Blumenstyk, Caroline. "U. of California at Irvine is Under Fire Again Over Research Ethics,"

 

Blumenstyk, Caroline. "U. of California at Irvine is Under Fire Again Over Research Ethics,"
The Chronicle of Higher Education, 8 January 1998, p. A52.

TWO YEARS after it quietly closed a laboratory developing experimental cancer therapies
because of a series of ethical and legal violations, the University of California at Irvine is
scrambling to explain why it didn't follow through on promised reforms.

One of the most "vexing" lapses, according to the campus's own chancellor, Ralph J. Cicerone,
was the university's failure to return some $20,000 in "donations " to the university's medical
center that officials had solicited from cancer patients seeking treatment.

"No one should ever make medical care contingent on a donation," he said in a Dear Colleague
letter to the campus last month, after The (grange County Register and the Los Angeles Times
began publishing stories about improprieties at the lab and the university's Chao Cancer Center,
where it was housed.

Mr. Cicerone, who became chancellor last July, said in the letter that the university had "properly
investigated" the research violations at the time, but didn't follow up adequately. Two faculty
members resigned and several others were disciplined as a result of the four investigations,
conducted from 1995 to 1997, university officials said. They have not revealed the names of the
all the researchers involved, or their punishments.

Mr. Cicerone said the institution is reviewing whether it has enough staff members and resources
to insure compliance with its own and federal research policies.

CONGRESSMAN INTERVENES

Meanwhile, a lawyer for a former lab employee, who had filed a complaint about the lab with the
university in September 1996, maintains that university and federal authorities did not respond
aggressively enough.

Many of the major offenders "remained at the university with, essentially, a slap on the wrist,"
said Thomas E. Rockett III, the lawyer, in an interview last month.

Back in July, Mr. Rockett and his client, Gene Ioli, brought information about the laboratory to
their U.S. Representative, Christopher Cox, and urged him to enlist the Food and Drug
Administration and the National Institutes of Health to investigate. The Congressman determined
that the allegations warranted further attention, and passed them along.

Mr. Rockett said his client's interest was to insure that "appropriate remedial measures" were put
in place for the protection of future patients. He declined to say whether Mr. Ioli was planning to
file a federal "whistle blower" lawsuit, which could entitle him to a share of damages if it was
found that the university had violated laws concerning the use of federal funds.

Officials at the Irvine campus padlocked the cancer-center research lab, the Mixed Lymphocyte
Culture lab, in December 1996.

The closing came one year after an internal investigation turned up information about the
questionable donations, about improper billing of patients for experimental treatments - which
violates F.D.A. policy - and repeated examples of sloppy monitoring and treatment of patients.

The violations occurred in research the lab was doing on an experimental cancer therapy that
involved mixing disease-fighting white blood cells from cancer patients with cells from healthy
donors. Once a patient's cells began reacting to the foreign cells and became more active, doctors
would inject them into a cancerous tumor.

In some instances, however, researchers and clinicians working with the lab grew cells without
the necessary approvals from the university or the F.D.A., according to reports based on
university investigations. They also violated research protocols by failing to give physical
examinations or take magnetic-resonance images of patients after injecting them with the
activated white blood cells.

According to one report, researchers also "routinely" failed to report adverse reactions to the
treatments that resulted in deaths, as required by the university board that oversees research
involving human subjects.

"The program as a whole suffers from a lack of oversight which, at its worst, has resulted in very
serious violations of federal regulations, University policies, and standards for ethical conduct,"
an internal panel concluded in an April 1997 report.

A CONTROVERSIAL RESEARCHER

The report also focused on the activities of a researcher in the lab, John C. Hiserodt, who in 1994
was barred from receiving federal research funds for five years because of a series of incidents
involving research misconduct by him at the University of Pittsburgh.

As a debarred researcher, Dr. Hiserodt was not to have benefited from any programs or facilities
financed with federal funds. Several times in 1994 and 1995, Irvine officials had warned him to
avoid any contact with doctors or programs at the university's cancer center, which receives tens
of millions in federal funds annually.

As an investigation in April 1997 confirmed, Dr. Hiserodt nonetheless had participated and
collaborated on several research projects in the lab that were associated with federal funds.

In July 1996, Dr. Hiserodt also helped to arrange for an experimental therapy to be transported
and administered to an 8-year-old girl in Florida, who was dying of brain cancer. She had
previously received mixed-lymphocyte treatments at the cancer center. The treatment that was
transported was not a mixed-lymphocyte, but was based on a manipulation of only her own white
blood cells. Although the action was in response to urgent pleas from the girl's parents who say
the treatment helped extend her life - such transporting of experimental therapies across state
lines violates federal law.

Bill Parker, Irvine's associate executive vice-chancellor, said the university subsequently
informed the F.D.A. of the incident. He said he was not aware of any action taken at the time,
although he understands that the agency is investigating it now, possibly as a result of
Representative Cox's intervention.

He said that the university also had informed appropriate agencies within the Department of
Health and Human Services about the other instances of wrongdoing found by university
investigators, and that those agencies were satisfied with the university's response.

At the time the lab was closed and the investigations were concluded, the Irvine campus was
facing public criticism over a series of disclosures in 1995 about unethical practices in a
university fertility clinic. Officials made no public announcements about the cancer-center lab.

GIVING UP PATENT RIGHTS

Mr. Parker said he was not aware of any other current federal investigations of the university.
However, news reports have said that the National Institutes of Health is also investigating the
university.

Neither the F.D.A. nor the NH.H. would comment.

The Chronicle was unable to reach Dr. Hiserodt, who took a leave of absence during 1997 and
resigned January 1, 1998.

Mr. Cicerone said he could not explain why the university, over the past three years, never repaid
27 patients who were improperly billed for treatment, or why it never refunded the donations
improperly solicited from nine others.

Last month, Mr. Cicerone announced that he had asked officials at the University of California
system to give up the institution's rights to patent applications that rely on data from the illegal
treatment of the Florida girl. "We do not want any part of a patent that was obtained this way,"
said Mr. Cicerone.

If the university chooses not to patent an idea, the rights go to inventors. Mr. Cicerone said that
he realized that his gesture might end up benefiting Dr. Hiserodt, but that he was trying to make a
broader point: "We need money, but we don't need that kind of money."

Meyer Pharmaceuticals, a company in Newport Beach, Cal., now holds the rights to that patent,
along with several others that came out of the cancer center. Michael O'Neill, the company's
president, said Meyer did not expect to commercialize the brain-tumor therapies, preferring
instead to focus on treatments for pancreatic cancer.

Dr. Hiserodt holds a minor financial interest in the company, as do several other scientists who
still work at the university. He has been employed by the company for the past year, although as a
"precautionary measure," the company placed him on administrative leave last month while it
conducted an internal review of his activities at Meyer. So far, Mr. O'Neill said, the inquiry has
turned up no problems.