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A Voice of Balance in Stem Cell Program

Dr. Zach W. Hall is one of our most distinguished scientists and experienced research administrators, with posts at USC’s medical school, UC San Francisco, and the National Institutes of Health on his glittering resume.

He is also interim president of the state’s new stem cell agency, the California Institute for Regenerative Research. So when St. Francis Memorial Hospital in San Francisco announced that the topic of his speech there last week would be “Stem Cell Research: Hope or Hype?” no one really expected him to accentuate the negative.

But Hall has taken on an indispensable role since assuming his temporary post in March: the voice of balance. He has been quietly tempering the public’s expectation that the $3-billion bond issue approved under Proposition 71 will yield instant medical therapies and cures.

Hall’s talk Wednesday evening was a step in that direction. “Based on my experience as a laboratory scientist,” he told me before taking the podium, “I know that to make an experiment work, we need to have someone in the lab who really believes in it -- and someone who is a skeptic all the way.”

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Skepticism about the potential of stem cell research was wholly absent from the campaign for Proposition 71. As a scientific undertaking, the stem cell program is unique in that its sponsors, the state’s voters, committed their money without receiving the slightest bit of professional scientific counsel. Before making a similar expenditure, any philanthropic foundation or university board would first seek advice from experts about the potential yield in knowledge from the effort, the obstacles ahead and the time frame required.

California voters received, instead, a TV campaign promising cures tomorrow for a host of diseases, some of which may never respond to stem cell therapy. The professional cautions are only appearing now, after the money is committed. The shock of discovery that “tomorrow” may be 20 or 30 years away (or may never come) could be severe.

Hall understands that sustaining public support requires, among other things, dialing back public expectations. The Proposition 71 campaign “tapped into an amazing reservoir of hope among California voters,” he says, “but we need to make people aware of how difficult it is to bring a new therapy to the market.”

In his speech, Hall described the challenges faced by researchers in this novel science. Embryonic stem cells are intriguing because they can differentiate into any of the specialized tissue cells of the body. This may allow scientists to culture healthy tissue cells in the lab to replace damaged ones in the human body. It may also give researchers a method of studying disease processes at the cellular level, yielding insights that could contribute to the development of other therapies.

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But scientists don’t yet fully understand how to control the differentiation process. Nor are they sure how well a patient’s body will accept stem cell treatments derived from cells donated by a stranger, or whether the growth of implanted cells can be managed.

The course of cutting-edge science, moreover, is never smooth. Is the public prepared for the disappointments, reversals, and dead ends that invariably accompany the scientific method?

Hall says he believes that a crucial part of the stem cell agency’s mission is public education, including admonitions that the journey from today’s knowledge to clinically effective treatments is “a long, hard road.”

In addition to listing some of the unknowns, he reminded his audience of the difficult histories of some other much-heralded and highly advanced medical technologies.

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Recombinant DNA was the stem cell-style biomedical panacea of the 1960s and early 1970s. Three decades later, its promise remains uncertain and has been hampered by unseemly haste: In 1999, an 18-year-old patient with a metabolic disorder, Jesse Gelsinger, died after undergoing an experimental treatment as a volunteer. The case arguably set back the cause of gene therapy by years; it raised questions about the researchers’ methodology and financial conflicts of interest, and drew out of the woodwork reports of hundreds of otherwise unpublicized adverse experimental events in the field.

Another eagerly anticipated technology -- the manufacture of monoclonal antibodies, “magic bullets” that act on specific tumors or antigens -- appeared in the mid-1970s. The first drugs were not approved for human treatment until 25 years later, and their efficacy is still under study.

Gene therapy and monoclonal antibodies didn’t arrive with even a fraction of the hype surrounding embryonic stem cell research. Plainly, it will take a superhuman effort to resist public demands for hasty human experimentation and clinical trials of stem cell discoveries. The same emotional appeals that stoked public enthusiasm for Proposition 71 from patients in wheelchairs, parents of diabetic children, celebrities with Parkinson’s -- might be mustered in the future to get treatments into the marketplace before they’re ready.

Hall’s combination of confidence in the ultimate success of stem cell research and humility about the challenges lying ahead is the most encouraging sign yet that the stem cell program will be a credit to the state, not a boondoggle. He has indicated plans to step down from his post as soon as a permanent president can be appointed; one can only hope that when he departs the agency, his discretion and good judgment don’t leave with him.

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Golden State appears every Monday and Thursday. You can reach Michael Hiltzik at golden.state@latimes.com.


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