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.”

California Stem Cell Director Marcy Feit Leaves ValleyCare CEO Post

Marcy Feit
CIRM photo

Marcy Feit, a member of the governing board of the $3 billion California stem cell agency, this week suddenly resigned as CEO of ValleyCare Health Systems in Pleasanton, Ca., a position she had held since 1997.

Feit has served on the stem cell board since 2005. She was one of the few minority women to head a California health care system.

Some members of the stem cell board serve as a result of their professional capacity. In the case of Feit, she is a patient advocate member. It is unclear how her resignation might affect her continued service on the board.

Feit's resignation was first reported by Jeb Bing of the Pleasanton Weekly.

California's $70 Million Alpha Stem Cell Clinic Competition Ratchets Up

A $70 million race was kicked off last month as the California stem cell agency invited eight institutions to compete to create what it calls Alpha Clinics, enterprises that would attract patients from throughout the world for stem cell therapies.

The agency hopes the plan will lay a foundation for the stem cell industry in California and capitalize on the growing allure of stem cell treatments. CIRM President Alan Trounson, who plans to leave the agency this year, has been pushing the Alpha Clinic plan since 2011.

Beyond the agency's millions, CIRM has told applicants rather delicately that they have an obligation as well. “Show us the money” is the message obliquely contained in the agency's request for applications (RFA) for the Alpha awards.

The issue of matching funds is a tender spot for the agency this week given the flap that arose in the recent $40 million stem cell genomics round. A requirement for contributions was not mentioned in that RFA, leading some unsuccessful applicants to not include any. Stanford won with what it says is $7 million in matching funds.

CIRM's Alpha Clinic RFA does not mention cash, matching or money. But it does say the selection criteria involves in-kind or “other forms of support” and “sustainability,” which usually means a plan for raising cash or showing that cash is in hand. A coupled RFA is a tad more explicit. It mentions criteria involving “financial strength,” leveraging “assets” and “effectiveness in attracting a funding steam” after the award runs out. One or more applicants may think that the best way to show effectiveness in funding is to demonstrate it from the very beginning with a handsome sum.

Eight existing academic centers with hospitals were invited to apply last month to become Alpha Clinics, which will be one of CIRM's signature efforts, given the size of the round and its scope. Up to five awards will be made in that $55 million plan.

In a related RFA, five applicants have been invited to apply for one $15 million award to create a stem cell information and data management center. Not all of the five have been invited to apply in the clinic round. Awards in both categories will be for five years.

Kevin McCormack, senior director for communications at CIRM, said the invitations to compete were culled from 14 letters of intent to apply. The stem cell agency generally declines to disclose the identities of applicants for awards, although it has done so on at least one occasion in the past.

CIRM says its Alpha Clinic plan is aimed at providing “critical operational support for the conduct of clinical trials for investigational stem cell therapies” and to create “centers of excellence” for approved stem cell therapies. Applicants should show that at least two “lead clinical trials” will be conducted at their institutions along with a “committed source of funding” for each trial. CIRM said it would not pay for the trials or construction or renovation of facilities.

In addition to gathering medical data, the $15 million information center will be involved in marketing to potential patients and public communication. The RFA calls for the center to campaign against the “dangers of stem cell tourism,” which is increasingly growing overseas. The information center will also be involved in developing data to convince insurance companies and governments to cover the cost of stem cell therapies, which are predicted to be very expensive.

Because no more than five clinics may be funded, the chances for the eight are good. However, the CIRM governing board is increasingly feeling financially pinched as the agency's funds dwindle. Cash for new grants is expected to run out in the latter part of 2017. The board could back away from the idea of five clinics depending on what grant reviewers say.

Applications are due March 14. Board action is expected this summer with funds going out next fall or shortly thereafter.

A Question of Orthodoxy: Would California Have Funded Vacanti?

As UC Davis stem cell scientist Paul Knoepfler points out, it was a blockbuster story that grabbed attention around the world.

Not only within the professional stem cell community, but outside it as well because of the promise that the use of human embryonic stem cells could be avoided.

