42-08 Slamming the Door Part V: Gilman’s Resignation

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This article is part of The Cancer Letter's Slamming The Door series.

Slamming the Door

Part V: Gilman’s Resignation

By Paul Goldberg

Gilman’s letter of resignation, dated May 8, 2012, concludes with a hard slam:

“The purpose of this letter is to indicate my intention to resign from CPRIT, effective (with your permission) on October 12, 2012. At that time I will have worked for CPRIT for over three years—I believe longer than originally anticipated.

“During that time we have launched strong programs because funding decisions have been based on high-level competitions, where the judges have been some of the best cancer researchers and physicians in the country—free of conflicts of interest and all coming from outside of Texas.

“It was exciting to launch this program, to design effective requests for applications, and to oversee the peer review process.

“The program is now essentially at a steady state.

“Research activities that are yielding exciting results should be continued, and new applications should continue to be received—but some programs will perhaps need to be constrained or curtailed because of the desire to fund competitive renewals and expand commercialization activities. I doubt it will be possible to launch new initiatives at this point.

“The job of Chief Scientific Officer has become routine. You no longer require a full-time person.

“Your most critical concern will be to keep the external peer review system intact—retaining as many of the current committee chairs as possible. Your ability to do so will be critically dependent on the attitudes of CPRIT leadership, especially including the Oversight Committee.

“I have chosen the resignation date of October 12 for a few specific reasons:

• The next Scientific Review Council meeting that is scheduled to approve a slate of recommended research grants is October 5. I will stay until then to be certain that those who are preparing applications to be submitted by May 31 will still encounter a functional peer review system.

• Major decisions about research funding will be made by the Oversight Committee in July. I will attend that meeting to champion the research slate and to make it clear to the Committee that negative decisions about it would have a fatal impact on CPRIT’s peer review system.

“Negative actions would in addition be extremely harmful to the research community’s view of science in Texas, and thus on the ability to recruit scientists to the state (or, for that matter, the ability to attract capital for commercialization efforts).

“The MIRA grants to be presented to the Oversight Committee in July should have been funded in March; further delay simply must not happen. Also, July will see a large number of recommended recruitment applications. [MIRAs are Multi-Investigator Research Applications, the largest and most complex grants funded by CPRIT.]

“The relevant institutions are already engaged in attempts to secure commitments from these excellent candidates; some have already succeeded.

• If additional incubator grants are to be approved at the July meeting of the Oversight Committee, I will be there to hope that the rules governing review and

funding of incubators have been revised to prevent further award of vast funds for research programs ostensibly within incubators that were not described

and therefore could not have been reviewed.

• A delay of my resignation until October provides you with an extended opportunity to find someone new to fill my position.

• I ask for one additional week after the October 5 meeting of the Scientific Review Council to complete my affairs, dispose of professional books and papers, vacate my office, etc. I will be ending my career during its 42nd year.”

***

Gilman’s message was clear: he would take no bullshit. The CPRIT politicos had until Oct. 5, 2012, to fix this mess. After that, Gilman et al. would go more public than they already had.

The letter from the scientific council was even tougher than Gilman’s letter of resignation.

A seasoned academic fighter, Gilman was leaving it to outsiders make his strongest points, which in this case were about the possible failure to fund the MIRAs, accusations of bias, and the MD Anderson incubator.

It was clear that, with the sanctity of peer review on the table, the council members didn’t need to be prompted.

Their letter, dated May 14, 2012, follows:

“We received the letter (on May 11) from [members of the politically-appointed CPRIT Oversight Committee] James Mansour, Joseph Bailes, and [CPRIT Chief Executive Officer] William Gimson proclaiming their faith in the peer review system established under the initiative of Al Gilman for CPRIT: ‘complete trust in the gold standard process that CPRIT has established.’

“Further, ‘we know that the Oversight Committee wholly supports, and will continue to support, this process and will expect the Institute to maintain the high level of integrity and excellence that has been established.’

“However, these statements seem inconsistent with recent actions taken by CPRIT management or its Oversight Committee, and these actions are the reasons for Al Gilman’s resignation. The following is a response to these statements set in the context of the related events as we understand them.

