A medical research team at the University of California, Los Angeles, performed a number of experiments on dying patients without the required approval of the medical school committee responsible for protecting human research subjects.
As a result of one set of unapproved experiments on leukemia patients, six researchers were reprimanded by the dean of the medical school, who told them further violations would end federal and university support for their work.
Among those warned were some of the most respected physicians on the UCLA faculty -- men with international reputations in medical science, including Dr. Robert P. Gale, who heads the bone marrow transplant unit where the experiments took place, and Dr. Martin J. Cline, who until recently was chief of hematology and oncology at the medical center.
Cline recently became the center of a separate controversy as a result of genetic engineering experiments on patients in Israel and Italy this summer.
Despite the stern warning to Cline, Gale and four others at an August meeting with the dean, the medical school's Human Subject Protection Committee remains dissatisfied with the university's response to apparent violations of federal and campus rules on human experimentation.
The committee's job under federal and university regulations is to ensure that potential benefits of any human experiment outweigh risks and that the patient is fully informed of the risks if he participates in the research.
On a number of occasions, according to committee records, experimental bone marrow transplants were performed without committee aproval.
Medical school officials, including the dean Dr. Sherman Mellinkoff, have confirmed the experiments violated rules.
The violations so upset members of the human protection committee that for several months the panel refused to approve any experiment in which Gale was chief investigator, unless risk to the patient was unmistakably trivial, records show.
The clash between the committee and Gale became a confrontation between the committee and the medical school dean, who contended panel members had usurped authority of the administration by trying to punish faculty member for infraction.
In October, Mellinkoff forced Dr. Jeremy Thompson to step down as chairman of the human protection committee, a job he had held for 12 years.
But Albert Barber, UCLA vice chancellor for research, and Mellinkoff insist Thompson's departure had nothing to do with the dispute over bone marrow transplants. Instead, they say they were trying to put an end to growing bad feelings between UCLA's medical research faculty and the committee, which had, according to Barber, developed a reputation for being needlessly "nitpicky" in reviewing human research plans.
Neither Gale, head of the bone marrow unit, nor Cline, former chief of the division in which the disputed eperiments took place, would agree to interviews.
Gale and other doctors on the unit told a special investigative panel of physicians that the procedures were not regarded as research, but were the best available therapy for terminal patients.
And some physicians on the bone marrow unit said in interviews that patients and their families frequently plead for experimental therapy when all else failed, even when they know that the chances for success are remote.
But some of those who worked on the bone marrow transplant team complained in interviews of what one physician called "the cavalier attitude" at times of the unit's physician-researchers toward patients.
"Once diagnosed as terminally ill, the patient is no longer a human being but a research subject with a disease to be fitted to a protocol [experimental plan]," said one team member.
While acknowledging infractions of rules at the UCLA medical center, Dean Mellinkoff argued the violations must be kept in perspective.
"I know of no case at the UCLA School of Medicine that has ever been done to the detriment of any patient," Mellinkoff said.
In bone marrow transplantation, marrow is removed from a healthy donor -- an identical twin is best, but a closely matched sibling can work -- by long needles.
The donor's marrow is then injected into the recipient, whose marrow has been destroyed by chemotherapy and radiation.
The treatment has become standard for certain forms of leukemia, a cancer of the bone marrow cells, and for aplastic anemia, a failure of the bone marrow to work properly.
But an unsuccessful bone marrow transplant can mean a quicker and more agonizing death than the terminal illness it is intended to cure.
In early 1979, nurses from medical center wards came to the Human Subject Protection Committee to complain about experiments on patients without plans and patient consent forms approved by the committee.
Increasingly, as they investigated the unit, committee members began to believe the apparent violations were deliberate.
In some cases, patients were being treated with high doses of anticancer drugs along with bone marrow transplants -- but the drugs had not been approved by the human protection committee.
In other cases, patients with one form of cancer were being treated with combinations of chemotherapy and bone marrow transplant that had been approved by the committee, but only for other varieties of cancer.
None of the alleged violations has been reported to the National Institutes of Health, the federal agency funding the bulk of medical research in the country. Reporting violations is not a requirement of federal rules.
Dr. Charles R. McCarthy, director of the Office for Protection From Research Risks at NIH, confirmed that medical schools and research centers are not required to report violations of human experiment regulations until the school or research center has completed its report of the violation.
There are proposed changes that will clarify these rules," he said. "The remedy we've proposed will indicate where in the federal government a report of a violation is to be made and give at least some idea as to when such a report is to be made. We would have liked to have heard of this [the UCLA] incident before it was published in the press."
McCarthy said he will ask UCLA to forward its report to his office "and I might add that I expect the university will forward it to us." McCarthy said the violations at UCLA sound as if they border the fine line between research and standard therapy in treatment of cancer.
"It's always a tough call to make," he said. "I think some of these things can honestly be described by one person as therapy and by another as research." c