publication date: Feb. 19, 2016

Slamming the Door

Part IV: Nobel Laureate in Crosshairs 

 

In early 2012, Gilman was under the impression that CPRIT was functioning smoothly.

Then, to his surprise, the first of a series of controversies surfaced.

CPRIT’s peer reviewers had evaluated 40 applications for Multi-Investigator Research Applications, the largest CPRIT grants designed to fund team science, recommending that seven of these project receive funding. This was no small undertaking. The applications described multiple projects and core facilities.

Proposals for these projects—abbreviated as MIRAs—take a long time to write and a long time to review. The CPRIT committees worked hard to complete the review, but committee members were enthusiastic. There was a lot of good science on the table. In fact, one of the grants received the best score ever for an application of that type.

The projects were distributed all over the state and most of the proposals were inter-institutional, but five of the seven principal investigators were at UT Southwestern. This was understandable. UT Southwestern is, hands-down, the leader in biomedical research in the state. And, not surprisingly, it received the highest proportion of CPRIT grants.

By way of comparison, MD Anderson’s strength is in clinical research and clinical care. The institution has been building its basic science, and the focus on basic science was likely one important reason the regents selected DePinho to lead that institution.

Cumulatively, since CPRIT’s formation through 2011, UT Southwestern received $173.6 million in funding for 91 grants. MD Anderson was second, with $128.7 million in funding for 81 grants.

 

 

The fact that some institutions got more money than others seemed to upset some Texas politicians.

Documents I would later obtain under the Texas Public Information Act show that at CPRIT, an oversight committee member named Mark Watson, from San Antonio, constantly raised questions about the amounts of research funds going to UT Southwestern as well as about the cost of peer review.

Watson ran an insurance office and a ranch. He had previously served as chairman of the board of the Cancer Therapy and Research Center and assisted in the CTRC merger with The University of Texas Health Science Center at San Antonio. Gilman was surprised to learn that CPRIT’s executive director, Bill Gimson, decided to give in to Watson by unilaterally removing the seven approved MIRAs from the research slate that was to go to the oversight committee in March 2012.

This cut the total awards for research by two-thirds.

CPRIT management’s eagerness to appease Watson by changing funding requests outraged Gilman. Some politico out there was second-guessing peer review of grant proposals conducted by some of the best scientists in the world. What did Watson want? Regional quotas?

“One person (as best I know) is turning us on our heads,” Gilman wrote in a March 9 email to Gimson. “Nobody I know has ever heard of this guy before. Because of him, you are suggesting cutting just about 50 percent of our recommended requests for research, including nearly two-thirds of that destined for UTSW, almost half of that for Baylor, 100 percent for UT Dallas, etc.

“If we don’t fight back, rather than try to sneak around the situation, we are not worthy of our jobs.”

Though furious, Gilman refrained from raising hell—not publicly, and not yet.

He decided to hold back, because Gimson had assured him that the MIRAs would be funded later in the year, in July 2012. Basically, the executive director was asking for three months during which he would socialize and educate Watson.

Gilman had to sell this to the scientific council, assuring its members that delay was caused by political budgetary problems and that the grants would be funded.

This made Gilman uncomfortable, but he did it anyway, he said.

Had he known what else was about to happen, he would have been unwilling to compromise, he told me later.

 

 

In early March 2012, another CPRIT official, Jerry Cobbs, who ran the commercialization program, asked Gilman to look over a six-and-a-half-page proposal submitted by the Institute for Applied Cancer Science, Lynda Chin’s institute at MD Anderson. The proposal was sent directly to Cobbs via email.

Gilman looked at the thing and immediately determined that it contained no scientific content.

There were no targets mentioned, no molecules, no diseases, no intellectual property. Nothing to review.

