Part XII: Scientists Vote with Their Feet

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Slamming the Door

Part XII: Scientists Vote with Their Feet

In their op-ed piece, Gilman and Sharp stated what it would take to fix CPRIT’s problems. That was the polite version of the Gilman Plan.

The spoken version was more blunt: get rid of the “assholes” on the oversight board, jettison the administrators, then—maybe—CPRIT’s credibility would be restored.

Maybe the place will become functional someday, but only the oversight committee is sent packing and after the Gogolesque characters are kicked out of CPRIT’s offices in Austin. Until that occurred, an effort to rebuild would require CPRIT to turn to the scientific establishment on some other planet.

Politicians who ran CPRIT didn’t seem to understand this. They continued to act as though they were going to win the war against those intellectuals.

I knew that CPRIT operatives were trying to recruit Raymond DuBois to take over after Al Gilman. That made sense for them, but not necessarily for DuBois.

With America’s premier scientists leaving CPRIT publically, Texas politicians needed a scientist who had a national name and a reputation for integrity. I could also see why DuBois would talk with these people. He is polite.

But he had already agreed to accept a job at the BioDesign Institute at Arizona State. How would it be okay to run a Texas state funding agency by a part-time employee out of Arizona? Would he want to work two jobs? Most importantly, the problems at CPRIT now boiled down to matters of principle: political meddling with peer review. Gilman’s entire cadre of scientists—all or nearly all of them—were about to walk out.

Why would DuBois want to get on the wrong side of that?

***

The letters of resignation kept arriving.

The stature of rank-and-file reviewers is perhaps the most remarkable aspect of the peer review structure Gilman constructed. Now, these reviewers are sending in their letters of resignation.

None of these people really had to resign. They left because they wanted to, and many of them sent their letters of resignation to CPRIT officials, with a cc: to The Cancer Letter. They wanted to join Gilman on the dais for the teachable moment. It was all the more extraordinary, because scientists as a group don’t like to go out of their way to make enemies.

I’ve seen many of my friends keep a straight face while former NCI Director Andrew von Eschenbach was expounding on his pledge to eliminate suffering and death due to cancer by 2015. Here, the scientists were jumping at the opportunity to declare that they would not accept political meddling. The Nobel laureate’s experiment was producing a show of solidarity of the magnitude you don’t usually see in the U.S. Scientists were acting in a manner you would expect from advocates.

Here are some of these letters:

Brian Dynlacht, professor of pathology at the New York University School of Medicine:

I am writing to formally resign my position as a scientific reviewer for the CPRIT Basic Science Cancer Research Committee-3, BCRC-3, effective immediately.

By way of introduction, I have been a scientific reviewer for the CPRIT BCRC-3 committee under the chairmanship of Dr. Charles Sherr. I have followed with much interest and, I must admit, substantial consternation, the series of events that have transpired at CPRIT over the past six months.

I am extremely disappointed by what I have heard, and especially upset by both accusations against Al Gilman and the direction of CPRIT leadership has chosen, which is apparently to promote commercialization at the expense of rigorous scientific review.

In all of my years in academia, I have never encountered two more honest, intellectually rigorous scientists than Al Gilman and Charles Sherr. I can say with complete certainty that their motives are, and always have been, completely free of bias.

They are the absolute cream of the crop. I wholeheartedly agree with their stance on matters that have recently surfaced at CPRIT, in particular, those matters stipulated in Dr. Sherr’s resignation letter, which I will not reiterate here. On that basis, I must follow them by submitting my resignation. I anticipate that you will be receiving an onslaught of letters similar in content and sentiment to my letter.

In addition, I will forward this letter to Dr. Sherr, CPRIT review Council members, and, in all likelihood, The Cancer Letter and The Houston Chronicle.

