A little over a year after AIDS researcher Sarah Schlesinger returned to New York City in 2002 to take a job at the International AIDS Vaccine Initiative (IAVI), she got a call to run one of the first DNA-based vaccine trials designed to prevent HIV infection. It was a bit of a career coming full-circle: The job offer came from David Ho and her old boss and mentor, Ralph Steinman at The Rockefeller University, where Schlesinger began her career at age 17, working in Steinman's lab through college and medical school.

Schlesinger, now 44, knew as a teenager growing up in nearby Scarsdale, NY, that she wanted to be a doctor. That was a given in a family where her grandmother was among the first class of women admitted to train at Bellevue Hospital – a building Schlesinger passes every day on her way to work at Aaron Diamond AIDS Research Center.

But she wasn't that excited about science, which seemed to be all about memorizing facts. That changed at a Rockefeller University lecture for high schoolers where she heard researchers talk about their work. "The idea that you could make up a question, any question, and design an experiment to answer it – that was what I wanted to do." She called up Rockefeller scientist Ralph Steinman and asked if she could work for him. He agreed.

The 17-year-old came to work in his lab in 1977, just a few years after Steinman and the late Zanvil Cohn published their discovery of dendritic cells.[1] The scientific community wouldn't embrace the discovery for years. "Science is not as creative an activity as it might appear," says Steinman. "It takes a hell of a long time for science to accept something new, particularly something no one sees a need for." Neither Steinman nor Schlesinger could have anticipated that Schlesinger would go on to head her own dendritic cell lab one day at the Walter Reed Army Institute of Research in Washington, DC.

Some 30 years after the discovery, Steinman and colleagues like Schlesinger hope to exploit the ability of dendritic cells to orchestrate the body's immune response. If they can harness these cells to both magnify and mute the immune system's function, they say, they may be able to develop therapies for diseases ranging from cancer to HIV.

Schlesinger saw the devastation of HIV/AIDS firsthand as a young doctor at Jacobi Hospital in the Bronx in the mid 1980s. There she watched young people with Pneumocystis carinii pneumonia die. "It looked like the end of the world," she recalls. "I feel tremendously privileged to be doing something to control the worst epidemic that's ever hit mankind."

And it would appear that many New Yorkers feel the same about helping to stem the disease. While other trials have been slow to enroll, hundreds called to participate in Phase I of the ADVAX vaccine trial, filling the enrollment goal of 45 in 5 months – far short of the two years originally projected by the researchers. The ADVAX trial is testing a synthetic DNA-based vaccine that contains five HIV genes (more genes than most vaccines). And, while the National Institutes of Health has expressed concern about the overall small numbers of women and minorities enrolled in clinical trials, New York City came through with flying colors, the diversity of the participants mirroring the diversity of the city. 60% were women; 15% African-American; and 15% Hispanic, which will help tell researchers how the vaccine works in a diverse population.

Living at the center of the epidemic, with more cases than San Francisco and Miami combined, a number of New Yorkers have friends and family affected by AIDS. Nearly half of the ADVAX participants have a friend or family member who is HIV+. Some are like 42-year-old Kay Marshall, who 10 years ago lost a close friend to AIDS. "It's not a big deal to get stuck a few times, to have your blood drawn a few times," she says. "People say it's a noble thing, but it feels like a privilege." (Marshall's brother and his partner, are also trial participants.) A second Phase I vaccine trial, with 48 subjects, and based on a modified smallpox virus containing the same genes, will begin this fall, and researchers are crossing their fingers that the public's response will be equally good.

Being in New York is great for her research, but these days, Schlesinger is just happy to be back in the city she loves. "How does the saying go?" she asks. "'Man plans and God laughs.' I couldn't have picked this life if I'd tried." Her 14-year-old son Zachary may be following in her footsteps. This past summer he helped to clone and sequence the next vaccine construct as an intern at the Aaron Diamond AIDS Research Center. Like mother, like son.