California's Stem Cell Genomics Award: Text of Remarks by Jeanne Loring of Scripps

Here is the text of comments from Jeanne Loring, director of the Center for Regenerative Medicine at the Scripps Research Institute, in response to questions from the California Stem Cell Report concerning the review process for applications in the $40 million stem cell genomics round.

Boldface within Loring's response is hers. Parenthetical identifications of terms or individuals have been inserted in Loring's remarks by the California Stem Cell Report.

California Stem Cell Report: What questions do you think need to be addressed considering the events surrounding the award?

Loring:

 "1. What instructions were given to first round applicants about merging applications?

"Alan (Trounson, CIRM's president) visited all of the first round applicants. On his visit to San Diego, Alan met separately with me and my Illumina partners, Larry Goldstein of UCSD and Craig Venter of the Venter Institute. Alan told me that Larry had taken him to a mens' club and Craig had taken him to a motorcycle dealership. I took him for a tour of Illumina's new facilities, which I thought was appropriate for a scientific site visit. 

"At his visit to all of the first round applicants, Alan Trounson suggested that we merge our applications if we could. My interpretation of that suggestion was that we actually merge our center proposals- UCSF's with ours, for example. I was not told that addition of subcontracts from other institutions could be interpreted as a merger with those institutions. The Stanford group's claim that Scripps and Illumina were consortium members of theirs was disingenuous, since our Scripps/ Illumina consortium was a competing genome center application, and we did not merge any part of our application with Stanford's. 

"To make the claim that they had 'merged' with Scripps and Illumina, Stanford added one project from a junior faculty member at Scripps, and contracted Illumina to do sequencing for them- they have had long-standing contracts with Illumina for services.

"The difference between Stanford's relationship with Illumina and my relationship with Illumina is analogous to Stanford paying a Tesla dealer to repair a car and me teaming up with Tesla to design a new type of car.

"We were not told who the other applicants were, which made it a challenge to determine who we might merge with. We chose to contact Pui Kwok, through my collaborator Susan Fisher at UCSF, Joe Ecker at Salk, Mike Snyder at Stanford, and Josh Stuart at UCSC about potential partnering.

"When I spoke with one of the people we contacted, he said that I could get a place in the consortium put together by Stanford if I were to get my institution to contribute $2 million in matching funds. This was not entirely a surprise; I had heard from colleagues at UCSD that UCSD's vice chancellor, David Brenner, had initiated the collection of matching funds by pledging $2 million to the consortium.

"2. At the Grants Working Group(GWG, the grant review group): what differences were there between the stated requirements in the RFA and what the reviewers were told to do during the meeting?

"Matching funds

"The RFA did NOT require contributions from grantees, and certainly did not suggest that such contributions would be considered to be items for the GWG to judge, since they were tasked with only on the quality of the science, the 'scientific merit.' To quote from the message sent to me from Gil Sambrano(the CIRM staffer who handles most of the review process), announcing my score and the GWG report, 'Applications were reviewed using the criteria detailed in the RFA and scored on scientific merit.'

"That makes me wonder if the reviewers told at the GWG meeting to include monetary contributions from the potential grantees positively in their scoring, in spite of the fact that their scoring is stated by CIRM as being solely on the basis of scientific merit?

"During the ICOC (the agency's governing board) meeting, Alan Trounson said that he had told us during his visit to all of the first round grantees that it would be important provide money for 'matching' funds. I state unequivocally that he did not tell me or anyone in my lab about this. 

"Scoring applications after removal of projects that the GWG scored poorly.

"We learned when the reviews were posted that the GWG scored two of the Stanford center projects very poorly. We do not know the actual scores they gave those projects, nor do we know what scores were given to our own projects. We do know that CIRM instructed the GWG to score the entire Stanford grant after removing the two low scoring projects. All three of our projects scored high enough to be included in the overall review of our application.

"The Stanford project received a range of scores from 70 to 95 after the two projects were removed. Our application received a range of scores from 70 to 88 with all projects left in place. It is not much of a stretch to imagine that if the low-scoring Stanford projects had been kept in, there would not have been scores of 95 by any of the reviewers. It is not too speculative to suggest that their scores would have been lower, perhaps lower than ours, if the low-scoring projects had not been removed.
We were not told of the practice of the GWG altering grants in order to improve the scores of those grants. I am also appalled that this was done, since it is not allowed in NIH review of multi project U and P awards, the closest equivalent to the CIRM genome center award. 'P' awards are Program Project Grants, in which several investigators write sub-proposals to be done in concert with each other. I review these grants, and we are instructed that we cannot remove subprojects in order to change the scores. Similarly, 'U' awards are for consortia that are to be coordinately managed. I also review these applications, and again, it is forbidden for us to alter the applications as written. The goal of the reviewers for these NIH awards is to 'review the grant we are given'.
CIRM staff indicated at the ICOC meeting that the GWG had recommended funding of the Stanford project. 

This is simply untrue. As the message from Gil Sambrano states: 'The GWG understood that this initiative will support only one or two centers and only a single data coordination and management component within a total budget of $40M.  However, as the GWG's scores and recommendations were based solely on scientific merit, the group did not select which center(s) should ultimately be funded as this is a programmatic assessment.'

The GWG was tasked with scoring based on 'scientific merit' (which CIRM instructed them would include monetary contributions). Programmatic assessment is required to choose an application, and CIRM is not part of the Programmatic committee, according to the following quote from the message from Sambrano:
'ICOC/Application Review Subcommittee MeetingFunding decisions will be made by the Application Review Subcommittee of CIRM’s governing board, the Independent Citizens Oversight Committee (ICOC), at a public meeting that will be held in Berkeley, CA on January 29, 2014.  The Subcommittee, which meets concurrently with the Board, is composed of 16 voting members (the Patient Advocate and Industry members of the Board, along with the Chair and statutory Vice Chair of the Board) and 13 non-voting members (the 13 members of the Board who are appointed from institutions that are eligible to receive CIRM funding).
'The Applications Review Subcommittee will conduct a programmatic assessment of applications reviewed by the GWG. The Subcommittee may consider any factors (such as availability of funds, overall grant portfolio, RFA priorities, strategic considerations) that might impact on their decision to fund or not fund applications. The Subcommittee aims to fund applications that are both scientifically meritorious and that bring programmatic value to the CIRM portfolio.'

In the meeting, CIRM did not present information about any application except Stanford's, giving the strong impression that this application was the only one of merit. The ICOC members of the Application Review Subcommittee were not provided with the applications in order to assess the factors they were charged to assess.

California Stem Cell Report: Are there structural issues created by Proposition 71, the measure that created the agency, that made things more or less difficult?

Loring: 

"The 29-member board (ICOC) is difficult enough to deal with, but now that most of the members are considered to be conflicted and are not allowed to even discuss the applications, we are left with a small number of non-scientists making decisions about scientific merit.

"I know that many members of the ICOC were very upset that they were unable to voice their opinions about what should be their mission- to guide CIRM's policies and choices for funding so that they are in the best interest of the voters."

