Stem Cell Central?

With its concentration of scientific know-how, San Diego looks to become world headquarters for stem cell research


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THE REVOLUTION IS AT HAND. It’s a medically mind-boggling transformation, where cells swap nuclei, organs regenerate and brain damage is repaired. It’s not science fiction—it’s stem cell research. And San Diego could become the world center for this scientific revolution.

Passage of Proposition 71 last November brought $3 billion in state funding for stem cell research over the next decade— nearly $300 million a year. That money will effect change in California’s scientific centers—San Diego, the San Francisco Bay Area and south San Francisco—profoundly. It will likely bring world-renowned scientific talent to all three, but especially San Diego. And not just because of our sunshine.

San Diego is unique—unlike biotech centers in the Bay Area or the Cambridge/Boston region—because it’s intellectually and geographically a life-sciences mecca. It’s one instance where crowding has benefits. We have the most densely packed cluster of biotech companies in the nation, and more than 500 life-science companies in the region, according to the industry group Biocom.

San Diego is home to more than a dozen academic research institutes. Several major ones—Scripps Research Institute, the Salk Institute, the Burnham Institute and the University of California San Diego—are within a 5-mile radius. In June, a study released by the Milken Institute, a nonprofit economic think tank in Santa Monica, ranked San Diego the number-one biotechnology cluster in the country.

This density creates a scientific paradise, an interactive intellectual environment that fosters easy collaboration among researchers. Last year, Edward Holmes, head of UCSD’s School of Medicine and vice chancellor for health sciences at the university, told Forbes Magazine, “There’s a spirit you just don’t find on the East Coast. Out here, the sin is not to try. People want to do bold experiments here.”

San Diego is already a medical research powerhouse, having received $750 million in National Institutes of Health (NIH) grants last year alone. Throughout the country, only a small percentage of working scientists at a limited number of institutes conduct stem cell research —and a large concentration of them work in San Diego. The Burnham Institute may have been at it the longest. Twenty years ago, scientists at Burnham studied developmental biology—how a developing fetus comes together —because they found that many cancers arise from embryonic-like cells. Seven years ago, Burnham established the Stem Cell Biology and Regeneration Program and began recruiting scientists from Harvard, Stanford and Europe. The institute’s scientists have taught researchers nationwide how to cultivate and manipulate human stem cells. Currently, Burnham has about 100 people working on stem cell technology—the largest effort in the state and one of the largest in the nation, says John Reed, the institute’s president and CEO.

Other local institutions also are involved with stem cell research. Using stem cells, scientists at Scripps last year were able to form new blood vessels in the damaged retinas of mice. In December, Sylvia Evans, an associate adjunct professor of medicine at UCSD, published new information about mice cardiac stem cells in the journal Cell.

Because of research under way, scientists here expect the region will receive a substantial portion of Proposition 71 funding. That money will, in turn, provide a golden recruitment opportunity.

“That was one of the implicit goals of the initiative,” says Reed. “Bring as many great minds to California as we can, and have the fruits of their intellectual labors.” San Diego has the critical mass to be the most attractive place for these minds—the more researchers and institutions there are, the more tend to follow. “It self-amplifies,” says Reed. “It’s all about interaction, and it’s not something you can easily duplicate over the Web.”

TOP SCIENTISTS working with stem cells first became interested in San Diego in September 2002, when the state legislature passed a bill officially allowing therapeutic cloning in California, which then-Governor Gray Davis signed into law.

The state became a safe haven for therapeutic cloning, also known as somatic-cell nuclear transfer, which creates a stem cell (not a human, as many believe). This happens when scientists take the nucleus from a cell in an adult’s body and put it into an egg whose nucleus has been removed. The egg then takes on the adult cell’s genetic characteristics.

Stem cells can also be harvested from human embryos, which early in development are called blastocysts, hollow spheres of cells with a bunch of other cells inside. Those inner cells—the stem cells—are capable of becoming any of the cells necessary to form a human being. Stem cells are usually taken from an embryo at the 32- cell stage, about five days old. To develop a “line” of stem cells, scientists separate the inner cells from the blastocyst and culture them on a plate of “feeder” cells.

Stem-cell harvesting has been a thorny issue for the Bush administration, which has ethical problems with the destruction of the 32-cell embryo (the embryos used for scientific research are those slated for destruction by in-vitro fertilization clinics). The president limited federal funding of stem cell research to lines of cells created before August 9, 2001; today, only about 11 lines are considered usable.

State Senator Deborah Ortiz, a Democrat from Sacramento, sponsored the therapeutic cloning resolution that passed in 2002, but a billion-dollar bond measure to fund the research was blocked. For many scientists in the field, that resolution, even without financial teeth, tipped the scales in California—and San Diego’s—favor.

“I moved out here two years ago because California is a better place to do this kind of research,” says Mark Mercola, a developmental biologist who left his position at Harvard Medical School after 20 years to join the Burnham Institute. “But it was the entrepreneurial spirit that exists in La Jolla that got me here. It’s easier here than in Boston to forge collaborations among scientists, and easier to move projects from academia to biotech.” Larry Goldstein, a professor of cellular and molecular medicine at UCSD who campaigned relentlessly for Proposition 71, says the “collegial, interdisciplinary tone” in the local scientific community is “great for getting things done. I’ve had collaborations with people all over La Jolla —physical chemists, marine biochemists, technicians, philosophers, engineers. You don’t have that in many places.”

Evan Snyder, director of Burnham’s stem cell and regeneration program, also came from Harvard to San Diego two years ago. Like Mercola, he found the passage of Ortiz’ resolution a turning point.

