UCI Cancer Lab Research Investigated

Federal health authorities are investigating past research practices at the UC Irvine Cancer Center laboratory, where a doctor barred from handling federally funded research may have violated the ban.

The inquiry follows a 1997 internal UCI investigation that uncovered violations of federal and university restrictions on experimental drugs used on cancer patients.

In one case, a cancer-stricken girl with a brain tumor received an unauthorized experimental treatment developed by the cancer center, the university inquiry determined. She later died at a Miami hospital, the report stated.

UCI’s internal preliminary inquiry led to reprimands last year against three researchers but not to a formal investigation. At the time, the U.S. National Institutes of Health concurred with the university’s findings and determined the school took “appropriate corrective action,” federal records show.

But U.S. Rep. Christopher Cox (R-Newport Beach) asked the U.S. Department of Health and Human Services to revisit the matter after he received a letter in June from a whistle-blower at the cancer center.

The whistle-blower, Gene Ioli, former manager of the center’s Immunotherapy Laboratory, filed his initial complaint with the university in 1996, prompting the first investigation. Ioli’s attorney, in the letter sent to Cox, complained that the university’s probe amounted to a mere “slap on the wrist” and was rubber-stamped by federal health officials.

“If the allegations have substance, they deserve to be looked at,” Cox said Thursday. “I’m confident that both the Department of Health and Human Service and the university, under its new management, will deal with it appropriately.”

Leadership at UCI changed last summer when Ralph J. Cicerone took over as chancellor from Laurel L. Wilkening, who stepped down.

Thomas Cesario, dean of the UCI College of Medicine, confirmed that the Food and Drug Administration is conducting an investigation but said the university is not the focus of the inquiry.

Cesario said the FDA has asked the university not to release any information about the matter. He said that UCI is “cooperating fully.”

“I feel that the university has acted very responsibly through all of this. We’re very, very careful with research in general,” Cesario said. “I’m confident, in this case, we have done what’s right.”

The renewed investigation comes in the wake of UCI’s national scandal at its now-defunct fertility clinic, where doctors were accused of ethical misconduct that included transplanting patients’ fertilized eggs without consent in other women.

School officials are confident the cancer center will remain unscathed in the current investigation.

Cox said FDA investigators launched their probe during the summer after he forwarded Ioli’s letter alleging the misuse of experimental cancer drugs at the center. FDA spokeswoman Lenore Geld said the agency cannot confirm or deny the existence of an investigation.

Officials from the National Institutes of Health also opened an inquiry because they were “concerned about what this all adds up to,” Cox said. NIH’s interest includes John Hiserodt, a cancer researcher and former staff pathologist at the UCI Medical Center, according to records obtained by The Times.

In 1994, federal health officials found that Hiserodt, then at the University of Pittsburgh, had engaged in “scientific misconduct” for fabricating cancer research data in an application for a federal grant, according to the Federal Register.

They banned him from receiving federal grant money for five years. Yet, while working at the UCI Cancer Center, he may have assisted in federally funded cancer research, the university’s internal investigation found.

“How could they allow this?” said Thomas Rockett, the Newport Beach attorney representing Ioli. “This is an important inquiry. It addresses the integrity and oversight of human research.”

Hiserodt could not be reached for comment Thursday. Cesario said the researcher left UCI a year ago.

Rockett contends that his client was improperly laid off from the cancer center laboratory after alerting university officials about the questionable research practices. Cesario said he didn’t know the circumstances, and other UCI officials weren’t available for comment.

Cesario said Hiserodt was already on staff at the UCI Medical Center when the federal research ban was imposed on him in 1994. University officials did “everything possible” to assure that Hiserodt did not violate the ban, Cesario said. The UCI facility is a federally designated cancer center, which means it was approved to receive federal grants.

UCI investigated 11 allegations of improper research involving cancer patients, according to its April 1997 preliminary inquiry. The Times obtained a copy of the report through the federal Freedom of Information Act.

The research, according to the report, involved the use of mixed lymphocyte cultures--white blood cells from patients--used to treat cancer.

“We believe that the program as a whole suffers from lack of oversight which, at its worst, has resulted in very serious violations of federal regulations, university policies and standards for ethical conduct,” the report concluded.

Among the findings of the preliminary inquiry:

* Researchers at the cancer center’s laboratory produced an experimental cancer treatment that was injected into a pediatric brain tumor patient at Miami Children’s Hospital in 1997 without authorization from the FDA or the university. The treatment reportedly was requested by the child’s father as a last-ditch effort to save her life, the report stated. However, the unauthorized treatment was transported across state lines, a violation of federal law.

* The treatment for the Florida cancer patient included an expired batch of Interleukin-2, a “major infraction” of FDA regulations.

* Hiserodt’s work at the cancer center laboratory may have violated the terms of the federal research ban imposed, and was worthy of further investigation. Three researchers knew of the restrictions on Hiserodt yet continued to collaborate with him.

Frederic Y.M. Yan, vice chancellor for research, told NIH authorities in an August 1997 letter that a formal investigation was not required because the researchers implicated agreed to the disciplinary actions imposed by the university, records show.

Cesario said the university acted swiftly when the allegations arose, and their actions were endorsed by federal health officials at the time.

“When you act responsibly and take care of a problem, I think you should be given credit,” he said.