California Stem Cell Report: Are there processes at CIRM that show weaknesses or need to be re-examined? Do you have any specific recommendations for changes?

Loring: 

"The ICOC members should be provided with all of the grant applications as well as the reviews. They can choose to ignore them, but if they find that certain grant apps or disease-specific areas require more high level consideration, they should have the tools to provide that guidance.

"I am concerned about the interference of the CIRM president in influencing the ICOC decisions. He has de facto power to promote or defeat specific applications, and he often wins by promoting one applicant over another. Stanford and Stanford faculty-founded companies such as Stem Cells Inc, are blatantly promoted over others. The relationship between the president and the head of the stem cell program at Stanford involves personal favors which make him conflicted and he should at the very least recuse himself from any discussion or recommendation of Stanford faculty's applications."

Loring also included the following:

Text of message from Gil Sambrano on Friday, January 10, 11:06 am
"Dear Dr. Loring:

Thank you for submitting your application under the California Institute for Regenerative Medicine’s (CIRM) Stem Cell Genomics Centers of Excellence Awards RFA 12-06. We are providing you this report as the Program Director (PD) and designated point of contact on the application, but it is your responsibility to share this information as appropriate with members of your team.

The applications underwent peer review at a meeting held on November 7-8, 2013 by the members of CIRM’s Grants Working Group (GWG). Applications were reviewed using the criteria detailed in the RFA and scored on scientific merit.

Review ReportBelow, please find the Review Report of your application.  This report includes the average scientific score and the funding recommendation of the GWG. Applications are scored on a scale that ranges from 1 – 100, with 100 being the highest achievable score.

Applications are separated into three funding tiers.  An application’s average score determines the funding tier as follows:

75-100 = Tier 1 - recommended for funding
65-74 = Tier 2 - moderate scientific quality or consensus on scientific merit cannot be reached, and may be suitable for programmatic consideration by the ICOC
1-64 = Tier 3 - not recommended for funding

The Review Report provides only a brief summary of the evaluation of your application by the GWG. The report is not an exhaustive critique and does not cover all of the factors that may have contributed to the final score or the final recommendation. The report highlights key points relevant to the review criteria that were captured from reviewers’ written comments and from the discussion of your proposal by the GWG during the review meeting.

ICOC/Application Review Subcommittee MeetingFunding decisions will be made by the Application Review Subcommittee of CIRM’s governing board, the Independent Citizens Oversight Committee (ICOC), at a public meeting that will be held in Berkeley, CA on January 29, 2014.  The Subcommittee, which meets concurrently with the Board, is composed of 16 voting members (the Patient Advocate and Industry members of the Board, along with the Chair and statutory Vice Chair of the Board) and 13 non-voting members (the 13 members of the Board who are appointed from institutions that are eligible to receive CIRM funding).

The Applications Review Subcommittee will conduct a programmatic assessment of applications reviewed by the GWG. The Subcommittee may consider any factors (such as availability of funds, overall grant portfolio, RFA priorities, strategic considerations) that might impact on their decision to fund or not fund applications. The Subcommittee aims to fund applications that are both scientifically meritorious and that bring programmatic value to the CIRM portfolio.

Under California’s open meeting laws, members of the public, including applicants for CIRM funding, may provide written and oral comments to the ICOC regarding items on the Board’s agenda. Applicants may attend and observe the ICOC meeting. Applicants may contribute oral comments for not more than three (3) minutes during the public comment periods. The ICOC Chairman will announce the public comment period, which typically occurs prior to the Board’s voting on any motion. Applicants may also provide written comments to the ICOC. All correspondence to the ICOC must be submitted to the Executive Director of the ICOC, Maria Bonneville, at mbonneville@cirm.ca.gov. Please do not send correspondence to the ICOC that relates to an appeal of a funding recommendation by the GWG as it will be redirected to the CIRM Review Office (see “Response to Review” below).

In preparation for the ICOC meeting, the Review Report (with PI and institution identities removed) will be posted no later than Friday, January 17, 2014 on our website at http://www.cirm.ca.gov/ReviewReports. Additional information for CIRM’s public meetings can also be found on our website.

Award NotificationCIRM will notify you by email of the ICOC’s funding decisions following the ICOC meeting.

Response to ReviewThe GWG conducts the scientific evaluation of proposals submitted to CIRM. If the applicant (PI/PD) wishes to appeal the scientific review by the GWG (or seek reconsideration of the recommendation), the PI/PD must first consult with the CIRM Review Office. All appeal requests must be made through the CIRM Review Office within 10 days of CIRM making this report available (i.e., deadline is January 21, 2014). Grounds for an appeal are limited to the circumstances described in “Guidance for Appeal of Scientific Review and Reconsideration Policy” available via this link: http://www.cirm.ca.gov/board-and-meetings/guidance-appeals-and-requests-reconsideration-grants-working-group-funding
--
Gilberto R. Sambrano, Ph.D.
Associate Director, Review
California Institute for Regenerative Medicine
210 King Street
San Francisco, CA 94107
(415) 396-9103
To:  jloring@scripps.edu; wynne@scripps.edu
REVIEW REPORT FOR CIRM RFA 12-06R GENOMICS CENTERS OF EXCELLENCE AWARDS (R)
Application: Center for Advanced Stem Cell Genomics

PI: Jeanne Loring
Institution: Scripps Research Institute

Recommendation Overview: The GWG provided two final scores for each application as follows: 1) an overall center score (covering the center-initiated projects, collaborative research activities, and center organization and operations plan) and 2) a data coordination and management component score.
The overall scientific merit and quality of the proposals submitted under this RFA were viewed by the GWG to be deserving of high scores. Overall center scores placed four proposals in Tier 1, one proposal in Tier 2 and none in Tier3. The separate data management and coordination component scores placed two proposals in Tier 1, two in Tier 2 and one in Tier 3.
The GWG understood that this initiative will support only one or two centers and only a single data coordination and management component within a total budget of $40M.  However, as the GWG's scores and recommendations were based solely on scientific merit, the group did not select which center(s) should ultimately be funded as this is a programmatic assessment. CIRM staff is recommending that the ICOC fund only the highest scoring genomics center and the corresponding highest data coordination and management center which together will fulfill the goals of this initiative.
The scores, GWG Tier recommendation and CIRM staff recommendation are as follows:

GWG Overall Center Recommendation: Tier 1GWG Overall Final Score: 76

GWG Data Center Recommendation: Tier 2GWG Data Center Final Score: 72
CIRM Staff Recommendation: Do not fund
EXECUTIVE SUMMARYThis Genomics Center will be led by a program director (PD) from an academic institution and a co-PD from an industry organization. Three Center-Initiated Projects (CIPs) are proposed, and, as required by the RFA, a plan for inclusion of Collaborative Research Projects and a Data Coordination and Management Center are described.


Center Organization and Operational Plan - The organization of the proposed Genomics Center is well conceived as a collaboration between highly qualified investigators from an academic institution and an industry partner, representing a diversity of competencies. The balance between expertise in stem cell biology and genomics technologies is a particular strength.

