42-06 Slamming the Door Part III: 18,000 Bosses

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Slamming the Door

Part III: 18,000 Bosses

By Paul Goldberg

Between the fall of 2011 and the spring of 2012, I watched MD Anderson from afar, and I didn’t think about CPRIT at all.

Friends who attended early meetings with Ronald DePinho soon after he became MD Anderson’s president said that he was literally grading presentations made to him by faculty members and administrators.

“This was a C-,” he would say.

It was difficult to get a B.

On the other hand, it was possible that he graded fairly.

Soon after he was named president, at a cocktail reception in Boston, an acquaintance asked him what it was like to run MD Anderson.

“It’s like this: I say, ‘Look to the left,’ and 18,000 people look to the left. I say ‘Look to the right,’ and 18,000 people look to the right.”

Around the same time, in October 2011, in a talk before the Board of Visitors, DePinho mentioned those 18,000 people in a strikingly different way.

He said his 88-year-old mother was proud she was that he would be the boss of 18,000 people.

“Well, I told her, not exactly—I will have 18,000 bosses,” he said. “My job will be to work for them, helping them realize their fullest potential and achieve great good for humanity. She understood completely as she and my father had instilled their children with certain core values—respect, integrity, altruism, and hard work.”

***

Lynda Chin quickly emerged as a key player in his administration.

DePinho first mentions her is an email to John Thornburgh, an official with the headhunting firm that was running the search.

“On the personal level, it would be helpful to get visibility on the top private school and housing,” DePinho wrote on April 7, 2011, a month before the job was offered to him. “Finally, we have Lynda’s professional career. I believe it would be most productive that she be approached as an independent entity. She needs to understand the potential scientific/programmatic opportunities for her at MDA. Given her record of achievement and national leadership, she may very well be the most accomplished scientist at MDA. Thus, it is important that whatever program she leads/shapes that it not be viewed as one derived from her personal relationship with the boss.”

The UT System ultimately set up an unwieldy system for managing Chin’s potential conflicts. She reported to the MD Anderson provost, while the provost reported to her husband. Poor Raymond DuBois got the task of saying no to Chin’s demands for a massively expensive construction of her office suite and her plans for travel.

***

Almost immediately after DePinho and Chin arrived in Houston, MD Anderson facilities staff started to prepare to construct the offices of the Institute for Applied Cancer Sciences.

Usually, office space at MD Anderson is strictly regimented and the furniture tends to be heavy-duty. (An ergonomic Herman Miller Aeron office chair was considered a trapping of luxury.) IACS would be different. As a place where industry would meet academia, the offices were intended to make pharmaceutical industry executives feel at home.

Construction was so expensive that variances from the UT System’s vice chancellor for health affairs, Kenneth Shine, had to be obtained.

I started hearing stories about translucent walls and modern classics. I heard something about a fabulously expensive red leather sofa that was purchased for Chin’s office.

That was intriguing, of course, but it was hardly an appropriate entry point to a story. It would look petty to start coverage by focusing on the sofas.

***

The MD Anderson moonshot—which would later come to be known as the Moon Shots Program—seemed to be the ray of hope DePinho planned to aim at physicians and scientists at the institution.

Sure, they would have to work harder, but at least they would know that, thanks to their efforts, cancer’s butt would be kicked. Surely, the good people of Texas would see greater promise in final eradication of cancer, and, surely, the docs at MD Anderson would be selfless enough to redouble their efforts.

In reality, physicians at MD Anderson are a busy bunch. A few years earlier, when MD Anderson was in financial trouble, then-President John Mendelsohn increased the faculty’s clinical revenues quotas. Now, thanks to the DePinho determination to boldly go, and explore, and all that, the quotas would rise again.

Alas, from where they sit, clinicians don’t see the proximity of the cure. They see a few advances, even some great advances, but mostly they see a lot of suffering and too much death.

***

DePinho’s role in AVEO Pharmaceuticals Inc., his drug company, wasn’t hidden. On his desk, he kept a tivozanib pill encased in clear acrylic.

It was a paperweight of sorts, which he showed to visiting dignitaries as an illustration of his orientation toward producing drugs patients could use right away. Indeed, patients in Eastern Europe were using these drugs in a clinical trial. On weekends, he was often seen sporting an AVEO windbreaker.

These displays of commercial tchotchkes reminded Houstonians that DePinho’s predecessor Mendelsohn was never seen wearing ImClone orange, even though his connection with that company was even tighter. Mendelsohn was the inventor of Erbitux; DePinho wasn’t the inventor of tivozanib.