I have served on many federal and private scientific review committees, and I have never served with such an accomplished and outstanding group of scientists. The elite panel assembled by Dr. Sherr was intellectually rigorous, honest, and conscientious. Al Gilman oversaw each meeting with professionalism beyond reproach. You will not find a better group of human beings or scientists no matter how hard you search. Let me repeat that: Drs. Gilman and Sherr have done something remarkable here, by assembling this group, and it is unlikely that you will be able to reproduce their accomplishments without them no matter how hard you try.

You may find that it was not worth subverting the entire scientific enterprise—and my understanding was that the intended goal of CPRIT was to fund the best cancer research in Texas—on account of this ostensibly new, politically-driven, commercialization-based mission.

Indeed, I am of the opinion that such a policy—wherein science that is judged meritorious by a highly esteemed group of scientists is discounted at the expense of science that has not been methodically reviewed–will not only fail to recognize and extract the best possible science from your state, but it will in fact succumb to mediocrity and systematic abuses.

It has been an honor to serve on this esteemed committee. It is a shame that it will be completely dismantled. While it was challenging and arduous work, it was indeed a genuine pleasure to work with this group of enlightened and brilliant scientists. It is extremely unlikely that I will serve with a better group of scientists in the future.

Monica Bertagnolli, professor of surgery at Harvard Medical School, chief of the DF/BWCC Division of Surgical Oncology, and group chair of the Alliance for Clinical Trials in Oncology:

I am writing to inform you of my decision to resign from my position on the CPRIT scientific review panel led by William Kaelin, MD, effective Oct. 12, 2012. I do so with regret, as my work on the panel provided me with tremendous professional satisfaction.

It was a great honor to work under the direction of Dr. Kaelin, whose grasp of basic and translational cancer research is truly remarkable. He led the committee to recognize and reward excellence where it was demonstrated, and to provide constructive feedback and encouragement to researchers whose proposals were not recommended for funding.

Working with Dr. Al Gilman was one of the highlights of my professional career. His is not only one of the greatest scientists of our age, he also is one of the rare individuals who understand the real world strategies that must be employed to achieve success. In their service to CPRIT, both Dr. Kaelin and Dr. Gilman demonstrated the highest professional and ethical standards without exception, and their single goal was to serve the citizens of Texas by promoting cancer research of the best possible scientific quality and integrity.

The implication that reviews were biased toward or against a particular awardee institution is simply ridiculous. In fact, the committee ignored mention of the institution unless there was a specific reason to consider it, e.g., if the research required access to a specific resource that was only available in a particular location. It is similarly outrageous to consider that many detailed applications so painstakingly prepared by Texas researchers could be reviewed and approved for funding in good faith, only to have this review negated by diverting funding to a briefly outlined “commercialization” proposal from MD Anderson/Rice.

This shows an appalling lack of respect for the applicants as well as the reviewers. Finally, in awarding funding, I believe that it is critically important for commercialization potential to be secondary at all times to scientific quality. Many projects that have significant commercialization potential in the short term also lack scientific validity.

Without placing scientific rigor above all else, the citizens of Texas risk supporting investments that ultimately prove wasteful, while diverting resources from important work that can improve the lives of cancer patients.

My experience on the committee was one of hard work, thoughtful deliberation, and respect for the goals set forth by CPRIT. Our committee reviewed a large number of outstanding proposals from Texas cancer researchers, and I am confident that those recommended for funding will benefit the state by achieving significant advances in the battle against cancer. Unfortunately, given the events of the past several months, I can no longer be certain that this will be the case going forward.

I therefore respectfully submit my resignation.

John Cleveland, professor and chair in the Department of Cancer Biology at the Scripps Research Institute:

I hereby tender my resignation as a Member of the CPRIT BCRC-3A Review Panel. This decision is based on the recent events that have unfolded at CPRIT, which appear to have driven by very misguided perceptions, special interests and agendas of the Oversight Committee that, very sadly, undermined the principles of grant peer-review.

I assure you that, under the leadership of our esteemed Chair, Dr. Charles Sherr, and that of Dr. Al Gilman, the very highest principles and standards were applied to the review of all IIRA, HIHR and MIRA grants, and that all funding decisions were made purely on the basis of the merit of the proposed science, and on their importance to the stated mission of CPRIT.

