The Doctor - Dr. Michael Gottlieb - Who First Saw AIDS Believes in a 'Possible Cure' / Early Days of HIV: Rare cancer seen in 41 gays in NY & LA / Linda Laubenstein
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A Cure for HIV is Possible
The fact that we're even talking about the possibility of a cure - that's the eradication of HIV from the body - is a huge milestone. We're not there yet but I think in the next 10-20 years, we'll have a cure for HIV. The cure is the next step and nowadays, we are having realistic conversation about it. This is truly amazing to me.
Am J Public Health. 2006 June
Michael S. Gottlieb and the Identification of AIDS
Elizabeth Fee and Theodore M. Brown
Elizabeth Fee is with the History of Medicine Division, National Library of Medicine, National Institutes of Health, Bethesda, Md. Theodore M. Brown is with the Department of History and the Department of Community and Preventive Medicine, University of Rochester, Rochester, NY.
Requests for reprints should be sent to Elizabeth Fee, History of Medicine Division, National Library of Medicine, National Institutes of Health, 8600 Rockville Pike, Bethesda, MD 20894
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.
1. Gottlieb MS. Discovering AIDS. Epidemiology. 1988; 9:365-367. [PubMed]
2. Bayer R, Oppenheimer GM, AIDS Doctors: Voices From the Epidemic. Oxford: Oxford University Press; 2000, 18.
3. Gottlieb MS. AIDS-Past and Future. New England Journal of Medicine 2001; 344:1788-1791. [PubMed]
4. Centers for Disease Control and Prevention (CDC). Kaposi's sarcoma and Pneumocystis pneumonia among homosexual men-New York City and California. MMWR Morb Mortal Wkly Rep. July 3, 1981;30:305-308. [PubMed]
5. Gottlieb MS. Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: Evidence of a new acquired cellular immunodeficiency. New England Journal of Medicine 1981; 305:1425-1431. [PubMed]
6. Durack DT. Opportunistic infections and Kaposi's sarcoma in homosexual men. New England Journal of Medicine 1981; 305:1465-1467. [PubMed]
7. Kinsella J. Covering the Plague: AIDS and the American Media. New Brunswick, NJ: Rutgers University Press; 1989, 115.
RARE CANCER SEEN IN 41 HOMOSEXUALS
By LAWRENCE K. ALTMAN NY Times
Published: July 3, 1981
Doctors in New York and California have diagnosed among homosexual men 41 cases of a rare and often rapidly fatal form of cancer. Eight of the victims died less than 24 months after the diagnosis was made.
The cause of the outbreak is unknown, and there is as yet no evidence of contagion. But the doctors who have made the diagnoses, mostly in New York City and the San Francisco Bay area, are alerting other physicians who treat large numbers of homosexual men to the problem in an effort to help identify more cases and to reduce the delay in offering chemotherapy treatment.
The sudden appearance of the cancer, called Kaposi's Sarcoma, has prompted a medical investigation that experts say could have as much scientific as public health importance because of what it may teach about determining the causes of more common types of cancer.
First Appears in Spots
Doctors have been taught in the past that the cancer usually appeared first in spots on the legs and that the disease took a slow course of up to 10 years. But these recent cases have shown that it appears in one or more violet-colored spots anywhere on the body. The spots generally do not itch or cause other symptoms, often can be mistaken for bruises, sometimes appear as lumps and can turn brown after a period of time. The cancer often causes swollen lymph glands, and then kills by spreading throughout the body.
Doctors investigating the outbreak believe that many cases have gone undetected because of the rarity of the condition and the difficulty even dermatologists may have in diagnosing it.
In a letter alerting other physicians to the problem, Dr. Alvin E. Friedman-Kien of New York University Medical Center, one of the investigators, described the appearance of the outbreak as ''rather devastating.''
Dr. Friedman-Kien said in an interview yesterday that he knew of 41 cases collated in the last five weeks, with the cases themselves dating to the past 30 months. The Federal Centers for Disease Control in Atlanta is expected to publish the first description of the outbreak in its weekly report today, according to a spokesman, Dr. James Curran. The report notes 26 of the cases - 20 in New York and six in California.
There is no national registry of cancer victims, but the nationwide incidence of Kaposi's Sarcoma in the past had been estimated by the Centers for Disease Control to be less than six-one-hundredths of a case per 100,000 people annually, or about two cases in every three million people. However, the disease accounts for up to 9 percent of all cancers in a belt across equatorial Africa, where it commonly affects children and young adults.
In the United States, it has primarily affected men older than 50 years. But in the recent cases, doctors at nine medical centers in New York and seven hospitals in California have been diagnosing the condition among younger men, all of whom said in the course of standard diagnostic interviews that they were homosexual. Although the ages of the patients have ranged from 26 to 51 years, many have been under 40, with the mean at 39.
