Stem cell grants come with dash of criticism

Carl T. Hall, Chronicle Science Writer

One of the state’s most prominent stem cell researchers was judged to be a little “naive” on some technical areas. Another scientist was questioned as to whether he has the “expertise” to carry out his research. One other veteran investigator was said to be taking a potentially irrelevant approach “from a clinical perspective.”

Public criticisms of scientists by other scientists are rare. But that’s part of the price for anyone obtaining a grant from California’s new $3 billion stem cell research program.

Twenty-nine of the state’s most senior biologists were chosen March 22 from 70 applicants seeking large multiyear awards from the California Institute for Regenerative Medicine, the state agency created in 2004 to administer the Proposition 71 effort.

A panel of out-of-state experts ranked the proposals in private meetings, and the identities of the also-rans were not revealed. But the names of the successful applicants and surprisingly candid summaries of the panel’s grant reviews can be found on the stem cell agency’s Web site,

Posted by the agency, the summaries offer a rare glimpse into the traditionally cloistered world of scientific peer review.

Other public grant-writing agencies, including the National Institutes of Health, generally keep such matters private.

“The NIH doesn’t show any of this kind of thing going on,” said Arlene Chiu, director of scientific programs and review at the California stem cell program. “This is the first time you can see how people criticize one another.”

One reason for the openness was to address criticisms that the state program has tried from the start to keep too many public matters private. Even so, the fact that the identities of grant applicants aren’t revealed until the winners are chosen is a continuing sore point for open-government advocates monitoring the independent stem cell enterprise, approved in the 2004 statewide general election.

To others, the system seems transparent enough already.

“Calls for yet more openness may be well intentioned, but they threaten to override the element of confidentiality that is inherent to fair peer review and to undercut the agency’s mission of supporting cutting-edge research from the best Californian scientists. There comes a point at which yet more sunshine leads to sunburn,” the journal Nature said in a recent editorial.

Dr. Arnold Kriegstein, the highly regarded chief of UCSF’s stem cell program, has seen no reason to complain about anything — even though he was the one who got to read that he was “naive” on some technical matters.

He also got the second-highest score in the grant review and a potential for $2.5 million over four years to study how stem cells might be used in an innovative approach to brain repair.

Kriegstein proposed using human embryonic stem cells to make a special type of brain cell known as an inhibitory interneuron. It’s a novel approach to be pursued by four labs at UCSF, and draws from animal studies suggesting that implants of the inhibitory cells may help tamp down overactive brain circuits implicated in Parkinson’s disease or epilepsy.

Grant reviewers found the project more than worthy, but also said that some of Kriegstein’s follow-up experiments seemed “a bit open-ended.”

“It is not at all clear” that the technical steps needed to achieve “the most critical step in this proposal” can be worked out in the four-year grant period, the reviewers found.

They also criticized Kriegstein for providing insufficient detail on how he planned to make sure he was generating the desired type of nerve cell.

“This is naive from a (principal investigator) who should know more about interneurons,” the panel observed.

Kriegstein said in some cases he was a victim of his own brevity, and may have been misunderstood in certain technical aspects.

“Because ours involved knitting preliminary data obtained from four separate laboratories into a single comprehensive proposal in a short time, some experimental details were not fully explained,” he said during an e-mail exchange.

Hans Keirstead of UC Irvine, whose video images of paralyzed rodents helped win votes for Prop. 71, submitted a proposal involving spinal cord repair. The panel deemed it “scientifically thin.”

Keirstead was judged to be “an excellent contributor to the field.” At the same time, grant reviewers said he hadn’t presented enough preliminary data or alternative plans should his main approach fail. “It is not clear whether the applicant has the expertise” to accomplish some of his key objectives, they added.

He wound up recommended for a $2.4 million grant anyway, partly because of the importance of his disease target. So perhaps it’s not surprising that he took the critique in stride.

“The project that I submitted … is one that explores a new approach to treating an understudied area, chronic spinal cord injury,” Keirstead said in an e-mail. “A new approach to an understudied area means an increased degree of scrutiny. This is as it should be.”

Alice Tarantal, a pediatrics professor at UC Davis, is in line for $2.3 million to study how stem cells might be used to treat kidney disease in infants. She was praised for submitting “a tour de force” proposal.

Not all the reviewers thought so, evidently.

Some said they were “ambivalent” and “questioned how relevant this model is from a clinical perspective.” In the end, Tarantal’s proposal scored only 66, compared with a 90 for Kriegstein and a 95 for the top-scoring proposal.

But a 66 proved to be good enough: The reviewers decided they “might have erred on the side of being hypercritical,” and recommended Tarantal’s project for funding.

Despite the somewhat rough handling, Tarantal said “it was a very fair process.”

“We welcome those comments,” she said. “They can be helpful when done in the spirit of constructive questioning. It can help you think about things a little differently.”

Agency decision-makers said it’s only reasonable to keep private the identities of those who failed to take home a prize in the first cycle.

“You don’t want to discourage people who don’t get a grant this time from coming back again by holding them up to public ridicule,” said Jeff Sheehy, who represents people with HIV/AIDS on the stem cell agency’s governing board and was among seven patient advocates who participated in some aspects of the grant review.

Sheehy, as a public information officer for an HIV/AIDS research institute at UCSF, has been a longtime advocate of open government who helped push through a “sunshine” initiative in San Francisco.

He defended the limited confidentiality written into the stem cell system, suggesting that it may have encouraged the reviewers to speak more openly, because they knew only the names of the successful applicants would be made public.

“The confidentiality that surrounds this is what enabled people to be as blunt as you’ve seen them be in their comments. So I think we’ve reached a pretty good balance,” Sheehy said.

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