Indeed, the rigor of these reviews, and the incredible group of scientists that were recruited by Dr. Sherr, made the CPRIT BCRC-3 Review Panel truly exceptional.

It was a true honor and privilege to serve on the CPRIT BCRC-3A Review Panel, and to provide these important services to the citizens of the great state of Texas for such a worthy cause. However, given the actions of the Oversight Committee I cannot in good conscience continue to serve as a reviewer for CPRIT.

I sincerely hope that in some way this action prompts the Oversight Committee to reconsider their current direction and restore sanctity to the proper review of CPRIT applications.

William Hahn, deputy chief scientific officer and chief of the division of molecular & cellular oncology at Dana-Farber Cancer Institute:

I write to inform you that I am resigning from the BCRC-1A Review Panel of the Cancer Prevention and Research Institute of Texas (CPRIT) effective immediately.

When I was asked to join this committee three years ago, I did so with enthusiasm for a program that I believed had real potential to accelerate cancer research and to eventually bring new treatments to patients. The citizens and legislature of Texas are to be applauded for

their foresight and generosity to establish CPRIT as a bold statement of what can be done to improve the lives of patients affected by cancer.

For the past three years, I thoroughly enjoyed working with top cancer scientists from around the country to provide CPRIT with rigorous and impartial review to ensure that these public funds would be allocated to those projects most likely to impact the prevention, diagnosis and/or treatment of cancer.

These deliberations occurred in an environment created by Dr. Al Gilman and the chairs of the CPRIT review panels that was entirely free of political influence or institutional bias. I have served on numerous international and national study sections and can say with confidence that these CPRIT panels were models for high quality, unbiased review.

Unfortunately, recent actions of the CPRIT Oversight Committee now undermine the basic tenets of this process. The accusation that applications were ranked by institutional bias rather than scientific merit is simply not correct and is an affront to all of us who participated in these reviews. At the same time, delaying the funding of highly ranked applications to fund incubator projects without scientific review emasculates the credibility of CPRIT and the entire review process.

Moreover, I am troubled by the Oversight Committee’s recent request that those of us that participated in the scientific review of commercialization applications reconsider our scoring in the absence of any additional substantive information or progress by the applicants to strengthen what were wholly naïve and underdeveloped applications.

These actions make it clear that the CPRIT Oversight Committee has elected to disregard scientific review to pursue a different agenda.

Under these circumstances, I cannot continue to serve on this panel. The Texans who made CPRIT possible deserve an unbiased process that ensures that these funds are allocated based on merit. I still believe in the potential of CPRIT and would consider serving again in the future but only if the CPRIT Oversight Committee commits to the principles of scientific rigor, intellectual integrity and impartiality that formed the basis of these original peer review panels.

If CPRIT Oversight Committee elects to bypass peer review, I fear that this will not only damage CPRIT’s reputation but may also erode the public’s confidence in cancer research.

J. Wade Harper, the Vallee Professor of Molecular Pathology at the Harvard Medical School Department of Cell Biology:

This letter is written to tender my resignation as a member of the CPRIT Basic Science Cancer Research Committee-3 (BCRC-3), effective immediately.

Having spent 15 years as a faculty member at Baylor College of Medicine and a resident of Houston, I was very excited to be asked by Dr. Sherr to participate in his review panel. This was especially the case because I have admired Dr. Sherr’s science and intellect for more than 2 decades.

Recognizing that Texas institutions have significant promise, I felt that the CPRIT model and the funds available would truly be transformative, but only if the best science was funded.

I was strengthened in this feeling of promise upon the first meeting of the BCRC-3 study section, where I discovered just how scientifically stellar the BCRC-3 study section actually was. Through Dr. Sherr’s vision, he was able to establish a national panel of experts who judged each application based solely on the science and the ability of that science to transform cancer treatment in Texas.

