PROGRAM: Gene Therapy

AUTHOR: John Rudolph

November 1998:

Producing a radio program means making choices. There are always interesting, informative, and sometimes funny moments of an audio interview that never make it into the final program.

For "Gene Therapy: Medicine for Your Genes," I recorded more than a dozen hours of tape: interviews with scientists, doctors, and gene therapy patients, activity at laboratories and hospital wards where gene therapy experiments are being conducted. I would have liked to include more of this material. But, as always, there just wasn't enough time in the one-hour program.

Two subjects that I wanted to explore in more detail were the history of gene therapy, and gene therapy's impact on scientific research. Here are two outtakes that deal with these areas:

In June 1998, I interviewed one of gene therapy's pioneers, Dr. Ted Friedman. He's a professor of pediatrics at the University of California at San Diego, and Director of the school's gene therapy program. Friedman actually came up with the phrase "gene therapy" in an article he wrote in 1972.

Since then he has become the unofficial scribe of the gene therapy movement, recording successes and failures, and interpreting them for scientists and non-scientists alike.

Dr. Friedman began the interview by talking about the very early days of gene therapy research.

JR: "When and how did this idea of gene therapy begin?"

TF: "It began way back with Mendel, I suppose, but the sort of scientific approach to gene therapy began in the late 1960s, during the advent of the golden era of molecular biology. And I think the first suggestions that it might be feasible came from a man named Renato Dulbecco...

"Dulbecco, who later went on to get the 1975 Nobel Prize, was studying the mechanism by which viruses convert normal cells to cancer cells. And he discovered that the viruses do that by infecting the cells, introducing their genes into the cells...and that those genes become...a permanent part of the infected cell machinery.

"And it was the expression of some of the genes, the viral genes, from this integrated piece of virus DNA that caused the cells to change properties. And it was the indication that there are agents in nature that know how to do the job of changing the genetic composition, and the gene expression in cells, by introducing new genes.

"And so it became possible-sort of late-sixties, early-seventies-that eventually, one would be able to introduce therapeutic genes into cells by replacing viral genes...with potentially therapeutic genes. I think that's where the notion came from."

Friedman firmly believes that gene therapy will eventually cure many diseases. He says the prospect of a definitive cure has revolutionized medicine, which until now has focused mainly on treating the symptoms of disease without actually offering a cure.

But there are also many skeptics. Dr. Alan Oliff is one of them. Oliff is Executive Director for Cancer Research at Merck and Company, the giant drug manufacturer. I interviewed Dr. Oliff in his office, which has some interesting decorations including an illuminated 3-D portrait of the Starship Enterprise.

Oliff may like Star Trek, but he rejects what he calls, the "Star Wars" approach to medicine.

JR: Many of the people-the gene therapy researchers that I've talked to from academia-say that even though gene therapy has not cured anyone yet, it has already revolutionized the practice of medicine. Do you agree with that?

AO: "I think that may be a little bit strong in terms of 'revolutionizing the practice of medicine.' It certainly has revolutionized some of the basic research elements in trying to discover...the pathophysiology or the basic molecular mechanisms...for getting disease. ... The gene therapy approaches are wonderful tools in the laboratory where you don't have to worry about these issues of tissue penetration and distribution. ...You're dealing with cells in a culture dish, for example, where it's easy to get the vectors to hit all of those cells, and you can look for the effects of putting those genes in.

"So, I think it's fair to say that's been a revolution, yes. Has it revolutionized the practice of medicine? I'm a clinical oncologist, and I have yet to see gene therapy-from an oncology standpoint-make a significant impact. Not to say that it won't, but I think at the moment, it's still up in the air."

And how do I feel about gene therapy after spending a year immersed in this subject? I hope it can be made to work. But I'm not holding my breath. And I am mindful of the fact that when I tell people about gene therapy, the first reaction most of them have is, "Wow, that sounds scary." It's going to take a while before we are willing to accept this new kind of medicine.