Gene Therapy: Medical Progress Has a Price, Says Ethicist

This transcript has been edited for clarity. 

Hi. I’m Art Caplan. I am at the Division of Medical Ethics at the NYU Grossman School of Medicine, located in New York City. 

I want to tell you about a story, in a way, of vindication, stick-to-itiveness, and showing the future of how genetic knowledge increasingly is going to be something that you need to be alert to. We certainly need to know where to send people when something is discovered that’s genetic. 

The tale involves a friend of mine named Jim Wilson. Wilson is a physician and scientist, still at the University of Pennsylvania. Just about 25 years ago, a young man, Jesse Gelsinger, traveled from Arizona to Philadelphia to participate in a study of gene therapy, which was then a very, very new idea.

This was the idea that if you had a genetic error in your body that was causing a disease, maybe you could change a virus and put a message into it instead of having it infect you with a cold or something like that. If you change the genes, maybe it would infect you with the missing genes causing the disease.

In this case, it was a strange, rare disease Jesse had, called ornithine transcarbamylase (OTC) disorder. Basically, he couldn’t metabolize or process a large number of foods. His body really couldn’t handle protein. 

With the severe form of the disease, when a baby was born, it would die quickly because it would have almost an allergic reaction to exposure to mother’s milk or artificial formula. You needed a special formula to make sure that reaction didn’t happen. 

Wilson’s idea was to put genes with the missing message causing this disorder into a virus, shoot it into the liver, and maybe it would make enough of the missing chemicals from the injected genes to give the baby a chance at life until you could get them over to the special diet.

Sadly, Jesse Gelsinger, an adult with a mild form of the disease who had volunteered (and, I think, understood the risks), died in this gene therapy experiment. Some of you may know that set the field of gene therapy back almost a decade. At that time, people were really disappointed after so much hype that somebody could be killed in an experiment involving gene therapy.

Wilson was accused of many research ethics violations, and I’m presuming that many people at that time — I was one of them — thought that would be the end of Jim Wilson’s career, and that maybe we wouldn’t see very much going on in the future in gene therapy. Well, both have turned out to be wrong.

Wilson announced just recently that he had done an experiment on a young boy with the same condition as Jesse Gelsinger, and that 6 months out, the boy was alive and well and making the chemicals that were not present because of his genetic disease. It’s a little early to say it’s a success, but it’s certainly promising.

Wilson believed that he had the right idea, even though he’d been involved in this terrible scandal that set back gene therapy and set back his own career. He kept at it. He changed the viruses. He tried to minimize the chance of an allergic reaction. 

There are some lessons here, I think. One, research always involves risk. When people come to you and say, I’ve been offered an opportunity to be in a study for a new cancer agent, a new ALS agent, or a new agent for a rare genetic disease that my child might have — because now we see many efforts to develop gene therapies for all manner of diseases, ranging from muscular dystrophy to sickle cell to cystic fibrosis — I think a physician counseling that family needs to be aware there’s always risk, and perhaps deadly risk. 

When you’re involved in genetic engineering, genes can go where they’re not wanted, genes can be ineffective, and genes can produce side effects in combination with other genes that nobody expected.

It’s risky. It’s not a cure-all yet, and I think that has to be clear. I think most parents are going to try, especially when there’s a deadly disease, to give the experiment a shot. Many people will say, “What have I got to lose?” In managing risk, I still think you have to go in with your eyes open.

I also believe there’s a lesson from this turnaround, or persistent effort, that some technologies are just going to have to bring along danger to move them along. That doesn’t mean that Wilson didn’t do something wrong 25 years ago in terms of reporting data or getting the best possible informed consent. That’s a debate for history. 

I do believe that sticking to it, trying to improve the viruses, and performing more animal research is important, as we watch new technologies emerge, including face transplants, animals being used as sources of organs for transplantation, and new and novel interventions aimed at controlling obesity.

This is not a risk-free world, and just as those who are the subjects need to understand from doctors that there’s risk for them, the medical profession and those who fund it need to understand that a death or an adverse event needs to be solved but isn’t necessarily a sign that a particular area of research needs to be stopped or halted.

We don’t want to have situations where we try to go fast, we try to find cures, there’s a single adverse event, and then everything shuts down. That’s not the way investors need to behave. They have to tolerate risk. That’s not the way the regulators need to behave. 

It’s not the way medical professionals, including physicians and nurses, should talk when they’re trying to influence public opinion or their patients’ views about whether or not progress should continue because progress, as this area of research — gene therapy — shows, has a price.

I’m Art Caplan. I’m at the Division of Medical Ethics at the NYU Langone Medical Center. Thanks for watching.