Beverly Davidson - The Medicine of the Future

BEVERLY DAVIDSON

The Medicine of the Future

A virus was once defined as "a piece of very bad news wrapped up in a protein." But viruses are the foundation of a new form of healing that promises to change the face of medicine in the next century.

"The problem," says Beverly Davidson, "is that most people have this negative association with the word 'infection'. So I've been trying to think of synonyms that are more . . . " She pauses as she searches for the right words. "More upbeat," she says.

Davidson knows how strange that sounds. And she's under no illusions about the pain and suffering microbes cause. On the contrary, growing up in the 1960s as the daughter of a small-town physician, Davidson saw more than her share of infectious diseases. Today, as an associate professor in the Department of Internal Medicine, she sees the ravages caused by microscopic invaders on an almost daily basis.

But it is precisely because of her deeper understanding of viruses that she can make statements, such as the one above, that may strike the uninitiated as bizarre.

"If you study viruses, you end up gaining this enormous respect for the mechanisms they've developed to get access to human cells," she explains. "And you begin to wonder: How can we put those mechanisms to use?"

The answer, according to Davidson, can be summed up in two words: gene therapy.

Gene therapy is to medicine what aikido is to martial arts. Both use the attacker's own force as a means of defense. In aikido, the practitioner redirects the aggressor's violence. In gene therapy, researchers harness the unique ability of viruses to evade the immune system and enter a cell. Once inside, however, instead of taking over the cell for its own purposes, the viruses engineered by Davidson and others are designed to cure, rather than cause, disease. The 400 new viruses created by Davidson's lab are like a fleet of microscopic FedEx trucks, delivering packages of new genes to cells that, for a variety of reasons, are either lacking them or have genes that aren't functioning properly.

"There are a lot of genetic diseases in which cells lack functional genes," Davidson explains. "Either the protein expressed from the genes is not functional, or it is not expressed at all. The most promising development in treating these diseases is to use viruses that we create in our labs to get those missing proteins back into the cells--literally, to infect them with our gene-bearing viruses."

Davidson emphasizes that gene therapy has a long way to go before it becomes a common clinical technique. But the potential impact of the process is staggering. Some researchers believe that it will revolutionize the practice of medicine in the 21st century in the same way that antibiotics changed the field in the 20th century. Davidson isn't willing to go quite that far, but she is enthusiastic about the future of the process.

"What excites me is that gene therapy is so multifaceted," she says. "It covers so many areas: virology, pathology, cell biology. And then there's the human dimension. When you sit around a table with families of children with these diseases, you realize what's at stake. It drives you back to the lab to work harder. It may sound like science fiction," she says, "but it's what we do here every day."

"Here" is the Center for Gene Therapy of Cystic Fibrosis and Other Genetic Diseases, a multidisciplinary center created this year, after The University of Iowa was selected by the National Institutes of Health (NIH) and the Cystic Fibrosis Foundation for an $8-million, five-year grant. Davidson is associate director of the center and head of the Vector Laboratory, the section that actually creates the new viruses used in gene therapy. John Engelhardt, director of the center, says that in addition to her many scientific talents, Davidson brings a tremendous collaborative spirit to the new enterprise.

"It's really amazing how she brings all sorts of different people together," he says. "There are so many different parts to gene therapy, and they're each terribly complex. A single researcher simply can't do it all alone. One of Bev's gifts is her ability to get people working together as a team, working toward a common goal. In fact, that's one of the reasons Iowa was picked for the center."

The University of Iowa already had a national reputation for its work in gene therapy before the center was created. Michael Welsh, for instance, is renowned for his work in developing gene therapy for use in treating cystic fibrosis.

"By being named a national center, we're able to build on the foundation started by Mike Welsh and others and greatly expand it," Engelhardt says.

That expansion includes getting junior scientists, who may never have thought about working on gene therapy, to head in that direction.

"We really want to target new people," Engelhardt explains, "young researchers who haven't received NIH grants and who are outside of the field of gene therapy. They bring new ideas to this area. We can help take those ideas and turn them into reality. Who knows what treatments they're going to come up with? That's part of the excitement of this work."

With the creation of the center at Iowa, gene therapy is entering a new, more mature phase. Nearly a decade ago, some researchers--and even more journalists--were trumpeting the still largely theoretical technique as the "next hot thing," as if family doctors would be prescribing gene therapy within the year. But boosters were confusing potential with reality. When the breakthroughs promised weren't forthcoming, the resulting reaction against gene therapy was almost inevitable.

Now that the dust has settled, however, Engelhardt says researchers are making steady progress toward fulfilling the early promise of gene therapy. Thirty-five UI investigators are now conducting research through the center, and one, Kevin Campbell, is about to take his gene therapy treatment for muscular dystrophy to clinical trials--the first step in taking a treatment out of a lab and into general usage.

Just don't expect to walk into a pharmacy anytime soon and ask for a gene therapy drug, Engelhardt cautions.

"That's still a long way off," he says. "But the majority of diseases will one day be treated by gene therapy. What we're working on at Iowa is the future of medicine."