I have served on numerous other study sections, including NIH. The BCRC-3 study section was by far the most rigorous and fair study section I have ever been associated with. This is due in no small part to Dr. Sherr’s efforts in bringing this incredible group together and keeping us together for 3 years.

Having talked to members of the other scientific review panels, I believe that they all feel this way about their individual groups. Prior to joining CPRIT’s review panel, I had not had the pleasure of knowing Dr. Gilman.

Through the 3 years I have known him, I have NEVER heard him say anything that would sway reviewers in either direction toward ANY grant. I have never seen him display favoritism in any form.

Thus, one of the most depressing things about the last 6 months has been the extent to which Dr. Gilman’s integrity has been challenged. He has my utmost respect. Also, I must say that the new policy of having a monitor present during our discussions is one of the most insulting things that have happened to me in my professional career.

In my view, the direction that CPRIT is going—putting commercialization schemes in place at the expense of well-grounded scientific studies—will ultimately degrade the process that CPRIT originally intended.

Without appropriate and rigorous scientific review, those with the greatest hype, rather than the greatest science, will likely receive the lion’s share of the funding, often I fear, with an outcome that is not in the best interest of the residents of Texas.

There is much more of a chance, using this mechanism, for favoritism to be given, and for politics to be inserted into the process. I am very much afraid that the enormous efforts that all of the study sections have given to the review process with the hope of transforming cancer research in Texas during the last three years will possibly be for naught if strict and rigorous scientific review is not maintained.

Given the dramatic changes in the approach being taken by CPRIT, I am unable to continue my support for this endeavor.

Kurt Zinn, professor in the Departments of Radiology, Medicine and Pathology, and director of the Division of Advanced Medical Imaging Research at the University of Alabama at Birmingham:

Thank you for the opportunity to serve as an external reviewer for the CPRIT program. I now inform you of my resignation as reviewer for the Interfaces Review Committee. I fully support Dr. Gilman and Dr. Gambhir in the positions they have taken against those in the CPRIT organization that decided to bypass scientific peer review for certain commercialization

projects.

Commercialization projects should be scientifically sound if they are to be funded, and how would that be determined if the projects are steered to bypass the peer review mechanism?

As you know, I was one of the reviewers that you specifically requested for a “second look” for a commercialization project that I scored not fundable on the original review. You did not inform me that Dr. Gilman had rejected your idea to contact reviewers for a “second look.” My “second look” showed the project was not different from my first review, and therefore my score was not changed.

However, upon further reflection, I think it was inappropriate for you to request a “second look” when Dr. Gilman rejected your plan. I think your style of making “on the fly” decisions during the review process is not transparent or fair to all applicants.

Eric Fearon, the Emanuel N. Maisel Professor of Oncology, a professor in the Departments of Internal Medicine, Human Genetics and Pathology, chief of the Division of Molecular Medicine & Genetics, and associate director for basic science and deputy director of the University of Michigan Comprehensive Cancer Center:

I am writing to offer my resignation as a member of the CPRIT Basic Science Cancer Research Committee-3 (BCRC-3), effective immediately.

The citizens of Texas and the Texas legislature are to be congratulated for their wisdom in supporting innovative cancer research and prevention efforts via the founding and funding of CPRIT. It was a great honor and privilege to serve over the past three years as a member of the BCRC-3 panel, in a scientific review process conceived by outstanding leaders such as Al Gilman, Phil Sharp, and the Cancer Research Committee chairs, alongside truly outstanding and committed cancer researchers from outside the state of Texas.

Our panel evaluated and discussed all scientific applications before the Committee without any bias or conflict of interest, with the singular goal of identifying only the most promising, innovative, and high impact cancer research proposals.

Having participated as a panel member and/or chair at numerous scientific review committees at the NIH and multiple foundations over the past two decades, the quality of the scientific review process at the BCRC-3 panel was the most outstanding of any such evaluative process that I can recall.