Charles Vacanti

So Knoepfler wangled an interview for his blog with Charles Vacanti, the man of the hour. He is head of the anethesiology department at Brigham and Women's Hospital in Boston. He is also a “virtual outsider to the highly competitive and fast-moving stem cell field,” says Carolyn Y. Johnson in a piece in the Boston Globe.

But it was Vacanti and his people who made the discovery that a simple acid bath could be used to generate pluripotent stem cells.

Sometimes people who catapult into the news as Vacanti did, especially in a controversial area, shy away from close questioning. Asked about how the interview came about, Knoepfler replied,

“I simply asked and amazingly he said 'yes' and was nice enough to answer 10 fairly tough questions.”

You can read the Q&A with Vacanti on Knoepfler's blog as they explore the science and the techniques. Knoepfler also has conducted a poll on whether people believe in Vacanti's stem cells. As of the latest voting, 25 percent are “not sure but leaning slightly towards they are real.”

One thing is fairly certain based on the Johnson's Globe piece on Vacanti, which was headlined,  “Ignorance led to invention of stem cell technique.”  Vacanti's research would not likely have been funded by California's $3 billion stem cell agency.

Its grant review process is dominated by persons who also dominate the current thinking in the stem cell arena. And Vacanti represents a departure from orthodoxy. He also would have been found lacking on a host of grounds, ranging from his professional background to his earlier research.

As Johnson reported in her story,

“'In science, the prevailing opinion is called dogma. And dogma is often right, and often wrong,' said Arnold Caplan, a biology professor at Case Western Reserve University and friend who has acted as a sounding board for some of Vacanti’s ideas.”

Moderate Media Coverage of Stem Cell Agency and Genomics Award

The California stem cell agency's $40 million stem cell genomics effort is receiving a moderate amount of attention in California media outlets and on some national online sites.

Some in the world of academic science might say, “So what.” The simple answer is that if the agency's work is unnoticed or unappreciated by the public, raising the cash to continue its awards beyond 2017 is unlikely. Funds will run out then for new grants, and the agency is looking for ways to stave off its demise. Its needs public recognition – particularly among well-endowed circles, be they private, industry or governmental.

The agency could be reasonably satisfied with its media play. This week's coverage represents an increase in media attention compared to the  usual meager stories about the agency's board meetings.

(After this item was posted, we caught up with an item by Kevin McCormack on the agency's blog. McCormack, the top communications person at CIRM, said,

("Reporters from newspapers, radio, TV and online news outlets around the state seemed to...appreciate the significance of the award.

("The story was carried in outlets from the Sacramento Bee and San Francisco Chronicle to the San Diego Union Tribune. ABC7 TV in San Francisco covered the meeting and NPR stations around the state also aired pieces about it. It even caught the interest of the sometimes-jaded scientific business press.

("The money we use to fund this research comes from the people of California, thanks to Proposition 71, so it’s important that they know how we are spending their money. This round of stories showed them it’s being used in ways that could one day help change the face of medicine.")

In California, stories appeared in the San Francisco Chronicle (Erin Allday writing), the San Diego U-T(Bradley Fikes), the San Francisco Business Times (Ron Leuty), the Sacramento Bee (David Jensen),  Palo Alto Online and San Diego Metro. Nationally, Xconomy (Bruce Bigelow)and Genetic Engineering News carried pieces.

The Associated Press did not carry a story, although the news service had one last Sunday, which was a rewrite of The Bee story that day. Duplicates of today's Bee story are likely to appear in California via the McClatchy-Tribune News Service, which distributes Bee articles to other outlets.

Most of the stories yesterday and today made little or no mention of the controversial aspects of the award process.

(Shortly after this item was posted, Nick Paul Taylor of FierceBiotech posted a piece that began,

“Illumina ($ILMN) is a company that has become used to success. Over the past year its share price has soared 180% as it has established a dominant position in what is potentially a $20 billion market. Yet this week it tasted defeat when Stanford University beat it to a $40 million grant to set up a stem cell genomics center in California.”

(GenomeWeb also filed a late story.)

