Pressures of stem cell studies

THE BALTIMORE SUN

Five years after his big breakthrough in stem cell research, the pressure is on John D. Gearhart to do it again.

It increased this month when South Korean scientists told the world they had cloned a human embryo to harvest its stem cells - prompting Gearhart's telephone to ring incessantly with calls for his expert opinion.

So it was that the 60-year-old coal miner's son sandwiched dozens of interviews with journalists between meetings in his Johns Hopkins University stem-cell laboratory and a trip to Capitol Hill to plead for broader stem cell research funding.

Then there was an ethics meeting, plus television appearances and e-mail to answer from patients with Parkinson's disease and other ailments who follow his research, desperately hoping it will lead to a cure.

"It is part of the life of an academic scientist," he said afterward, interrupting an outing with his 15-year-old for a cell-phone interview. "These are the things that we do."

Gearhart was one of the first two researchers to isolate and grow the most basic human stem cells. They're the raw material from which all other cells in the body can be coaxed: muscles, nerves, bones and organs. Theoretically, stem cells hold the secret to treatments for a wide variety of conditions ranging from Parkinson's to diabetes.

Scientists of decades past might spend an entire anonymous career sequencing a single gene. But the searing pace of biotechnology today has put top academic researchers like Gearhart under the gun to churn out breakthroughs at the same time they're handling familiar problems from the old days - such as scraping together grants to keep their labs running.

Thrown into politics

When Gearhart's original work was published in November 1998, the news catapulted him from anonymity into the limelight and the heart of a scientific, political and cultural controversy over the nature of life and when it begins.

Today, continuing that research is just one part of an equation that includes tempering the hopes of desperate patients, defining the ethical limits of science and answering critics who believe that stem cell research is destructive of life itself.

People "can't draw a line between stem cells and cloning and the human genome and Frankenstein out the other end," Gearhart says. "We've got to educate."

While critics press him to slow down his experiments - controversial because they use cells from aborted fetuses - patients demand that he turn his discoveries into marketable cures. Academic institutions competing for prestige and money increasingly demand the same.

Dr. Chi V. Dang, vice dean for research at Hopkins' medical school, isn't shy about it. To be sure, Gearhart's 1998 discovery was ground-breaking work. Now, Dang says, "Let's make the cells do something."

Hopkins has just opened a gleaming research building occupied largely by the Institute for Cell Engineering - an anonymous donor's $58.5 million bet on the work of Gearhart and colleagues. The visibility of Gearhart's lab has risen - literally - from the basement to a glass-encased upper floor. His title, C. Michael Armstrong Professor of Medicine, is courtesy of an endowment by Comcast Corp.'s chairman and university trustee. Across the street is a future business park that hopes to attract biotech firms exploiting Hopkins' discoveries.

"The responsibility and the expectations that build around you are enormous," Gearhart observes.

It was tragedy that set Gearhart on a path from Homer City, Pa., a tiny mining town 50 miles east of Pittsburgh. His father died on the operating table when Gearhart was 4, leaving the family destitute. Two years later, his mother sent Gearhart and his brother to Girard College in Philadelphia, a boarding school for fatherless children.

Girard controlled every aspect of their lives, right down to the knickers they wore on their trips home. The experience left Gearhart with a habit of rising early, a loner's personality and a propensity to rebel - however quietly - against control.

"You kind of walk against traffic sometimes," his brother, Donald, now a Philadelphia contractor, said of the experience. "You're just not afraid."

Gearhart's penchant for doing things his own way was evident in the lab at Cornell University, where he would sit for days, plotting a complex experiment before heading to the bench to try it. "Get away from the desk and do something," mentor Ross J. MacIntyre would tell him. Gearhart would only laugh and say, "In time, in time."

He had what scientists refer to as "good hands," which allowed him to do intricate fruit-fly dissections in experiments that other scientists were afraid to try. The skill carried over to the Philadelphia laboratory of Beatrice Mintz, where he isolated stem cells from tumors in mouse testes and coaxed those cells to morph into muscle.

Years afterward at Hopkins, Gearhart's interest in early genetic development led him to Down syndrome - but he grew frustrated. "Our information was telling us that events, the features you're seeing in Down syndrome, these were events that happen very early in [embryo development] that you couldn't get to," he said.

He thought he could figure it out if he were able to study human stem cells. But how to get them?

Ultimately, Gearhart proposed deriving stem cells from the tissue of fetuses that had been aborted for personal, nonscientific reasons.

Peter J. Donovan, a scientist whose early work with mouse stem cells foreshadowed Gearhart's, was initially skittish. But a visit to the lab as Gearhart discussed the ethics of the proposal with his co-workers convinced him that Gearhart cared deeply about the issues.

"John had ... thought it through very carefully," Donovan said, and Gearhart's arguments persuaded him that the potential benefits of the research made it worthwhile. "It wasn't just rushing to do it because he could."

After many failures, Gearhart got his stem cells to live and multiply - a major breakthrough. About a month after the results were published, the basement bench scientist from Homer City was testifying before a packed congressional hearing room.

Gearhart, a sandy-haired man with the kind but firm manner of a country doctor, was stunned by the attention - and by what he perceived as the ignorance of his audiences. He recalled telling one lawmaker that stem cells might help diabetics, at which point the politician asked a staffer, "Do we have any diabetics in our district?"

He got lessons from media handlers and accepted speaking engagements. His visibility escalated after President Bush - responding to pressure from abortion foes - restricted federal funding of embryonic stem cell research to lines that had already been developed as of August 2001. Gearhart was angry: Bush had made a unilateral decision to control science, something he felt was the responsibility of society at large.

'Responsible speaker'

Last year, Gearhart accepted at least 43 engagements away from Hopkins, risking the ire of some administrators and patients who preferred that he remain in the lab. He spent hours helping Dr. Leon R. Kass, chairman of the President's Council on Bioethics, edit factual errors out of a report on the state of stem cell research.

Although the two are on opposite sides in the embryonic stem cell debate, Kass said he trusts Gearhart implicitly. "He's been an extremely effective and responsible speaker for scientific research," Kass said.

There's a constant demand for new cures. One ailing patient punched him after a presentation, when Gearhart inadvertently devastated him by explaining human stem-cell treatments were years away. Another spit at him.

Gearhart's department chairman, Dr. Harold E. Fox, supports his speaking schedule, as has his wife of six years, Dr. Shannon Fisher, a Hopkins geneticist - though she's been urging him to cut back because of the stress.

C. Michael Armstrong, the businessman who endowed the chair Gearhart occupies, also believes it is a scientist's responsibility to educate. But, Armstrong said, "Do I expect him just to be out speechmaking? I certainly do not. I endowed outcome."

Meanwhile, Gearhart presses ahead with his lab's research, some of which has moved into early safety tests in primates. He doesn't feel old, but he knows the bulk of his career is behind him. He struggles with how to spend the time left. Job offers pour in. So do desperate e-mail messages from patients.

"You do have a bit of anxiety level about where this is all going in a political sense, in a personal sense," Gearhart said. "What do people think about what I'm doing? You want people to understand why you're doing it. You're not a lunatic."

John D. Gearhart

Born: April 3, 1943

Title: C. Michael Armstrong Professor of Medicine, the Johns Hopkins University

Hometown: Homer City, Pa.

Education: B.S., Penn State University; Ph.D., Cornell University

Family: Wife, Dr. Shannon Fisher, and daughters Sarah, 15, and Elizabeth, 22 months

Research: One of the first scientists to isolate and grow human embryonic stem cells.

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