Editor’s note: This is an article from the Winter 1999 issue of UCLA Magazine.
In the enticing beauty and tranquility of Santa Fe, Janis Giorgi is worrying over a scientific puzzle. “I just don’t get it,” she says suddenly, shaking her head of short black curls. “Why does the virus come back to the same level as before?”
It’s 11 p.m. on a chill October night and Giorgi, clad in a white silk dressing gown, her bare feet propped on a table, a glass of merlot in one hand, is referring to HIV, the maddeningly clever virus that causes AIDS. It’s a topic that frequently occupies her curious mind. Even here, in this charming adobe cottage, hundreds of miles from her 12th-floor lab in the Factor building at UCLA, the scientist in her can’t be still.
Some of that obsession is understandable. Giorgi has come to this quaint New Mexico town to speak at the Santa Fe Institute, a prestigious think-tank that brings together scholars of various disciplines to work out problems of society and science. Two hours earlier, the 52-year-old immunologist, wearing a stylish black suit, was on stage, explaining to an audience her lab’s amazing findings concerning people’s resistance to HIV. For 15 years, she has been involved with the Multicenter AIDS Cohort Study, or MACS, one of the most significant long-term investigations of HIV and AIDS, trying to discern the specific ways in which the immune system protects against the deadly virus. Among her other achievements, Giorgi was the first to discover that different people respond differently to HIV.
It’s a measure of her quiet confidence that 15 minutes before she was supposed to leave for her lecture, Giorgi was not going over her notes or getting dressed. Instead, one of the world’s leading immunologists was standing over a hot, greasy pan, frying up a batch of chicken livers for her friends. Besides science, Giorgi’s other passion is cooking. Not surprisingly, she’s good at it.
For Giorgi, this visit to Santa Fe is something of a spiritual journey — a coming together of her past and present lives. She was invited here a year ago by Ellen Goldberg, an engaging scientist who is the institute’s director. Goldberg was one of Giorgi’s mentors at the University of New Mexico, where the bright young graduate student was one of just six women in the microbiology and immunology program. The two have remained close ever since. At the lecture, Goldberg’s introduction of her former student was lavish with pride and praise. “She’s a remarkable scientist and her work has resulted in, and will continue to result in, insights into this terrible disease,” she told the audience.
Giorgi has also brought along some of the people she treasures most in the world. There is her longtime partner, Duane Keith, a research specialist in the biochemistry of narcotics addiction, and three members of her staff and a longtime friend. Unlike many top researchers, Giorgi is exceptionally close to those with whom she works. Every Christmas, she throws a lavish party at the airy, Eichler-style Woodland Hills home she shares with Keith, cooking everything herself, from the turkey crepes to the cheesecake. It’s her way of thanking her staff for their long hours and devotion. “Her enthusiasm is inspirational,” says Mary Ann Hausner, who runs the scientist’s immune function laboratory. “She has a way of reaching out to people. Everybody in the lab strives to meet her requirements.”
Giorgi lived in New Mexico for nine years and she loves the Southwest. The high mountains and open blue sky with its huge cottony clouds are like a tonic to her. On this visit, she went fly-fishing for the first time, standing in a cold stream in waders, a hat and fishing vest. She didn’t catch a single trout, but she was radiant nonetheless. “It was like being home again,” she says of New Mexico, after returning to Los Angeles.
A year ago, Giorgi couldn’t have imagined such a journey. A year ago, she could barely get out of bed. In a perverse roll of the dice, Giorgi, who has spent the better part of her professional life determinedly searching for the kind of answers that could conquer HIV, was battling her own deadly disease: uterine cancer.
When the participants in her study learned the news, they, perhaps better than anyone else, understood what it meant. “The men who are HIV-infected were so supportive, so concerned,” recalls Giorgi, a thoughtful woman with deep brown eyes and fair skin. “It gives you a sense of what it must be like for people who have this problem that they can’t get rid of.”
Giorgi is now in remission. Her greatest daily struggle is with fatigue. “All I want to do is go home and sleep,” she says with a laugh one afternoon while standing in a hallway near her office.
She is philosophical about how the disease has changed her, brushing off suggestions that she is stoic. “Everyone has difficulties in their lives,” she says. “I guess the reason we care so much about people when they have an illness is it gives us strength in how to deal with life. Duane says I’m happier than I’ve ever been. Maybe I’ve learned that you don’t have to worry all the time in order to live.”
These days Giorgi spends more time on leisure — learning to fly-fish, seeing paintings she’s longed to see, chasing life from the back of a Harley. Yet her resolve to help find a way to prevent HIV remains strong.
