Did Gelsinger’s high ammonia levels play a role in his death? The question prompts a long pause from Wilson. “Well, I don’t think so,” he says softly. “But things are rarely proven in biology.” No one knows for sure just how the procedure, Gelsinger’s liver function and his immune response are all connected, but Wilson now believes that the teen died from a rare phenomenon called antibody-dependent enhancement. He may have been exposed to a similar adenovirus in the past, which caused his body to create antibodies against it, Wilson explains. Normally antibodies control a virus when the body encounters it again. But occasionally they elicit a dangerous immune response. Wilson admits, however, that there is no way to prove it, because none of Gelsinger’s pretreatment blood samples remain.
Wilson says that even if Gelsinger did die from a rare and unforeseeable complication, he is not trying to dodge responsibility. “The university here, the field and the families who were relying on us to succeed—I just feel as if I’ve disappointed all of them,” he says. “Quite frankly I don’t know how many different ways I can say it. [I feel] regret, remorse, awful. I’m sorry.” The university settled a wrongful death lawsuit brought by the Gelsinger family for an undisclosed sum.
In his “lessons learned” article, Wilson advises researchers against putting themselves in situations that might create potential financial conflicts (in 1992 Wilson had founded a biotechnology company focused on gene therapy). He also argues that scientists who develop therapies should not be the ones testing them in humans. “You can’t be the person who acts on behalf of the research subject,” he says. Ultimately, Wilson argues, clinical scientists should always ask themselves this question: “If the worst-case scenario played itself out—not the potential or likely, but the worst—would that be acceptable?” If he had asked himself that question in 1999, Wilson says, he would not have proceeded.
It has been a difficult decade for gene therapy, but Wilson believes that its fall from favor was inevitable. Gelsinger’s death “clearly was a precipitating event,” he says, but “stars were lining up, and the field was just going to encounter a difficult time.” Although some gene therapy trials have seen limited success, many have produced adverse reactions in volunteers.
Wilson hasn’t given up on the field, though—he is trying to make it safer. Since 1999, with a grant from GlaxoSmithKline, his lab has identified 120 new adenovirus-associated viruses that can more easily sneak past the immune system and deliver gene therapies with lower risk, and he has distributed them to 700 investigators around the world for further study. He hopes, as do others, that there will be no more Jesse Gelsingers.
Note: This article was originally printed with the title, "Tribulations of a Trial."
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13 Comments
Add CommentWhether it is the tone of the author, or that there is an actual lack of sincerity in Glesingers comments on the result of his experiment Im not sure. But Gelsingers failure to acknowledge the loss of life his rash actions and his direct responsibility is quite disturbing. the protocol was not written in a way in which there was enough clarity to know when the ammonia had to be what [level], and that was a significant shortcoming. This statement is shockingly obvious to me to be a sick attempt at avoiding the blame he claims to accept. From what I can gather from this article his lesson learned was how not to be the person who catches the blame when things go wrong, not how to be more cautious when dealing with another human beings life. I think the only person he is convincing of his regret and remorse is himself.
Reply | Report Abuse | Link to thisWhether it is the tone of the author, or that there is an actual lack of sincerity in Glesinger’s comments on the result of his experiment I’m not sure. But Gelsinger’s failure to acknowledge the loss of life his rash actions and his direct responsibility is quite disturbing. “the protocol was not written in a way in which there was enough clarity to know when the ammonia had to be what [level], and that was a significant shortcoming.” This statement is shockingly obvious to me to be a sick attempt at avoiding the blame he claims to accept. From what I can gather from this article his lesson learned was how not to be the person who catches the blame when things go wrong, not how you should be more cautious when dealing with another human beings life. I think the only person he is convincing of his regret and remorse is himself.
Reply | Report Abuse | Link to thisWell ... I dunno. I didn't think "insincere" or "sick attempt" ... not even after rereading the story twice after reading Ameyjo's comment.
Reply | Report Abuse | Link to thisIt is easy to stand in judgment.