Perhaps this different attitude toward conflicts of interest could be chalked up to generational differences. Perhaps old rules no longer applied. Perhaps there is an underestimated virtue in conflicts. Perhaps efficiently developing drugs should trump conflict-of-interest safeguards that shield patients from research risks.

***

In March 2012, a couple of months before I started covering the CPRIT and MD Anderson story, I got a call from an old acquaintance, Leonard Zwelling.

Zwelling called more or less out of the blue, to tell me that he liked How We Do Harm, a book I co-wrote with Otis Brawley, the chief medical officer of the American Cancer Society. Our book had just come out.

A decade earlier, when our paths first crossed, Zwelling was an MD Anderson company man all the way.

His job was to defend MD Anderson and Mendelsohn in the ImClone crises. Mendelsohn served on the boards of directors of both companies. As we were exchanging pleasantries, I remembered that Zwelling would have unparalleled perspective on conflicts of interest

In his old job as vice president for research administration, Zwelling had been a chief advocate for Mendelsohn—and later became an architect of the MD Anderson policy on conflicts of interest.

Cautiously, I asked Zwelling what he thought of the new president.

Cautiously, he said that he was concerned.

Cautiously still, I asked what he was concerned about.

Conflicts of interest, he said. I had to start putting cards on the table.

“The shit you said about ImClone about ten years ago was pretty audacious,” I said.

I was referring to the comment Zwelling made to The Washington Post more than a decade earlier. He said that some colon cancer patients on the MD Anderson study deliberately sought out Erbitux and viewed Mendelsohn’s three roles—as the drug’s inventor, an ImClone board member, and president of the cancer center conducting the trial—as a positive.

“When they find out their doctor is the person that invented something, they think that’s just sliced bread,” Zwelling said to the Post. “They say, ‘I’ve come to the right place. This is the best I could hope for.’”

His statement was likely true, but irrelevant.

Yes, some patients don’t worry about conflicts of interest, but all patients need to be informed about conflicts in a systematic manner. There has to be disclosure, and it has to be uniform.

Yet, it was probably a good thing that Zwelling didn’t quit. In response to the ImClone debacle, MD Anderson set up a strict policy on managing institutional conflicts of interest.

To his credit, Mendelsohn had been thinking about these issues. Mendelsohn was a clinician, formerly chief of hematology and oncology at Memorial Sloan-Kettering Cancer Center.

Even before the Post story, he didn’t directly treat the patients in the Erbitux trials, and the institution continued to enroll patients in studies of other colon cancer drugs. When an MD Anderson investigator, James Abbruzzese, declined to test Erbitux in pancreatic cancer, Mendelsohn didn’t try to convince him to rethink his decision.

When Post reporter Justin Gillis questioned him in 2002, Mendelsohn acknowledged that his roles as MD Anderson president and a board member at ImClone could present ethical problems.

Also he noted that MD Anderson strengthened its policies in 2001, requiring that patients be informed uniformly about conflicts, and prohibiting doctors who may have a financial stake in an experimental therapy from direct involvement in clinical care of a patient who is getting that therapy.

These actions were triggered by the death of Jesse Gelsinger, an 18-year-old patient with a genetic disorder who died at the University of Pennsylvania in 1999, after volunteering to test an experimental treatment for ornithine transcarbamylase deficiency.

“I’m not sure it’s necessary even today,” Mendelsohn said to Gillis in 2002. “But I think you move with the times. I don’t want to take any chances that a patient will feel they’ve been deceived at MD Anderson.”

After the Post’s story, and acting on request from Mendelsohn, MD Anderson further tightened its conflict-of-interest rules. Zwelling was one of the key players in that rewrite.

Now, a decade later, DePinho and Chin were keeping their advisory and fiduciary roles at some of their companies.

The COI policy Zwelling helped craft states that “no faculty member, trainee, or institutional decision maker may serve as either a member of a board of directors, executive, or as an officer of any of the following: (1) a business, (2) other legal entity, or (3) a competitor of MD Anderson.”

Did that mean that DePinho and Chin were operating in violation of the MD Anderson COI policy? The answer had to be yes.

Of course, the UT System officials knew about DePinho and Chin’s industry involvements. The conflicts and plans for their management were noted in Shine’s offer letters to the couple.