- The PD has extensive research experience at the interface of stem cell biology and genomics and is committed to serving the stem cell community; he/she is well suited to lead this program.

- The industry partner institution, and especially the co-PD, is well positioned to develop novel cutting edge genomics technologies and make them accessible to customers.
- The teams from the two applicant institutions have a well-established, strong working relationship; reviewers considered this an important attribute of this proposal.

- All elements necessary for the establishment and operation of a successful Genomics Center are in place; the structure and composition of the proposed administrative and oversight committees are appropriate and should ensure both delivery of projects and high standards of work.

- The three CIPs are designed to support the service aspects of this Genomics Center by focusing on the development of tools that can be generally used to explore genomics data. Reviewers considered it a strength that, if successful, these projects will both create novel tools and technologies and validate them. There was some concern that some of the tools may not be made easily and widely available.

- Although a letter from leadership indicates enthusiastic institutional support from the academic institution, no additional funds or specific dedicated space have been designated. Reviewers expressed serious concern about this lack of material commitment.

- Some reviewers expressed concern that both the PD and co-PD are already heavily committed individuals and questioned whether they would have the capacity to fully provide a strong commitment to this project.


Center Organization and Operational Plan - The proposed Genomics Center appears well designed to support collaborative research projects and to make relevant state-of-the-art genomics technologies readily accessible to investigators with primary expertise in stem cell biology or translational research.

- The proposed application process is appropriate, review procedures and criteria are well thought out.

- The offer to culture cells for external collaborators in the Genomics Center's core lab is especially appealing, as that would remove a variable from the experiments and thus help with standardization of conditions for genomics assays.

- Concern was expressed about whether potential collaborators who have limited experience in genomics would receive adequate assistance in designing their proposed studies.


CIP-1The applicants propose to develop an updated and expanded version of an existing genomics tool. They plan to make available global gene expression and epigenomic data, obtained through a series of systematic analyses of human pluripotent stem cells and their derivatives, to serve as reference for future experiments. They also propose to analyze the heterogeneity of stem cell populations and to develop genomic tools for the assessment of stem cell quality. Finally, they intend to use disease-specific induced pluripotent stem cells (iPSC) to study the molecular basis of two neurodevelopmental diseases and identify disease-modifying compounds.

- This project adopts a broad approach toward developing pragmatic, accessible tools for basic research on stem cells in vitro, and to lay the groundwork for more effective clinical translation. This would represent a valuable resource to the stem cell community.

- Enthusiasm was diminished by the notion that most of the activities are applications of existing tools or extensions of existing work. While important goals, the activities were not viewed as particularly innovative.

- The goals of this project are overly ambitious, raising doubt that all aims can be achieved. Given the tremendous track record of the principal investigator (PI), though, it is expected that substantial progress will be made.

- Reviewers' opinions about the utility of an already existing analytical tool, to be further developed under this award, were divided. Some judged it positively as an important tool that has been made freely available in its current form and were enthusiastic about the plan for dissemination of the updated version. Conceptually, they considered the proposed approach to be very valuable, as it has the potential to provide objective standards for assessing cell fate and for quality control of cell populations. Other reviewers expressed concern that the current tool has not been widely adopted in the stem cell community, calling into question its usefulness.
- The proposed work on neurodevelopmental diseases is disconnected from the central focus of this project and might have been better developed as a separate project.
- Reviewers criticized the general lack of experimental detail, particularly in aims 4 and 5, which impeded assessment of feasibility.
- The project plays to the strengths of the PI as a well-established leader in the stem cell field with a strong record of productivity and innovation.

- The broad scope of the project is matched by the experience and expertise of the team involved.

CIP-2This project addresses the integrity of stem cells for clinical transplantations and their utility in translational and clinical research. The goals are to establish informatics tools for determining the functional significance of genome wide molecular variations in therapeutic stem cell populations and to develop and validate methods for assessing the prevalence of deleterious alterations in stem cell populations. The applicants also plan to develop and validate a workflow for integrating genomics information with identification of potential therapeutic compounds and their effects on patient-derived induced pluripotent stem cells and on patient treatment outcomes. Finally, the plan is to disseminate all developed tools and protocols to the stem cell community.

- The utility of the proposed tools and protocols for translational genomics-based research would be high.
- The first goal is straightforward and feasible. Reviewers emphasized that input data must be high quality, as noted by the applicants, and suggested that applicants consider that the cellular differentiation state may affect functional significance of specific genomics variation.

- Other goals are more risky, but if successfully developed, they should be widely applicable and help stimulate the use of stem cell-based systems to explore both disease mechanisms and potential therapies.
- Toward assessing prevalence of deleterious alterations in stem cell populations, reviewers recommended that a variety of additional stem cell datasets, especially some originating outside the team, be included in the project.

- The feasibility of a key component of the study, linking genomic information from patients to potential therapeutics and individualized treatments, was difficult to assess, since the applicants did not specify the types of diseases to be studied.
- Reviewers observed that parts of this proposal are vague and hard to follow, and it was unclear what some of the deliverables would be.

- There is a clear plan for dissemination of the acquired expertise and knowledge.

- The PI is well qualified for this work and has assembled a powerful leadership team that possesses the necessary expertise.


CIP-3This project is led by the industry partner organization and is focused on the development of several single cell genomic technologies and tools for large-scale epigenetic analyses.

- Reviewers noted that only one of the technologies under development is truly stem cell-specific, but the proposed work would nevertheless deliver technologies extremely valuable to the stem cell community.

- The tools to be improved or developed are at the forefront of technical advances.

- Reviewers geatly appreciated the novelty of one of the proposed technologies.
- Some reviewers were concerned that the project essentially constitutes commercial development of genomic products and questioned whether it was appropriate for CIRM to support this activity.  Others felt that the developed technologies would provide valuable research tools and could have great potential impact on stem cell science.
- Concern was expressed about whether the new technologies would be specifically disseminated to California investigators and whether their cost might be prohibitive to many researchers.

- The basic technologies underlying this proposal have already been developed and it should therefore be feasible to complete the proposed developments in the proposed time scale.

- The PI and team are exceptionally well qualified to deliver on this project.


Data Coordination and Management - The DCM team is led by two individuals. One has a track record of developing a highly successful, adaptable, user-friendly platform. The other is an expert in medical informatics, although reviewers expressed concern that a biosketch for this individual was not included in the proposal.

-The proposed DCM structure and leadership would likely ensure solid database structure, data access and visualization capabilities.
- Reviewers considered the details provided on the data management plan to be inadequate; there was little description of how the DCM Center will participate in data integration and analysis or interact with various projects.

- Reviewers acknowledged the importance of patient privacy protection but felt the focus on this issue in the application was overemphasized and distracting.

- The descriptions of data visualization tools are reasonable but not particularly innovative or tailored to the specific needs of the stem cell community."

California's Stem Cell Genomics Award: Text of Critique of Award Process

Here are comments concerning the process involving a $40 million stem cell genomics award by the California stem cell agency last month. The remarks were provided at the request of the California Stem Cell Report with the promise that they would be carried verbatim. The person providing them asked not to be identified by name, but is familiar with the agency.

