Scientist Mixes Triumphs and Troubles

Yutaka Kikkawa will never forget the day in 1996 his star cancer researcher and protege, John C. Hiserodt, came up with a mix of cells in a test tube he thought could save the life of a small girl dying of a brain tumor.

“I still remember him showing me, saying, ‘See what happens? It works!’ ” said Kikkawa, chair of the department of pathology at UCI Medical Center in Orange and the man who hired and promoted Hiserodt despite knowing a federal investigation had determined the cancer specialist falsified research at a previous job.

“He was walking around the corridor, holding the results, in triumph and excitement. It was infectious.”

Just weeks later, Hiserodt sent the treated cells to a hospital in Miami to be injected into the brain of 8-year-old Jennifer Turken, allegedly breaking university regulations and a federal law.

In its brilliance, its impulsiveness and its recklessness, the tale adds up to pure Hiserodt, say current and former colleagues of the cancer specialist who never seems to be far from the cutting edge or from trouble.

Today, Hiserodt’s high-flying career has been brought low. He is the subject of a federal criminal and regulatory investigation into allegations that his research violated both federal and university rules.

The federal probe includes UCI’s own finding that Hiserodt shipped an unapproved cancer vaccine to the Florida girl who later died.

This week, the 43-year-old researcher was put on leave from the Newport Beach pharmaceuticals company he helped found.

“We are dealing with a very interesting, a very difficult individual,” said Massimo Trucco, a professor of pediatric immunology at the University of Pittsburgh who worked across the hall from Hiserodt for years at the university’s Cancer Institute.

“He’s a very bright guy, very driven, very passionate about what he does. But for reasons that are not completely clear to me, he always finds himself on the edge of what’s right. . . . He is motivated by an incredible drive to expand research, a noble character in doctors. But we have a system we all try to go by that requires following rules, seeking approvals, getting along with people. He always tries to bypass these roadblocks that he doesn’t recognize as valid in a democratic society.”

The current FDA investigation comes just four years after the National Institutes of Health barred him from participating in federally funded research for five years. The NIH debarment was punishment for its determination that Hiserodt falsified data on a grant application while a cancer researcher at the University of Pittsburgh Medical Center.

Hiserodt had been dismissed from his position in Pittsburgh in 1989, when an inquiry by the university came to similar conclusions.

But Hiserodt, who several years ago co-founded a medical research firm called Meyer Pharmaceuticals, is as unrepentant today as he was when the Pittsburgh scandal broke. In a brief telephone interview Friday from the Huntington Beach home where he lives with his wife and two children, he bemoaned the focus on the rules he broke rather than on his cancer research, which he called “very promising.”

“It was not a crime, it was not a deliberate alteration of protocol,” Hiserodt said of the alleged unauthorized research, which involved mixing healthy cells with cancerous cells to produce a treatment for tumors. “You do the best you can when you’re dealing with biological therapies.”

Hiserodt said the accusations against him at UC Irvine and at Pittsburgh were motivated by jealousy.

“When you’re playing with things--when you start talking about things like finding cures for cancer, it raises a lot of hackles on people who haven’t found it,” Hiserodt said. “And then you get attacked.”

Fiercely competitive, Hiserodt began his career with no hint of the controversy that was to overtake him later.

As a doctoral student in immunology and biochemistry in the late 1970s at UCI, Hiserodt developed a reputation as “a brilliant student, one of the best,” said Gale Granger, who mentored Hiserodt as a professor of immunology in the department of molecular biology at the university. Hiserodt had gotten a bachelor of science degree at UC San Diego and an M.D. in 1983 from the UCLA School of Medicine.

Years later it was in Granger’s laboratory that Hiserodt, Granger and others conducted the cancer cell studies that were the subject of the UCI inquiry.

In Pittsburgh, he was a rising star in the competitive world of cancer research. He had his own lab and the admiration of researchers around the country.

Devoted to his work, Hiserodt, who was single at the time, regularly toiled in his laboratory on Saturday nights and Sunday mornings, Trucco recalled.

Hiserodt’s troubles in Pittsburgh began in 1989, just three years after the then-35-year-old joined the research staff at the cancer institute.

At the time, he had the trust of Cancer Institute director Ronald Herberman, who had hired him. Hiserodt was considered one of an elite group of young researchers leading the exciting new field of cancer immunotherapy. The researchers focused on studying ways to enhance the body’s natural defenses against certain types of cancer.

