ASGT Opinion Editorial

MILWAUKEE-The heartbreaking death of Jesse Gelsinger during a clinical trail at the University of Pennsylvania threatens public confidence in gene therapy research and must not become a barrier to future scientific breakthroughs. This type of research offers the tantalizing prospect of a dramatic and historical reduction in the suffering and burden of disease.

It is now apparent, according to the Federal Food and Drug Administration findings, some procedures in the existing protocol at Penn were violated. Those violations should be swiftly dealt with by the FDA. Researchers and the government together should move forward to make sure that protocols are tightened up and standardized. Volunteers for clinical trials must be adequately protected and fully informed of the certain medical risks they face on the new frontiers of medicine.

The field of gene therapy is only 15 years old and the first patient was enrolled less than a decade ago. The initial trials were greeted with immense anticipation. The excitement was genuine, but regretfully, was accompanied by great hype and unrealistic expectations. There were unexpected hurdles. Looking back, as researchers, we ask: Should we have developed better technologies, conducted more animal tests and gotten more adequate data before moving to human trials? The answers to those are yes and were indeed the focus of research conducted during the last few years. And we are just now beginning to witness some limited successes.

Dr. Alain Fischer, working in Paris, describes the complete cure of two young children suffering from a rare form of immunodeficiency. These are early results but it appears these two children (and at least two additional ones) have been producing the deficient protein for nearly a year without any sign of decline. These kids now have competent immune systems and could live normal lives. There is some preliminary good news on the gene therapy trials of several hemophilic B. patients. and we are hearing many tantalizing anecdotes of limited success in cancer gene therapy.

The fallout from Jesse Gelsinger's death has been intense. The gene therapy trials at Penn have been halted. Other trials around the world are under the microscope and the story was extensively covered in the press. It was later reported, base on highly preliminary lab testing that suggested a gene therapy experiments in Memphis and Houston might have exposed children dying of cancer with HIV or hepatitis C virus. After extensive testing the FDA , several days later, said it was a false alarm. The patients, in reality, had not been exposed to the virus. But the credibility of gene therapy was damaged again even though "the facts" turned out to be mistaken assumptions.

Increased scrutiny of gene therapy trials is called for. Researchers should immediately report serious adverse events in trial patients to the federal agencies overseeing gene therapy trials according to their rules and guidelines. That will be a means where any pattern of problem can be discovered and then shared with all of the investigators conducting trials, as well as with the public.

Researchers should follow standard operating procedures and follow protocols during their clinical trials to insure that they are acting in compliance with federally approved procedures.

Researchers also have another area that must be openly and honestly dealt with: potential conflicts of interest between profit pressures and the pursuit of progress in clinical trials. This is new territory that encompasses many different areas of clinical research in addition to gene therapy today and must be carefully navigated. We at the American Society of Gene Therapy are working on conflict of interest standards to insure that the profit motive can be eliminated from the conduct of clinical research.

The basic concept of gene therapy is simple and fundamentally sound: introduce a gene whose product has the ability to either cure or slow down or prevent the progression of disease. Its broad scope encompasses the correction of genetic defects, killing cancer cells, preventing cardio-vascular disease, interfering with the progression of neurological disorders and eliminating infectious pathogens.

Tragic incidences like the unexpected death of Jesse Gelsinger give us a reason to pause and take stock of the progress and pitfalls of gene therapy. We must learn from past mistakes, but continue to move forward to realize the untapped potential of this novel technology that in the long run could extend and improve the quality of the lives of millions of people.

• Savio Woo Ph.D. is the President of the American Society of Gene Therapy and Professor at Mount. Sinai School of Medicine, New York City.

• Inder Verma Ph.D. is President elect of the American Society of Gene Therapy and Professor of Genetics at The Salk Institute, La Jolla, California.

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