“1. It appears that CIRM staff took a lot of liberties behind closed doors in driving this initiative to its final outcome. For example, what happened to require a resubmission and re-review etc. Did they change anything about this initiative in the process?  Were certain criteria shared with some but not all applicants?
“2. It also appears that the board was taken by surprise and not prepared to deal with the complexities in this initiative.  Clearly staff has not kept them in the loop and they had little access to the details of the process and how reviewers were managed.  They have always funded the vast majority of what the reviewers scored highly, and still did not break the bank.  This is a brand new situation where the reviewers recommended more grants than they could afford to fund.  This happens a lot in the NIH (especially today with severe budget cuts), so NIH has developed many processes to deal with this.  CIRM has not seen anything like this before.
“3.  The process of board approval, and the tiny amount of information they were provided in order to make their decisions, means that they had to rely completely on what staff says.  This means they have no way to do anything but accept staff recommendations.  The questions (all legitimate) raised by the certain members of the board were by and large not understood or picked up by the other voting members, so they went nowhere.
“4. Whereas the staff was fully prepared to deal with questions raised in letters from the dissatisfied applicants, the board had no context to really appreciate these questions, nor the details of the applications to 'get' the implications of these concerns.
“5. (This comment was excised because it could identify the commentator.)
“6. I did not like their final compromise.  They could have just funded the co-ordinating center, then go into closed session, asked to see the applications in private and picked to fund the best individual projects.  Now Stanford got even more money than they had asked for, and Stanford gets to decide which of their competitors to fund.  Incredible!
“7. Too many thoughtful board members were conflicted out, leaving the decision-making to a handful who are not prepared to deal with this complex situation.  I blame the IOM (Institute of Medicine) report in giving too much power, without the appropriate process, to staff.  Staff can recommend, but if the board has no information other than what staff provides, then they are acting in the dark.”

California's Stem Cell Genomics Award: Text of Comments from Stanford-Salk Consortium

In response to a query from the California Stem Cell Report seeking comment on the review process for a $40 million stem genomics award, Michael Snyder of Stanford and Joe Ecker of the Salk Institute in La Jolla provided these remarks. Their application was the ultimate winner.

“The goal of this program was to create a cutting edge center that would accelerate stem cell research with the power of new genomics technologies and to help all researchers get access to these technologies.  Our group made considerable effort to bring together world leading genomics and stem cell researchers from across the state of California. This exceptional group has extensive experience with all types of genomics activities (genome sequencing, gene expression analysis, regulatory site mapping, genome methylation analysis, single cell genomics, and in fact has many of inventors of these technologies. We have the sophisticated ability of handling large datasets, processing them in unified fashion and making them accessible to other researchers. The Directors and many of the participants have unique experience managing large genomics projects and working in large consortia, and very importantly, has a great deal of experience in helping hundreds of researchers within and outside our institutions with diverse genomics technologies which is a major goal of the program. The team received considerable of institutional support from each of the seven participating institutions (Stanford, Salk, UCSC, UCSD, Scripps, JCVI, Ludwig Institute, in addition to HHMI), and many members have strong interface with industry and in founding biotechnology companies. The net result is that this center will help bring cutting edge technologies to all Stem Cell Researchers in California and along with the funded projects will help keep California at the leading edge of two important fields: Stem Cell Research and Genomics, and thereby help accelerate both the science and therapeutics treatments possible in this field, and spur industry and economic development.”

Stanford Consortium Wins $40 Million to Create Stem Cell Genomics Center

Directors of the California stem cell agency today approved a $40 million proposal ultimately targeted at creating medical treatments tailored to a patient's genetic makeup and making the state a world leader in stem cell genomics.

The proposal by a seven-member consortium led by Stanford University was approved on a 6-1 vote of the 29-member board. Most of those not voting were disqualified because of conflicts of interest.

The action came despite charges by Stanford's competitors that the grant review process was tainted by unfairness, apparent preferential treatment and manipulation of scientific scores.

The award is the largest research grant that the agency has made in its nine-year history although the cash is being divided among the seven participants over five years.

The board added $7 million to the Stanford award to help possibly fund proposals from institutions that lost out in the round. They would have to apply to the consortium, which might have their own proposals in the same areas already underway.

The stem cell agency has high hopes for the genomics project, which is supposed to provide resources for all researchers in California. CIRM President Alan Trounson has predicted that the effort will build “an effective stem-cell genomics infrastructure that will be unique in the world, thus positioning California as a leader in this critical area of basic and translational research while genomic technologies build steam in the next five years.”

In addition to Stanford, the other enterprises involved its proposal include UC Santa Cruz, the Venter and the Salk institutes and Illumina, Inc., all in San Diego,  A complete list was not immediately available this afternoon because the stem cell agency withholds their names until after the board votes. They are expected to be disclosed shortly in an official press release.

(Here is a link to the CIRM press release.)

The top competitors against Stanford were groups led by UCLA, UC San Francisco and the Scripps Research Institute in La Jolla. UC San Francisco and Scripps both sent letters to the agency's board protesting the grant review process.

In a letter last week to the board, Pui-Yan Kwok of UC San Francisco, criticized the manipulation of the Stanford's grant application in such a way that its scientific score was improved. Kwok, leader of the bid that also involved UC Berkeley, called the situation “appalling.” The stem cell agency said, however, the changes were permitted under the terms that the agency had laid out in advance.

Jeanne Loring of Scripps, leader of an effort also involving the genomics firm, Illumina, Inc., of San Diego, said in a letter that the agency had failed to disclose in its request for applications that one of the key criteria for the “scientific merit” of the grants would be matching funds. Stanford was praised by reviewers for its “substantial” matching funds. Scripps' application was cited for a “serious” deficiency in that area.

Loring said that Illumina, a world leader in genomics, added major value to their proposal. The firm was also involved in the Stanford proposal in a lesser manner.

Michael Snyder, leader of the winning consortium, told the board that his group promised $7 million in matching funds. 

During the meeting, Trounson said he had told all applicants, with the exception of Stanford, that financial matching would be considered during the review. However, that was not included in the RFA.

Several board members earlier raised questions about the problem with the RFA and said it could create confusion and lead to perceptions of unfairness.

The RFA called for creation of one or two centers. Trounson recommended funding only the Stanford effort.

Michael Yaffe, associate director of CIRM's research activities, said the Stanford proposal would fulfill all goals of the RFA. He said the staff did not see a "compelling need" for a second center nor would it fit within the budgeted $40 million.

The California Stem Cell Report first reported on Friday that Stanford was set to win the award. 

(Editor's note: An earlier version of this article incorrectly stated the vote was 6-2. The correct vote is 6-1 with board member Steve Juelsgaard voting no.) 

Tracking the Evolution of the Stem Cell Genomics Applicants

The plan to create one or two stem cell genomics centers in California at a cost of $40 million began in 2012. Since then there have been some changes, some of which resulted from the failure of reviewers to recommend any proposals in 2013.