“1. The seven Multi-Investigator Research Applications that the Review Committee recommended for funding (out of the 40 that were reviewed) were never brought to the Oversight Committee for approval and funding at its March meeting. As related by Gilman, Mr. Gimson stated that the reason was that he feared they would not be approved because of opposition from certain Oversight Committee members over the fact that a substantial fraction of the funding would go to UT Southwestern. By this action, members of the Oversight Committee essentially accused Al of somehow biasing the system. Such an accusation of bias implies further that we and the members of our review committees participated in the scheme, a point that we vigorously deny. We judge the review system managed by Al Gilman and led by us to not have been biased in any way relative to any institute or individual. At every point in this process, we have attempted to select the best cancer research and cancer scientists in the service of the citizens of Texas.

“2. At the same meeting of the Oversight Committee in March 2012, a $20M award for one year’s effort was approved for an incubator at Rice University and for research at The Institute for Applied Cancer Science (IACS) at MD Anderson. Approximately $18M of that award is slated for the IACS at MD Anderson. The IACS proposal was 6.5 pages long. It was submitted just a few weeks before the Oversight Committee meeting, and it contained essentially no scientific detail. The stated intent of the IACS is to discover anti-cancer drugs. From the proposal, it appears to have been developed to:

• Expand current target biology and small molecule discovery efforts

• Fund counter-screens against related protein family members

• Expand pipeline to include biologics

• Invest in efforts to develop novel chemistry platforms to address traditionally undruggable protein targets

“Although the brief document was strikingly lacking in specific research plans, we would characterize these activities as research. Apparently, the absence of a specific research plan was taken by CPRIT leadership as the justification for bypassing any review by CPRIT’s panel of reviewers.

“As we understand it, CPRIT leadership determined that incubator proposals were to be considered under the category of commercialization, not research.

“However, no product candidates are mentioned in the IACS proposal, nor is a company involved. After concluding that this proposal should be considered under the rules governing incubators, CPRIT followed the letter of their own law, in that incubator proposals were not to be reviewed for scientific content.

“We are surprised and disappointed by the failure of proposals of this sort to receive scientific (research) peer review. The $20M one-year award is by far the biggest that CPRIT has ever made.

“As members of the body that has been authorized to pass judgment on the merits of scientific proposals made to CPRIT, we will be viewed to have approved this award, and the failure to include us in the process calls into question our roles and the integrity of the review program in general.

“More importantly, this bypass is inherently unfair to every scientist in Texas who participates in the CPRIT program. Over this past two years, we have reviewed proposals from many Institutions in Texas that include one or more of the four scientific objectives listed above. These scientists have played by the rules that we understood were established by CPRIT’s Oversight Committee and publically stated in the announcements of the program.

“As the Oversight Committee is aware, in order to reduce possible conflict of interest, all members of the research peer-review teams are not from Texas and that we and the reviewers are excluded from discussions in which a real (or perceived) conflict of interest might arise because of a relationship with a Texas institution or investigator.

“Moreover Gilman, when present at the meetings, is there as an observer and to answer procedural questions. During the review process, Gilman does not offer an opinion on the scientific merit of a proposal, investigator, or institution. In fact, Gilman’s reputation for integrity and high standards of scientific leadership is what attracted us to serve as chairs and panelists in the peer review process for CPRIT.

“We firmly believe that the integrity of the CPRIT review process and its proper implementation are essential for advancing cancer research and cancer care in Texas.

“We would appreciate it if you would please forward this letter to the other members of CPRIT’s Oversight Committee and let us know when you have done so. It is essential that all members of this group are informed about the issues that face CPRIT.

“We are distributing copies of this letter to all members of CPRIT’s research peer review committees.

“Sincerely yours,

Phillip A. Sharp [Koch Institute for Integrative Cancer Research Massachusetts Institute of Technology]

Clara Bloomfield [Ohio State University Comprehensive Cancer Center]

Sanjiv Gambhir [Stanford Cancer Institute]

Tyler Jacks [MIT Koch Institute for Integrative Cancer Research]

William George Kaelin, Jr. [Dana-Farber Cancer Institute]

Richard Kolodner [University of California San Diego]

Charles J. Sherr [St. Jude Children’s Research Hospital and Howard Hughes Medical Institute]

Everett Vokes [The University of Chicago]”

***

“I built something I am proud of, and now it’s being taken apart,” Gilman

said to me much later, when it appeared that the game seemed lost. “I can’t work for people who are pushing their own interests at the expense of the interests of cancer patients.”