Nine of the 41 cases known to Dr. Friedman-Kien were diagnosed in California, and several of those victims reported that they had been in New York in the period preceding the diagnosis. Dr. Friedman-Kien said that his colleagues were checking on reports of two victims diagnosed in Copenhagen, one of whom had visited New York. Viral Infections Indicated
No one medical investigator has yet interviewed all the victims, Dr. Curran said. According to Dr. Friedman-Kien, the reporting doctors said that most cases had involved homosexual men who have had multiple and frequent sexual encounters with different partners, as many as 10 sexual encounters each night up to four times a week.
Many of the patients have also been treated for viral infections such as herpes, cytomegalovirus and hepatitis B as well as parasitic infections such as amebiasis and giardiasis. Many patients also reported that they had used drugs such as amyl nitrite and LSD to heighten sexual pleasure.
Cancer is not believed to be contagious, but conditions that might precipitate it, such as particular viruses or environmental factors, might account for an outbreak among a single group.
The medical investigators say some indirect evidence actually points away from contagion as a cause. None of the patients knew each other, although the theoretical possibility that some may have had sexual contact with a person with Kaposi's Sarcoma at some point in the past could not be excluded, Dr. Friedman-Kien said.
Dr. Curran said there was no apparent danger to nonhomosexuals from contagion. ''The best evidence against contagion,'' he said, ''is that no cases have been reported to date outside the homosexual community or in women.''
Dr. Friedman-Kien said he had tested nine of the victims and found severe defects in their immunological systems. The patients had serious malfunctions of two types of cells called T and B cell lymphocytes, which have important roles in fighting infections and cancer.
But Dr. Friedman-Kien emphasized that the researchers did not know whether the immunological defects were the underlying problem or had developed secondarily to the infections or drug use.
The research team is testing various hypotheses, one of which is a possible link between past infection with cytomegalovirus and development of Kaposi's Sarcoma.
Linda Laubenstein, 45, Physician And Leader in Detection of AIDS
By BRUCE LAMBERT
Published: August 17, 1992
Linda J. Laubenstein, a Manhattan physician who in 1981 discovered some of the first mysterious cases of what became the worldwide AIDS epidemic, died on Saturday at her summer home in Chatham, Mass., on Cape Cod. She was 45 years old.
Her family said an autopsy was pending. She suffered from severe asthma and weakness from childhood polio, an illness that required three major operations and left her a paraplegic at the age of 5.
"She is incredibly important in the history of AIDS, a genuine pioneer and a real fighter for what she believed," said Larry Kramer, an author and a leader in AIDS causes.
Dr. Laubenstein inspired the character of Dr. Emma Brookner, a principal role in Mr. Kramer's play on acquired immune deficiency syndrome, "The Normal Heart." He said an agreement was near on the production of a movie version by Barbra Streisand, with Ms. Streisand playing the Laubenstein-Brookner part.
Dr. Jeffrey B. Greene, a colleague, called Dr. Laubenstein "the ultimate AIDS physician." Despite her handicap, she met patients in the emergency room in the middle of the night and even made house calls, using her motorized wheelchair and public buses. "She was sicker than most of her patients but didn't let it stop her," Dr. Greene said. First Paper on Subject
Dr. Laubenstein and Dr. Alvin Friedman-Kien wrote the first paper to be published in a medical journal on the alarming appearance of Kaposi's sarcoma, a previously rare disease of lesions of the skin and other tissues. Most of the cases were in young gay men suffering a puzzling collapse of the immune system.
Recalling one of the first cases, she described a 33-year-old man with two purple spots behind his ears. Initially he responded to the cancer drugs she prescribed. But 18 months later he was dead, his body covered with 75 lesions.
Many more cases followed. By May 1982, she had seen 62 patients with AIDS -- a fourth of the national total recorded at the time. She said then that "this problem certainly is not going away."
Her father, George Laubenstein, said yesterday, "She told us from the very beginning that this is going to be a terrible epidemic."
Dr. Laubenstein's private practice grew to be predominantly AIDS cases. She and Dr. Freidman-Kien arranged the first full-scale medical conference on AIDS, at New York University in 1983. She also help to found the Kaposi's Sarcoma Research Fund in 1983.
Jobs in Office Services
In 1989, she and Dr. Greene founded Multitasking, a nonprofit organization selling office services to other businesses and employing people with AIDS as the workers. Her concern was that AIDS patients often lost their jobs and that work was vital to emotional and physical health as well as for financial support.
Dr. Laubenstein was outspoken about what she said was the neglect by government and society in fighting AIDS. Some of her views were controversial among gay groups, particularly her belief that bathhouses should be shut down to discourage unsafe sex.
Born in Boston, she grew up in Barrington, R.I. She graduated from Barnard College and New York University Medical School. Her specialties were hematology and oncology, and she was a clinical professor at the New York University Medical Center.
Surviving are her parents, George and Priscilla of Harwich Port, Mass., and a brother, Peter of Melvin Village, N.H.