Gilman said he had heard of that proposal before, and that the proposal should be submitted as a MIRA, accompanied by sufficient detail. Cobbs concurred, telling Gilman that the Chin proposal would go nowhere, at least for now. Wrote Cobbs: “Much too complicated as presented. Will just focus on Rice/TMC INCU. Will revisit the pipeline build opportunity with MDA at later date.” Based on the Cobbs response, Gilman assumed that this issue was dead for the time being.

But the Cobbs email warrants unpacking. Cobbs was referring to the incubator that was proposed by Rice University. That institution had made what Gilman regarded as a well-formulated and somewhat more modest request—about $4 million per year. The proposal received thumbs-up from reviewers and was heading toward approval by the CPRIT Oversight Committee.

Gilman was still unable to see what was coming.

 

 

Internal documents I obtained under the Texas open records law make it possible to see the things Gilman couldn’t have known at the time.

For starters, he couldn’t have known that DePinho and Chin were working with Charles Tate, a venture capitalist who served on the executive committee of CPRIT’s oversight committee, chaired the economic development and commercialization subcommittee, and served on the MD Anderson Board of Visitors, a group composed of wealthy supporters.

Tate had advocated the loophole for incubators, making them subject to review based on their commercial, as opposed to scientific, promises. He did not seem to understand that weak science would not be the progenitor of great products, Gilman would say to me later.

Documents show that, unbeknownst to Gilman, Tate was working on a plan to combine Chin’s incubator with the incubator proposed by Rice. The two proposals would be combined and sped through to oversight committee for approval.

In an email to Cobbs, the CPRIT commercialization officer, on March 14, 2012, Gimson writes that Tate had warned him about considering the Rice proposal first, to be followed by the MD Anderson proposal: “Jerry: Charles just called me—he is concerned about timing and bifurcated approach of the Rice/IACS Incubator. Let’s talk tomorrow early. Bill.”

Other emails similarly identify Tate as the author—or at the very least a co-author of the plan to combine the Rice and MD Anderson proposals.

A March 12, 2012, email from Gimson traces that idea to around March 2011. “[Tate] was very engaged (and vocal about the proposed structure of the incubator and more specifically the decision-making process for potential projects—he wanted a “one time” approval for the incubator with individual projects (to be funded from incubator’s grant) to be approved by a ‘strategic steering committee.’”

On April 23, Chin, reported that she had gone through her calendar and found that “the date at which point we decided to definitively move forward with putting the two [proposals] together occurred on Dec. 1, 2011, through two meetings…first with Charles Tate, at which point he indicated that IACS would fit very well with the incubator concept.”

Why were these behind-the-scenes activities necessary?

Possibly, giving money to Chin’s institute was a part of the deal—formal or not—that may have been struck at the time of DePinho’s and Chin’s couple’s arrival in Texas. Indeed, $75 million over three years would have given IACS a healthy start. Had it been funded, the purported incubator could have become a powerful tool for dispensing money by methods less cumbersome than peer review.

The money would have been placed in a black box, which IACS leadership would control.

Tate understood the complex interplay of government and industry in Texas. He also understood how lucrative such arrangements can be.

The financier has contributed $465,000 to the political campaigns of Texas Lt. Gov. David Dewhurst. Three years earlier, an investigation by The Dallas Morning News found that Tate and other donors to Gov. Rick Perry benefited from investments from the Texas Emerging Technology Fund. http://dallasne.ws/dNtkZ0

Tate appeared to be well compensated for his generosity.

A Tate company, called ThromboVision Inc., received $1.5 million in state funds, almost four times the amount Tate had contributed to Perry.

The company has since declared bankruptcy.

 

 

In the afternoon of March 22, 2012, a week before the CPRIT oversight committee meeting, Gilman’s administrative assistant walked into his office to tell him that CPRIT had just put up the slates for the oversight committee, and that the slates included a $20 million incubator grant for one year to Rice and MD Anderson.

“Bullshit,” said Gilman. “You are crazy.”

She said, “No, I am not.”

“That can’t be.”

“Take a look.”

She wasn’t crazy.