He was disappointed but not surprised.

“A wise and experienced friend said to me: ‘This is always the way it works when you put a large amount of public money on the table. The vultures and the hyenas lie low for two or three years to see how the system really works. And then they come in for their feast.’”

We will return to this statement a few times.

If the Gilman letter was akin to a stop sign, the letter from the scientific council was equivalent to flashing lights of a police cruiser in a rear-view mirror. Who could possibly ignore something like that?

In late May 2012, I wasn’t sure how the Texas politicians would handle Gilman’s departure.

Would they look for another world-class scientist to replace him? Would they be able to find someone who would have the credibility and skills to hold CPRIT’s peer review system together?

***

In those days, anyone could log on to the MD Anderson faculty blog to see what the insiders were saying.

Faculty and staff members used pseudonyms, but no great deductive leaps were required to see that the pseudonymous “Moonshot Marvin” was none other than MD Anderson’s former apologist Len Zwelling.

On May 21, 2012, Moonshot Marvin posted the following:

“I think everyone involved needs to consider a round of damage control by telling the truth about the money, the suspension of the CPRIT scientific review procedures in this case, the obvious conflict of interest at MD Anderson and…our state’s credibility. We seem to be living up to what New Yorkers think of us anyway.

“Quick responses involving great transparency and the elimination of the conflict of interest immediately would go a long way to save the reputation of CPRIT and MD Anderson and the role of both in generating the most important product of any scientific endeavor. The truth!

“So here are a few other questions for the principals:

• How did MD Anderson and the UT System allow this conflict of interest/nepotism arrangement to be established?

• Who sanctioned it and what are the safeguards in the system to allow oversight and manage the conflict at the very top of MD Anderson?

• We know the President’s conflict-of-interest disclosures are reviewed at the UT System level, but surely his wife’s are reviewed like all the rest of the Anderson faculty by its conflict of interest committee. Is this so?

• With money so difficult to acquire to support research, how could so much of it go to one project, especially one purported to be ill-defined as yet?

• How was it possible to bypass the scientific system established by a highly-respected Nobel laureate who was so instrumental in establishing the credibility of CPR IT with the rest of the scientific world?

• Who allowed any of this to happen?

• Where was the oversight by the leadership of the health components of the UT System and the UT Board of Regents?

“I think the leadership of MD Anderson should try to get control of this story by simply telling the absolute truth, preferably through an interview of Dr. DePinho by Mr. Berger.

“CPRIT’s Executive Director also has some explaining to do. The leadership of the UT System health care programs as well as the Board of Regents need to weigh in, too.

“How about it? Is there really any other way to get this behind us and all of us back to work?”

Comments by Moonshot Marvin notwithstanding, a subsequent audit by the UT System found no impropriety in the handling of the application.

In one of our on-record conversations, DePinho said he didn’t “attempt to influence a specific award decision by CPRIT or any funding agency, period.”

“I will, however, continue to be the most dedicated advocate for great science and drug development that’s occurring at MD Anderson, and that is my job,” he said. “I will continue to advocate the need to repair the broken ecosystem of drug development through greater joint efforts between academic entities and industries—it’s vital for patients.”

When I called him a few weeks after the CPRIT scandal became visible, DePinho declined to discuss the role the venture capitalist and CPRIT Oversight Committee member Charles Tate may have played in formulating the incubator proposal.

***

In an interview in January 2016, MD Anderson Executive Chief of Staff Dan Fontaine said the idea of combining IACS with the Rice incubator came from several directions at once.

“I’m not sure we ever really accurately portrayed the reason for having the [IACS] joined with Rice’s application for incubator infrastructure. And perhaps it’s the benefit of hindsight, the [IACS] was important for having to add to that because it created a pipeline of both scientists and potential products that would have fed that incubator in a very successful way.

