As the saga of a gene therapy experiment gone terribly wrong has unfolded, media coverage of Jesse Gelsinger's death and its aftermath has played an active role in exposing disturbing problems in that field of experimental medicine. Since September 1999, when Jesse died after receiving a high-dose viral vector and therapeutic gene at the University of Pennsylvania, journalists have helped trace what began as a mystery and is emerging as a tale of botched oversight and misplaced research ethics.

Throughout the reporting has run a recurring theme: to how much privacy concerning human clinical trials and research mistakes is the biotechnology industry entitled, versus the public's right to know about these trials. Facts about irregularities in the Pennsylvania trial, along with unreported adverse effects and deaths in other gene transfer experiments, have come to light since September, casting a long shadow on this mostly unproven field, and raising questions in the public's mind about how safe it is and what protection they have when they participate in such trials. Indeed, President Clinton, in a recent address before the American Association for the Advancement of Science (AAAS), called for speedier Food and Drug Administration (FDA) and National Institutes of Health (NIH) investigations.

Reporting about lapses in research ethics in Gelsinger's and other trials has been, for the most part, factual and nonsensationalistic, energizing a public debate concerning the safety of gene therapy and whether sufficient patient protections are in place. Over time, salient facts have emerged that call much about the gene therapy endeavor into question:

(1) Jesse and his family may not have been advised of the risks inherent in his trial, including information concerning the deaths of primates.

(2) Jesse and other patients, thus, may not have given informed consent.

(3) Jesse was not eligible to be included the trial due to high ammonia levels at its outset.

(4) Inherent conflicts of interest may exist concerning researchers' and biotech companies' ability to protect their own financial interests and at the same time protect patients from undue risk.

(5) The lion's share of adverse effects in gene therapy trials have not been reported to the public oversight body, the The Recombinant DNA Advisory Committee (RAC).

(6) Some patient deaths in gene therapy trials may have been wrongly ascribed to underlying diseases rather than the treatment itself.

Early reporting focused upon Jesse's apparent mysterious death, as well as upon Jesse himself, and his desire to serve as a research subject to help others with more severe diseases, even though he was told the experiment would most likely not benefit him. As facts began to emerge telling of irregularities with the trial, some reporters began exploring the complex issue of informed consent given by sick patients, and which patients are appropriate to participate in clinical trials - the sickest, or those who were, like Jesse, not terminally ill.

Key to uncovering problems with this and other gene therapy trials has been excellent investigational reporting by the Washington Post's Rick Weiss and Deborah Nelson, who first revealed troubling lapses in protocol and other deaths linked to additional gene therapy trials; on February 11, they added yet another disturbing chapter. They revealed that researchers at St. Jude's Children's Research Hospital in Memphis and the Baylor College of Medicine in Houston discovered in December 1999 possible accidental exposure of patients to HIV and hepatitis C viruses, but informed the FDA of the problem only in February 2000. Final results are pending, raising the question for some whether the problem should be reported to the public before it is definitively known to be a problem.

The debate has broadened, as local and wire reports followed the RAC as it proposed to clarify its reporting requirements in December 1999, as the FDA shut down all eight of Penn's gene therapy trials in late January 2000, and as the U.S. Senate's Subcommittee on Public Health held a hearing on February 2 to determine whether oversight of gene therapy is adequate. Fallout includes Massachusetts General Hospital's voluntary suspension of its own gene transfer trials. Opinions as to the appropriateness of such caution have been presented pro and con, with Boston University bioethicist George Annas stating that a moratorium should be placed on gene therapy; this was countered by RAC chairperson Claudia Mickelson.

Missing from the reporting, however, is a view of the problems with gene therapy in context with other research problems. There is a correlation between the difficulties with gene therapy trials and what is happening on the larger stage of research trials in general. In early 2000, the FDA shut down clinical trials at two eminent research institutions, Duke University and the University of Alabama at Birmingham. At the same time, the National Academy of Sciences issued a proposal that medical errors be made available to the public, a proposal that was vetoed by federal health officials.

What the news reports following the Penn debacle have failed to mention is that the state of oversight of all clinical trials and medical mistakes is, and has been for some time, in crisis. Recently uncovered problems with gene therapy trials are part of a larger picture of problems with human clinical research and the protection of research subjects. In 1998, the Health and Human Services' Office of the Inspector General issued a report stating that the oversight of all multicenter clinical trials is woefully inadequate due to their size, decentralization, and the increasing funding of research by private sources; the office called for reform at the local institutional review board (IRB) level. This report was preceded by congressional hearings in May 1997, at which serious issues were aired concerning the protection of research subjects, problems with informed consent, and lapses in the oversight and regulation of multicenter trials.

While the lapses in reporting recently brought to light in gene therapy trials are regrettable and disturbing, they should not be surprising given reports of such failures in other clinical research. For years, the media has reported shocking lapses in protocol, oversight, reports of adverse events, and judgment of some clinical investigators at a wide range of top academic institutions, including the University of California at Los Angeles and Columbia University. And now, problems with gene therapy trials.

In January, Biotechnology Industry Organization head Carl Feldbaum asserted in an opinion piece in the Washington Times that "gene therapy is subject to greater oversight than virtually any other medical technology." While this is technically correct, the minimal power left to the RAC, after former head of the NIH Harold Varmus stripped it of most of its authority in 1996, does not currently allow for sufficient oversight of research subjects in gene therapy trials. The reporting of current events in gene therapy and other clinical trials can and should only lead the public to question whether adequate protections are in place to ensure a reasonable amount of safety - given the experimental nature of all clinical trials.

In February 2000, the Wall Street Journal described the launching of new Internet efforts to recruit patients for clinical trials. Drug companies and medical researchers are currently facing a huge crisis in finding and retaining patients for trials. With the RAC's public oversight power currently still hampered, the responsibility of helping inform the public as to the current state of oversight of gene therapy trials, and indeed, in all human research, falls in the laps of reporters. Reporting should keep in mind a wider perspective of oversight in all human trials when considering science's need to move forward through responsible experimentation with good risk-benefit ratio, adequate protection for subjects, and its responsibility to keep the public well-informed. Responsible reporting must continue to serve two vital goals: promoting responsible research, and helping the public make informed choices concerning participation in medical research.