The grant to Rice was expanded to include MD Anderson. Actually, the way Gilman saw it, the title page of the Rice proposal remained unchanged and the six-and-a-half-page business plan describing Chin’s institute was fused to the rear of the Rice proposal. The Rice proposal was unchanged: it requested $12 million over three years.

The two documents didn’t refer to each other. They were completely independent; they were simply fused.

Suddenly, everything became clear to Gilman.

The delay in funding the seven approved Multi-Investigator Research Applications was directly related to the MD Anderson incubator. In fact, the desire to fund IACS without proper peer review had caused a delay in funding excellent research projects that went through review.

 

 

There were other problems with the way the incubator proposal was handled:

• The MD Anderson portion of the proposal was, in fact, submitted without review by any provost. Officials at Rice said that they reviewed only their own portion of the proposal. Rice officials said they “saw” the MD Anderson portion of the proposal only after it was first submitted to CPRIT.

• After bypassing standard institutional review, the MD Anderson portion of the proposal was submitted to CPRIT in a way that bypassed the procedures specified in the state agency’s request for proposals. The proposal was submitted by an official of Chin’s unit of MD Anderson directly to CPRIT chief commercialization officer via email, completely omitting the signature of MD Anderson Provost Raymond DuBois.

• The CPRIT official then turned around and, bypassing the electronic filing procedures, forwarded the email over to the contractor that manages grant awards for the state agency, knowledgeable sources said. The contractor then forwarded the application to the commercialization reviewers.

• In another departure from rules, a meeting of outside advisors who reviewed the commercialization proposal was convened by the CPRIT general counsel, rather than the contractor, sources said.

• At that meeting, which was held March 21, 2012, a reviewer who recused himself—citing his role on the board of directors of a company founded by Chin and DePinho—was nonetheless invited to address the committee and describe the track record of the individuals involved.

• The chair of the five-member review committee and one member of the board figured on the Rice portion of the application, which had been reviewed earlier. The committee’s chair didn’t cast a vote, but the conflicted committee member voted on the MD Anderson portion of the application, state officials confirmed.

 

 

Gilman went ballistic.

He arranged a meeting with Texas Speaker of the House Joe Strauss, but that accomplished little.

Also, he approached Francisco Cigarroa, the chancellor of the UT System. Cigarroa, who got an undergraduate degree from Yale and an MD from UT Southwestern, had the authority to stop the project.

Gilman and others had extensive conversations with Cigarroa. “Well, I just don’t think there is anything I can do about this,” Cigarroa said to them.

Later, Cigarroa would turn up at MD Anderson events, expressing support for DePinho and his Moon Shots.

Kenneth Shine, the executive vice chancellor for health affairs, found an ingenuous way to appease Gilman, yet not get in the way of approval of the giveaway of state funds to Chin. “Bill, I just received this email (from Gilman),” he wrote to Bill Gimson on March 28, the day before the CPRIT board approved the incubator. “It does suggest that postponing action and obtaining additional scientific review of the proposal makes sense. Ken.”

This choice of recipients is fascinating, because Gimson didn’t report to Shine. DePinho and Chin did.

Had he really wanted to stop this project, Shine would have sent instruction to them.

Gilman spoke with members of the CPRIT review council. There would be no way any member of the committee would stay in the job if the CPRIT higher-ups so blatantly disregard peer review.

The situation would be particularly egregious if the seven MIRAs remain unfunded while the IACS incubator would get a massive handout.

 

 

Internal documents later obtained from CPRIT made it possible to watch state officials make sure that the grant to the incubator cleared all the hurdles to final approval.

As they try to deliver $18 million to MD Anderson, officials sound a bit like car salesmen in a dealership’s smoking lounge.

“As a cautionary note, nothing is a done deal until it’s in the ‘hip-pocket-national bank’ but taking an optimistic view of tomorrow’s Board meeting, I would like your input on the announcement,” CPRIT Chief Commercialization Officer Jerry Cobbs wrote in a March 28, 2012, email to Chin.