I'm sure he had long and hard thought about his guilt during his 6-year ban from performing clinical trials, and maybe at this point his comments are targeted at the current clinical researchers reading the article who could learn from what happens when a protocol isn't properly thought out or reviewed by other specialists...but hey, I'm an optimist when it comes to human nature
Reply | Report Abuse | Link to thisI'm glad that today we have all these protocols preventing dangerous accidents, but a certain part of me wonders if it's really in the best interest of science. Would past scientists have made the discoveries they did if they were so afraid of the potential consequences? I have no desire to see further loss of life, but in many fields of science some risk is required to reap the full benefits of research. Just think of what would have happened, had this trial gone according to plan - Gelsinger would have been celebrated and at the most chided briefly for the risk, and the technology developed could have saved countless lives.
Reply | Report Abuse | Link to thisThere seems to be a double standard in experimentation that goes something like this: "We'll let you experiment as long as the outcome isn't disastrous". Sometimes experiments do go horribly wrong, in ways we can't predict. This particular case isn't a great example (as they could have predicted some of the danger), but experimentation is founded on the idea of poking and prodding science we're not totally sure about. We shouldn't shy away from gene therapy simply because there's risk involved.
SciAm writes:
Reply | Report Abuse | Link to thisWilson argues, clinical scientists should always ask themselves this question: If the worst-case scenario played itself outnot the potential or likely, but the worstwould that be acceptable? If he had asked himself that question in 1999, Wilson says, he would not have proceeded.
This is the kind of question so often ignored in *any* kind of risk management discussion, not just in a scientific context. This is why the banking industry fell apart, health care is in crisis, companies are laying off/not hiring people. People tend to write off the worst case scenario as statistically unlikely and therefore not worth consideration, instead of seriously asking, "What will we do if the worst happens?"
Regardless of Dr. Wilson's feelings (which read as sincere to me, although obviously I can't look out of his eyes), the message he is promoting is a valuable one, worth incorporating in any discussion of risk.
Ameyjo, Gelsinger was the name of the person who died during the trial; Wilson is the name of the doctor who ran the trial. Aside from that, I disagree with you. Wilson appeared sincere enough to me.
Reply | Report Abuse | Link to thisThank you danshil, I thought I was crazy for a minute with Dr. Wilson's name confused. Not only did he sound sincere to me - though I wished I could read the whole text on his " lessons learned "- but I am convinced his actions will teach all of us.
Reply | Report Abuse | Link to thisOops - just realized I made that mistake too. Thanks danshil.
Reply | Report Abuse | Link to thisSeems to me Dr. Wilson is being candid about this protocol. . In order for Science to become good Medicine clinical trials must eventually be done in humans. Clinical trials,(especially Phase I trials in which a new drug or device is first used in humans) are always risky. If the patient fully understands the potential risks and benefits involved and makes a decision to participateI think it's an ethical and often noble process. Many patients with terminal illness find alot of satisfaction in finding a cure even if only the next guy may receive a benefit. Bottom line...Protocols are tough to write and review but most of the time the process works well.
Reply | Report Abuse | Link to thisthere is no benefit without some risk! even if you live in a ball of cotton, you risk small airway dis-ease! not to mention problems of nutrition, excretion and increased fire risks! worst case scenarios/disaster? you can exaggerate to the point of absurdity! INFINITE SAFETY TAKES INFINITE RESOURCES! unfortunately true, be real!
Reply | Report Abuse | Link to thisSee the commentary by Jesse Gelsinger's father, Paul Gelsinger, in The Philadelphia Inquirer, http://www.philly.com/inquirer/opinion/20090917_Seeking_justice_for_my_son.html
Reply | Report Abuse | Link to thisI was deeply touched by Dr.Wilson experience. I believe in his sincere words and I regret his misfortune, that is to be shared with all mankind. It is very hard to deal with trials involving human lives, but forward it will be a further stone covering the science way.
Reply | Report Abuse | Link to thisMRLacerda.