BY MARY J. LOFTUS

“The butterflies, we call ’em,” says a local, who is manning a table for the Norris Lake Neighborhood Association. “They come flocking through here every spring in red, yellow, and green.”

Harriet Robinson, Asa Griggs Candler Professor and chief of Emory’s Division of Microbiology and Immunology, has come out this Saturday morning to cheer on the riders. She stands in the Phillips gas station parking lot, eagerly scanning the horizon.

“Here they are!” she says, spotting the front-runners in their Day-Glo orange biking jerseys, helmets, and padded black shorts. The first arrivals pull into the lot just after 9 a.m. and descend on the support van to grab Powerade, pretzels, apples, candy bars, and bananas.

Robinson, dressed casually in a sleeveless white top and blue slacks, circulates among them, joking and making conversation. She is accompanied by her four-year-old grandson, Jack, who is visiting from Pittsburgh with his parents and younger brother, Gus.

“Do you want to finish the ride instead of me?” a rider asks Jack, noticing him admiring the sleek racing bikes.

The group’s de facto leader, John Beal, organized Action Cycling of Atlanta (motto: “pedaling for a purpose”) and has ridden in races in Alaska, Canada, and across Montana that raised millions of dollars for AIDS research.

“Basically, a bunch of Atlanta riders did a European ride a few years ago, and so little of the money went to where it was supposed to that we resolved to start a ride here and make sure the money went to the right place,” Beal says. The group raised $65,000 for the Vaccine Research Center last year and an additional $20,000 so far this year.

Robinson is a celebrity of sorts to this group. “Most of the bikers know Harriet,” Beal says. “She’s the scientist from Emory who has an AIDS vaccine in clinical trials. She came to Athens last year and talked to us. She’s probably not as well known as she will be one day.”

By 9:30 a.m., almost all the cyclists have checked in, reenergized, and are ready to start out for Walnut Grove, the next stop. Two riders, though, haven’t shown up yet. A few minutes later, they pull in together– Michele Hennessy, who went an extra four miles after missing a turn-off sign, and Joy Martin, who looks flushed but elated.

“I’ve never ridden this far in my life,” Martin announces.

“Well, I tell you, you are courageous,” Robinson replies.

The same may well be said of the sixty-six-year-old Robinson, a top researcher at Emory’s Vaccine Research Center who–through sheer tenacity and despite a number of obstacles that might have discouraged those with less gumption–has developed one of the most promising AIDS vaccines in clinical trials today.

For much of her career, Robinson was a single mother of three boys, the sole woman in a roomful of male scientists (“They would call the men ‘Dr. so-and-so,’ and I would just be ‘Harriet,’ ”) and an independent thinker who often fell outside of the scientific mainstream.

Her early successes in using DNA to create vaccines were met with skepticism–professional journals wouldn’t publish her results and her grant proposals were routinely refused. “You don’t think this will ever be useful, do you?” read one reviewer’s comment.

Still, Robinson has taken her groundbreaking DNA-based AIDS vaccine from the lab through successful primate trials and into human testing–even when she’s had to brave machine-gun fire during rebel insurrections to do so.

“I believe our vaccine has real potential,” Robinson says. “There is a subset of the research community that is discouraged. They criticize us for being overly optimistic. But the fact remains that our vaccine works in monkeys.”

After years of combatting the naysayers, Robinson’s life runs fairly smoothly these days–her research is well funded, she is highly regarded as a scientist, and she lives quietly in a modest brick ranch on a wooded lot near the Emory campus, a short drive from her lab at the Yerkes National Primate Research Center.

“We used to walk our dogs together in the mornings,” says Tom Insel, former director of Yerkes who is now head of the National Institute of Mental Health, “and the great thing about Harriet is that she was always thinking about science–how to get the next project completed, what the most recent results might mean, where to get the best advice. Her concerns were never about personal gain or recognition. I have never known a scientist with so much talent and so little ego.”

And the spread continues. Almost five million people were infected last year, the largest number of new cases since AIDS was discovered, and three million died. Young people fifteen to twenty-four years old account for nearly half of all new infections worldwide. Sixty-eight million people are projected to die from AIDS by 2020–more than the entire population of Great Britain.

The scientist who develops an affordable, effective AIDS vaccine will save more lives than have ever before been spared by a single medical innovation save, perhaps, the discovery of penicillin.