This exchange is all the more remarkable because it shows high-level CPRIT and MD Anderson officials focusing on chiseling the language of the press announcement of the Chin incubator before it went to the CPRIT board for final approval.

In another email the next day, Gimson asks Chin for a strong quote for use in a press release.

“We are experiencing some internal pushback that the [Institute of Applied Cancer Science] proposal is not an incubator—and should have a ‘science’ review,” Gimson writes. “I would like a quote from you in this release to show strong support.”

Later that morning, Chin emails him this quote from her husband, DePinho:

“The cancer drug development system is broken. Today’s biotech paradigm of driving academic discoveries to effective clinical endpoints suffers a 95 percent failure rate. The IACS is a novel organizational construct designed to dramatically increase success by bringing together the best attributes of academia and industry to yield targeted drugs with clear applications in specific cancers. IACS comprises industry-seasoned professionals with proven capabilities in developing drugs, crating highly successful companies and forging productive alliances with biopharma. CPRIT support for this effort will catapult Texas to the forefront of the biotech industry in the decades to come.”

 

 

Many strings of emails begin with Gilman’s morally outraged discourses on what he sees as the obvious illogic of deviating from rigorous peer review or bowing to political pressures.

As these emails bounce around CPRIT and its governing board, state bureaucrats and advisors add in disrespectful remarks.

“I believe Al is upset because he wants these [incubator] proposals to come as MIRA proposals so that he has control over it…If this is accurate, then once again Al is operating from improper motives,” writes Jimmy Mansour, chair of CPRIT’s oversight committee and a telecommunications entrepreneur. His March 22 email, addressed to oversight committee member Joseph Bailes, was prompted by Gilman’s objection to the effort to approve the MD Anderson incubator without considering the assessing the scientific projects it would undertake.

As Gilman continues to disagree, Mansour instructs CPRIT chief executive Gimson and CPRIT attorney Kristen Doyle March 31: “I would simply tell Al that we must follow the rules in this matter. CPRIT policies and procedures and consistent application thereof are essential to the health and credibility of those [sic] organization.”

 

 

Other events were occurring outside Gilman’s purview included the approval of $11 million to Peloton Therapeutics. The decision to award these funds was made without any peer review by CPRIT.

Later this would lead to criminal charges against Cobb. Cobb, who was acquitted, had rushed the application through approval without arranging peer review. This case—the only criminal prosecution to result from the CPRIT scandals—surprised Gilman.

The funding was approved on June 18, 2010. The company—which grew out of research by Steven McKnight, UT Southwestern’s Department of Biochemistry chair—didn’t seek special treatment. And, presumably, it would have easily withstood rigorous review. Gilman made CPRIT aware of the McKnight proposal and the interest from the Column Group, a California-based venture capital firm. That was the end of his involvement.

When we discussed Peloton, Gilman said the Peloton grant was outside his purview. Review procedures were not well established for commercialization applications, particularly for nascent companies that did not have a previous track record. CPRIT never asked Gilman or the scientific reviewers to examine the Peloton application, and he never had a reason to see it—and never did.

He had no idea the application had not undergone formal review, but he told me that the review it clearly did get from Column Group was as good as it gets. The scientific leadership of the partnership included David Goeddel, a founder of Genentech. Other advisors included David Baltimore, a Nobel laureate; former NCI Director Richard Klausner; Columbia University’s Thomas Maniatis, one of the founders of modern molecular cloning; and Mike Brown and Joe Goldstein, both Nobel laureates from UT Southwestern.

The Column Group was putting its own millions of dollars into the venture.

“Peloton was the best investment CPRIT ever made,” Gilman said to me after that scandal started to emerge.

That said, he had no idea why anyone would skip peer review and thought that Cobbs didn’t deserve to face criminal charges for what was at worst a screw-up.

