The recent death of Jolee Mohr is likely to have a seismic impact on the future of gene therapy research.
Biotech companies, private investors and government funders will shy away from sponsoring further research because Mohr died while a subject in an experiment using genetic engineering to treat disease.
But giving up on gene therapy is not the right lesson to learn from this tragedy.
Mohr had rheumatoid arthritis, an immune system disorder that caused pain and stiffness in her joints.
By using HUMIRA, a relatively new anti-inflammatory drug made by Abbott Laboratories, she was able to keep her symptoms under control.
Despite her arthritis, Mohr played with her 5-year-old daughter, gardened, went boating and accompanied her husband, Robb, to church. She even volunteered at county fairs.
So how did it happen that this active 36-year-old woman wound up dead in a Chicago hospital?
Jolee Mohr died soon after her right knee was injected with genetically altered viruses as part of a research trial of gene therapy for rheumatoid arthritis. The viruses were aimed only at the cells in her arthritic knee, hopefully making this approach to treatment safer than the existing drug treatments. Targeted Genetics Corp., the Seattle-based company that sponsored the rheumatoid arthritis study, has halted the work and dozens of participants are being monitored.
The irony of gene therapy is that despite its name, it has achieved little in the past decade in terms of therapy but has, rather, been associated with serious problems including deaths. Eight years ago, 18-year-old Jesse Gelsinger died in an early experiment with gene therapy at the University of Pennsylvania. Ironically, Targeted Genetics Corp. had acquired some of the genetic technology that had been used in the experiment in which Gelsinger died.
The death of Jolee Mohr may be seen as the latest best reason to give up on gene therapy.
The finger-pointing about her death is well underway. Targeted Genetics Corp. has already hinted that maybe Mohr died not because of the gene therapy, but as a result of problems associated with HUMIRA, the arthritis drug she was taking before she signed up for the gene therapy trial.
Robb Mohr says his wife did not understand that she had agreed to be in a safety study of gene therapy, which was not intended to benefit her in any way. Dr. Robert Trapp of the Arthritis Center of Springfield, Ill., who had been Jolee Mohrs physician for seven years and recruited her into the study, says she signed a 15-page informed consent form and that he answered all her questions about the study. The study and its consent forms were reviewed and approved as U.S. law requires by an institutional review board, this one set up for the for-profit research.
If in fact Mohr did not understand the nature of the research she agreed to participate in, is this board partly to blame?
This question leads to another: Did the doctor closely monitor Mohrs health before enrolling her in the gene therapy trial? And another: Shouldnt someone other than her doctor have made the request for her to participate in a safety study of gene therapy since it might be easy for a patient to assume that a request from her doctor to try something would not be made unless the doctor thought there was some benefit in it?
I have had the chance to see the informed consent form that Jolee Mohr signed. In my opinion it is hard to read and not as clear as it should have been about the fact that she was being asked to participate in a safety study with risks but no expected benefits whatsoever for treating her arthritis.
It will take months if not years before these questions about who knew what when to get answered. Lawyers will have a fine old time running the meter while they battle out who is to blame and what is to be paid for the death of Jolee Mohr.
Lost in all of this mess are three key points.
First, there is no excuse none for someone to be allowed to sign up for a study of an experimental drug or treatment never before used in human beings if they dont clearly understand when the sole aim of such a study is to see whether the drug or treatment is safe. If people cannot really understand complex 15-page consent forms, then why are those documents still being used?
Second, if research is to advance, including gene therapy but also embryonic stem cell research and other novel therapies, then someone has to go first after all the animal testing and lab work has been done. Those first subjects face very real risks, including death. But there is nothing anyone can do to completely eliminate those risks.
Third, there is no national insurance program for those injured in early-stage research studies, meaning bereaved families may have to go through the rigmarole of a costly and slow trial so that they can pay their medical bills when a loved one dies or is severely injured in this type of medical research. Since those willing to be in safety studies are really helping future patients, dont we owe it to them to help in the rare case where something unexpectedly goes terribly wrong?
And lastly, questions remain about the system we have had in place for decades to protect human subjects in research. Subjects have to give informed consent, and committees, known as institutional review boards, have to sign off on the research and the consent forms before a study can start. But in a world where drug companies sponsor more and more research approved by for-profit review committees and carried out locally by private doctors who can make a lot of money recruiting subjects these protections may not be enough.
Jolee Mohrs death is a horrible tragedy. It should not, however, end research on gene therapy, which may be the only way to treat a variety of ailments and diseases. That death should, however, cause us to reexamine whether we are adequately protecting the heroes who help medicine make progress.
Arthur Caplan, Ph.D., is director of the Center for Bioethics at the University of Pennsylvania.