“AIDS is an extraordinary kind of crisis; it is both an emergency and a long-term development issue,” states the 2004 United Nations AIDS Report on the global epidemic. “Despite increased funding, political commitment, and progress in expanding access to HIV treatment, the AIDS epidemic continues to outpace the global response. No region of the world has been spared. The epidemic remains extremely dynamic, growing and changing character as the virus exploits new opportunities for transmission.”

By now, the devastatingly effective strategy of the AIDS virus is well known: the virus invades the human immune system, targeting helper T-cells and macrophages–the very white blood cells sent to destroy it. Opportunistic infections and cancers that the body could normally fight off quite easily ravage people with AIDS, once their immune systems start shutting down.

No successful treatment for AIDS existed until 1987, when the first antiretroviral drug was discovered. Antiretrovirals, which work by slowing the reproduction of the virus, are now given in combinations (anti-HIV “cocktails”) that can reduce death rates by more than 80 percent.

But such drug regimes, which must be taken consistently and for life, are expensive–from $12,000 to $45,000 a year per person–and the vast majority of those with the virus live in developing countries where such costly treatments are not an option.

Researchers also worry that widespread misuse of anti-HIV drugs by patients who take them only sporadically, compounded by haphazard manufacturing practices in labs that don’t meet rigorous standards, could spawn future epidemics of drug-resistant strains of the virus.

“The real solution for the world,” says Robinson, “is a vaccine.”

Vaccines prime the immune system to recognize disease-causing organisms–similar to providing a mug shot (“Look out for this guy, he’s dangerous”) so that the body’s defenses will spring into action when they encounter the virus.

The impact of vaccines on public health over the last century has been substantial: smallpox has been eradicated, polio has been greatly reduced, and cases of measles and Hib (haemophilus influenzae type b, at one time the leading cause of childhood bacterial meningitis and mental retardation) are at a record low.

But developing a vaccine for AIDS is especially difficult, says Rafi Ahmed, director of Emory’s Vaccine Research Center, because the virus is constantly changing and mutating. “HIV presents a moving target, essentially,” says Ahmed. “You have to understand both the virus and the immune system to develop an effective vaccine.”

Traditional vaccines are made from the virus itself, which has been killed or weakened. The danger is that such a vaccine, if not properly inactivated, might actually induce the illness; the original version of Jonas Salk’s polio vaccine caused two hundred and sixty cases of the disease, resulting in ten deaths.

But Robinson’s vaccine, developed in collaboration with the National Institutes of Health (NIH) and the Centers for Disease Control and Prevention (CDC), is unique in that it is a DNA-based vaccine–a technique Robinson pioneered. DNA vaccines stimulate an immune response by using only pieces of the virus instead of the virus itself, so the recipient is never placed at risk of infection.

Robinson’s AIDS vaccine requires three shots: a DNA-based inoculation to prime the immune system, followed by two poxvirus booster shots, which increase the body’s immune response. “The DNA vaccine establishes the breadth of the immune response,” she says, “while the poxvirus boosters affect the height of the response. The result is that the combination is more effective than either one alone.”

Robinson chose poxvirus, a version of the virus first used as a smallpox vaccine, for the booster because it was large enough to carry several extra HIV genes.

“The pox viruses are enormous,” she says. “They are like the Battleship Galactica of viruses.”

Robinson’s vaccine has tested well in trials with rhesus macaque monkeys at Yerkes. Twenty-three of twenty-four monkeys given the DNA vaccine and poxvirus booster failed to develop AIDS symptoms even after exposure to high levels of the virus. In the control group, five of six non-vaccinated monkeys died of AIDS within six months of being infected with the virus.

“To our knowledge, no other HIV vaccine or large-size trial, has reported such a high level of protection for such a long period of time,” Robinson says.

The vaccine has been approved by the Food and Drug Administration for human trials, which began in January of 2003. HIV-negative volunteers were randomly assigned to receive one of the following: high-dose vaccine, low-dose vaccine, or placebo.

“We’ve had the DNA vaccine in clinical trials for a year and a half at three different sites–Seattle, San Francisco, and Birmingham–in thirty people,” Robinson says. “These trials have been very successful in showing that the vaccine is safe for humans.”