“It created an inviting legal environment so that data, rather than politics, could dictate what your next step would be,” says Snyder. “But it also signaled the scientific community that it was time to step up to the plate and start creating a Manhattan Project–style effort to support regenerative medicine,” he says, referring to the United States project that developed the atomic bomb. “Proposition 71 gave fuel to the effort.”

Snyder says scientists at the top of their game are competitive by nature. But San Diego is refreshingly different, he believes. “I’ve found there is this notion that everyone succeeds if the team succeeds. I find, in fact, that the culture here demands a collaborative atmosphere. Even while we were all campaigning for Proposition 71, we were looking for ways we could synergize our efforts among research institutions.”

The community is betting on a scientific migration to this region, by top scientists as well as up-and-coming researchers. Mercola says it’s likely to resemble what happened in the late 1970s when, for a while, the Massachusetts city of Cambridge banned recombinant DNA work out of concern for potential misuse.

“Boston lost a lot of young minds to the UC system,” he says. “Some went back, but many stayed. We may benefit in the same way.”

Joe Panetta, president and CEO of San Diego’s Biocom, says the trade association is “actively discussing going after at least five big-name scientists from around the world. We asked research institutes here to come up with their wish lists,” he says.

UCSD chancellor Marye Anne Fox says the university also is actively courting scientists around the country, as it usually does, but Proposition 71 has “reinvigorated” that effort.

Just in terms of economics, many scientists will have to come. “The ones who do basic research survive on grant funding,” says Panetta. “They are going to follow the money.” The NIH spent $25 million in 2003 for stem cell research (2004 figures were not available).

Many states are trying to hold on to their sought-after scientific talent with efforts to fund stem cell research. In January, New Jersey’s acting governor, Richard J. Codey, proposed spending $380 million on it; construction of the Stem Cell Institute of New Jersey is slated to begin this summer. Illinois is considering a tax on elective cosmetic surgery to raise millions for stem cell research. And Wisconsin’s governor has pledged $375 million for a biomedical research institute. Massachusetts, New York, New Hampshire and Washington states all are likely to consider bills favorable to stem cell research this year.

It will be hard, however, to compete with San Diego. In addition to this collaborative scientific atmosphere, there’s the weather. “If I’m trying to recruit someone from the frigid northeast,” says UCSD’s Goldstein, “I bring them here in January.”

ULTIMATELY, THE IMPETUS for the money and minds is the hope that today’s basic research will become tomorrow’s life-saving therapies. New lines of stem cells for research are especially important now. A study published in January in the journal Nature Medicine says all stem cell lines available for federally funded research in the United States are contaminated.

 Proposition 71 money gives scientists the freedom to use and develop new lines of stem cells, although it’s too early to know what therapies are likely to come out of the research. Much depends on where the money goes. The Independent Citizens Oversight Committee for the new California Institute of Regenerative Medicine hasn’t (at press time) assembled a committee to oversee grant funding. Four of its 29 members are San Diegans. It’s not yet known where the institute’s headquarters will be.

But researchers in San Diego were working with stem cells before Proposition 71 existed—using NIH money and money acquired through private fundraising. Scientists have been experimenting with ways to coax stem cells into producing insulin and dopamine, which could eventually treat Type I diabetes and Parkinson’s disease, respectively. These are considered two of the better candidates for stem cell therapies, because they require just one kind of cell to solve the problem and can be introduced anywhere in the body that has access to the blood supply.

“The new cells don’t have to be interwoven into what would be their native structure—the pancreas or the brain, in these cases. It doesn’t have to be perfect to work,” explains Mark Mercola, who is working with Fred Levine at the UCSD Cancer Center on creating insulin-producing cells.

Scientists are also interested in turning stem cells into heart muscle cells. Those, however, would have to be interwoven in the fabric of the heart, which makes stem cell treatment for heart failure more complicated than for diabetes or Parkinson’s disease.

The more difficult conditions to treat are those with complex causes, such as kidney failure, spinal cord injuries (which involve not just the spine but atrophying muscles) and Alzheimer’s disease. Although Alzheimer’s is often cited as a potential beneficiary of this research, treatment using stem cells is a long way off. Mercola explains it’s the complexity of the tissue, the number of cells that have to be regenerated and the degree of integration into the damaged tissue that make some conditions a longer shot than others.

At some point, though, discoveries will be made, patented and licensed to biomedical companies that will create clinically useful therapies. Jeff Guise, a partner specializing in intellectual property protection and venture capital financing at the San Diego law firm of Wilson Sonsini Goodrich & Rosati, says there will likely be an explosion of small businesses centered on stem cell research.

“Traditionally,” Guise says, “large breakthroughs come from basic research at academic institutions. But it is companies that commercialize the products.” The Burnham Institute’s John Reed says it takes about $800 million and 10 years to commercialize a scientific discovery. “You can’t do that alone,” he says. Guise thinks that in five to seven years San Diego could see a new crop of companies created with the purpose of bringing stem cell therapies to market. The Torrey Pines area, already home to so much biotech research and development, could also become California’s first “Stem Cell Corridor.”

And that’s in line with what State Senator Ortiz was thinking when she authored legislation authorizing stem cell research in the state and placed Proposition 71 on the ballot. “We anticipated the growth of these clusters,” she says, “particularly in San Diego and the Bay Area.”

At a dinner several years ago, attended by the late Francis Crick—the Nobel laureate who, with James Watson discovered the double-helix structure of DNA —a reporter asked why so many Nobel Prize winners come to San Diego. (A dozen currently reside here.) Crick responded, “We can go anywhere in the world we want to, and San Diego has the best climate,” recalls Biocom’s Joe Panetta, who attended the dinner and knew Crick well.

Says Panetta: “It was clear he wasn’t just talking about the weather.”

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