She may be facing her greatest professional challenge yet. Come January, Giorgi will embark on a landmark vaccine study with Peter Anton, a UCLA gastroenterologist who specializes in treating people with AIDS. The trial — the first of its kind to be done in humans — will test a cowpox vaccine combined with non-infectious HIV genes. The vaccine will be inserted in an unusual area — near the groin — so that it can travel directly to the lymph nodes, a major site for HIV infection. It’s a route that’s never been tried. By delivering the vaccine this novel way, Giorgi believes it will stimulate the right cellular immune response. If so, the study could hold far-reaching implications for controlling AIDS, as well as other sexually transmitted diseases.
Meanwhile, the clock is ticking. For the estimated 16,000 people worldwide newly infected with HIV every day. For Giorgi. “It’s caught up with our worst expectations about how global the spread will be,” she says of the epidemic. “Without a vaccine …” Her voice trails off.
On a shelf in one of Giorgi’s labs is a collection of thick blue notebooks. They date to 1984, when she and her colleagues began drawing blood samples from 1,637 gay men. Filled with pages of T-cell counts and other measures, they record the sobering history of the AIDS epidemic. Of the 962 men who were infected, 584 have died of AIDS, 27 of other causes. Some 351 remain, as well as hundreds of uninfected men still involved in the study. For Giorgi, their cellular histories have provided crucial insights into HIV.
Giorgi’s research focuses on understanding the specific function of immune cells and how they protect against HIV. This is not a straightforward task. The immune system is extremely complicated; in defending against disease, it has an amazing ability to distinguish between which invaders are a mere nuisance and essentially harmless and which are potentially lethal. In HIV, the immune system relies on various T-cells, including CD4, so-called helper T-cells, to fight the virus. It also provokes the activity of CD8 cells, or killer T-cells, which attack HIV and produce agents that prevent the virus from replicating. The importance of these killer cells in the immune system’s war against HIV can’t be overstated. As one of Giorgi’s colleagues once remarked, “Without CD8 cells, we’re toast.”
While most AIDS researchers were focused on the virus itself, Giorgi believed the immune system held vital clues to protection against HIV. Some individuals, for example, become sick and die within months of infection, but most people can live with the virus for 10 years before their immune systems finally collapse. And a small number of people, despite repeated exposures to HIV, have yet to become ill even after 20 years.
Observing this pattern, Giorgi was intrigued. What was making the difference? At the time, searching for clues in the immune system wasn’t a conventional approach. The money and glamour in AIDS was concentrated in virology, not in the quagmire of immunology. But Giorgi didn’t much care about conventional approaches. Using the state-of-the-art process of flow cytometry, which sorts and counts cells with remarkable precision, Giorgi was able to show that CD8 cells were a potent force in protection against the virus. It was a landmark discovery.
“Janis won’t let go of something until it makes sense,” says Anton, the gastroenterologist with whom she will conduct the vaccine study. “She’s focused, intense, extremely clear-thinking and very smart.” When Giorgi began her research, the population of people infected with AIDS who were not getting sick was very small, he points out. “If you had 100 infected people, and 95 were dying pretty quickly and you said, ‘I’m going to focus on the other five,’ the response was ‘What are you doing?’”
But to Giorgi, who tends to downplay her accomplishments, it was a matter of logic, pure and simple. “When I started in HIV in ’84,” she recalls, “the emphasis was on what the virus did to the host and how it destroyed the immune system. If you look at HIV effects in-vitro, in two to four weeks, every single CD4 cell in an infected culture is dead. But if you look at clinical outcome, most people live at least 18 months. So you wonder what is going on?”
Using flow cytometry, Giorgi’s lab has also provided important insights into how HIV depletes the immune system. In one groundbreaking study, Giorgi and colleague Rita Effros found that killer T-cells in infected individuals showed signs of deterioration similar to that seen in people who had lived 100 years. It’s a discovery that still amazes her. “You realize how incredible the immune system is in fighting off HIV, even though it ultimately fails,” she says.
Giorgi’s greatest achievement, perhaps, is her discovery of the significance of an elevated expression of a molecule called CD38. CD38 sits on the surface of CD8 cells and its expression is related to immune control of viral infection. It has also proved to be a fiercely reliable tool to predict disease progression in HIV. Giorgi’s lab was the first to reveal that the more elevated an infected person’s CD38, the worse the clinical outcome. In further studies, she showed that the little-understood molecule was an even better measure of disease progression than viral load. For doctors and their infected patients, the knowledge was like peering into a crystal ball.
