FDA Inquiry Targets Ex-Researcher at UCI

A former UC Irvine cancer specialist who answered a father’s pleas to try to save his dying daughter in 1996 now finds himself the target of a criminal investigation by the Food and Drug Administration.

John C. Hiserodt sent an unapproved cancer-fighting drug to Miami Children’s Hospital as a treatment aimed at destroying a brain tumor in the Florida girl, according to an internal UCI investigation.

Now the FDA is looking into reports that Hiserodt may have violated federal restrictions on using experimental treatments on cancer patients and on shipping an unauthorized pharmaceutical to another state, a university official who was interviewed by the FDA said Monday.

The circumstances prompted a UCI inquiry in 1996, after which Hiserodt resigned.

Hiserodt could not be reached Monday for comment.

After the girl’s death, her father wrote a letter to a UCI Medical Center director calling questions about Hiserodt’s actions “offensive and reprehensible.” He said he begged Hiserodt to intervene, and that the experimental treatment Hiserodt shipped to Miami actually shrank her tumor. But not enough. She died a few days later, on Sept. 7, 1996.

“Is it possible that your institution has devolved to the point where it has completely lost sight that its reason for existence is to help people?” the father asked in his Dec. 13, 1996, letter to Dr. Yutaka Kikkawa, Hiserodt’s supervisor at the UCI Medical Center.

The letter was obtained by The Times under the Freedom of Information Act.

Dr. Frank Meyskens, director of UCI’s Choa Family Comprehensive Cancer Center, said Monday that Hiserodt was in a difficult situation--one cancer researchers must face on occasion--but said it doesn’t excuse the use of an unapproved experimental drug on a patient.

“Of course, it’s all a very emotional topic. The tough problem they have is dealing with the life-and-death situation with this little girl and a physician doing something he felt was useful, but was against the law,” Meyskens said. “But these rules and regulations are set up for a reason--to protect patients.”

Meyskens said he doubts the current inquiries will threaten UCI’s federal funding for cancer research, which tops $35 million a year. But, he said, “it makes you nervous.”

Meyskens said he was interviewed by an FDA criminal investigator shortly after Thanksgiving and was told Hiserodt was the target of the federal probe.

The incident was the focus of an internal UCI inquiry, which found that Hiserodt and other UCI cancer researchers conducted unauthorized cancer treatment experiments on patients in the mid-1990s.

The inquiry also determined that Hiserodt may have violated a National Institutes of Health sanction prohibiting him from participating in federally funded research. The ban was imposed in March 1994, after the agency determined Hiserodt fabricated research data in a federal grant application while at the University of Pittsburgh Medical Center.

Along with the criminal probe, the FDA and the NIH have ongoing regulatory investigations into the unauthorized drug tests and possible violations of Hiserodt’s research ban.

University officials said Hiserodt ignored repeated warning letters while on staff, including two letters specifically banning him from being associated with federally funded research at the cancer center.

Meyskens said Hiserodt and other researchers at the center are repeatedly reminded about the federal laws and university guidelines restricting clinical drug experiments, especially those involving patients. Seeking FDA approval on an experimental cancer treatment is a very long, painstaking process that requires meticulous record-keeping and oversight, he said.

“I think that Dr. Hiserodt knew all this stuff, but he chose to ignore it,” Meyskens said. “Certainly, this day and age, people doing clinical research are very sensitized to these issues.”

Ultimately, after a whistle-blower alerted the university about the drug-test violations, UCI officials padlocked the laboratory where Hiserodt conducted his research. Hiserodt later took a leave of absence and resigned from the university in 1997. The university sanctioned two other researchers by putting letters of censure in their personnel files.

“We took all the appropriate steps,” said Frederic Y.M. Wan, UCI’s vice chancellor for research.

Wan said the sanctions against the researchers were adequate, especially since their research was shut down. No action was taken against Hiserodt because he had resigned, Wan said.

Meyskens said FDA investigators are seeking detailed information about Hiserodt’s laboratory work and general background information about his career.

FDA spokeswoman Lenore Geld said the agency cannot confirm or deny the existence of an investigation. However, Geld said that the agency has criminal investigators and that transporting unapproved drugs across state lines is a crime.

UCI biochemist Gale Granger, who supervised Hiserodt at the now-defunct research lab, said the incident involving the cancer-stricken Florida girl was the only major problem investigators uncovered during their six-month probe.

“Most of it fell by the wayside,” Granger said Monday.

Hiserodt, who had been a UCI graduate student studying under Granger, now works for Meyer Pharmaceuticals LLC, which has offices in Newport Beach and Anaheim.

In 1996, Meyer Pharmaceuticals signed a licensing agreement with UCI to use cancer-fighting “mixed lymphocyte culture technology” developed by Granger, company President Michael F. O’Neill said in a letter to The Times on Monday.

The company also helped sponsor two research projects at UCI. The first provided $250,000 to Granger’s laboratory from March 1997-98. The second provided $151,000 in 1997 to the laboratory of UCI cancer researcher Dr. James Thompson, who also worked with Hiserodt at UCI.

Currently, the company does not sponsor research at UCI.

Meyer Pharmaceutical recently received FDA approval to conduct trials in the treatment of pancreatic cancer, the fifth leading cause of cancer deaths in the United States, O’Neill said.