Air Date: Week of August 2, 2002

In the final installment of our series "Generation Next, Remaking the Human Race" producer Bob Carty looks at the potential for repairing and remaking our own bodies through gene therapy. Recent medical developments in this technology offer the promise of cures for many diseases. But, others warn that there’s a dark side to the science.

Transcript

CURWOOD: It’s Living on Earth. I’m Steve Curwood. The genetic code found in each and every one of our cells tells our bodies what to do. Genes may order us to grow black hair, be vulnerable to breast cancer, or develop an uncanny knack for composing music.

Today, science is approaching the point at which the genes given to us at birth can be altered with what’s called gene therapy. Gene therapy may someday make it possible to cure such deadly disorders as heart disease, HIV/AIDS, and cancer. Gene therapy also could alter body shape, athletic ability and even hairlines.

As Bob Carty reports in the final installment of our series Generation Next: Remaking the Human Race, gene therapy not only raises hopes for human progress, but also poses disturbing ethical questions.

NURSE: We’ll put all the electrodes on your chest. We’ll connect the wires. And then we’ll get you to walk on the treadmill for a while.

CARTY: In a Toronto hospital, a 54-year-old man stands on a treadmill, naked to the waist, wires attached to his chest flowing off to a battery of blinking machines.

MALE: I want you to take nice long steps. The machine is going to start slow, and gradually we’re going to increase the speed of the machine. Take it easy, and see how much you can do.

[SOUND OF TRADMILL]

CARTY: The treadmill starts moving, and so does the patient, walking slowly at first, then faster. The electrodes monitoring his heart and lungs will tell researchers whether they’re making another step toward a new kind of medicine, gene therapy, a kind of therapy that offers this patient his only hope of living. His name is Clayton Parsons.

PARSONS: Before my gene therapy, I couldn’t go on the treadmill for more than a minute and a half, two minutes maximum.

CARTY: Clayton Parsons was a factory worker for 20 years. But then he began to have chest pains. The problem was his heart.

PARSONS: I had a quadruple bypass done in 1983. I had a double bypass done in 1984. I wasn’t supposed to go back to work. But I went back to work until about 1995, I started to have more trouble. My arteries are blocked, and it restricts the blood flow. And I was just having a lot of angina. It was like a real bad, bad heartburn. I couldn’t walk. I couldn’t do nothing.

CARTY: Clayton Parsons’ coronary arteries became so blocked he couldn’t have yet another bypass surgery. He was running out of options.

PARSONS: Two years ago, doctors told me they couldn’t do nothing else for me. In fact, one doctor told me I only had about two years to live, a dead end. Well then I got a hold of a doctor. And he said he knew some doctors in Toronto that were trying this new gene therapy thing out.

CARTY: One of the Toronto doctors Clayton Parsons went to see was Duncan Stewart, a cardiologist at St. Michael’s Hospital. Dr. Stewart explains that genes are just combinations of basic chemicals, or enzymes, that make proteins. These proteins tell our cells, be they heart cells or liver cells or skin cells, how to do their work.

Scientists think they can use gene therapy to replace a missing gene or fix a bad one, and thereby restore cell growth, or stop the growth of cancerous cells, or infectious diseases. In fact, most gene therapy experiments are in the fields of cancer, HIV/AIDS and heart disease.

When Clayton Parsons turned up on his doorstep, Dr. Stewart recognized a good participant for a gene therapy trial for heart disease.

STEWART: We enrolled him in a clinical trial, a phase one of a gene therapy trial, which means that we’re predominantly interested in the safety of the procedure, and though we’re also obviously looking at whether it works or not.

PARSONS: Gene therapy is – they inject genes into the heart muscle. If it works, it’ll grow new arteries, if it works. I phoned Toronto and made an appointment, because I had no choice.

STEWART: We attempted to improve the blood supply by injecting genes into the heart muscle, that code for factors that stimulate growth of new blood vessels.

CARTY: The surgery happened just over a year ago. Dr. Stewart and his colleagues opened up Clayton Parsons’ chest, and injected specifically designed genes into the heart arteries. Then they closed him up. The hope was that the genes would fuse with tissue cells of the arteries, and help them start growing again.

