Subcommittee okays human gene transfer.

Subcommittee okays human gene transfer

After presenting new and previously withheld data to a National Institutes of Health (NIH) subcommittee, federal reserchers last week received the panel's long-awaited approval to inject, for the first time, genetically engineered cells into humans.

The researchers still must gain final approval from NIH Director James B. Wyngaarden and the Food and Drug Administration. But the unanimous approval of the key NIH subcommittee dealing with human gene therapy appears to signal the end of a months-long controversy that has had researchers, NIH officials and scientific journal editors at odds over the circumstances under which new scientific data may be reported and published.

The experiments -- proposed by W. French Anderson of the National Heart, Lung, and Blood Institute and Steven A. Rosenberg and R. Michael Blaese, both of the National Cancer Institute -- are not designed to benefit patients directly but may aid in the development of better cancer therapies. They passed muster with the NIH's Recombinant DNA Advisory Committee (RAC) in October, despite a failure to win approval from the RAC's Human Gene Therapy subcommittee (SN: 10/8/88, p. 228). Wyngaarden nixed the experiments later that month. He and others were reportedly miffed upon learning that the researchers had withheld from the RAC certain data so as not to jeopardize their publication in a major scientific journal. The NEW ENGLAND JOURNAL OF MEDICINE (NEJM) and SCIENCE, for instance, generally do not publish work scientists already have reported in detail elsewhere.

In a written response to Wyngaarden's statement that the "RAC will not be held hostage to the NEW ENGLAND JOURNAL OF MEDICINE," NEJM Editor-in Chief Arnold S. Relman reassured the director that "our policy is not to interfere with authors responding to requests for information from dully constituted government bodies." NIH officials now want similar clarifications from other journal editors, according to Gerard J. McGarrity, a consultant to the Human Gene Therapy subcommittee that approved the Anderson proposal last week.

At that meeting, Rosenberg presented unpublished results of a novel cancer therapy in which the researchers remove tumor-attacking cells (called TIL cells) from patients with advanced melanoma. They cultivate those cells in the laboratory, then reinject about 1 trillion of them into the patient from whom the original cells were taken (SN: 6/25/88, p. 404). "Given the information we now have, there's no question that some patients are benefited by this treatment," Rosenberg told the panel. "Of about 20 patients treated with TIL's, we see a good response rate of 60 percent. So we're on to something that can cause a substantial number of tumor regressions, but it certainly requires a lot of improvement." The results are scheduled for publication in the Dec. 22 NEJM.

By adding a genetic marker to the TIL cells before reinfusing them, to the researchers hope to determine the cells' fate in the body and to see whether some types of TIL cells attack tumors more efficiently than others do. "We're giving 10 cells, but it's possible that a very tiny percentage are the effective cells. And if we can grow them 10 we might improve the potency by hundreds of fold." Rosenberg said.

At the same meeting, Anderson presented new experimental evidence suggesting the chances of the procedure infecting a patient with a dangerous virus are less than one in a million. Anderson says he expects the FDA to complete its review within the next two months, and he hopes to perform the first human studies by March. The subcommittee limited its approval to 10 consenting patients with life expectancies of 90 days or less.