As it turned out, to follow up on your question, I think that Rice has gone on with their incubator project. To be perfectly honest with you, I have not stayed that keyed into it. But certainly the [IACS] has proceeded on its pathway with a great deal of success.

“So I think the concept over time of the [IACS] and the idea that there needed to be a bridging link between discoveries and developing products has actually been proven out as being a very worthwhile investment on MD Anderson’s part because we’ve certainly invested in, and I think will continue to reap the benefits from the [IACS].

“Stepping back in time, as Ron arrived at MD Anderson, one of the things that I think he made pretty clear during his recruitment process is that he really believed that there needed to be something built so that we had a better chance of developing new drugs for cancer patients but didn’t have the same failure rate,” Fontaine said to me.

“And I think his theory at the time, based upon the work that he had done at the Belfer Institute [at Dana-Farber Cancer Institute], was that there needed to be a deeper level of chemistry, biology—those sorts of things in-house, with an academic component—which would then hopefully validate some of these inventions and move them along towards products.

“And he wasn’t just talking about internally at MD Anderson, he was being invited to make presentations on his thoughts in that regard in numerous forms around Houston and Texas. One that I know took place, and I’m not quite sure as to the timing, was at the Houston Technology Center. But remember that when he officially started in November of 2011, but when he first started coming down prior to his official first day in the late summer of 2011, he had numerous appointments with people around the state—both in the technology world and the biotech world, but also with folks who were on our Board of Visitors.

“In talking about one of the things that he wanted to build, being this thing called the Institute of Applied Cancer Science, was something that he was spending a great deal of time talking to people about. Because of that, I’m not quite sure which person was first, but I think there were people that were tied into the Houston Technology Center, people that were tied into biotech and the Venture Center, people that were tied into other areas that were knowledgeable about CPRIT, who said that sounds like something that might work well with a CPRIT grant.

“But since, I think, the RFA had been out for a while at that point in time—I’m not quite sure who made that introduction to Rice—but I think somewhere in those multiple discussions about it, this is probably one of those things that as you think about CPRIT funding for.

“The discussion about Rice having something that they were submitting might have come up. It may very well have been a conversation between Ron and someone at Rice, or it may have been a conversation between someone that knew what Rice was doing and had heard about the IACS presentation.”

***

I first called Gilman after he submitted his letter of resignation.

Gilman took my call.

I assured him that I would be fine with our conversations staying on background. He preferred that, because he wanted to make sure that CPRIT would be able to maintain its scientific integrity.

For starters, he wanted to make sure that the MIRAs would get funded, and he wanted assurances that the peer review system he built would remain intact.

He wanted the Texas politicos to understand that if they play nice, he would leave quietly, without slamming the door. Conversely, if they don’t give him what he wanted for CPRIT, the door would slam. Publicly.

The Nobel laureate was prepared to turn whistleblower.

Then Gilman casually let it drop that the MD Anderson proposal was never reviewed by the provost—Ray DuBois.

This was astonishing, because the role of the provost is to promote the academic mission of an institution. The rule of thumb in academic medicine is that the provost gets to sign off on any grant application that contains a budget.

The idea that the provost wouldn’t be consulted on something this was all the more astonishing, because the application asked for funds for expanding the capacity to conduct phase I trials, opening the potential for ethical problems to spill over into the clinic.

I asked Gilman whether he was absolutely certain. He was. Had DuBois signed off on the application, it would have been submitted through the CPRIT portal, which Gilman watched.

“Have you called DuBois?” I asked.

“I called and asked what the fuck,” said Gilman. “He said he never saw it.”

I realized that there would be no way for DuBois to stay at MD Anderson much longer. After all, he had been a contender for the president’s job. You’d think an alpha male like DePinho wouldn’t want him around.

I didn’t know DuBois well, but he was almost always described in the same way by almost everyone: a nice guy, polite, respectful, collegial, clean, honorable, plays by the rules.

Unfortunately, the only move open to me for my first foray into Texas oncopolitics was to put unsuspecting DuBois on the spot.

Would he tell the truth?

Next week: Part VI – DuBois Responds

Click Here to read the full series of Slamming the Door.

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