Last week, the California Stem Cell Report (CSCR) asked the California stem cell agency(CIRM), which is scheduled to make a decision today on an at least one application, about several of the changes. Here are the texts of the questions and answers from the agency.

CSCR: Has the cast of applicants changed since the initial review in early 2013? Have some dropped out or been added? Have the applications been recast significantly for the most recent review?

CIRM: Applicants to the first round of review were eligible to participate in the second round.  Although review criteria remained the same as those stated in the RFA, applicants were allowed to change proposal components, establish new collaborations and/or combine efforts.  

CSCR: How many letters of intent (LOI) were received with a breakdown on the number from academic and business enterprises?  How many applications were received, also with a breakdown on academic and business?

CIRM: For the first round, there were 9 LOI's; 7 of these submitted applications.  No LOI was required for the second round.  All first round applicants participated in the second round of competition, but several have combined efforts, so there were 5 applications in the second round.  Three of these applications were collaborative proposals combining both for-profit and not-for-profit organizations, while the other two were from not-for-profit institutions.

Groundbreaking Ahead? Geron's Stem Cell Program Officially Goes to Biotime/Asteria

Geron's once-heralded stem cell therapy program -- financed at one point with $25 million from the California stem cell agency – has officially landed in the hands of an Alameda, Ca., enterprise involving two former CEOs of Geron.

Completion of the transaction was announced Tuesday by BioTime, which acquired the Geron assets. The move “could jump start groundbreaking but not yet clinically successful stem cell programs,” according to an article by Ron Leuty of the San Francisco Business Times. Leuty also outlined the complicated financial terms.

Geron, based in Menlo Park, Ca., was the first in the nation to launch a clinical trial for a human embryonic stem cell therapy. In 2011, in a major departure from its usual procedures, the stem cell agency loaned Geron $25 million to help with the trial. About three months after the loan agreement was signed on Aug 1, 2011, Geron announced it was abandoning the trial for financial reasons. Four patients had been enrolled in the trial.

Geron repaid the loan with $36,732.33 in interest, laid off 38 percent of its staff (66 persons connected to the stem cell program) and began an effort to sell off the stem cell effort.

About a year later, BioTime, which is headed by Michael West, who founded Geron, began expressing an interest. Tom Okarma, another Geron CEO, hooked up with West on the effort and is now head of Asteria Biotherapeutics, a BioTime subsidiary that is taking control of the old Geron stem cell program.

Geron let Okarma go in February 2011. He was head of the company as it plowed through the arduous FDA process to begin the clinical trial of the stem cell treatment for spinal injuries.

The stem cell agency has said that the loan to Geron is not transferable automatically to BioTime. The firm will have to compete for funding under the agency's established rules.

Both Geron and BioTime are publicly traded. In the last 12 months, Geron stock has traded at a range from 91 cents to $3.95, closing at $3.40 yesterday. BioTime has traded in a range from $2.67 to $5.02, closing at $3.88 yesterday.

As part of the deal with Geron, the stem cell agency received 537,893 warrants to buy Geron stock at $3.98 each. The warrants expire in 2021.

Here are other news articles on completion of the transaction, which was announced earlier this year: by Jef Akst at The Scientist, by Damian Garde at Fierce Biotech.

Trivializing Conflicts of Interest at a $3 Billion California State Agency

The California stem cell agency is planning minor changes in its conflict-of-interest rules that narrowly target a violation that arose last spring involving two internationally known scientists.

The proposal was triggered by a situation in which Lee Hood of Seattle, Wash., was recruited to serve as a scientist-member of the group that was reviewing applications in a $40 million grant round last spring. One of the applications involved stem cell scientist Irv Weissman of Stanford University, a close friend of Hood. The men also own a ranch in Montana together and have scientific and professional links. Alan Trounson, the stem cell agency's president, has been a guest of Weissman's at the ranch and recruited Hood, an expert in genomics, as a grant reviewer.

CIRM, as the $3 billion stem cell agency is known, said it did not detect the relationship between Hood and Weissman until it was called to their attention by another reviewer who was also participating in the closed-door review of applications.

A staff memo prepared for next week's meeting  of the agency governing board described the violation as “inadvertent and highly technical.”

On Monday, the California Stem Cell Report reported that unspecified changes were being considered in the conflict rules. Following publication of the item, more information on the proposal was posted on the agency's Web site in preparation for next Wednesday's meeting of the agency's governing board in Burlingame, Ca.

The memo, prepared by the agency's attorneys, said, 

“In order to prevent both the reality and appearance of a conflict, while preserving CIRM's ability to attract the best reviewers available, the rules should flag only those interests that could genuinely be deemed material.”

The changes would create a threshold of $5,000 a year for conflicts involving salary or consulting fees. Less than that would not trigger a conflict situation. Other proposed changes to be taken up by the agency board involve personal and professional conflicts along with the nature of the economic disclosures that reviewers, all of whom are from out-of-state, must disclose privately to a handful of agency officials.

The agency's scientific reviewers do not have to disclose publicly their financial and professional interests despite the fact that they have made all of the decisions on 98 percent of the applications for the $1.8 billion the agency has handed out. The interests of the reviewers are also withheld from applicants, many of whom may have competing or professional interests. The agency requires that reviewers who have conflicts must be removed from consideration of applications where conflicts exist. However, there is no way to determine whether that is actually done because the applications are reviewed behind closed doors and the economic and professional disclosures are withheld from the public.

Our take:
The agency's position on the conflict involving Weissman and Hood is disingenuous. To say that it is “highly technical” trivializes the entire matter. The conflict problem does not necessarily arise because Hood's friend (Weissman) could have received a few thousand dollars through approval of a grant. It involves much, much more. The application was for $24 million to create the first-ever stem cell genomics center in California. Should Weissman's employer, Stanford University, have been selected for the facility, it would have accrued to the great benefit of that institution, both monetarily and otherwise. Indirectly, it would have also enhanced Weissman's already substantial reputation and prestige as a person whose name can sway actions by California's state research effort. In the world of science, reputation and prestige often count for more than money.
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Tracking the Fruits of California Stem Cell Agency Research

The California stem cell agency yesterday shed some interesting light on the awards in its $41 million round this week and their pathway to actually producing a product that can be used to treat persons who are suffering from diseases.

It is a difficult and long journey to generate usable therapies, a process poorly understood by the public, which was promised in 2004 that the stem cell agency would produce cures for ailments afflicting half the population of the state.

Writing on the agency’s blog, Amy Adams, CIRM communications manager, dealt with the issue indirectly. She said,

“Many scientists who receive our early translation awards first got their idea for a therapy while carrying out research with one of our other awards. In fact, eight of the scientists in this round of funding had previous CIRM funding for an earlier stage of research. If a scientist's early translation award provides good results, the scientists are then able to apply for one of our disease team awards, which fund the effort of compiling data to convince the Food and Drug Administration to allow them to test it in people.  Other organizations fund only early discovery research or only preclinical research. Under those conditions, researchers continually pause their projects to look for new sources of funding as the project moves through the phases toward clinical trial.”

