Hutch leader Lee Hartwell guided center's ride to top, will retire next June

When Lee Hartwell was hired to lead the Fred Hutchinson Cancer Research Center in 1997, some eyebrows shot up.

The Hutch built its reputation by pioneering bone-marrow transplants for desperately ill cancer patients. All previous directors were medical doctors.

Hartwell studied yeast.

"My first reaction was: Hmmmmm. I'm not sure this is a good fit," recalled Ken Stuart, president of the Seattle Biomedical Research Institute.

But just as Hartwell's Nobel-prize-winning research on simple cells helped revolutionize the understanding of human malignancies, his focus on fundamentals helped the Hutch sharpen its strategy in the battle against cancer, Stuart said.

"You can see the fruits of his leadership in the phenomenal growth the Hutch has undergone."

In Hartwell's 12 years at the Hutch, its budget has more than doubled and the staff has grown by 500, to 2,600. The Hutch now pulls in more money from the National Institutes of Health than any other independent research center.

Hartwell, 69, announced recently he will retire next June.

His planned departure comes at a time when the Hutch generally is acknowledged as the nation's premier basic cancer-research institution.

But the organization is approaching a crossroads: Will it continue to stress basic research or shift toward more "translational" studies aimed at moving science out of the laboratory and into the clinic?

Federal research dollars are migrating to projects with near-term payoff for patients, said Dr. Richard Klausner, former director of the National Cancer Institute. "It's a very profound choice the Hutch will face in the future."

Broad growth

During Hartwell's tenure, the Hutch not only grew in size but scope.

Once known primarily for transplantation, the Hutch today is a research leader in early detection of cancer — a passion of Hartwell's — and efforts to harness the immune system to fight the disease.

Scientists from the Hutch are key players in the search for an AIDS vaccine. Others coordinated a landmark study that showed hormone-replacement therapy can raise women's risks of heart disease, stroke and breast cancer.

"It's a much broader institution than it was when Lee started," said Leroy Hood, leader of Seattle's Institute for Systems Biology.

The Hutch also weathered its biggest crisis with Hartwell at the helm.

In 2001, The Seattle Times reported that scientists with a financial stake in two experimental cancer treatments tested in the 1980s and early 1990s failed to fully warn patients of the risks. Most patients who participated in the trials died, including some who had a good chance of survival had they received more conventional treatments.

Families of several patients sued. The Food and Drug Administration temporarily halted some other, ongoing experiments, citing "systemic problems" in the Hutch's approach to clinical trials.

Hartwell vigorously defended the center, saying patients were fully briefed and researchers did not stand to profit. But he also convened an advisory panel, and accepted its recommendation to strengthen patient safeguards and adopt one of the nation's toughest conflict-of-interest rules.

A jury concluded the center was not negligent in most of the deaths but awarded more than $1 million to the family of a man whose donor bone marrow was lost. The court dismissed the conflict-of-interest claims.

The center settled out of court on a related case, in which a judge ruled a patient had not been told a critical fact about the experiment.

The controversy rattled the Hutch and research centers across the country, and led to stronger policies.

"We all looked at this and said: If a place as reputable as the Fred Hutchinson Cancer Research Center could get into this trouble, we had better bend over backward to avoid any possible appearance of conflict of interest," said Dr. John Mendelsohn, director of M.D. Anderson Cancer Center in Houston.

Better regulated

Today, Hartwell agrees clinical trials are better regulated, although he maintains there was nothing wrong with the Hutch's approach at the time.

Hartwell himself set a high standard on conflicts of interest.

When he took over at the Hutch, he donated $3 million worth of shares in a local biotech to the institution.

If the storm over clinical trials was a low point, the Hutch soared later in 2001 when Hartwell was awarded the Nobel Prize in Medicine or Physiology for research on cell division in yeast, conducted largely at the University of Washington.

Though seemingly remote from human biology, the lessons learned from cell replication in yeast apply directly to cancer and other disorders where that replication goes awry.

Hartwell's appointment at the Hutch reflected a growing understanding that the basic processes in living things are more similar than realized, Klausner said.

"In many ways," Klausner said, "it freed cancer research to go beyond traditional boundaries, and Lee was a leader in that."

Experts collaborate

Hartwell encouraged Hutch scientists to forge collaborations with experts from many fields. The HIV Vaccine Trials Network led by Hutch researchers includes experts in 27 cities worldwide.

Such collaborations are increasingly important in medical research. And while Hartwell carries his Nobel Prize with modesty, there's little doubt it helps him pull in participants, Mendelsohn said. "If Lee Hartwell calls any scientist in the country, they will call him right back."

Hartwell's cachet also helped extend the Hutch's reach abroad. He conceived the Pacific Health Summit, now held annually in Seattle. Originally focused on health issues of Pacific nations, the conference has grown into the "Davos of global health," attracting the top players in the battle against tuberculosis, malaria, flu and other scourges.

Hartwell likens the Hutch to an artists cooperative, where brilliant individuals pursue their passions and bring in federal grants to keep the work going. His job, he said, "is to make sure everybody's got enough paint and brushes."

But Hartwell's priorities have shaped the organization, particularly its growing focus on early detection.

"For decades, we've been curing almost all cancers that are detected early, with surgery and radiation," Hartwell said. "So if you can just detect all cancer early, then the game would be over."

Hartwell preaches this message every time he speaks to the public or scientists. But investment in early detection has been small compared with the money spent on the development of more profitable drugs.

The Hutch is helping coordinate an international project to screen and analyze thousands of blood proteins, looking for those whose concentrations shift when cancer begins. One group discovered DNA changes that presage a type of esophageal cancer, and which now provide regular screening for people at risk.

It's painstaking work, and recent questions about the value of the PSA test for detecting prostate cancer show how difficult it can be.

"I think all of us are frustrated by the slowness of progress," Hartwell said.

Entrepreneur

An entrepreneur himself, Hartwell beefed up the Hutch's efforts to spin off technology into commercial ventures. Results have been mixed, with about 20 licensing agreements a year, but few that attract major financial backing.

One that did grew out of MacArthur "genius" grant winner Mark Roth's studies of suspended animation. The company pulled in more than $10 million in venture capital and is working on ways to induce a kind of protective hibernation in patients with trauma or heart attacks.

Hartwell's affinity for basic science alienated some of the center's more hands-on physicians. Dr. Rainer Storb, a founding scientist and head of transplantation biology, said Hartwell showed little interest in his group's work.

"Even with early detection, cancers are going to occur, and we need to develop ways to actually help these people," Storb said.

Alliance for patients

Cancer patients have reaped benefits from the Hutch's increased collaborations with the University of Washington and Seattle Children's hospital through the Seattle Cancer Care Alliance, said Dr. Paul Ramsey, dean of the University of Washington Medical School. The idea for the alliance predated Hartwell, but he helped make it happen.

Today, patients can participate in clinical trials and receive care from UW surgeons, Hutch experts in leukemia and lymphoma, or top pediatricians — all in the same building, Ramsey said.

After he steps down as director, Hartwell will continue working with a partnership he helped found to accelerate clinical trials on promising biomarkers.

His biggest concern for the Hutch's future is financial.

"The institution has always lived from hand to mouth," he said. The Hutch cut more than 80 jobs this year, as donations and the value of its investments dropped.

Federal grants continue to roll in, but it would be nice to have the cushion of an endowment, Hartwell said.

"That's certainly something the institution needs."

Sandi Doughton: 206-464-2491 or sdoughton@seattletimes.com