a three-week course in Atlanta. New officers were taught the rudiments of outbreak investigation, such as how to do a "case-control study," in which people with the disease being investigated are compared to people who don't have it. Then they were sent off to learn on the job.

Shandera had applied for many postings: His father was dying of colon cancer in San Antonio, and he'd hoped for someplace in the South. He got Los Angeles instead.

In his first year, Shandera investigated about a dozen outbreaks. Patients with muscle weakness in Santa Monica, stillbirths in Long Beach, meningitis in Watts, hepatitis in a transfusion center, cancer clusters, diarrhea outbreaks. Only some could be run to ground.

During that year he read "The Long Loneliness," the autobiography of Dorothy Day, who founded the Catholic Worker movement. He identified
with Day's search for a way to be socially useful. Also, with her loneliness.

In his call to Shandera, Gottlieb remembers asking, with intentional vagueness, whether he was aware of anything going on in gay men. He recalls the answer was no. Gottlieb says he then recounted the three cases of men with immune deficiency, fevers, chronic CMV infection and pneumocystis pneumonia.

Shandera's office was in the county health department, and he was one of the people who got reports of unusual microbiological cultures or autopsy findings. As it happened, sitting on his desk that day was a report that a man at a hospital in Santa Monica had been diagnosed with pneumocystis pneumonia.

Shandera called the hospital and got permission to look at the chart. He drove down and read it. The patient, a gay man, was still there, and Shandera interviewed him and his lover. Three years earlier the patient had been treated for Hodgkin's disease, a form of lymphoma. The treatment had been successful, and there was no sign of the cancer. But now, at 29, he was deathly ill with PCP. In fact he died soon after the visit, and on autopsy, CMV was also found in his lungs.

The case was not perfect. The patient had had a cancer, and both cancer and its treatment can cause immune suppression. Still, it was close. Shandera called Gottlieb back.

"I remember when he told me about it that I was impressed by his resourcefulness," Gottlieb recalls. "That's when a shiver went down my
spine. With just a little bit of information, he was able to go right out and find a case."

In April, a fifth case -- a 36-year-old homosexual man with PCP, fever, and previously diagnosed CMV infection -- came to Gottlieb's attention
from another doctor.

One hot Sunday afternoon in May, Gottlieb went to Shandera's apartment in West Los Angeles. In a couple of hours, they wrote up the five cases. The report was seven paragraphs. The "editorial note" that follows MMWR reports (and which they also wrote most of) was two paragraphs.

Gottlieb threw out the handwritten manuscript a couple of years later. The table on which they wrote the report is still Shandera's dining room
table.

"Pneumocystis Pneumonia -- Los Angeles" appeared as the second article in MMWR on June 5, 1981. In the "Reported by" line, it lists six people, but not Shandera, as EIS officers are never mentioned by name. The lead article was about dengue fever brought into the United States by travelers to the Caribbean.

Gottlieb's phone soon began ringing with reports of similar cases in San Francisco and New York. A week after publication, Shandera went over to L.A. County Hospital. Three men were in the intensive-care unit with PCP.

Whatever this new syndrome was, it was everywhere.

Investigating Further

Since that first report, AIDS has had 60 million victims, living and dead. It's no surprise it changed the lives of the men who helped find it.

"The next year was kind of a blur," Weisman says. One thing was clear to him, though: The new immune deficiency disease was sexually transmitted. Like many others, he originally believed a killer strain of CMV was the cause. He put no stock in the theory it was caused by inhalation of amyl nitrate ("poppers," popular in gay lovemaking at the time) or other lifestyle exposures.

In 1982, he helped organize the first public forum on the disease in Los Angeles. He'd adopted safer-sex practices himself two years earlier in response to the epidemic of venereal disease. Now he felt free to speculate on the disease's origin -- and make behavioral recommendations -- in ways that public health authorities couldn't or wouldn't.

His practice soon became almost entirely AIDS patients. He was the first chairman of AIDS Project Los Angeles. He helped found the American Foundation for AIDS Research (AmFAR), and served as its chairman from 1987 to 1991.