One of the virtues of the California stem cell agency is its promise of a continued stream of funding. Former Chairman Robert Klein used to tout that particular aspect of the agency, particularly in light of limited federal resources.

Adams’ comments implicitly raise important questions concerning CIRM’s entire portfolio. How many CIRM grants have led to additional funding from CIRM? How many are basically one-off shots that have not led to research that has advanced the development of stem cell therapies, either via CIRM or other funding. What is the therapeutic and scientific significance of the research that is linked by more than one CIRM award?  What previously funded CIRM research could be fruitfully funded again to advance the science and not necessarily through the traditional grant rounds, which sometimes have awkward timing?

Unmentioned in Adams’ item is an application from a UC Irvine researcher that came up at Wednesday’s meeting of the governing board of the stem cell agency. The woman, whose name was not clearly audible on the Internet audiocast, publicly appealed rejection of her application by reviewers. She noted that it was an extension of work that was previously funded by the agency. She also noted that the score on her review was all but identical to work that was funded. The board, however, turned her appeal aside, which had already been rejected behind closed doors by CIRM staff.

Hers is not the only such case in CIRM history. But they are virtually impossible to track systematically because of the structure of the CIRM grant-making progress. It is also not clear whether the agency itself is tracking its research awards to determine if they result in continuing, fruitful research in a specific area. Nonetheless, the matter deserves some public attention. 

$41 Million in California Stem Cell Grants Virtually Approved

Directors of the California stem cell agency today all but approved about $41 million in early translational grants, rejecting all appeals by applicants and accepting staff recommendations on marginal grants.

The roll call vote was held open this morning to record a vote by one board member who was not present at the time. It is virtually certain that the member will vote in favor of affirmative action on the applications in question.

One member of the board, Joan Samuelson, abstained from voting on any of the applications. She said she did not think the board had adequate information on its total grant portfolio, particularly in view of the declining amount of money available.

The agency has about $600 million in uncommitted funds and is scheduled to run out of cash for new grants in 2017.

The research acted on today is aimed at “proof of concept for development of a therapy candidate and/or studies to select a development candidate. The approved grants can be found on this CIRM website page and are listed in tier one and tier two.  Identities of the applicants are withheld by CIRM to avoid embarrassing rejected candidates and to avoid disclosing the names of applicants to board members before they vote. However, applicants often appear before the board, as they did today, and identify themselves.

Five applicants appealed negative decisions on their applications by grant reviewers. The agency declined to disclose the appeal letters or identify the applicants, information that was a public record under the previous appeal procedures. New processes were put in place this spring that moved the appeals behind closed doors and made them subject to staff instead of board review. Nonetheless, rejected researchers have a legal right to address the board on appeals or any other matters.

At the request of the California Stem Cell Report, the agency provided the numbers of the grants on which appeals were filed. They are: 06787, 06888, 06761, 06793 and 06830. Review summaries on the applications can be found here. 

We have asked the agency to provide its legal and policy justification for now withholding information that was once a public record.

California Stem Cell Board Moves Positively on 'Wobbler' Grant Application

Directors of the California stem cell agency this morning ratified a staff recommendation for funding of a $1.8 million application that was a "wobbler" when it was examined behind closed doors by agency reviewers.

The CIRM staff had recommended funding of the application (No. 6823) with the condition that the agency staff be satisfied with the support to be provided by a collaborator. Reviewers had declined to approve the application outright.

The agency has not disclosed the identity of the applicant.

New Procedures at CIRM: California Stem Cell Agency Staff Nixes Grant Application

For the first time in its nine-year history, the staff of the $3 billion California stem cell agency this week  formally and publicly weighed in on grant approval actions by its prestigious reviewers, recommending that one application be rejected and another approved with conditions.

The staff, led by CIRM President Alan Trounson and Patricia Olson, the agency’s executive director of scientific activities, made recommendations to the agency governing board on three applications that can be described as “wobblers.” In other words, the board could go either way on the proposals when it considers them at its meeting in La Jolla on Wednesday.

Trounson recommended that the governing board reject one of the wobblers  (No. 6666),  a $2.0 million proposal, even though it received a higher scientific score – 70 – than the other two applications. Trounson recommended approval of two $1.8 million projects (Nos. 6831 with a scientific score of 66 and 6832 with a scientific score of 69), with staff-imposed conditions on one.

 Trounson said the agency is or 

 "will be funding 2 similar approaches to address photoreceptor degenerative disorders so addi-tional investment in an earlier stage project is harder to justify.”

All three fall into a newly defined category, called tier 2, for ranking of applications. The CIRM web site said tier 2 proposals are now ones that possess “moderate scientific quality, or consensus on scientific merit cannot be reached and may be suitable for programmatic consideration by the ICOC(the governing board).”

A fourth application  (No. 6648) for $4.3 million that scored below all three at 64 was approved, however, by reviewers after they imposed a condition on the proposal.  CIRM staff did not publicly address that application. The application review summary said that the researcher – who was not identified – must “demonstrate, within 12 months, the ability to make the hESC–derived 3-D sheets. This is a go no/go milestone for the project.”

The agency’s standard practice is withhold the identities of applicants prior to board action because they might be embarrassed.

In the other instance where conditions are to be imposed, they appeared to deal with an in-kind contribution of “essential services, technology and expertise.”

The new process for evaluating marginal or wobbler applications was established last March in response to an Institute of Medicine study last year that made a host of recommendations for improvements at the stem cell agency.

The staff recommendations on applications came in a $70 million early translational round that is aimed at “proof of concept for development of a therapy candidate and/or studies to select a development candidate.

In all, including staff and reviewer actions, 13 applications were recommended for funding, although the board has almost never rejected reviewer decisions. The 11 grants initially approved by reviewers total $37 million. With the two more recommended by staff, the figure would be about $41 million. A total of 39 applications were considered for funding.

Five applicants filed appeals of reviewer rejections, a CIRM spokesman said today. The  California Stem Cell Report has asked for copies of those appeals and CIRM staff action on them. Appeals are also being conducted under a new staff-dominated procedure, although all applicants have the right under state law to appear before the board to address any subject.

Budgeted grant funds that are unused are available to the board for future grant rounds in any area they so desire.

(An earlier version of this item incorrectly said six applicants had filed appeals, based on information from the agency. The correct figure is five.)

(Editor's note: Kevin McCormick, CIRM's spokesman, later commented on the agency's practice of withholding the identities of applicants to avoid embarrassment to applicants who are not approved. He said,  "Actually they are withheld so that the board doesn't know the identities of the researchers or the institutions whose applications they are voting on." 
(We should note that official CIRM policy is to withhold all applicant names until board action, but it does not release any of the names of denied applicants even after board action. However, it has in the past released in advance of board action the names of applicants when it suits its purposes . Also, the names of many applicants can be discerned based on information provided in the review summaries of the applications. The identities of applicant institutions can also be determined based on which board members are allowed to participate in discussion of specific applications as well as being allowed to vote. For more on the practice of withholding names, see here, here, here and here. )

New Ties to Big Pharma and Venture Capital Proposed at California Stem Cell Agency

The $3 billion California stem cell agency wants to recruit major biotech and venture capital firms to help provide tens of millions of dollars in research awards to California enterprises.

