Chair of CPRIT Oversight Committee: “Better to Get Them All Out of the Way Now”

What were Texas politicians and CPRIT officials thinking as they were pounded by blistering letters of resignation?

Condemnation seemed to be rolling off their backs as they marched toward what they thought was their great triumph.

Jimmy Mansour, chairman of CPRIT’s oversight committee, mistakenly hit Reply All, sending an especially contemptuous email to a scientist who was announcing his resignation from CPRIT. In the email that came into public view because of his sloppiness, Mansour, a telecommunications entrepreneur, belittles scientists and the peer review process.

The email is also remarkable because it illustrates the reluctance on the part of CPRIT officials to recognize that the institute that distributes $300 million a year in state funds is, in fact, in the midst of a crisis.

Here is what Mansour had to say about the resignations:

This wasn’t the first time Mansour slammed Gilman in an email.

In an earlier email, Mansour said Gilman’s opposition to funding the MD Anderson-Rice incubator was a power grab.

“I believe Al is upset because he wants these [incubator] proposals to come as [multi-institutional research grants] proposals so that he has control over it…If this is accurate, then once again Al is operating from improper motives,” he wrote in a March 22 email to CPRIT oversight board member Joseph Bailes, which was obtained by The Cancer Letter (The Cancer Letter, Sept. 28, 2012).

In a clumsy effort to get out of the nasty mess, Mansour said he didn’t intend to be disrespectful: “My comment was referring to getting the resignations out of the way, not the reviewers. I felt that rather than having them trickle in over time, it was better to have them come in all at once and get them out of the way. I have tremendous respect for our peer reviewers and have a deep appreciation for the work they do for CPRIT. It is understandable that peer reviewers would leave when Drs. Gilman and Sharp leave—and make way for a new Chief Scientific Officer.”

Gilman was seeing confirmation of his concerns.

“The message I am getting is that they no longer want to be constricted by rigorous scientific review,” Gilman said to me. “They want freedom to follow the path of increased commercialization, whether or not they get meritorious proposals. CPRIT will not be able to solve its problems by issuing a call for new scientific reviewers, as no responsible scientist would join the organization without clear evidence that CPRIT has addressed the causes of its current problems. They need to clean house and they don’t seem to want to clean house.”

Mansour’s clumsy Reply All triggered an editorial in Nature.

“Mansour would make an almost comic villain were the stakes not so high. He is responsible for the $3 billion that more than 60 percent of voting Texans approved in 2007 to fight cancer over ten years; his term at the head of the governing board does not expire until 2015,” the editorial reads.

“Yet it is clear that, if the institute hopes to recruit independent peer reviewers of the caliber that have just departed in droves, its leadership must change at the very highest levels. Mansour’s removal is essential; at least one ethicist has suggested that Gimson should go as well. Such housecleaning is also the only way to begin rebuilding the trust of the Texas public, which has every right to expect that the $2 billion as yet unspent by the CPRIT be awarded through unimpeachable peer review. After all, when they voted five years ago, Texans authorized the state to borrow $3 billion ‘for research in Texas to find the causes of and cures for cancer,’ They did not vote for awards to bypass scientific scrutiny, for cronyism or for the equal distribution of grants between Texas institutions, regardless of the quality of proposed projects.”

Gilman couldn’t have said it better.

The state’s enthusiasm for commercialization spilled out in another important way: the UT System granted a waiver for MD Anderson President Ronald DePinho to continue to play a role in three companies he co-founded.

“Among the major issues which I considered was your unique history and experience in developing new agents to help patients and create companies and procedures which would bring research results to the bedside,” said Kenneth Shine, then the UT System executive vice chancellor of health affairs, in a letter to DePinho. “The Regents of the University of Texas believe that this experience is valuable to the MDACC and the University of Texas System.”

In a Q&A with The Cancer Letter at the time, Shine said the decision is consistent with the conditions under which DePinho accepted employment. The UT System declined to grant waivers covering several of DePinho’s conflicts.

“Dr. DePinho and his wife have to divest themselves of stock and consultation fees and other benefits, which, in fact, have great financial value,” Shine said. “In other cases, no waiver was granted and there were no financial implications. But I’m not going to go into detail as to what companies were there for a whole variety of reasons.”

MD Anderson officials released the cover letter conveying the decisions, and the UT System released the actual decisions memorandum under the Texas Public Information Act. The waiver also covers DePinho’s wife Lynda Chin, a senior scientist at MD Anderson and his partner in biotech ventures. She is covered by the waivers by virtue of being his spouse, officials said.

Chin was also a key figure in the CPRIT controversy. The explosion at the state institute that spends $300 million a year was caused by the decision to fund an $18 million biotech incubator in which Chin was a co-leader. The proposal was approved as a “commercialization” activity, and received no scientific review.

The waiver covered DePinho’s interactions with three companies: AVEO Pharmaceuticals Inc., Karyopharm Inc., and Metamark Genetics Inc. According to documents that had been leaked to the Houston Chronicle, DePinho was seeking a broad waiver covering 12 entities (The Cancer Letter, Sept. 21, 2012).