Weisman's lover soon developed AIDS. Weisman himself had an inverted helper/suppressor lymphocyte ratio the one time he tested it, in 1981 or 1982. But as it happened, that result was a fluke. In 1985, a blood test for the AIDS virus became available. Weisman took it many times before he believed he was uninfected. His lover died in 1991 after a decade of tweaking every advantage he could out of every drug that came along.

"I could never separate myself from HIV," Weisman says. "I did it from 7:30 until 7:30, and then I did it from 7:30 until 7:30. It was always there in front of you even if you weren't talking about it."

Frankly, he doesn't think the public appreciates the emotional toll caring for AIDS patients had on doctors. In any case, by 1998, he was ready for a change. He left medicine, left Los Angeles, and moved to New York City. In his fifties, he feels reborn into a new life.

Last January, he and his new partner bought a bed-and-breakfast on the New York side of the Berkshires and moved into the country. He's no longer known to everyone, immediately, as one of the original describers of AIDS. "There's something refreshing about that," he says. "About not having even that positive baggage."

Shandera left Los Angeles less than a month after the MMWR report appeared. His requested transfer to CDC's Atlanta headquarters came through, and he worked there for another year in the gastrointestinal infections branch. Out of personal interest, he attended the first few meetings of the CDC task force on the new disease, but soon had to stop as his own work piled up.

He returned to AIDS, though, and has been involved with the disease for much of the last two decades.

He took further training in infectious diseases at Massachusetts General Hospital. He spent some of the darkest days of the AIDS epidemic -- 1986 to 1988 -- in Dallas. The caseload was huge and nearly all the patients died. A church downtown had a sign proclaiming "AIDS -- The Wrath of God." He recalls that "there wasn't a nursing home in the whole Metroplex that would take AIDS patients."

In 1988 he moved to Houston, where he's on the faculty at Baylor College of Medicine. He sees patients at Ben Taub Hospital, and at Thomas Street Clinic, the city's biggest HIV clinic. He has written papers on mathematical modeling of the AIDS epidemic, and done clinical research on tuberculous meningitis and neurocysticercosis, two unusual infections seen occasionally in the city's large immigrant population.

Shandera, who has never married, leads a life he suspects is more ascetic "than 99 percent of physicians." His principal sources of pleasure are music -- both listening to it, and playing the pipe organ at his church -- and languages. He speaks Spanish, German and Russian, and has been studying Mandarin Chinese. Every spring he does a one-week stint at a rural clinic in Honduras or Guatemala. If anything, his Catholic faith is even more important now.

He characterizes his role in the first report as small.

"I did something in it," he admits, "but I have enough of a spiritual background to know that it's something working through me. A lot of what you're called to do in life is not something you initially choose to do. I didn't want to go to Los Angeles -- it was the last place I wanted to go."

So maybe there was a point to being there.

Michael Gottlieb loves Los Angeles and never left.

He was the main author of the first big clinical description of AIDS, in the New England Journal of Medicine, in December 1981. He was Rock Hudson's physician when the actor was ill with AIDS. He obtained for UCLA one of the earliest National Institutes of Health grants for AIDS research. However, the university didn't grant him tenure.

Gottlieb went into private practice in 1987. In 1989 he and two medical partners were reprimanded by the state medical board for allegedly over-prescribing controlled substances to Elizabeth Taylor. He's married to a former local TV anchorwoman -- his second marriage -- and they have an 11-year-old daughter.

He has served on innumerable AIDS-related boards, and has been an investigator in several clinical trials of anti-retroviral drugs. His practice is 85 percent AIDS patients. In AIDS and medical circles in Los Angeles, his is still a familiar face.

About six months ago Gottlieb was at Gelson's, a grocery store in the San Fernando Valley, when a man behind him in the checkout line introduced himself.

"You don't know me, but I was Chuck's lover." Chuck was one of the five patients in the original report. "You tried everything you could to keep him alive, and I appreciated that, and his mom appreciated it."

They talked for a minute about Chuck, who was from Oregon and liked to wear cowboy boots. He'd been dead 19 years. The man thanked him again. It made Gottlieb feel good.

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