It's part of a move to “jump start” partnerships in a relatively new, $80 million, business-friendly program that is aimed at pushing therapies into the marketplace. The recruitment plan will come before the agency's governing board at its meeting next Wednesday in San Diego. 

Participating companies will have a special relationship with the state agency, including early input into concept funding proposals prior to their being presented to the agency's governing board. The “industry collaborators” will also be able to attend agency workshops and meetings involving hundreds of grant recipients. Presumably other, non-collaborating firms would be barred.

Other provisions of the plan call for special event-hosting arrangements aimed at creating more collaborations and posting of information from the selected collaborators on the CIRM website.

According to a CIRM staff document, the initiative would be limited to biotech and pharmaceutical firms with a market capitalization of at least $500 million and “qualified venture capital firms.” The document did not define what a “qualified a venture capital firm” is. The document also appeared to bar participation of privately held firms because of the “market capitalization” criteria, which typically uses a formula involving publicly traded shares.

Elona Baum, the agency's general counsel and vice president, business development, said in a statement provided to the California Stem Cell Report,

“This is aimed at trying to jump start the creation of the partnerships that are required to satisfy the commercial validation requirements of the Strategic Partnership Funding Initiative so that timelines are better synced-up as between our review and approval cycles for the Strategic Partnership RFAs and the lengthy time required for investors to conduct due diligence and negotiate an agreement with prospective applicants to Strategic Partnership RFAs.  CIRM's independent review and approval remains the same and is wholly independent. While there may be input given to a particular RFA it only at the high level concept stage and of course CIRM has no obligation to agree. In the context of the Strategic Partnership awards, CIRM wants to fund innovative high quality science that has attracted additional  investors.  Investors will help leverage CIRM fund and will be an important source of future funding to further the project.”  

$35 Million Research Grant Round to Remove Stem Cell Roadblocks

Directors of the California stem cell agency today approved a $35 million program aimed at removing bottlenecks to pushing stem cell therapies into the marketplace.

The plan would provide grants of up$1.2 million for about 20 awards with competition open to both business and non-profit institutions. Pre-applications are expected to be due in October with approval next summer.

Bluebird bio of Massachusetts Still Waiting for California Stem Cell Money

Seven months after the California stem cell agency awarded $9.4 million to bluebird bio of Cambridge, Mass., the company has yet to receive any of the cash from the Golden State.

Kevin McCormack, a spokesman for the $3 billion agency, this week said negotiations are still underway with the bluebird, which is planning to go public,  but did not elaborate. Post-award negotiations are common at the agency, but generally take much less time.

The cash from CIRM is scheduled to assist in clinical trials for a stem cell-gene therapy to correct a genetic disease in young patients with B-thalassemia, a rare blood disorder that can cause widespread organ damage and premature death.

Earlier this month, bluebird bio, which prefers the lower case lettering for its name, announced that it intends to take the company public in an $86 million offering. In March, it announced a collaboration with Celgene that provided for an upfront payment of $75 million and promised up to $225 million per product in potential option fees and clinical and regulatory milestones. The CIRM grant is conditioned on a matching commitment from bluebird.

Cash from the stem cell agency can only be spent on operations within California. According to the CIRM summary of the review of the bluebird application, which was scored at 73, the company said,

“We will have at least two clinical sites in California, and more likely up to 4 sites, 2) our viral vector manufacturing will occur in California, 3) our cell processing will occur in California, 4) we will hire several consultants and full-time employees within California to support the program. Overall, several million dollars will be spent employing the services of people, academic institutions, and other companies within the state of California.”

The company has said that it is working with Donald Kohn at UCLA and Elliot Vichinsky at Oakland's Children's Hospital.

The bluebird web site lists a California location for bluebird at 1001 Bayhill Dr, Suite 200, in San Bruno, which is south of San Francisco. An Internet search indicates that is a generic address for a number of business including a realty firm, a roof repair business and a family law attorney. The California Stem Cell Report has asked bluebird to clarify the nature of the address.

In an interview last October with Ron Leuty of the San Francisco Business Times, David Davidson, the lead scientist on the project, said,

“We began the process (with CIRM) early in (2012) but discussions have been going on for over a year about potentially pursuing this.

“The interaction with CIRM has been extraordinarily collaborative. We had contact with the coordinators at CIRM that helped us manage the process. It took a lot of effort on our part to put together a dossier providing support for our program. It was really like a mini-regulatory filing — on the science, the preclinical toxicology work that we’ve done, a detailed plan for the trial, a detailed plan for the budgets, a detailed plan on how we intended to spend the CIRM money in California. That was an important part of it. They wanted a clear plan on how this investment would be spent."

Sacramento Bee: Ongoing Conflict Problems No Help for Future Funding of Stem Cell Agency

The Sacramento Bee says conflict of interest problems continue to trouble the California stem cell agency despite its assertions that it has “turned a page” on the issues.

In an editorial Saturday, The Bee said that CIRM Chairman Jonathan Thomas “has vowed to be aggressive in avoiding conflicts in dispersing millions of public dollars for stem cell research. Yet serious conflicts continue to be revealed involving CIRM.”

The Bee cited articles on the California Stem Cell Report earlier this month about a $21,630 gift by its former chairman, Robert Klein, and the employment by Klein of Vice Chairman Art Torres. The Bee said the situation “throws into question a $20 million grant awarded last year to StemCells Inc., a company that wants to transplant neural stem cells to treat Alzheimer's disease.” (See here, here and here)

The Bee also cited the case of Lee Hood, an internationally renown scientist who violated the agency's conflict of interest policy. Hood failed to disclose to CIRM a conflict involving an application that he was reviewing on behalf of the agency. The Bee said the agency's failure to detect the conflict was “serious oversight."

Eight readers commented on the editorial and agency, generally unfavorably about CIRM.

But reader “bchild” said,

“It took a couple years for them to start funding projects and it may take years to see results. Wall Street got 1.5 trillion and the promise of 10x that if they get into trouble again, the scientists (and their business buds) just want a couple billion...In the end who do you trust more with public money? At least there is the appearance of public benefit here..."

The Bee concluded,

“None of this helps CIRM's reputation in being fair and impartial in spending $3 billion in public funds. It surely won't help the institute's standing with the Legislature and the public, should it need help staying in operation when its funding is exhausted in a few years.”

The editorial was also carried by at least one other paper in the McClatchy chain.

Multimillion Dollar Carrots for Stem Cell Research in California

Directors of the California stem cell agency approved an $80 million business-friendly plan that will dangle multimillion dollar carrots before biotech firms in an effort to push therapies into the marketplace.

The upfront payment effort will allow CIRM to take part in early stage clinical trials at no risk and could generate a list of achievements that will be useful in creating support for fresh funding after CIRM's money runs out in 2017.

The proposal is the first-ever from CIRM that involves no upfront payments. Instead, recipients will have to meet agreed-upon criteria to receive either grants or loans.