Describing the waivers to the MD Anderson staff, DePinho wrote:

Limited waivers have been approved for three companies—AVEO, Karyopharm and Metamark—and my holdings in those companies will be put into blind trusts, so that I will have no knowledge of the status of my holdings and no right to intervene in their handling.

For other companies, I have divested or will divest my interests in a timely manner so that no waiver is required or granted.

Dr. Shine’s waiver decision has been provided to our conflict-of-interest committee, which will formulate specific management and monitoring plans for overseeing any research at MD Anderson involving products of these companies. The UT System conflicts committee will evaluate and finalize those plans along with Dr. Shine.

Of course, our institutional review board also will have every opportunity to review any research involving an IRB protocol, which will provide an additional safeguard to protect patients and ensure research integrity.

It’s not publicly known whether the blind trust was ever set up. Also, the UT System didn’t release any materials from the advisory group of chairs of conflict of interest committees of all six UT System campuses. The system obtained a ruling of the state Attorney General to keep these materials shielded from requirements of the state’s open records law. The recommendations of that committee are unknown.

Arthur Caplan, director of the Division of Medical Ethics in the Department of Population Health at NYU Langone Medical Center, said the waiver would undermine the trust in MD Anderson’s top executives.

“In trying to allow its new CEO to retain some of the corporate ties he created in his prior position, the administration of the University of Texas System is walking a narrow and sharp ethical edge,” Caplan said after reviewing the documents I sent him.

“Allowing lucrative ties to exist at the highest levels risks undermining the trust of the faculty and staff in the neutrality of the key institutional decision-maker and potentially the faith subjects bring to the cancer center’s clinical trials that what is recommended to them is not driven by commercial interest.

“As pressure builds to link financially stressed, research focused academic institutions to companies large and small, trustees, chancellors, presidents and government agencies need to bring 20th century thinking about how to handle conflicts of interest into the 21st century world, where large monetary returns and the entrepreneurship that creates them collides with the credibility institutions need in order to merit tax payer support and public trust.”

Eric Campbell, an associate professor of Medicine at Harvard Medical School and a researcher at the Mongan Institute for Health Policy, said publicly available information is insufficiently detailed to make it possible to evaluate Shine’s decision.

Campbell said he couldn’t understand why the waiver was necessary.

“The key unanswered question is why these companies need to interact with MD Anderson,” he said. “Why can’t they find similar resources at other major cancer centers?”

DePinho accepted Shine’s decision.

“A scientist’s dream is to work on something that ultimately benefits patients,” he wrote in a dispatch to the staff. “I have deep respect for all of our scientists and clinicians working to attain this goal. I also recognize how important it is to manage conflicts of interest or perceptions of such. Dr. Shine’s decision further confirms MD Anderson’s focus on protecting our patients first and making great strides in accomplishing our mission to eliminate cancer.”

Scientists across the U.S. viewed events at CPRIT as lamentable: the dissolution of a world-class peer review system that helped dispense $300 million a year. Top Texas politicians didn’t want any part of these blues.

Days after Gilman’s departure, Governor Rick Perry made a surprise appearance at the institute’s conference.

“Since CPRITs creation, you all have helped lay a sound foundation to establish one of the greatest cancer-fighting tools in human history,” Perry said. “The challenge that remains before us is to build on that foundation, and finally begin curing cancer once and for all. It’s a lofty goal, but I have full confidence that with your collective intelligence, passion and drive, we can take the next step. We can foresee a day when those waiting for the drug that will shrink their tumor will be waiting no longer.”

This statement could mean either that:

(a) Perry doesn’t realize that his claim that Texas has done all the basic science required to proceed to cranking out cancer cures would not gain wide traction among scientists and clinicians, or

(b) CPRIT has become precisely what the governor and others in Texas politics want it to be: a pot of public money that can be dispensed for commercial or political purposes.

A few days later, Perry, joined by Lt. Gov. David Dewhurst and Speaker of the House Joe Straus wrote a letter to CPRIT officials, urging them to move beyond funding basic research and broaden the institute’s mandate to commercialization.

The letter, dated Oct. 19, 2012, was written a week after Gilman’s departure from CPRIT, the blistering op-ed piece by Gilman and Sharp.

It was an odd time to strike the tone of triumphalism.

Here is the text of the letter:

I called Gilman to discuss these developments.

He seemed to be in good spirits. After getting out of CPRIT offices, he was spending a lot of time on the golf course.

Indeed, Gilman’s opponents appeared to have prevailed. He was out, top Texas politicos were writing love letters to CPRIT, pointing it in the direction of commercialization, and the conflict-of-interest controversy surrounding DePinho and Chin was waived.

As we spoke, Gilman was holding the cellphone while operating a mechanical branch chainsaw, the sort attached to a long pole.

“Assholes,” he said, as a branch of a red oak fell to the ground.

Click Here to read The Cancer Letter’s series Slamming the Door.