Four Researchers Appeal Grant Reviewer Decisions; Stanford Scientist Cites Broader Concerns

Four scientists from UCLA and Stanford are seeking next week to overturn negative decisions by CIRM's scientific grant reviewers on their bids for close to $2 million each. One Stanford researcher is raising important policy questions that go well beyond the scientific merit of the proposed research.

The appeals to the full board of the California stem cell agency come in the $40 millon tools and technology round, which is aimed at addressing "technical bottlenecks and (enabling) novel translational approaches." The awards are scheduled to be given out by the agency's directors Thursday in Burlingame.

The researchers who appealing directly to the CIRM board are Guoping Fan and Martin G. Martin, both of UCLA, who are seeking $1.8 million each, and Craig Levin and Stefan Heller, both of Stanford, who are seeking $1.9 million each.

Most of the appeals to the CIRM board focused heavily on science issues, but the letter by Heller addressed additional, broader issues.

Stefan Heller
Stanford Photo

Heller, who has financial ties to a San Diego firm dealing with hearing disorders, already holds a $2.5 million grant from CIRM that was awarded in 2007. Heller used the funds for research dealing with potential cures for deafness through human embryonic stem cells. Both he and CIRM reviewers say he is one of the few scientists working in that area, although some 3.5 million Californians suffer from debilitating hearing problems.

Heller's pitch to the CIRM board defended his science but also implicitly raised questions about the quality of CIRM's grant oversight. And he said that without additional funding, CIRM's initial $2.5 million investment could well be damaged. Heller wrote,

"Now is the time to build on this asset and not to stop the funding and to disperse the researchers."

He argued that hearing losses are a widespread affliction and deserve more attention. He said his research could create jobs in California, an economic argument that CIRM has been touting widely as justification for its efforts.

According to the CIRM review summary, Heller's application was denied "due to strong concerns regarding feasibility of developing an adequate hESC-derived otic cell model, especially because little progress was reported despite an ongoing CIRM-funded effort in this laboratory, reviewers were doubtful that technical hurdles would be overcome." Heller rejected the contention that he had made "little progress." CIRM monitors the progress of its grantees and has pulled grants from three recipients.

Heller said,

"We believe that the reviewers were not appropriately calibrated with respect to the state of the science in our field, which consists of only a few laboratories – compared to larger fields with many well-funded laboratories. On the other hand, successful development of novel therapies for hearing loss and balance disorders would affect the lives of millions of patients. Therefore, research activity in our field clearly remains disproportionate to the major medical need."

He continued,

"The Heller lab is CIRM funded for 3 1/2 years and we have had several publications arising from CIRM funding including a major recent one in the journal Cell on mouse ESC guidance. The main results of our human ESC study are unpublished, we agree with this critique, but this does not mean that we have not made progress....Our ongoing CIRM comprehensive research grant has been funded based on a specific time plan and our current progress is very much in line with the original time plan."

Heller wrote,

"We are one of less than five laboratories working on stem cell related approaches to find treatments for hearing loss. We strongly believe that our science has to be exemplary as one of the few representative laboratories of the field."

Heller said,

"Our research group is an asset for CIRM in a small and specialized field with a high medical need. We have established a working and productive CIRM-funded group of people that joined us from outside the inner ear field that now, after 3 years, has reached a level of competence and productivity that comes close to groups working in much larger fields with more depth in basic science, as well as a much larger pool of personnel that readily joins these laboratories. Without the investment from CIRM, this group would not exist! Now is the time to build on this asset and not to stop the funding and to disperse the researchers. There are few laboratories in our field and progress is carried by a much smaller group of people than some of the larger fields that are well-supported by CIRM. Yet, a larger field much easier absorbs a major individual funding gap, whereas lack of sufficient funds will most certainly substantially hamper any progress in the hearing loss treatment field because we will lose the best and brightest coworkers of our laboratory. Our inner ear hESC group at Stanford would be in danger of dissolving, and research on the topic would have to start all over again, possibly severely slowing down the translation of hESC technology into the hearing loss field, thereby affecting millions of patients."

In his job creation argument, Heller said his application

"...directly deals with removing the only existing bottleneck preventing the development of the first high-throughput drug discovery screens in the hearing space. We have been extensively talking with potential investors as well as with multiple big pharmaceutical corporations about feasibility of our approach particularly with respect of using the assay as asset for a new biotech firm. We have been meeting with high-throughput screening experts from two out of the top ten big pharmaceutical companies and have discussed our planned hESC-based screening assays with them. Removal of the existing bottleneck, the main topic of our grant application, will directly expedite the founding of a new drug-discovery company in the hearing field locally in the SF Bay area."

Stanford's web site shows that Heller has financial links with Otonomy, Inc., a San Diego company "developing novel drug therapies for disorders of the inner and middle ear." According to Otonomy's web site,

"This field represents a large opportunity as there are no approved drug treatments for the nearly 30 million Americans facing debilitating hearing and balance disorders such as Ménière's disease, sudden sensorineural hearing loss, noise-induced hearing loss, age-related hearing impairment, and tinnitus."

Heller reported that he receives more than $5,000 in consulting fees from the company and has more than $5,000 in equity in the firm. He also serves on the company's advisory board.

Here are links to the other appeal petitions and review summaries.

Fan appeal, review summary; Levin appeal, review summary; Martin appeal, review summary.