A CIRM staff document said,

“The major development milestone and success criteria will be mutually agreed upon between CIRM and the applicant at the beginning of the project(s) and at a minimum will require completion of a clinical trial that shows some level of biological activity/clinical efficacy and safety. The advantage to CIRM of this...is that CIRM funds will only be applied to projects that are successful.”

The proposal was wrapped into what the agency calls its strategic partnership plan, which also has a more conventional aspect, providing loans and grants in advance.

As part of the program, the CIRM board also today approved a $6.4 million award to Sangamo BioSciences of Richmond, Ca., to help develop a therapy for beta-thalassemia. The firm will have to match the amount of the award.

Nature Reports on Lee Hood Conflict Case

The journal Nature and genomeweb.com today picked up the story from the California Stem Cell Report about the conflict of interest case at the California stem cell agency involving renown scientist Lee Hood of Seattle, Wash.

Science news aggregators on the Internet also relayed various versions of the story. The facts were first reported on this blog yesterday. The matter involved a $24 million application for a genome project involving Irv Weissman of Stanford. Hood was one of the reviewers in the round. Hood and Weissman are longtime friends and own property together in Montana. They have also have a number of professional relationships.

In piece by Ewen Callaway, Nature additionally referred to ongoing conflict of interest issues at the agency, including the findings of an Institute of Medicine study. Harold Shapiro, head of the study, said the agency directors make "proposals to themselves, essentially, regarding what should be funded. They cannot exert independent oversight." 

The genomeweb item was also brief and did not mention the IOM study.

Grant Reviewer Conflict in $40 Million Round at California Stem Cell Agency

Internationally renown scientist Lee Hood, winner of a National Medal of Science, violated the conflict of interest policies of the California stem cell agency earlier this year when he was involved in reviewing applications in a $40 million round to create genomics centers in California.

Lee Hood
Institute of Systems Biology photo

The agency quietly disclosed the February violation in letters dated April 2 to the leadership of the California Legislature. The letter (full text below) said that Hood “agreed that there was a conflict of interest that he had overlooked.”

The conflict of interest involved a $24 million application that included participation by another eminent scientist, Irv Weissman of Stanford University, and funding for facilities at Stanford.

Hood owns property jointly with Weissman in Montana. In 2008, San Francisco Magazine, in a well-reported piece on the ballot measure that created the stem cell agency, described the property as a ranch and Hood as Weissman's “good buddy.” Hood has co-authored research papers with Weissman. Both are on the scientific advisory board of Cellerant Therapeutics, Inc., of San Carlos, Ca., a firm co-founded by Weissman. Hood's nonprofit firm, Institute for Systems Biology in Seattle, lists Stanford as a partner in the genetics of aging in humans. At Stanford, Weissman is director of the Institute for Stem Cell Biology and Regenerative Medicine, whose research involves aging. Weissman also serves on the Hood's institute's scientific advisory board.

Hood has not responded to an inquiry yesterday by the California Stem Cell Report for his perspective on the conflict of interest matter.

The conflict was not discovered by the agency during the review. It was raised by another reviewer at the end of the review, which, for the first time in CIRM history, failed to conclude with a decision supporting any of the proposals. Reviewers' comments have been sent back to applicants with another review scheduled for November. The agency said Hood will not take part in that session.

CIRM spokesman Kevin McCormack said today that Hood's conflict was “clearly a case of a new reviewer making an innocent error.” McCormack said it was not a violation of the state's conflict of interest law. The agency's conflict policies go beyond economic issues and deal with personal and professional conflicts. 

The agency's letter to the state legislative leadership said,

“Dr. Hood had not previously participated in a meeting of the GWG(grant review group), and as a result, he was not familiar with CIRM’s conflict of interest policy, particularly the policy’s inclusion of 'personal' conflicts of interest.  Thus, when he completed the conflict of interest form for the Genomics Awards review, he inadvertently neglected to indicate that he had a personal relationship with an investigator who was involved in one component of a joint application submitted by two institutions. Dr. Hood and the investigator are close personal friends and their families own vacation property together. Because of his personal relationship with the investigator, Dr. Hood had a conflict of interest with respect to the joint application under CIRM’s conflict of interest policies.”

The agency's letter said that Weissman would have received $11,000 over five years under the terms of the application, but that it also involved  "creation of a data center at one institution and three research projects that would be undertaken at (Weissman's) institution (Stanford). 

The California Stem Cell Report asked the agency about the involvement of CIRM President Alan Trounson, who has been a guest at the Montana ranch, and whether he recruited Hood as a reviewer. Last year, Trounson excused himself from participating in public discussion of another application involving Weissman.

McCormack said,

“Alan helps recruit many reviewers, including in this case Dr. Hood, but he is not involved in assigning reviewers to individual applications.”

The conflict of interest involving Hood was easily detectable in routine searches on the Internet, including a Google search on the search term “lee hood irv weissman.” The first two entries in that search yesterday turned up serious red flags.

Asked whether the agency performed “any sort of serious examination” of the confidential statements of interests filed by reviewers prior to review sessions, McCormack said,

“Yes, we do a serious examination of statements of interest from all our reviewers. However, this conflict was not identified by the reviewer either in the financial disclosure statement or identified in the conflict of interest list. Normally we do not check Google for all possible combinations of 15 GWG reviewers times about 200 individuals listed in these applications. That would be about 3000 independent Google searches to identify a possible conflict.”

The agency's legislative letter said that it plans to “amend its regulations to add greater clarity in an effort to prevent future conflicts from arising and to augment its efforts to educate reviewers, particularly new reviewers.”

Our take?

This is the latest in a series of questionable activities involving the stem cell agency, which is trying to come up with a plan to sustain itself after its state funding runs out in 2017(see here, here and here). The agency is giving more-than-serious consideration to an effort to raise funds from the private sector, which can lead to new and more difficult ethical considerations than a state-funded agency would normally face.

What these questionable activities demonstrate is that the $3 billion agency needs to give much more thought, to put it mildly, to its policies ranging from conflicts of interest to incompatible employee/director activities to the conduct of top management in providing special treatment for donors.

It also is clear that the statements of interests of reviewers are not examined closely for their accuracy by CIRM staff and attorneys. McCormack's remarks clearly indicate that the agency does not think it has time to be sure that no conflicts exist among its plethora of reviewers. That is precisely the reason reviewers' statements of interests – economic, professional and personal – should be made public rather than kept under wraps by CIRM. Then, interested parties, presumably mainly applicants, can check a panel of reviewers, if they wish, for conflicts in a particular round. Obviously, the agency can and should withhold the names of reviewers examining a specific application – the release of the names on the panel in a given review session is sufficient.

Tomorrow the CIRM governing board's evaluation subcommittee meets privately to discuss Alan Trounson's performance. It appears to be the second part of an evaluation process that began last October. Trounson's involvement with Weissman and Hood -- and his actions in connection with a $21,630 gift from a member of the public, albeit a not-so-ordinary member of the public -- should also be on the evaluation subcommittee agenda.

  California Stem Cell Agency Letter Re Lee Hood Conflict