The Chronicle story by Allday noted that the award was the board's “first formal foray” into genomics. Fikes' story in the San Diego U-T carried brief remarks from Jeanne Loring of Scripps, whose genomics proposal was rejected by CIRM, and Joe Panetta, president of the San Diego life sciences industry group, Biocom.

Panetta was attending his first meeting as a member of the agency's governing board. At the session, Panetta pressed for broader geographic representation, which would have favored Scripps' proposal. He told Fikes that he intends to become “a lot more engaged” in the grant review process.

Loring said the value of Illumina, Inc., as her partner was undervalued in the CIRM grant review process.

Here is Stanford's press release by Krista Conger, which carries the names of other researchers involved in addition to ones previously identified.

Correction

In the item yesterday “Stanford Consortium Wins....,” the vote on the genomics award was incorrectly stated as 6-2. The vote was actually 6-1.

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.) 

Genomics Center Discussion Begins

Deliberations in the $40 million genomics round at the California stem cell agency have begun.

California's Stem Cell Directors Back at Work

Directors of the California stem cell agency have resumed their meeting and expect to take up the $40 million genomics round after dealing with three brief items.

California Stem Cell Directors Working Through Lunch

Directors of the California stem cell agency are fetching their meals for a working lunch as they continue with their agenda at their meeting in Berkeley. Still to be heard are applications in the $40 million genomics round.

Just prior to lunch, the directors paid tribute to Michael Goldberg, who is leaving the board after serving since its inception in 2004. In his remarks after hearing his colleagues and noting the arduous history of the agency, he said,

"They tried to kill us. They failed. Let's eat."

$27 Million Approved for Basic Stem Cell Research in California

Directors of the California stem cell today approved, 11-0, about $27 million for basic research into workings of stem cells.

The round was originally budgeted for $40 million, but grant reviewers did not approve grants that would have required that level of funding.

Reviewers recommended 21 grants for approval for a total of $21 million. CIRM staff recommended another five costing $4.8 million. The 29-member board added another two grants totaling $1.1 million.

The board rejected other pitches by reviewer-rejected applicants for reconsideration. The stem cell agency later today is expected to release the names of all the winners. It never releases the names of rejected applicants.
 (Here is a link to the CIRM press release with the names of the winners.)

Stem Cell Ethics to be Examined in March

In its $700,000 study of the California stem cell agency, the Institute of Medicine recommended that it finance more work dealing with ethical issues in stem cell research. 

Today, CIRM President Alan Trounson announced that the agency was participating in a workshop in Berkeley in March. The above chart was presented at the meeting of governing board of the agency this morning. 

For more information, email the agency at info@cirm.ca.gov

$21 Million of Basic Research Being Discussed by Stem Cell Agency

Directors of the California stem cell agency have begun discussion of applications in its grant round involving basic biology research. The board is expected to award at least $21 million in this round. 

Conflicts Listed in Upcoming Voting in California's $40 Million Genomics Round

Here is a list of members of the governing board of the California stem cell and the conflicts of interest that exist on each application in the $40 million genomics round.

The list was provided by the stem cell agency at the request of the California Stem Cell Report.

The members listed in each row are are barred from voting on the grant listed in the far left column. (Following the first posting of this list, the agency said, "Steve Juelsgaard is erroneously listed as being in conflict with genomics application 6683 under the Data and Coordination Management category." Later in the day, the agency also reported another error.  "Jacob Levin is included for application 6708, but does not have a conflict.")

List of California Stem Cell Agency Directors with Conflicts of Interest on Voting in the Genomics Round by DavidJensen

A Reading List for California's $40 Million Stem Cell Genomics Round

Here are links to recent stories dealing with the California stem cell agency's $40 million stem cell genomics round -- a plan to make the state the world leader in the new field.

Thursday Jan. 23, 2014
California's Stem Cell Genomics Awards: An Untidy Affair
The California stem cell agency's $40 million genomics round seems to be turning into a bit of a muddle.

Friday Jan. 24, 2014
Stanford Genomics Consortium Likely Winner in $33 Million Stem Cell Agency Project
A seven-member consortium led by Stanford University's Center for Genomics and Personalized Medicine is expected next week to win a $33 million award from the California stem cell agency to create a stem cell genomics center.