PARSONS: About four months after my surgery, I just started to walk, and doing a bit of exercise. And before my surgery, I couldn’t walk the length of my living room. I think it’s great. It gave me a new lease on life. I feel great. I feel great.

CARTY: Cases like Clayton Parsons are generating a lot of hope, and also a lot of scientific and corporate interest in gene therapy. Around the world, there are now 600 trials underway. But it’s been a rocky road. Gene therapy began almost 12 years ago. But it’s only had a handful of clinical successes. And it is still not an approved treatment.

You wouldn’t expect that given the amount of media attention gene therapy has received, though. So much, in fact, that in 1995, the U.S. government slapped the wrists of the research and development companies, telling them to cool it. Their glowing promises for gene therapy were just not justified by clinical results.

Still, press releases continued to suggest that gene treatments were just around the corner. Then came a major and tragic setback.

GELSINGER: I am addressing this committee in the hope of bringing to light some very serious concerns that I have as a result of my son’s death.

CARTY: In early 2000, Paul Gelsinger appeared before a Senate Committee in Washington. His son, Jesse Gelsinger, had died in a gene therapy trial. It became a case that illustrated both gene therapy’s health risks and its commercial temptations. It happened at the University of Pennsylvania where scientists were testing a gene therapy for a liver disease known as OCT.

Ironically, Jesse did not need to join the trial. His OCT was not life-threatening. The trial would do him no good. But doctors at Penn University told him he would be helping other children. And Jesse agreed to take part. He was 18.

GELSINGER: He believed, after discussions with the representatives from Penn, that the worst that could happen in the trial would be he would have flu-like symptoms for a week. I trusted this to be a well-controlled and purely ethical effort.

CARTY: Paul Gelsinger only learned later about the safety risks of gene therapy. The most pressing risk is in the way genes are introduced into patients, usually with the use of viruses. Stuart Newman is a Professor of Cell Biology at the New York Medical College. He says viruses can do what scientists have a hard time doing – they can get inside human cells. In fact, that’s how they reproduce. So gene therapy uses viruses as a vector or vehicle to carry genetic material into millions of cells, just like infecting them with the flu, but with a virus that is disarmed.

NEWMAN: The idea was to take one of these viruses to try to knock out what it is about the virus that makes it cause a disease, and put in the desired gene, and then inject it into the desired tissue. But there is always the chance that the gene that you put in will be carried to other places besides the tissue that you’re targeting, and that the virus that’s been debilitated in order to perform this function, even that virus itself may not be so innocuous. And in the case at the University of Pennsylvania, a young man died.

GELSINGER: Less than 24 hours after they injected Jesse with the vector in an amount only one other person had ever been given, Jesse’s entire body began reacting adversely. He went into a coma before I could get to Philadelphia and see him, and died two days after my arrival, directly as a result of that gene therapy experiment.

NEWMAN: It looked like it was like an allergic effect to something that the virus was making. The claim was that the virus was innocuous. But they put in very large amounts of the virus. And the administration of the virus was an unapproved route of administration. And they were just using this person as an experimental model.

CARTY: Jesse’s allergic reaction to the virus vector was not the only anomaly in the experiment. The autopsy found the virus vector not just in Jesse’s liver, where it was supposed to be, but elsewhere in his body. That raises the concern that genes could migrate to reproductive cells, and cause unintended genetic changes to future generations. Also at Jesse’s autopsy, doctors found the virus vector had mutated. The concern here is that, if viral vectors can change inside humans, or mix with other virus DNA inside of us, they could create an entirely new disease. That’s why there are proposals that gene therapy patients should be monitored for such diseases for up to 20 years. Researchers are also trying to improve other methods of getting genes into patients.

The scientific issues raised by the Gelsinger case are matched by the ethical ones. It was later revealed that the director of the University of Pennsylvania Institute, where Jesse’s trial was conducted, was heavily invested in the stock of the company that helped finance that very institute. Testifying before Congress, Jesse’s father, Paul Gelsinger, suggested that commercial interest may have been the reason he and his son were not fully informed of the risks.

GELSINGER: Looking back, I can see that it was very naive to have been as trusting as I was. I learned after Jesse’s death that Penn had removed from the information they gave Jesse and me any reference to deaths of monkeys, which had previously appeared in their documents. The secretive nature of gene therapy research and the motivations behind the race for results are what trouble me most.