 

 

After CPRIT made the decision to fund the Rice-MD Anderson incubator grant, Tate made a fascinating statement:

“One of the biggest obstacles to getting life-saving treatments to patients is not a lack of good ideas or good science, but a lack of business expertise,” he said in a Rice press release, suggesting that there are plenty of good cancer drugs, and that commercializing them is all that needs to be done.

Of course, Gilman and his team of scientists regarded this statement as outrageous.

Venture capitalist Robert Ulrich, chair of the CPRIT commercialization panel, appears to be at least as pleased as Tate.

In an email, Ulrich projects that CPRIT would now spend 40 to 45 percent of its funds on such projects. “Incubators are just getting off the ground,” he writes in a May 2 email to Gimson. “In the near term, I suspect their funding requirements will be two to four times what they are for the first incubator… Bottom line, I can see an allocation of 10% Administration, 10% Prevention, 40% Research, and 40% Commercialization.”

On May 15, a week after announcing his plans to resign, Gilman prods Gimson to produce meaningful guidelines on incubators.

“It’s a simple question, I think: how much local autonomy on the amount of money to be handed out to any project or nascent company? And how do you judge the total amount that should be awarded to an incubator?

“$4M a year is really quite a lot. A related question: what is the density of the science in the area served by the incubator? An incubator in Houston should get more than one in Lubbock.

“It’s frankly hard to imagine an incubator in Lubbock.”

 

 

In internal memos, Gilman appears to be an alone, and often despised, advocate of science at a state agency suddenly gone political. Trust appears to be a deficit commodity on all sides. Pressure and isolation appear to get to Gilman.

“So I’m not a complete jerk,” he vents to CPRIT colleagues in an email March 8. “I just like to bay at the moon and yell at the jerks and otherwise make a complete pain in the ass of myself. I’ve become a curmudgeon. Or, as the old cigarette ad used to say, I would rather fight than switch.”

In an effort to get Gilman to leave voluntarily, Gimson starts pressuring him to leave the UT Southwestern campus.

In an email dated April 19, Gimson updates the oversight committee members Mansour and Joseph Bailes on the progress of that operation.

“[Gilman] is aware that peer review process will change and he must leave the UTSW campus if he is to continue at CPRIT.”

On May 5, three days before handing in his letter of resignation, Gilman writes:

“One of the things that has annoyed me the most over the past while is having Mark Watson and perhaps others question the integrity of the peer review system.

“Its establishment has been the one thing of value that I have accomplished over the past nearly three years.”

In a May 8, 2012, email to CPRIT scientific council member William Kaelin, a Dana-Farber Cancer Institute scientist, Gilman writes: “There are some really evil people on the [CPRIT] Oversight Committee now. Can they be taken out? I will not continue to work for them or with them. There are the ‘UT Southwestern is getting too much money’ people and there are the ‘we should spend much more money on commercialization’ people.”

Though decisions made at MD Anderson were contributing to the turmoil at CPRIT, officials at MD Anderson say the CPRIT emails weren’t reaching them.

“I don’t think, quite frankly, that anyone here at MD Anderson, including Ron, was aware of the level of discussion that was going on internally at CPRIT at that point in time. I don’t think there’s any question that we became more aware of this as it played out,” Fontaine said to me during a January 2016 interview.

“But in terms of Dr. Gilman’s view of what should be apportioned to basic science research or pure research versus commercialization; versus some of the other things that CPRIT was supposed to be doing in prevention, and getting companies to relocate to Texas, I don’t think anybody here—I can’t speak for 18,000 folks—but I would be surprised if anybody here was knowledgeable about what was going on there as other may have been that were more closely involved.

“I do believe that there had been some discussions kind of generally out there, amongst our faculty and others, that the number of awards that were going to MD Anderson versus other institutions, but I don’t think it ever got to the granular level of commercialization versus research, on our radar screen, until this story started coming about.”

 

Next week: Part V – Gilman’s Resignation Letter. Read the entire series of Slamming the Door here.

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