Not all of those firsts necessarily enhanced the reputation of the California Institute of Regenerative Medicine (CIRM), as the $3 billion agency is formally known.
The unusual events and irregularities
surrounding the award, CIRM's largest research grant, merit additional attention, given
their implications about the integrity of the agency's grant review
process and how the agency does its business.
The California Stem Cell Report
recently asked a number of persons connected with the round and other
knowledgeable individuals about the process. Their comments included a judgment that the agency staff “took a lot of liberties behind
closed doors.” One of the rejected applicants "unequivocally" disputed assertions by CIRM President Alan Trounson that all applicants were
informed by him about the need for matching funds, a key criteria for
grant reviewers. The request for applications did not contain such a
requirement.
The comments came in addition to
earlier complaints by rejected applicants that scores had been
manipulated in an “appalling” fashion and that scientific merit
was not the first order of business in assessing the top four
applications.
Also surfacing was a problem generated
by
Proposition 71, the ballot initiative that created the stem cell
agency in 2004. The measure set up a 29-member governing board,
including deans of medical schools and others with ties to research
organizations. The board was supposed to exercise its expertise on
funding decisions. However, only seven members of the board actually voted in the genomics round. Most of
the rest had legal conflicts of interest and were not allowed to even participate in the discussion.
It is not unusual for that sort of situation to arise during funding
decisions by the board.
The CIRM stem cell genomics story began
publicly in a scientifically big way with an article in the journal
Nature Biotechnology in January 2012 by Trounson and two members of his staff. In it,
Trounson said his proposal was needed so that the agency could take a "firm and lasting grip" on stem cell leadership.
Later that month, the governing board of the agency
approved the concept for one or two genomics award. In February 2013, grant reviewers
for CIRM, whose identities are withheld by the agency, took a crack
at the applications. However, they declined to send any applications forward to
the board for final action. It was the first time in the agency's
nine-year history that has occurred. The reviewers offered no public
explanation for the move.
The closed-door review session was
marked by
a conflict-of-interest violation by Lee Hood of Seattle,
Wash., an internationally known genomics specialist, who was
recruited by Trounson to be a reviewer in the round. Hood is a close friend of
Irv
Weissman, who heads
Stanford University's stem cell institute. Weissman was named in Stanford's then $24 million application. Hood and Weissman also own a ranch together in Montana.
Trounson has
been a guest at the ranch. In 2012, he recused himself during CIRM board
discussions of two applications involving Weissman. The applications were from
StemCells, Inc., of
Newark, Ca., for $20 million each. StemCells, Inc., was founded by
Weissman, who still holds a large amount of stock in the firm and
serves on its board of directors.
Following the unsuccessful genomics review in February 2013, the applications were sent back to researchers with reviewer comments.
The proposals could be retooled for a re-review in the fall, they were
told.
After the fall review, the
reviewers – minus Hood -- sent the applications to the board with
recommendations to fund all four despite the fact that they would
cost $146 million, well above the $40 million budgeted for the round.
It was the first time that reviewers had made such a decision.
Normally they stay within the budget, but they offered no public
explanation for their actions in the genomics round.
At that point the CIRM staff, headed by
Trounson, became more involved. Under new procedures, the staff may make
recommendations concerning applications. In this case, they
recommended that only the Stanford application be funded, but only
after restoring a provision eliminated by reviewers. Trounson also
recommended no funding for the three other top applications in the
round. It was the first such major intervention by Trounson and the
most aggressive staff move on grant applications.
Trounson offered only a 23-word phrase
for recommending the Stanford application and no explanation for
rejecting the other three. Stripped from the public review summaries
for the three competing applications were the dollar amounts that
they had requested. It has been the longstanding practice of the
agency to include those figures. The amounts ultimately were made
available to the board at its Jan. 29 meeting.
At that meeting, Trounson strongly
backed retention of funding in the Stanford application for a project
led by
Michael Clarke,
associate director of Weissman's stem cell institute at Stanford. Following the 2013 conflict violation
involving Hood and Weissman, Weissman was removed from Stanford's application. Clarke was included, however. No questions were raised at last month's board meeting about
whether Clarke could be regarded as a surrogate for Weissman's interests and
whether that would involve a conflict of interest for Trounson.
Late in the meeting, Trounson
also said that he had personally told all the applicants, with the
exception of Stanford, that matching funds were expected as part of
the applications, an assertion disputed following the meeting by
J
eanne Loring of the
Scripps Research Institute, whose rejected
proposal contained no matching funds.
She said in an email,
"During the ICOC (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." (Loring's boldface)
Stanford said its application
contained $7 million in matching funds.
The agency withheld the figures when they were requested by the California Stem Cell Report prior to the Jan. 29 board meeting, although it has
released the figures in at least one other grant round.
Complaints about
manipulation of the scores were raised
prior to the board meeting by
Pui-Yan Kwok, leader for an
application from
UC San Francisco and
UC Berkeley. He said that the
scores of the top to applications were “based on the reviewers
removing from consideration the poorest performing center-initiated
projects.” He described the situation as appalling.
The agency defended its practices at the board meeting and in response to questions. It said
the scoring procedures were permitted under the RFA. It said that while the procedures may be different than those of the NIH so is the stem cell agency. It said that all persons involved had been screened for conflicts of interest
under CIRM rules and state law.
In response to a query by the
California Stem Cell Report concerning the process and the questions
that needed to be addressed, Loring replied,
“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., should
not be so 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 continued,
“The 29-member board 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 at least 5 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.”
Other critical comments came from a longtime observer of the agency, who asked not to be identified, and who said,
“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?
“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.”
During the board meeting, some board
members questioned parts of the grant review process. The anonymous observer said,
“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.
“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.”
In response to the same query, Michael
Snyder of Stanford and Joe Ecker of the Salk Institute in La Jolla,
co-leaders of the Stanford-led effort, did not raise any questions about
the CIRM review process. They said,
“The net result (of their proposal)
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. questions.”