I have read that my son’s death has been called by one of the leaders in this field as ‘a pothole’ on the road to gene therapy. His death was no pothole. It was an avoidable tragedy. I am not against gene therapy. However, when lives are at stake, and my son’s life was at stake, money and fame should take a backseat. No more fathers should lose their sons.

CARTY: After the Gelsinger scandal, American authorities temporarily shut down gene trials at the University of Pennsylvania. But they found the problems there were not unique. They found more than 600 other cases of adverse reactions in gene therapy trials, including deaths that had not been reported.

That led to changes in reporting systems, and better informed consent procedures to prevent companies from hiding information from patients and regulators in the name of protecting their proprietary or commercial information. The Gelsinger family received an out of court settlement from the University of Pennsylvania.

Since the Gelsinger setback, gene therapy trials have resumed. And there have been a host of positive results, but also a couple of new problems.

SPORTS ANNOUNCER: And it’s a clean start. This Men’s 100 meters… let’s watch Maurice Green in lane 5. Maurice Green coming down. It looks like Maurice Green all the way. Maurice Green is the 100-meter champion!

CARTY: One problem is the possible abuse of gene therapy by competitive sports. Gene therapy could be used not just for treating diseases, but also for enhancing performance, giving an athlete an edge, for example, with stronger muscles or more tolerance for pain.

Lori Andrews is worried about these so-called ‘off-label uses’ for gene therapy. Andrews is the director of the Center for Science, Law and Technology at the Illinois Institute of Technology and the co-author of a book called Body Bazar.

ANDREWS: There’s a technology that’s being proposed to genetically enhance people’s hearts after they’ve had a heart attack to get them back to normal. But athletes also want to use that technology to get more oxygen to their heart for sports. And once a technology is approved by our Food and Drug Administration, doctors have the right to use it for about any other use they want in patients. It’s like using aspirin as a blood thinner for heart patients and so forth. One problem with off-label uses of genetic technologies is that means there’s going to be no safety data kept. And another big problem is it will take decades, if not generations, to find out what the side effects were.

CARTY: Olympic officials are so worried about gene therapy that they recently held a major international consultation. They’re concerned gene therapy will become like drug doping, a way to cheat the clock or beat the record, but one that would be very difficult to detect. And if that is not troublesome enough, gene therapy could also change the way we look at war. Lori Andrews:

ANDREWS: I’ve gotten several calls from groups who want to explore the possibility of using genetic engineering to create soldiers who are going to be less affected by toxins like Agent Orange, or using genetic information about people for biowarfare, in fact, to be able to create an anthrax that hones on to a genetic code so that you can target certain ethnic groups.

CARTY: People have actually approached you with these ideas?

ANDREWS: People have approached me with those ideas. This could lead to an ethno-bomb where, as opposed to the smart bombs that target particular buildings, this would target particular ethnic groups.

[SOUND OF TREADMILL]

NURSE: Stop the treadmill. Come on back and have a seat. How are you doing?

PARSONS: I just feel a little tired right now. And other than that, I feel pretty good.

CARTY: Back in Toronto, Clayton Parsons has just finished his treadmill testing. The results are encouraging.

PARSONS: Before my gene therapy, I couldn’t go on the treadmill for more than a minute and a half, two minutes. This time, I was on it nine minutes.

CARTY: Clayton’s doctors are cautious about drawing conclusions from these results. They can’t really say whether the gene therapy is working, or if it’s a placebo effect, or the result of invasive surgery itself. More controlled Phase Two trials are now underway. Many experts believe some form of gene therapy will be a reality within five years.

Gene therapy has not generated the opposition that’s been experienced by technologies like cloning and germ line manipulation. But as a society, we will still have to address some of the major issues it raises, whether it should be used as a weapon of war, or as a way to cheat in sport. And above all, who will have access to this revolution in medicine, and for what reason? For Living on Earth, I’m Bob Carty in Toronto.

[MUSIC UP AND UNDER: BIONAUT, "LUBRICATE YOUR LIVING ROOM," LUBRICATE YOUR LIVING ROOM, MATADOR, 1996]