Portal de Periódicos da CAPES

Michael S. Gottlieb and the Identification of AIDS

2006; American Public Health Association; Volume: 96; Issue: 6 Linguagem: Inglês

10.2105/ajph.2006.088435

1541-0048

Elizabeth Fee, Theodore M. Brown,

HIV/AIDS Research and Interventions

THE LEAD AUTHOR OF THIS paper, Michael S. Gottlieb, was, in 1981, a 33 year-old assistant professor specializing in immunology at the University of California Los Angeles (UCLA) Medical Center. When he asked one of his immunology fellows to look for interesting “teaching cases,” he learned of a young gay man with unexplained fevers, dramatic weight loss, and a severely damaged immune system. His mouth was full of thrush, or candidiasis, which was usually seen in patients with a defect in one particular component of the immune system, the T-lymphocytes. Gottlieb later described a process of reasoning that led him to conclude that that this patient was suffering from some syndrome that had not previously been reported.1 He discussed the unusual case with his clinical immunology postdoctoral fellows and internal medicine residents. Additional blood tests confirmed a marked deficiency of T-lymphocyte numbers and functions. Then a postdoctoral fellow who was using a series of new monoclonal antibodies to identify subclasses of T-lymphocytes was asked to examine a sample of the patient’s blood and found that the T-cells bearing the surface marker CD4, the “helper” cells, were virtually absent. The patient was discharged from hospital without a definite diagnosis but 1 week later was readmitted, this time with fever and pneumonia. The resident physician was concerned about an opportunistic infection in this individual, who was known to have an immune deficiency, and he convinced a pulmonary specialist to perform a bronchoscopy and retrieve a sample of lung tissue for analysis. This procedure is commonly done in immunedeficient patients to identify particular microorganisms, thus allowing for rapid specific diagnosis and treatment. The diagnosis was Pneumocystis carinii, a rare but well-known cause of pneumonia found in some organ transplant patients and children with immune deficiency. The patient was treated and again discharged. Soon thereafter, Gottlieb heard about 2 patients of Joel Weisman. Weisman and his partner were gay physicians with a largely gay practice.2 Both patients had chronic fevers, swollen lymph nodes, diarrhea, and thrush. Gottlieb tested the T-cells of Weisman’s patients and found they had the same abnormality as his original patient. Over the next several months, both were diagnosed by bronchoscopy with Pneumocystis carinii. Both also had the DNA virus cytomegalovirus (CMV). The fourth case came to Gottlieb through a former student, Wayne Shandera, who had become the CDC’s Epidemic Control Officer in Los Angeles. Gottlieb told him that there was a new disease in gay men that seemed to have something to do with CMV and pneumocystis pneumonia and asked Shandera to see what he could find out. Shandera had a report sitting on his desk about a man in Santa Monica who had been diagnosed with pneumocystis pneumonia. Shandera went to see the patient and found that the man was deathly ill. The patient died soon after the visit; on autopsy, CMV was found in his lungs. A fifth case came from a Beverly Hills internist. This patient too had Pneumocystis carinii and CMV. Several of these patients went on to develop Kaposi’s sarcoma, a rare skin cancer sometimes found in older men or immunosuppressed kidney transplant recipients. Gottlieb, an ambitious young man, was excited to think he might have made a significant discovery. He telephoned Arnold Relman, the editor of the New England Journal of Medicine, and declared that he had a story that was “possibly a bigger story than Legionnaire’s disease.”3(p1788) When Gottlieb described his patients suffering from this complicated new malady, Relman advised that, because publication in the New England Journal would take a minimum of three months, Gottlieb should first submit a brief article to the CDC Morbidity and Mortality Weekly Report. This would serve the dual function of alerting public health officials and physicians to the new disease and also stake Gottlieb’s claim to be its “discoverer.” A longer and more detailed account could then be submitted to the New England Journal. Gottlieb followed this good advice and the result was the rather terse announcement reprinted here. It was generally overlooked; few physicians bothered to read the MMWR. A few weeks later, however, when Alvin Friedman-Kien published a description of twenty-six cases of Karposi’s sarcoma in gay men in New York and California, the media began to pay more attention.4 National Public Radio, the Cable News Network, the Associated Press, the New York Times, and the Washington Post all followed with stories. Gottlieb’s article in the New England Journal of Medicine was published a few months later and attracted enormous attention.5 As Gottlieb said later, the publication of this article changed his life. For several years, it was one of the most heavily quoted papers in the medical literature. The story would unfortunately prove to be a great deal more important than Legionnaire’s Disease. In the New England Journal article, Gottlieb and his co-authors described a “potentially transmissible immune deficiency”5(p1425) and suggested that a sexually transmissible agent contracted at different times by the patients was the common factor. Asymptomatic infection with CMV had recently been found to be common among the male homosexual population, and acute CMV infection had been associated with immunologic abnormalities, including reduction in CD4 cells. They therefore hypothesized that a new strain of CMV had emerged in the homosexual population and was causing immune deficiency. They also acknowledged the possibility that CMV was a result rather than a cause of the T-cell deficiency and that some other undetected microorganism, drug, or toxin might be making these patients susceptible to opportunistic organisms, including CMV. In an editorial accompanying the publication of the article, DT Durack asserted that CMV infection was more likely to be an opportunistic consequence of immune deficiency than its cause.6 In the early 1980s, Gottlieb treated a growing number of patients with AIDS and continued his clinical research at UCLA, publishing over 50 papers on various aspects of HIV infection and treatment. He obtained one of the earliest National Institutes of Health grants for AIDS research, served on many AIDS-related boards, and became physician to the stars: Rock Hudson, perhaps the most famous of all people with AIDS, was his patient. Gottlieb was also one of the few scientists who were willing to talk openly to reporters in the early years of the epidemic. His colleagues and superiors let it be known that his frequent appearances in the media were unbecoming to an academic.7 Part of the problem, said Gottlieb, was that the UCLA Medical Center aspired to develop cardiac and liver transplant programs, and the physicians feared that if the hospital became too well known for AIDS, transplant patients might stay away.2(p98) They also foresaw that there would ultimately be a lot of AIDS patients without good health care coverage. AIDS loomed as a threat to the well-being of the hospital and Gottlieb, so publicly and professionally identified with the disease, was becoming a nuisance. Despite or perhaps because of his fame, Gottlieb was denied tenure at UCLA and went into private practice in 1987. In 1985, Gottlieb and Mathilde Krim became the Founding Chairmen of the American Foundation for AIDS Research (amfAR), with Elizabeth Taylor as its Founding National Chairman. AmfAR would make a crucial contribution to AIDS research by supporting innovative projects; it would also help craft AIDS legislation, accelerate research on new treatments, and argue for rapid access to experimental HIV/AIDS drugs.