He quickly landed three NIH grants--more than many researchers get in their entire career. He was a prolific contributor to scientific journals.

Hiserodt’s most notable contribution to his field came during those years, when he developed new technologies to identify and study natural killer cells, white blood cells with an innate ability to recognize and kill tumor cells.

Papers Hiserodt published on his findings “were very important contributions to the field of natural immunity,” said Robert H. Wiltrout, a senior investigator at the National Cancer Institute of the National Institutes of Health. “He was very definitely a rising star.”

Michael W. Olszowy, a postdoctoral student whose ex-wife was romantically involved with Hiserodt, accused him of falsifying research on a grant application. The allegations led to an investigation that for a time derailed Hiserodt’s promising career.

Olszowy, who had started in Hiserodt’s lab as a technician and later been accepted as a doctoral candidate, was working with Hiserodt to identify a special protein on the surface of natural killer cells, which, Hiserodt theorized, acted like a laser to direct the killer cell to a cancer cell and destroy it.

Hiserodt wrote in a $1-million federal grant application that he had found the protein, according to the Department of Health and Human Services findings against Hiserodt.

But Olszowy--whose own doctoral thesis rested on the existence of the protein--told federal officials he was unable to duplicate Hiserodt’s findings. He charged Hiserodt with altering the results of the research to make it appear the protein he was searching for existed.

The charges were taken up first by university officials and then by federal investigators, who found that Hiserodt had falsified an entire notebook, presenting one he wrote over the Christmas 1989 vacation, when he was already under investigation by the university, as one assembled over a period of years. A federal inquiry completed in 1994 of the charges also found that Hiserodt had labeled a rat specimen as from a human, had deliberately altered data throughout the grant application, and had consistently lied to federal investigators.

In a strongly worded report barring Hiserodt from participating in federally funded research for five years, the federal investigators wrote that Hiserodt’s “dishonest behavior was not limited to an isolated incident; rather, he engaged in an unremitting pattern of behavior evidencing indifference to the truth.”

“He was a smart guy and he was very driven and a very hard worker and very insightful and he had a lot of very good scientific ideas,” Wiltrout said. “But clearly at Pittsburgh he ran afoul of the system.”

Well before the federal report was issued, however, he was dismissed from the university in 1989. But he didn’t fade away. He taught himself a new field--forensic pathology, taking a job with the Allegheny County coroner’s office as a coroner and expert witness in criminal trials.

“It was devastating, he went through a lot of emotional hell,” said Aurelia Koros, an assistant research professor at the University of Pittsburgh Graduate School of Public Health. As a researcher at the cancer institute in the 1980s, Koros became a close friend of Hiserodt, and collaborated closely with him on several research projects, she said.

Hiserodt is “bright, he’s impulsive, maybe somewhat indiscreet,” Koros said. “There were jealousies.”

Several years later, when the furor over his controversial career at the University of Pittsburgh had died down, Hiserodt applied for a job at UC Irvine, answering an ad in trade journals.

At UCI, Kikkawa and other pathologists were impressed by Hiserodt despite his past. Alone among the eight applicants for the job, Hiserodt had written or co-written more than 90 articles in prestigious scientific journals and done seminal work in breeding cancer-fighting cells. UCI offered Hiserodt a job.

When the NIH report was released a year later, Hiserodt was already on staff at UCI, excelling as a researcher, a teacher and a forensic pathologist in the small pathology department Kikkawa was trying so hard to build. Skeptical of the NIH findings, Kikkawa conducted his own inquiry into the matter. Eventually he and senior university officials gave Hiserodt a second chance.

By shipping the cancer vaccine to Turken last year, Hiserodt squandered those opportunities, colleagues say.

Hiserodt left UCI in 1997, as the university was conducting its own probe of his activities.

“As a researcher he broke the rules, and the federal government holds us to certain standards,” said Michael Brodsky, professor of medicine at UCI and chair of the faculty committee whose inquiry into Hiserodt’s research preceded the federal probe. The inquiry found that Hiserodt may have violated the ban on his involvement in any federally funded research and may have conducted unauthorized experiments in his search for a cure for cancer.

“Looking at what he did [in sending the vaccine to Turken], I can understand. But at the same time, from the position I’m in, of looking out for the benefit of the institution and of federal regulatory agencies, he created a nightmare. In our work you can’t just walk around doing whatever you want,” Brodsky added.