On top of this, Giorgi has also published countless papers in top academic journals, served on the boards of prestigious scientific organizations, including the National Institutes of Allergy and Infectious Diseases, and been an inspiration to those around her. “She’s devoted to the issue of HIV and AIDS research and trying to move it toward a cure or better treatments or a vaccine,” says Charlie Price, the project manager in Giorgi’s lab. “She wants us all to get there and it shows.”
Giorgi also stands out simply because she is that rare find: a prominent female scientist. “The way academics works, unless you’ve gone to the top and made some huge discovery, your work is always talked about as ‘less than,’” says Anton. “The field of medicine is very competitive. To just keep publishing and keep yourself in the forefront of the field is an enormous accomplishment. Then to actually contribute some leading ideas, which Janis has several times, is just awesome.”
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Janis Giorgi grew up in a happy, nontraditional household, in Jacksonville Beach, Fla., the youngest of two girls. Her father was an engineer and salesman in the steel industry, and her mother had a thriving career managing dress shops. Giorgi’s parents hadn’t originally intended to have children, and by the time she was born, in May 1947, her father was 50 and retired. It didn’t matter. “My parents loved each other, and they loved us,” she said.
Giorgi’s mother was the breadwinner in the family, while her father kept house and cooked dinner every night and was there when the girls got home from school. Although stay-at-home dads were even more rare at the time than working moms, Giorgi didn’t think anything of it. Having a mother who earned money made a positive impression on her. She later learned that her father had been forced out of his job over an ethical stand. “He refused to sell some steel the company wanted him to,” she recalled. “It wasn’t made for the purpose it was being sold for, and it would have harmed people.”
Giorgi may have been a girl growing up in the conservative 1950s, but her parents didn’t treat her like one. They encouraged their daughter to excel. As a child, Giorgi enjoyed watching her father work with tools, and when she was 7, he gave her an electric set. In high school, she was one of only two girls in her advanced chemistry and physics classes. In the summer of 10th grade, she took her first class in hematology. “My dad didn’t go for the idea of us not doing anything ‘useful’ over the summer,” she jokes.
After earning her degree at the University of Florida, Giorgi applied to several graduate schools. She had never been to the Southwest, but she’d seen pictures and the stark, open landscape appealed to her. So when the University of New Mexico wooed her with an attractive offer, she headed west.
It was, in retrospect, a beautiful move. The field of immunology was in its infancy, and the University of New Mexico was full of opportunities. Giorgi not only did her formative work in cellular immunology there, she began developing her skills in flow cytometry. Ellen Goldberg, Giorgi’s graduate adviser, still laughs when she recalls the 25-year-old’s memorable arrival in 1972. Giorgi blew into Albuquerque in a dark blue 1962 Cadillac, all her worldly belongings loaded inside, including a 6-foot boa constrictor coiled in one of her cowboy boots.
Giorgi has a bit of a wild streak. She drives an’89 Ford mustang convertible and has been known to pack her beloved golden retriever Choppers into a ’78 Dodge van and head down to Baja for a few weeks of solitude along the Sea of Cortez. Every year on her birthday, she and Keith take off for a long ride on his classic Harley, a black Sturgis belt-drive, the same bike on which he arrived for their first date in the summer of 1981, when she was a visiting scientist at Stanford. In her office, there’s a photo showing Giorgi with two other women researchers at a party; they’re decked out in short blue satin evening gowns and big hairdos, a la the Supremes.
Giorgi finished her doctorate in 1977, and spent a brief stint at Harvard and Massachusetts General Hospital. In 1984, she was lured to UCLA by a unique opportunity. Just getting under way was the Multicenter AIDS Cohort Study, an ambitious research project on the natural history of AIDS being conducted at four universities. The young scientist was tapped to set up the project’s flow cytometry lab and do research.
Although at first Giorgi focused her attention on the virus, she soon switched to the immune system when she noticed something extraordinary going on. Some men, despite hundreds of exposures to HIV, were not getting sick. In fact, they were staying amazingly healthy. Giorgi surmised that there must be something about their immune systems that was protecting them from HIV. But what? Giorgi believed it was probably a genetic component.
Determined to solve this mystery, she embarked on a study of 32 exposed uninfected men. The study was of such great scientific import, as well as such general interest, that it drew the attention of a writer for The New Yorker, who described Giorgi’s research in a lengthy story in July 1998. At the time, the results were not yet known but seemed promising. Scientists had found only one trait — a genetic defect associated with resistance — but this mutation was found in only about 4 percent of uninfected men. There wasn’t any explanation for the majority.
“When I started my study on cellular immunity to HIV, I thought everybody who had been exposed would have it,” says Giorgi. “If I looked in the lymph nodes, I thought I would find this in everybody. But I didn’t find it convincingly in anybody. If these men are protected, it’s not because of an immune response localized to the lymph nodes. Or if it were ever there, it didn’t last very long.”
