The patient's inoculation was as routine as any Dr. Robert Johnston had seen. Roll up the sleeve, a cotton swab of alcohol on the upper arm and a "this shouldn't hurt much."
What was in the syringe, though, was anything but typical: a genetically engineered Venezuela equine encephalitis bug laden with pieces of HIV, the virus that causes AIDS.
As nasty as that shot sounds, the biotechnology brew injected into the volunteer's body that July day was not infectious — it was designed to save lives. In fact, Johnston's research at the University of North Carolina is just one of the latest AIDS vaccine experiments that are moving from the laboratory to human tests.
An increasing number of human experiments, spurred by biotechnology breakthroughs, has added a new word — optimism — to a research field noted more for its failures than its successes over the last two decades.
"I'm certainly more optimistic than just a couple of years ago," said Dr. Robert Gallo, who 20 years ago co-discovered the virus that causes AIDS. "We can see the light at the end of tunnel."
Gallo, who heads the Institute for Human Virology at the University of Maryland, expects to begin testing his own experimental vaccine on humans soon.
Most AIDS researchers agree that vaccines will be the only effective way to control a pandemic that has killed 28 million people and infected 42 million more, most of them in Africa.
Unfortunately, most also agree that things will get worse before they get better. Some five million people were infected last year and another 3.1 million died.
"I tend to stay away from the word `optimism,"' said Dr. Anthony Fauci, director of the National Institute of Allergy and Infectious Disease. "I see things happening that make me feel better about the process. But I don't want to give an impression that this is a new dawn in America. We still have a long way to go."
AIDS is notoriously wily in beating the body's immune system and so far has survived every drug thrown at it. In February, VaxGen Inc. reported that the world's most advanced human vaccine experiment — involving 5,000 volunteers — had flopped.
Nonetheless, a gathering two weeks ago in New York at the AIDS Vaccine conference was palpably more upbeat and better attended than years past, attendees said.
"There's cause for optimism," said Dr. Laurence Peiperl, an AIDS researcher at the University of California, San Francisco. "There are more interesting products going into clinical trials."
About two dozen potential vaccines are being tested by 12,000 human volunteers in experiments around the world. Several more human experiments are about to start.
Fauci's federal institute has budgeted $456 million for HIV vaccine research in fiscal 2004 — up from $413.6 million in 2003 and $182 million in 1999. Last Monday, it awarded $81 million in contracts to four biotechnology companies for vaccine development.
"A safe and effective HIV vaccine is critical to the control of HIV globally," Fauci said.
At least a dozen drug companies, including Merck & Co., the world's largest, are developing AIDS vaccines. The projects range from the commonplace to the exotic, like Large Scale Biology Corp.'s attempt to grow a vaccine in genetically engineered tobacco plants.
Most of these projects take one of two basic approaches.
One research approach is aimed at provoking the body's immune system to make disease-fighting proteins called antibodies that will forever fight off AIDS infections.
The other approach is designed to train specialized cells, known as cytotoxic T lymphocytes and dubbed killer T-cells, to identify and eliminate infected cells after someone contracts HIV.
The antibody defense is most desirable but the T-cell work has shown more promising results. The vaccine Johnston helped created employs both approaches.
The volunteers in vaccine experiments have not been infected with the AIDS virus when they begin the trials but some are considered at high risk of infection. Researchers judge the vaccine's effectiveness by comparing the number of their subjects who get HIV against an expected infection rate.
Nearly all vaccine researchers are attempting to provoke immune responses in two ways: by engineering other viruses with bits of HIV or injecting key bits of HIV's genetic material directly.
Ronald Walent of San Francisco has tried both types of experimental vaccines. He volunteered for an experiment three years ago that tested how two vaccines taken in combination would work. Results are expected soon.
In August, the experiment was "unblinded" and participants were told whether they received the combination or placebo. Walent got the combination.
"It's like getting a regular inoculation," said Walent, whose partner died of AIDS. "But initially you do wonder what this stuff is going to do you."
AIDS researchers said Walent, and all other human volunteers, need not worry about contracting AIDS from the experimental vaccines. Because HIV is so unpredictable, vaccine researchers don't use the live virus in human experiments.
Walent said he practices safe sex and has little fear of getting infected. Instead, the 54-year-old registered nurse was motivated on several different levels to act as human guinea pig.
"It isn't just my little gay community that's affected, but huge parts of Africa and Asia," he said. "You get older and a light bulb finally goes off: Now is the time to make a difference."