In the third and final session of his preceptorial on gene therapy, Director of Penn's Institute for Human Gene Therapy James M. Wilson took Tuesday night to discuss the current state of his field and the 1999 clinical trial that resulted in the death of one of the subjects, 18-year-old Jesse Gelsinger.
Wilson, whose ability to conduct research studies on humans is currently being questioned by the Food and Drug Administration, utilized the trial to illustrate to students how a scientific discovery gives way to a clinical study.
In the trial in which Gelsinger was involved, Wilson and his team of researchers were giving Gelsinger a treatment they had previously tested on animals. Gelsinger had a specific disease for which the therapy was being tested.
Before the preceptorial, Wilson said he would attempt to convey an understanding of Gelsinger's genetic disease and what the IHGT was trying to do to comprehend and cure it at the time of his death.
"What I'm going to try to do is describe accurately the disease, the strategy for treating this disease, the data generated to support testing this in humans, the clinical trial, how it was designed... and that two years of work in which we've dedicated ourselves to try to understand the basis for the severe mutant reaction that we observed in Jesse Gelsinger," Wilson said in an interview prior to the most recent class.
Gelsinger suffered from a form of ornithine transcarbamylase, or OTC, deficiency, a disease which inhibits the liver's ability to process proteins. The disease normally appears in newborn males after their first meal, and it usually leads to coma and death.
Wilson spent a portion of Tuesday's lesson describing why subjects like Gelsinger -- relatively healthy adults with a milder form of the genetic defect -- were used instead of the terminally ill newborns.
"[There was] a counter-view which is, since this is the first time this vector would ever be tried in humans and we don't know what the risks are, that it may be better to enroll patients who aren't very sick with the disease..., the reason being that they can provide their own consent, you don't have to go to a guardian, that they're healthy, that they're there really just to participate in gaining new knowledge," he said.
He added that in this type of trial, known as a phase one, there are no guaranteed health benefits to the patient, so presenting such a study to the parents of a newborn, terminally-ill child can pose ethical problems.
"The doctor runs into this room and says there is this experimental therapy, [and parents are] almost in a position where they can't turn it down because they're faced with some really terrible circumstances," he continued.
College sophomore Tim Pirolli, who works in a gene therapy lab on campus and attended the lecture, said it was interesting to hear about the study from the scientist himself rather than through the media.
He added that he believed Wilson was not at fault in the death of Gelsinger, but that the trial was unpredictable.
"The way he's portrayed is he let [something] slip through the cracks, but the science says there were no cracks... It would be different if they missed something, but they didn't, that's not the problem. They don't know why he died," Pirolli said.
Wilson said that what happened to Gelsinger could not have been predicted based on the experiments done before the trial. "It represents the fact that animal models are not always predictive of what you'll eventually see in humans."
Gelsinger's father, Paul, has alleged that researchers failed to report that monkeys who were given smaller doses of the vector -- the gene therapy that was eventually given to Gelsinger -- either became ill or died, with many of them exhibiting the same symptoms as Gelsinger did.
Wilson explained that the study was set up so that at various levels subjects received increasingly strong doses of the virus that carries the vector.
"Another important point that we learned is that there are some individuals that are much more sensitive to this vector than others," he added. "The example being that for the highest dose vector, we enrolled two patients, a woman and a man, and the woman did fine... but the same dose vector in Jesse Gelsinger, the second patient, had an unbelievably tragic outcome."
Students said that they enjoyed Wilson's discussion of the research, trial and experimentation process in the gene therapy field.
"He did a really good job on it. He explained... the whole research process of how it gets from laboratory research to clinical trials, bench to bedside," Pirolli said.
One student, speaking on the condition of anonymity, said Wilson was a good professor and that the class was very informative.
"I thought [the preceptorial] was very interesting. He told us a lot of things I didn't know about," the student said. "He took a lot of questions and he was very clear. He was very knowledgeable of what he was talking about."
Wilson took time to answer the students' questions and said that he enjoyed the opportunity to work with students interested in his field of study.
"I think a lot about the importance of providing, in the context of a liberal arts education, an understanding of the key aspects of science," he said. "So, just because students are not science majors, I get excited by that, because this may be one important opportunity for them to expand their knowledge and experience of science. It's also exciting to have people interested in science because that's what I've dedicated my life to."
Some secrecy surrounded the first meeting of the preceptorial. Wilson and the preceptorial committee made efforts to prevent The Daily Pennsylvanian from obtaining information about the class. Its location was kept a secret until class time, reporters were not allowed to attend and students were asked not to comment to them.
"The classroom is a very, very special place where we try to encourage the open exchange of ideas and discussion, and anything that would potentially stifle that would be something that I'd want to discourage," Wilson said. "Having press in the classroom I feel would deter from the educational experience, and there's a time and a place for everything. Speaking with members of the press is also important. Teaching is important. Mixing the two -- if you can avoid it, I think you should."
Wilson emphasized, however, that he and the IHGT have been forthcoming with the scientific community.
"We have been aggressive at sharing with the scientific community any and all aspects of this case, both before the data that we generated during the trial and since then, with the hope that this information will be useful to others and assuring that this will eventually be successful, and hopefully to avoid any similar circumstances in other trials," he said.
"When we undertook this study, as well as any of these studies, we make a commitment that we will learn as much as we possibly can to assure that this will ultimately succeed," he added. "We can't promise that any one strategy is going to be the one that will ultimately be successful, but our obligation is to assure that we learn from the experience and share the information."
In the first session of the preceptorial, Wilson attempted to convey the rudimentary basis behind the gene therapy field, and in the second he tried to illustrate those principles in a laboratory setting.