Based on my reading of news articles over the past few months in various forums (e.g., Houston Chronicle, Dallas Morning News) and opinion pieces (e.g., the June 29, 2012 Houston Chronicle piece from Charles W Tate, chairman and founding partner of Capital Royalty LP, a leading investment firm focused on providing growth capital to the biopharma industry and a member of CPRIT’s Oversight Committee, who chairs its Economic Development and Commercialization Subcommittee) discussing CPRIT’s likely intentions going forward, I am left with the impression that “grand” science and “commercialization” projects may represent much of the future for CPRIT.

As a result, I am uncertain that the robust scientific review process for CPRIT applications of all types that was conceived by Drs. Gilman, Sharp and the other review panel chairs, and executed by the varied review panels will be needed going forward. Indeed, I found the press release from CPRIT on their website (Sept. 21, 2012) stating that “we look forward to continuing and expanding our support for MD Anderson’s prevention, research and commercialization projects, particularly the multidisciplinary groups of researchers and clinicians that are mounting comprehensive attacks on the eight target cancers” to be a most remarkable statement, especially so, in light of the fact that the statement is a forward-looking one.

To me, the CPRIT press release seems to imply that certain, yet-to-be-submitted MD Anderson applications to CPRIT have already been judged to be sufficiently meritorious to deserve CPRIT support, even though the hypothetical applications have presumably not yet been fully conceived or submitted in final version to CPRIT by MD Anderson scientists and clinicians, nor have the hypothetical applications been subjected to full scientific evaluation by outside, independent review panels.

Perhaps for some in the cancer research field such as myself, the CPRIT press release statement on their website could be seen as consistent with the view that unencumbered and unbiased expert peer-review of cancer research applications submitted to CPRIT might simply be a quaint relic of the past.

Scott Kern, associate professor of oncology and pathology at Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center:

It is ironic that I again find myself in the undesirable position of resigning from a hard-working and highest-quality scientific study section. As Twain noted, history does not repeat itself, but it does rhyme.

Ten years ago, I served on the scientific review board of a private philanthropic organization. In an unusual development, I was asked to review two special grant applications that had arrived out-of-cycle.

After my review, I was informed by the organization that they had beforehand decided to fund the two grants, a decision made prior to obtaining the reviews from the scientific board.

They had in this instance perhaps operated as a direct money conduit and not as a peer review-guided granting operation.

Owing to the deprecated role of scientific review under such procedures, I regretfully

resigned from their board. To my knowledge, subsequently they adhered tightly to the procedures established in their founding document, pursued a stellar and constructive path, and remain a healthy organization.

I now find that a somewhat similar situation exists at CPRIT.

The irony is as follows. The PI of a grant receiving questionable dispensation ten years ago, and a PI of a grant recently under critical scrutiny for improper dispensation at CPRIT, were the identical person.

For history to rhyme,

I must resign.

I wish CPRIT well.

Gregory Longmore, director of the Section of Molecular Oncology at Washington University in St. Louis:

I am writing to inform you that I am resigning my position as member of the CPRIT Basic Science Cancer Research Committee-3 (BCRC-3), effective immediately.

Carolyn Anderson, professor of radiology and pharmacology & chemical biology, and director of the Molecular Imaging Laboratory at the University of Pittsburgh:

This e-mail is to inform you of my resignation, effective immediately, as a reviewer for CPRIT Interfaces Review Committee.

I thoroughly enjoyed working with outstanding scientists on the review panel, as well as our esteemed chair, Dr. Gambhir.

I am also privileged to have had the opportunity to work with Dr. Al Gilman, who was incredibly supportive of the peer review process and of all the reviewers, which lead to the funding of outstanding cancer research in the state of Texas.

Working with consummate professionals such as JoAnn Eckert and the SRA staff, especially Rajan Munshi, made the experience of reviewing for CPRIT feel a pleasure more than hard work.

I sincerely hope that the unfortunate circumstances that have led to the numerous resignations of the council leaders and reviewers can be rectified.

CPRIT has done the field of cancer research and cancer patients in Texas a tremendous service, and hopefully this can continue in an honorable fashion that abides by the principles of scientific peer review.

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