Saturday Jan. 25, 2014
California's $40 Million Genomics Round: Charges of Unfairness, Factual Error and More
Scientists at two major California research institutions have leveled charges that the state stem cell agency's $40 million genomics round is tainted with unfair and non-scientific considerations along with factual errors, manipulation of scores and apparent preferential treatment.

Sunday Jan. 26, 2014

Sacramento Bee: California Stem Cell Agency Betting Big on Genomics
The Sacramento Bee today published an article by the publisher of the California Stem Cell Report on this week's $40 million genomics round and its significance. The Associated Press picked up the story and distributed it nationally.

Sunday Jan. 26, 2014
Alan Trounson's Opaque Messages, Genomics and $40 Million
Cryptic is probably a good word for the messages delivered last week by the president of the California stem cell agency, Alan Trounson, in his recommendations in the agency's $40 million genomics round. Odd might be another.

Monday Jan. 27, 2014
California's $40 Million Genomics Round and Conflicts of Interest
Concerns about conflicts of interest have dogged the California stem cell agency since its earliest days, and they continue into this week's $40 million genomics round.

Monday Jan. 27, 2014
California's $40 Million Genomics Awards: Stem Cell Agency Defends its Review Practices
The California stem cell agency today defended itself against charges that scoring on grant applications was manipulated in its $40 million genomics grant round to the benefit of a consortium headed by Stanford University researchers.

Wednesday Jan. 29, 2014
California Stem Cell Agency Withholds Key Information in $40 Million Genomics Proposals

The California stem cell agency has declined to disclose publicly a critical criteria – the amount of matching funds offered by each applicant -- in its ambitious $40 million genomics round scheduled to be acted on later today.

Wednesday, Jan. 29, 2014
The California Report -- Stem Cell Agency Puts $40 Million Up For Grabs in Genomic Research Grant This is a public radio show produced by KQED in San Francisco.

Wednesday Jan. 29, 2014

Stanford Consortium Wins $40 Million to Create Stem Cell Genomics CenterDirectors 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.

New CEO for California Stem Cell Agency in May

The California stem cell agency expects to make a decision on a candidate for a new president by May, the chairman of its governing board said this morning.

J.T. Thomas opened this morning's meeting by addressing the search for a new president to replace Alan Trounson, who has resigned but is serving temporarily.

Warren Roth, a representative of the Korn Ferry search firm, said that it expects to present candidates in late March. He said the board would be able to interview candidates in April.

The board has a regular meeting scheduled for May 29.

California Stem Cell Agency Opens Meeting to Discuss $40 Million Genomics Proposals

Directors of the California stem cell agency began their meeting today in Berkeley at 9:11 a.m. It is not yet clear at what time they will take up the proposals in the $40 million stem cell genomics round.

Stem Cell Agency Yet to Begin

Today's meeting of the governing board of the California stem cell agency appears to be a bit late in starting. We are checking on the situation.

California Stem Cell Agency Withholds Key Information in $40 Million Genomics Proposals

The California stem cell agency has declined to disclose publicly a critical criteria – the amount of matching funds offered by each applicant -- in its ambitious $40 million genomics round scheduled to be acted on later today.

A spokesman for the $3 billion state agency yesterday said the figures were not a public record. However, the agency has public revealed such figures in the past.

The matching funds played a major role in the top ranking of a $33 million genomics proposal by a Stanford-led consortium. Lack of matching funds also was deemed a serious problem by the agency's grant reviewers, who operate behind closed doors, in an application led by the Scripps Research Institute.

When asked for the figures, Kevin McCormack, senior director for public communications, said,

 “That is proprietary information, and so it's not available.”

He has not yet responded a follow-up question about the rationale for cloaking such figures in secrecy that goes beyond the simple assertion that they are proprietary. Generally, proprietary information is considered to be trade secrets or involve intellectual property or unique business methods.

Financing is commonly disclosed by businesses and is even required by federal law when a company is publicly traded.