The state’s stem cell institute, which so far has approved $554 million in taxpayer-funded research grants, is basing its funding decisions on recommendations from panels of scientists who sometimes make significant factual errors in their reviews of grant requests, some applicants say.
Yet there is no way for applicants to point out or rebut the errors – at least not through a formal appeals process, such as the one used by the National Institutes of Health.
“I cannot tell you how frustrating it is to get turned down for a grant and have no recourse other than to shred it and all the time you spent doing it,” said Jeanne Loring, a researcher at the Scripps Research Institute in La Jolla.
The California Institute for Regenerative Medicine said it has no immediate plans to change its policy.
“Our mandate is to get therapies to the clinic and to respond to the real urgency in the suffering of patients with chronic disease and injury,” said Robert Klein, chairman of the institute. “To do that, we have to be as efficient as possible. Using the NIH appeals process, it can take two years for someone to get their (grant) money. That is not acceptable.”
The stem cell institute’s grants schedule is rapid-fire. Applicants turned down for one grant can apply for funding in one of the next rounds of grants, and use the critique of their first application to improve the next one, Klein said.
That is unacceptable to some scientists, who say their research and the different grant requirements are not one-size-fits-all.
As a result, some grant applicants have devised methods of getting around the institute’s rules, to point out errors and plead their case for funding.
In one instance, reviewers questioned the expertise that Salk Institute scientists had in the field of hemophilia when, in fact, one of the scientists is a leader in that area.
Scientist Fred Gage sent a letter to the institute’s board to rebut that and several factual mistakes. Ultimately, Gage received a $1.74 million grant.
In another case, John Reed, president of the Burnham Institute and a member of the stem cell institute’s board, became the target of an ethical investigation for trying to rebut what he thought were factual errors in the review of an application submitted by Burnham scientists. Reed had called the institute staff to talk about the issue at the urging of Klein.
Taxpayer advocates and scientists said the stem cell institute’s “scattershot” approach is not the proper way to distribute up to $3 billion in public funds for stem cell research. They suggest that the institute, which prides itself on being the world’s largest source of funds for embryonic stem cell research, slow down its grant giving while working out a better appeals process.
“It might slow the process down a bit, but every grant applicant should have an opportunity to rebut the points made in the review, particularly if there are errors of fact,” said John Simpson of the nonprofit Consumer Watchdog in Santa Monica.
At least one of the institute’s board members agreed that the process may be flawed by human error but said the research that has been funded was top-notch.
“We may have missed some good science, but I don’t think we have funded (bad science),” said Jeff Sheehy, a patient advocate on the board.
Scientists agree that grant review is a human process and therefore never perfect.
“Every one of us sent grants in to the NIH or other agencies, or sent papers into journals, and reviewers have made errors. Sometimes they are really important facts and sometimes they aren’t,” said Larry Goldstein, a University of California San Diego stem cell researcher.
“It wouldn’t be bad to have a thoughtful discussion about an appeal process, but you don’t necessarily want to open it up to every unsuccessful appeal. I don’t think that’s what anyone wants because it can get very time-consuming.”
At the center of this issue are the review panels made up of scientists from outside California who are paid $2,000 stipends for spending several days reviewing and scoring dozens of grant applications, thick with complicated and cutting-edge science.
“All of us who have been reviewers know it is not a happy lot in life. It’s a lot of work that you do to be part of the scientific community and drive science forward,” Loring said.
There is a general understanding that it is hard to review grants involving science that may be outside someone’s direct field of expertise, Loring said.
Under the institute’s current policy, applicants have 30 days to appeal the review of their proposal only if there is a potential conflict of interest with a reviewer.
If a scientist wants to rebut an error of fact of great scientific importance, he or she should point it out to institute President Alan Trounson or Chief Scientific Officer Marie Csete, Klein said.
Those scientists could then sort out the issue with the reviewers and decide whether it needs to be brought to the board’s attention, he said.
Gage, from the Salk Institute, bypassed the institute’s scientific staff and sent a letter directly to the board rebutting what he thought were factual errors in his review.
Since it was directed to all board members, Sheehy thought the state’s public information law required him to read it into the record. Board member Oswald Steward, chairman of the Reeve-Irvine Research Center at UC Irvine, had a problem with the letter being considered, saying it created an uneven playing field for other applicants whose rebuttal of errors could not be heard.
Gage’s grant was ultimately approved because it was scored well, just two points below the next-lowest-scored application that reviewers had recommended for funding, Sheehy said.
Sheehy said he thought the application might have received more votes for approval if Gage had not sent the letter and made some board members uncomfortable about an inconsistent policy.
Gage could not be reached for comment.
Kenneth Woolcott of San Diego-based Cascade Life Sciences, a startup biotechnology company, also took issue with what he said were complicated factual errors in the review of his company’s application.
The errors may have led to a cascade of erroneous reasoning that resulted in a low score of the application, said Woolcott, Cascade’s chief business officer.
For instance, the review panel misstated the company’s success rate for cloning the embryonic stem cells of a nonhuman primate. The company was seeking funding to translate this science into human cells, which has never been done.
The company’s application said that it has had a success rate of 3 percent, or 3 successful stem cell lines created out of every 100 nonprimate eggs that were used. The success rate is a crucial factor because of the scarcity of human eggs for the experiments.
The company has since improved its success rate to 10 percent, Woolcott said.
However, scientists who reviewed the application misstated the company’s success rate as 0.3 percent
“This is factually incorrect at two levels, and we are unsure of where the reviewer got the 0.3 percent efficiency rate,” Woolcott said. The reviewers also said the company’s planned science lacked novelty, though the work has never before been transferred successfully to human cells, he said.
“This seems to defy logic and the mission of human therapeutics,” Woolcott said. “It’s not consistent with the objectives published by (the institute) in its (request for grant applications).”
The board did not change its vote to deny Cascade the grant funding.
Contact the author, Terri Somers, at: (619) 293-2028; [email protected]