The next series of human trials is scheduled for early 2005 to determine the safety of the DNA prime combined with the poxvirus booster, and to establish a dosing schedule. After this, a third series of trials will be conducted in a population at high risk for acquiring AIDS, with some volunteers receiving the vaccine and others receiving a placebo, to gauge effectiveness.

Robinson believes a usable AIDS vaccine is still five to seven years away but, she adds, “I have great hopes.”

Giving up isn’t in Robinson’s lexicon, says Helen Drake-Perrow, her office manager of seven years. “She inherited from her parents a sense of ‘can do’–working things out for herself instead of relying on others. She is independent, has clear logic, and is full of confidence, yet is still humble.”

Harriet Latham Robinson was reared in Boston, the only girl among three brothers. She remembers her mechanical engineer father, Allen “Jack” Latham, tinkering in the basement with his inventions. He was later named New England inventor of the year for creating a disposable centrifuge to separate blood.

Her mother, Ruth Latham, earned a master’s degree in chemistry from Oberlin and taught organic chemistry at Smith College before staying home to raise a family.

“She would say sodium bicarbonate for baking soda, or H2O for water,” Robinson recalls. “We were always doing interesting things. As kids, we made tents and spent a lot of time outdoors. We had an enormous garden. I think we were the last family in the city of Boston to keep chickens.”

Despite her mother telling her “an educated woman can never be happy,” Robinson became a scientist–and an academic. “I went to Swarthmore intending to major in history,” she said, “but I became fascinated by the development of organisms.” She went on to attend MIT, where she earned a master’s degree in molecular biology and a Ph.D. in microbiology.

Receiving her doctorate in 1965, a time when just 8 percent of science Ph.D. graduates were women, didn’t faze Robinson. She loved being one of the new recruits in the fledgling molecular biology department at MIT and thrived on the synergistic environment of the lab.

She won a postdoctoral fellowship in the virus laboratory at the University of California at Berkeley, where she met her husband, William Robinson, who was also a scientist. They had three sons.

“I basically became a full-time mother,” she says. “I worked two mornings a week in a lab, but I found being a mother very interesting. Some of my very best friends are from that part of my life–all the hours we spent at the playground and the swimming pool. I don’t regret that time at all.”

When her sons were five, six, and seven, Robinson went through a divorce and became a single mother.

“I tried to get a job in California, but no one would hire me as faculty or a technician,” she says. “So I looked all over the country, and ended up back in Massachusetts, at the Worcester Foundation [for Experimental Biology.] I had a lab, and they had their new scientist.”

Robinson stayed at the Worcester Foundation–famous as the lab where “The Pill” was developed–for ten years. Her research on viral-induced cancers led to the identification of host genes that can be mutated by viruses into cancer-inducing genes. Robinson also discovered that an immune response could be triggered if viral DNA was injected into chickens.

“Harriet became enchanted with the idea of using DNA itself as an immunizing agent,” says Thoru Pedersen, professor of biochemistry and molecular pharmacology at the University of Massachusetts Medical School, who was Robinson’s colleague of many years at the Worcester Foundation. “Harriet has absolutely fearless courage to pursue new ideas. She’s willing to try things off the beaten path, and through this, she has become quite famous in the field of virology.”

While Robinson worked nine to five, a live-in housekeeper managed the homefront. But Robinson put in plenty of parenting time herself. Colleagues remember that her license plate spelled out, “HEY MOM.”

After her sons left home one after the other to attend Stanford University, where their father was a professor, Robinson began working more hours in the lab. “I had the worst case of empty nest syndrome,” she says.

In 1988, she was recruited to a research position in the pathology department at the University of Massachusetts.

“Harriet was working on a type of molecular pathology that was technically very advanced, but conceptually very simple: since vaccine production is essentially a matter of protein synthesis, the fastest way to generate the specific protein is to teach the cell how to make it by providing it with specific, ready-made DNA,” says Guido Majno, then chair of the pathology department. “It seemed so obvious and promising, why had it not been done before?”

Robinson began developing a simian version of the AIDS vaccine. The thinking in the scientific community at the time, though, was that DNA vaccines would never work because the DNA would not be taken up by enough cells to produce an immune response.

“No journals would publish my results. My grants kept getting turned down. My department chair actually used department funds to keep me going at a critical point. But I didn’t abandon it,” she says. “I always thought it would come through, because the lab results were so good.”

