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Harvard biologist lured to La Jolla

November 19, 2002
By Bruce Lieberman

Dr. Evan Snyder, one of the country's most prominent researchers in regenerative medicine, will join the Burnham Institute in La Jolla Dec. 1 to direct a kind of Manhattan Project in human stem-cell research.

The Burnham's new Stem Cell and Regeneration program will seek answers to some of human biology's most fundamental questions, such as how cells and organs develop as well as finding new treatments for disease.

"This is a hot topic," said Stuart Lipton, director of Burnham's Del E. Webb Center for Neurosciences and Aging and a vocal advocate for stem-cell research. "There's a lot of very basic science that we do and we want to move very quickly," he said.

Snyder, who is leaving Harvard Medical School after 22 years, was enticed by the Burnham's ambitious program to bring together top minds to tackle stem-cell research, an emerging and controversial science.

"They approached me mostly by saying this was a very serious, multidisciplinary effort that they were really committed to," he said.

After working for years as one of a handful of stem-cell biologists at Harvard, Snyder said he had grown frustrated by the university's hesitation to embrace the science as an important, albeit fledgling, area of study.

"It's an old institution, and it's very slow to change and put programs together," he said. "I think they were kind of sitting out to see whether this stem-cell thing was going to go anywhere, and I was just getting very, very impatient to try to really get the whole stem-cell biology into hyperdrive and really push the biology."

Early in his career as a pediatrician in Boston, Snyder was astounded at how infants with brain injuries often recovered so well, and wondered why.

That question and others inspired Snyder's career in regenerative medicine, specifically the study of specialized cells in the brain called neural stem cells.

In 1998, Snyder was the first to announce he had isolated neural stem cells from a single sample of human fetal tissue, grown them in culture and then implanted them in the brains of mice.

The procedure demonstrated that transplanted cells responded to normal cues in the animal's brain, replaced diseased brain cells and brought in new genes. Since then, he has successfully transplanted human neural stem cells into the brains of monkeys.

Scientists hope to use neural and other stem cells to replace tissue in a variety of diseases, including heart, Parkinson's, Alzheimer's and Lou Gehrig's, multiple sclerosis, diabetes and cancer, and in brain and spinal-cord injuries.

Stem cells taken from embryos are believed to be master cells that can grow into any type of cell in the body. In fetuses and adults, stem cells are thought to be master cells for a particular organ.

Snyder has studied the latter. Using neural stem cells derived from a single sample of fetal tissue, he hopes to show they can be transplanted into patients with a variety of brain disorders and diseases to replace abnormal or damaged cells. He has likened the procedure to re-seeding an old or damaged lawn.

Standard fetal tissue treatments for people with brain disease, in which material from several aborted fetuses is transplanted into the patient, remains logistically difficult and ethically controversial, he said.

Embryonic stem-cell research, meanwhile, also has been the subject of great debate because scientists must destroy an embryo to extract its stem cells.

President Bush and other foes of abortion oppose embryonic stem-cell research, and this summer the U.S. Senate considered debating a bill to criminalize the work. The bill stalled in June after Democratic and Republican leaders could not agree on how to bring the measure to the floor for a vote.

California Gov. Gray Davis, meanwhile, signed a new law Sept. 22 that affirms the state's support of embryonic stem-cell research. That is another reason Snyder was encouraged to move to San Diego.

"I think the new law may go a long way toward making California a place that almost becomes a magnet for stem-cell biologists," he said.

Larry Goldstein, a professor of pharmacology at the University of California San Diego Department of Cellular and Molecular Medicine who lobbied for the state law, said the welcoming political climate could also bring research funding.

"If you're trying to attract private investment, it's more likely to come to a state where (stem-cell research) is legal than in a state where there's uncertainty," Goldstein said.

Snyder is the latest of several stem-cell biologists to join Burnham in recent years.

Lipton, the director of Burnham's center for neurosciences and aging who studied at Harvard with Snyder and worked with him at Children's Hospital in Boston, made the move three years ago.

Mark Mercola, who is heading research into how stem cells can be used to treat cardiac disease, came to Burnham from Harvard Aug. 1.

And Alexey Terskikh, studying the genes responsible for stem-cell replication in blood and the brain, also joined Burnham last summer after postdoctoral training with Irving Weissman, a prominent stem-cell biologist at Stanford University.

Many of Snyder's colleagues, including Lipton and Fred Gage at the Salk Institute for Biological Studies in La Jolla, are deeply involved in stem-cell research. Others are active in the San Francisco Bay Area and at the California Institute of Technology in Pasadena.

"I was finding many, many more colleagues and collaborators here than I certainly was finding in Boston," Snyder said.

At the Burnham Institute, Snyder said he hopes to advance stem-cell biology to better understand how cells in the body develop, and how they go wrong.

"The stem cell is essentially the building block," Snyder said. "It's the most primordial cell of the body or of any one organ, and it's part of a mechanism that nature has used to put organs together."

Certain degenerative diseases, he said, may actually be diseases of stem cells.

"If we understand that, we can then try to rejump-start development where it has either gone wrong or needs to be invoked to fix something that has been damaged."

Snyder's observations of newborn brain damage and recovery runs in opposition to classical biology, which views the brain's development as a rigid process that cannot adapt well to injury.

Stem cells in the young, developing brain, however, may be fueling recovery in ways that scientists do not yet fully understand, he said.

"There's some kind of plasticity in the human brain, and now it's time to figure out what's going on there," he said.

Snyder, a 1980 graduate of the University of Pennsylvania's medical school, has spent his entire professional life at Harvard, where he works as a pediatrician with a specialty in neonatology, or intensive care for newborns.

Snyder studied psychology as an undergraduate, and he soon became interested in brain physiology.

"I kept on asking, 'How does this work, and how does that work, and how does that work,' and before you knew it I was looking at a single nerve cell in a dish," he said.

Snyder and his, wife, Angela Vieira, recently bought a home in La Jolla. Vieira now works as the general counsel for Children's Hospital in San Diego.

© Copyright 2002 Union-Tribune Publishing Co