Asked if she was disappointed by that finding, Giorgi retreats into one of her long pauses. Sitting at her desk, her head cupped in one hand, she looks away, her dark brows furrowing. Giorgi likes to consider questions carefully and often takes several minutes before she answers. “It just makes me more puzzled,” she finally says. “Puzzled about whether it’s a short-term immunity so we don’t see it, or puzzled about whether we’re looking for the wrong thing. I don’t know.”
But by the time The New Yorker article was published, Giorgi had more pressing concerns. On the day the magazine came out, she was in a hospital bed, racked with nausea, an IV dripping chemo drugs into her veins.
In the spring of 1998, life for Giorgi was going well. The New Yorker profile was in the works; plans for the vaccine trial were moving ahead; and she was excited about her collaboration with Anton and British scientist Thomas Lehner, whose success with the vaccine in monkeys had paved the way for human tests. The trio had formulated their plan for the human vaccine study that March at an AIDS symposium in Palm Springs. Earlier that year, Giorgi had applied for an AIDS vaccine grant to the American Foundation for AIDS Research, the nonprofit organization founded by Elizabeth Taylor. The following spring, she would be one of only nine investigators in the country to receive one.
On April 9, 1998, Giorgi went to the doctor for her routine annual exam. Her appointment was at 11 a.m. She’d recently switched health-care plans, and was seeing a new physician for the first time. In the midst of the exam, the doctor said he’d found something worrisome; he wanted to check it out immediately. Three hours later, Giorgi had a sonogram. The test could hardly have revealed an image more disturbing. Inside Giorgi’s uterus was a tumor the size of a grapefruit.
Surgery was scheduled for five days later. Giorgi downplayed her illness, telling her staff she’d need to be out of the office for several weeks to have a “little” surgery. “It’s a 99 percent chance it’s nothing,” she told Mary Ann Hausner.
It wasn’t. Giorgi had an extremely rare form of uterine cancer, a type present in only 1 percent of women with the disease. Without treatment, the chances of survival after four years are 20 percent.
Over the next year, Giorgi disappeared from her lab. She underwent surgery and six rounds of aggressive chemotherapy. Her mane of long ebony hair — her trademark — fell out. Intensely protective of those she loves, she suffered in private, telling few of the gravity of her disease. Even so, she continued to work. Twice a day, Hausner would make the 40-minute commute from Westwood to Giorgi’s Woodland Hills home to drop off and retrieve packages for the scientist. “I can’t believe how many papers she published that year. It was phenomenal,” Hausner says.
In her absence, Giorgi’s close-knit staff carried on. Giorgi likes to joke that things ran even better because she wasn’t around to interfere. Her colleagues put a different spin on it. “One of Janis’ incredible achievements is based on her interpersonal skills and team-building capacity,” says Anton. “She has always had that as a strength and has built an incredibly stable team. The persistence and productivity of the team during the time she was out are a testament to that.”
Giorgi doesn’t like to dwell on her illness; she is trying to stay positive. “I have to believe the tumor is gone,” she says. But there is no denying that cancer has changed her in profound ways: She tires easily and sleeps more so she can function better when she’s awake. Her health remains uncertain. “Of course, they want me to be cured and for everything to be perfect,” she says of her doctors, a rare edge of frustration to her soft voice. “If it’s not, I worry they will be disappointed with me.”
At the same time, she has also stopped putting her personal life on hold. “When you have cancer, you try to experience every bit of life that you possibly can and you recognize …” She sighs and looks down. “You recognize that people can be so incredibly generous. It allows you to see them at their best.”
Meanwhile, she is forging ahead with the vaccine trial. Giorgi knows full well that approaches that work in primates often fail in humans, but she is convinced that this unexplored route of immunization — one that goes directly to the site for HIV infection to induce immunity — holds promise. Indeed, many AIDS researchers are beginning to consider this approach. Says Anton: “We all remember the polio vaccine as a kid, how the gut was used as a route of immunization. There’s lots of research being done now in putting immunizing sequences into food or pills, to put into the gut because it’s the body’s largest immune organ. It also happens to be one of the major sites for HIV infection.”
These days, more than anything, one senses that Janis Giorgi feels hopeful and embraces a deep reverence for life’s possibilities. There is so much left for her to do and see. “I think what’s learned from AIDS vaccines will be translated to other diseases as well,” says the scientist. “Along with the severity of the epidemic, that’s what justifies the predominance of effort given to an AIDS vaccine, the belief if we more fully understand the immune responses to this pathogen, we can apply it to other pathogens.
“All of us,” she says, “are so committed to achieving a vaccine that works.”