By 1992, more scientists were working on DNA vaccines, which had become more widely acceptable; Robinson’s results were published in the Proceedings of the National Academy of Sciences and in the journal Vaccine.

Now Robinson was able to turn her attention more fully to developing a human AIDS vaccine. The complexity of the virus itself fascinated her: the way it killed the helper T-cells of the immune system, its resistance to containment.

“If you vaccinate but you don’t protect the helper cells, you’ve lost your supply lines.” she says. “It’s like Napoleon’s army in Moscow after winter comes.”

“The closest I’ve come to the MIT environment is the Vaccine Research Center here,” says Robinson, “just in the confluence of people and the excitement about what’s going on.”

The Vaccine Research Center at Yerkes was the perfect fit for another reason as well: Developing an AIDS vaccine is the center’s primary goal.

“Harriet had a different strategy for approaching vaccine development,” says Insel, the former director of Yerkes who recruited Robinson. “All of the major companies had shut down their AIDS vaccine programs and moved to developing retroviral drugs, so she was already a bit of a maverick for committing to a vaccine. Her DNA approach, which was revolutionary at that time, was really intriguing because it represented a new way of thinking about vaccines. DNA is heat stable, so if the vaccine was effective it could be used in Africa or Asia without refrigeration–an obvious plus for global health.”

In 2001, results from Robinson’s monkey trials were published in the journal Science, with Yerkes Assistant Research Professor Rama Amara as lead author. It became the most cited paper in immunology for several months, and Robinson joined the elite group of researchers at the front of the AIDS vaccine race.

Make no mistake–for these scientists, this is the Tour de France, and they want to win. There is cooperation, but there is quite a bit of competition as well. Once a vaccine is available, the demand will be abundant: market estimates are between four billion to ten billion dollars per year.

Merck, Chiron, Aventis-Pasteur, Glaxo-Smith Kline and the NIH Vaccine Center are all working on AIDS vaccines, as are several other universities, including Oxford, Yale, and the University of North Carolina.

“In a sense, the competition has been consciously generated by funding agencies and the NIH,” says Neal Nathanson, vice provost for research at the University of Pennsylvania and former director of the Office of AIDS Research at NIH. “They put out enough money to bring into the field anyone who has a credible idea.”

Robinson believes that in the end, there may be more than one AIDS vaccine, just as there is more than one polio vaccine. “Typically, after a vaccine is developed in a lab, it is handed over to a large pharmaceutical company for commercialization,” she says. “But I really want to retain control through the efficacy trials.”

Still, her reserves of courage and tenacity are sometimes called upon.

In the fall of 2002, Robinson flew to the Ivory Coast for a series of meetings organized by the CDC and the health ministry about testing a version of her vaccine in Africa. The plan was to establish a vaccine clinic in Abdijan, the capital city.

At her hotel, she awoke in the middle of the night to a sound like a truck running into a wall and scattered machine-gun fire. “I just stayed in bed through the whole thing,” she says.

“I don’t think any of us had any idea how bad it was,” says Jeff Lennox, an Emory professor of infectious diseases and director of the Ponce AIDS clinic, who was also in Abdijan for the meeting. “When we got up the next morning, the door to the hotel was shot out. We were told to stay inside. You could see buildings burning, but there were no vehicles moving outside. It was totally quiet.”

The team was trapped in the hotel for two days. “Harriet was great,” Lennox says. “Some people were very stressed out, but she was very calm.”

They were finally hustled into a van and taken to the airport, where an Air France 747 touched down long enough to fill with Americans, embassy workers, and airline staff. It was the one plane allowed to leave the city.

“Harriet was mostly upset that so much planning and organizing had gone into this multi-country effort to have HIV trials in Africa, and it wasn’t going to happen,” Lennox said.

Robinson admits it was a great disappointment. “It was the perfect place to do a trial. We lost so much to political instability, it’s just tragic.”

But the Ivory Coast setback seems only to have increased Robinson’s determination to see her vaccine through to production and distribution. Her team is now getting two vaccines ready for developing countries–one for Africa and one for India–so that at least one will make it through testing.

“We still have very hard work ahead,” she says. “A lot of critical junctures. We only go down in AIDS history if we make it across the finish line.”