One thing that Dave Pauza drills into his graduate students is the inevitability of seemingly endless, maddening failure in the work they do in the lab. He refuses to give pep talks, telling them they should quit if they can't handle the frustration.
But if you get the sense that Pauza is a pessimist, you get the wrong sense of the man.
He and others at the University of Maryland's Institute of Human Virology are testing what could be a vaccine to halt the spread of HIV -- or what could just as easily be another setback on a path already lousy with them.
The absence of a vaccine more than two decades after the discovery of HIV -- despite the considerable investment of money and intellect -- disturbs Pauza in that it continues to devastate the lives of millions across the planet.
Yet the way Pauza sees it, failure simply means the possible ways to conquer AIDS have been narrowed down. More is learned about what doesn't work, leaving valuable clues to what someday will.
"In the vaccine game, you have to be pretty naive about the history of vaccine research, naive to think you're going to walk into a lab and have a Eureka moment. It's putting one foot in front of the other," he said. "I understand that this could be a total and enormous failure, but we also understand the process.
"You wouldn't do it unless you thought the goal was enormously important."
C. David Pauza is well-known in scientific circles -- for his research into a version of the virus that affects other primates, for his work on limiting mother-to-child HIV transmission in developing nations, for his attempts to develop a vaccine of his own.
At the virology institute, Pauza is one of many top scientists who have devoted their careers to solving the mystery of why this virus is so difficult to stop. They are now working on the institute's latest, best hope for a vaccine, research that was recently granted $15 million from the Bill & Melinda Gates Foundation.
Dr. Robert Gallo, who is credited with co-discovering the AIDS virus and who runs the 300-employee institute, brought Pauza to Baltimore seven years ago.
"[Pauza] makes for an interesting balance to Dr. Gallo," says Martin Delaney, the founder of Project Inform, one of the first advocacy organizations for people with AIDS. Gallo "can make enormous leaps sometimes, and he can be right. There are few people out there like that. ... That's got to be balanced by people like Pauza, who take one step at a time."
There are likely two-dozen groups worldwide actively pursuing an HIV vaccine. Few clinical trials have been conducted, and nothing has succeeded.
In a huge blow to the effort, a test of a very promising vaccine by the drugmaker Merck & Co. was halted midstream in September after more people receiving it got the virus than those who received a placebo. Instead of protecting people, Merck officials said this month, their vaccine might have increased the HIV risk for those who received it.
Merck's vaccine had passed "every kind of conceivable early stage," Pauza said. "Biology is a humbling thing. You do your absolute best, and this can happen."
Pauza was born in 1953, the year James Watson and Francis Crick published the double-helix structure of DNA. The year was a turning point in science. After 1953, a new world of discovery opened, allowing a detailed understanding of the body's components and how they work together as a well-functioning machine.
He grew up in the San Francisco area with an airplane-mechanic father who loved to run his eldest child through mental exercises at the dinner table. "My father loved to pose questions," Pauza recalled. "`How does this work? How does that work?'"
After graduating from San Jose State University, Pauza went to the University of California at Berkeley, where he received a doctorate in molecular biology in 1981. He then went to England to study the biology of the human T-cell, the white blood cells that help the body fight infections.
It would soon be clear that T-cells were the very things under attack by a virus suddenly appearing back home in San Francisco.
Doctors knew the immune system was malfunctioning. They saw diseases that previously had been found only in transplant patients or those with serious cancers. But no one could figure out why people were getting so sick.
He was in England when one of his genetics teacher called: "You've got to get back here."
"The teacher had some high standing in the gay community. He was seeing his friends drop around him like flies," explained Maria Salvato, a fellow researcher at the human virology institute who is Pauza's wife. "He just thought getting more researchers on his side would be a way to impact the problem."
Pauza went to work in 1985 at the Salk Institute for Biological Studies in La Jolla, Calif., named for Dr. Jonas Salk, the man who developed the polio vaccine that ushered in an era of mass inoculation and is credited with helping to eradicate polio in this country.