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."
Well-rounded scientist
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.
As a boy, Pauza was among the first children to receive the Salk vaccine, an injection of dead polio virus that helps the body develop protective antibodies. That concept is at the heart of nearly every vaccine. So early AIDS researchers figured they'd kill some virus and make a vaccine. But HIV, it turns out, is a different animal.
First off, HIV attacks the immune system that should be fighting infection, invading and killing the cells that respond to the arrival of a virus. The body does what it's supposed to do, while the virus treats this immune response as food.
"You couldn't design a better virus," Pauza says. "It's the perfect mousetrap."
Secondly, HIV is often transmitted sexually, and until recently, when a vaccine was introduced for the human papillomavirus (HPV), there were no vaccines for sexually transmitted diseases. Most vaccines need to foster some sort of population-wide resistance. A vaccine for an STD must engage each individual's immune system against attack.
The Merck vaccine was designed to elicit a cellular response to HIV -- that is, the vaccine should recognize the virus once it has a foothold in the body. The human virology institute vaccine is designed to keep the virus from making inroads. "We think this virus is built to defy an immune response if you let it get established first in the body," Pauza said.
So he and his colleagues -- led by Gallo and his deputies, George Lewis and Tony DeVico -- are working on a twist to the traditional vaccines, based on triggering an antibody response using the most stable part of an ever-changing virus.
Plan of attack
The institute's vaccine focuses on a sequence of the virus that shows itself only in the instant it enters a healthy cell. That sequence doesn't change because like a key in a lock, the virus-cell match must be exact, or infection wouldn't be possible.
Antibodies made by the vaccine see the quick flash of this sequence and stop the virus before it enters the cell. These viruses are then destroyed in the body.
At least that is the theory behind the vaccine.
The institute's vaccine is in its animal trial stage. Pauza is an expert with monkeys -- his wife marvels at his ability to concoct a coconut oil pill a monkey will take.
Gallo said he brought in Pauza from the University of Wisconsin partly because of his work with monkeys. Nonhuman primates are the closest models to people in learning how the virus -- and any vaccine -- behaves in the body, Gallo said.
So much goes into making an AIDS vaccine, said Dr. Gary Nabel, director of the National Institutes of Health's Vaccine Research Center. Not everyone needs to be a Nobel laureate. Scientists such as Pauza, team players with their own promising avenues of research and unusual talents, are often the key to great discoveries.
"You wouldn't win a basketball game if you had five centers who were all 7-foot-3," Nabel said. "You need point guards, you need centers, you need a coach."
Gallo, whose work in virology involves studying how the AIDS virus infects cells, called the trial and error of early vaccine research "mind-numbing."
The way Pauza sees it, there are small victories. "You have the chance, for an hour a day, to actually learn something that no one else knows out of 7 billion people on the planet," he said. "That's more addictive than anything they sell on the street in Baltimore."
There are so many things still to learn about the virus.
Pauza doesn't just spend time in the lab. He also interacts with AIDS patients, a key reason why he came to Baltimore from Wisconsin, where few have HIV.
Thoughts of solving the puzzle that is the AIDS virus are never far from his mind -- not when he's mowing the lawn of his Roland Park home, or listening to his 13-year-old daughter Victoria play piano, or playing Mr. Fix-It for his elderly neighbors.
Pauza used to give a lot of public talks about AIDS. More than once, he was asked angrily: "Why haven't you made a vaccine yet?"
"The answer I give is: It's hard. It's pushed the brightest people in this field to the limit. ... It's not for lack of trying, for lack of hard work. It's just a hard thing to do."
stephanie.desmon@baltsun.com