May 2004

The Global Threat of Infectious Diseases

Battling AIDS on the Front Lines

Investigating the Mechanisms of Tumorigenesis

Effecting Change in the Health Care System

Understanding the Psychology of Terrorism

Shifting Sands

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Bryn Mawr College
A newsletter on research, teaching, management, policy making and leadership in Science and Technology

Battling AIDS on the Front Lines
By Barbara Spector

In 1977, Donna Mildvan ’63, chief of the infectious diseases division at New York’s Beth Israel Medical Center, investigated sexual transmission of amoebae and other enteric pathogens in gay men. These diseases were rarely acquired in the United States, yet the patients she examined had not traveled outside New York. Mildvan also observed swollen lymph glands in some of these patients.

Donna MildvanShe thought of those cases in July 1980, when a very sick patient came to the hospital. The German-born gay man, who had been a chef in Haiti, was soon ravaged by disease — starting with bloody diarrhea and ending with encephalopathy. When the patient began to lose sight in one eye, a colleague suggested culturing the vitreous fluid. “We sent the sample to the lab, and it grew cytomegalovirus,” says Mildvan. By December, the man was dead.

Two weeks later, Mildvan recalls, “a nurse from our hospital was admitted with Pneumocystis carinii.” He died within 10 days. “It was the most fulminant course imaginable,” she says. An autopsy revealed that the nurse, like the chef, was inexplicably infected with cytomegalovirus.

These cases led Mildvan to two realizations. First, “This was a new disease.” Second, “The lymphadenopathy we were seeing in the amoeba study was the early stage of this disease.”

Turning Points

Mildvan made a lunch date with Dan William, her collaborator on the amoeba study, who had opened a medical practice serving the gay community. He had been seeing young men with Kaposi’s sarcoma, which, like cytomegalovirus, occurs only in immunocompromised patients. “We sat there, not able to eat,” Mildvan recalls, as they realized that a new epidemic — ultimately called AIDS — had begun.

In February 1981, Mildvan called back patients from her 1977 study and examined 42 of them in the first longitudinal cohort study of the epidemic. By September or October, several had developed Kaposi’s sarcoma. In October 1982, she and colleagues presented these results to a skeptical audience at the Interscience Conference on Antimicrobial Agents and Chemotherapy.

By this time, AIDS could not be diagnosed except in its advanced stages, and physicians did not know the cause or how it spread. The greatest advance in our understanding of AIDS, Mildvan notes, was the 1983 discovery of the virus that would become known as HIV. Now rational therapies could be designed to attack the virus. Another breakthrough came when the polymerase chain reaction (PCR)-based assay began to be used in AIDS research, enabling investigators to measure the level of HIV RNA in patients’ blood instead of counting T cells — an indirect measurement of viral activity. After that, Mildvan says, “We could count virus particles and determine quickly if they were being reduced by treatment.” Counting viral particles led to the realization that combination therapy was needed.

Skepticism and Faith

Mildvan says that although she was a German major, “I learned at Bryn Mawr all of the key principles that have guided my subsequent career in medicine.” These principles include skepticism and faith in one’s own judgment or intuition, she says. “You were allowed, and ultimately encouraged, to go your own way and find your own path.”

Mildvan wanted to write her senior honors thesis on illness and crisis in the works of Hermann Hesse. Department chairman Christoph Schweitzer turned down her proposal, saying that Hesse was not a sufficiently substantive author. “Somehow I found the courage to challenge him,” Mildvan recalls, “because I had learned how over those three years.” Ultimately, she was allowed to write her thesis on the topic of her choice.

Mildvan went on to the Johns Hopkins University School of Medicine, Baltimore, and did postgraduate training at New York’s Mount Sinai Hospital. “I just loved infectious diseases,” she recalls. “At the time, it was such an optimistic field — we were taught that if you could find the bug, you could cure the disease. The reality that new diseases could appear suddenly and become global epidemics, as revealed most starkly by AIDS, couldn’t have been farther from people’s minds.”

In 2000, Mildvan received a Heroes in Medicine Award from the International Association of Physicians in AIDS Care. One of her more than 200 publications, which dates from the early years of the epidemic (D. Mildvan et al., “Opportunistic infections and immune deficiency in homosexual men,” Annals of Internal Medicine, 96:700-4, 1982), was ranked among the 100 most-cited articles in the Science Citation Index. “It has been an amazing privilege to have been involved in this work,” she says.

Mildvan co-chaired the Surrogate Markers Collaborative Group — with membership from academia, industry and government — which in 1997 confirmed RNA’s effectiveness as a surrogate marker for licensing of new anti-HIV drugs by the Food and Drug Administration. Today AIDS drugs can be licensed more quickly on the basis of their ability to lower levels of plasma HIV RNA. Her current research is aimed at validating new biomarkers that will be used to optimize the response to treatment.

Mildvan considers herself very lucky to have landed her first job at Beth Israel, which she joined in 1972. “The most interesting cases, the most challenging problems just present themselves,” she says. “It is never boring.”

Barbara Spector writes on science and technology as well as business topics. She is the editor-in-chief of Family Business magazine and former editor of The Scientist.

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