Yet, no formal waiver was issued. Did that mean that, from day one, DePinho and Chin were employed in violation of the COI policy?

I asked Zwelling whether he thought I was hallucinating. He assured me that I wasn’t. He couldn’t see how anything less than a waiver would suffice.

The waiver would indeed be issued, but not until late 2012, which meant that DePinho and Chin operated in violation of MD Anderson’s COI policies for more than a year.

I knew that eventually I would have to jump in and write something about MD Anderson, but I wanted my first story to be more than a recap of the Houston Chronicle’s excellent coverage. I was waiting for something with oomph.

I recall his sign-off that afternoon:

“Gotta run,” Zwelling said. “We are going to the moon.”

***

In May 2012, I learned about an effort to obtain at least $18 million a year in CPRIT funds to fund Chin’s Institute of Applied Cancer Science.

Was CPRIT funding promised to DePinho and Chin at the time they were being recruited to relocate to Texas?

Earlier this year, I asked Dan Fontaine, executive chief of staff at MD Anderson, whether they were promised that CPRIT money would be used to fund IACS.

Actually, in terms of the conversation between the University of Texas System and Dr. DePinho and Dr. Chin, the only thing that I’m aware of on the CPRIT front was the encouragement for the application for recruitment dollars, I believe, for Dr. Chin, which I believe was successfully done. And I’m going on memory here,” Fontaine said. Indeed, Chin received a recruitment grant from CPRIT.

“On the other side, at [IACS], I don’t think there was ever a promise of CPRIT funding for that. To the contrary, I think as the institution made its commitment to the funding of the [IACS], the UT System impressed upon both us, as well as with other conversations I think with Dr. [Guilio] Draetta [director of IACS], that there was certainly a desire on UT System’s part for [IACS] to look for support and external funding.

“And at that point in time I’m sure CPRIT was pointed to as a source, because CPRIT was not only funding research—but also, as reflected back in the stuff that you looked at at that time—was also putting forward grants to attract companies to Texas. And to transfer other types of things that would help build the type of infrastructure, an ecosystem if you would, for the biomedical development that CPRIT was trying to accomplish for cancer.

“So I don’t think there was ever a promise of CPRIT funding, but to the contrary, I think the UT System officials, both us at MD Anderson as well as people at CPRIT, to look and make applications if the opportunity arose to support IACS.”

***

At CPRIT, the maneuvers to undermine Al Gilman began subtly, invisibly.

In 2011, CPRIT altered its rules to allow biotechnology incubators to be funded with review by a panel that would focus exclusively on the commercialization potential of the project.

In those cases, a review of the science underlying the project wouldn’t be required.

Indeed, review of all of the small incubator projects would be cumbersome, and the incubators needed to move quickly and flexibly with their decisions. The scientific quality of their operations could be judged after a few years of experience.

Gilman did not object to this, although this move would become a crucial element in all of the bad things that nearly led to CPRIT’s demise.

The fact that the move was proposed by Charles Tate, a financier with close ties to the governor and lieutenant governor, didn’t excessively alarm Gilman either.

Provenance notwithstanding, the idea made sense. Incubators are usually places where scientists can do research in a non-academic environment to explore the commercial potential of an idea, hopefully getting it to the point where investors can be brought in.

This separation is good. It safeguards commercial research from being confused with campus research. This separation also makes it possible to separate university employees from employees of private companies.

Gilman was no opponent of commercialization. Though a creature of campus, he serves on two corporate boards. He is a member of the board of directors of Eli Lilly & Co. and Regeneron Pharmaceuticals Inc.

Gilman saw no cause for concern. At the time, he didn’t even know he had adversaries.

When the regents announced that they had selected DePinho to lead MD Anderson, Gilman remained neutral about the choice. He knew a bit about DePinho and next to nothing about Chin.

When MD Anderson applied for a $5 million grant to enable the recruitment of Chin as a CPRIT scholar, several members of the scientific council noted that she is abrasive and has even higher self-esteem than her husband. But her science was good enough, and that was all that mattered. The people of Texas were well served by having a decent scientist like her relocate to the state.

***

In December 2011, Bill Gimson, CPRIT’s executive director, asked Gilman to meet with Chin. A three-way videoconference conference was arranged.

Chin presented what struck Gilman as a quasi-business plan, free from scientific detail, for early drug discovery research that would be conducted at her institute. The institute would employ people Chin brought with her from Boston as well as former business people. The institute was a new construct.

MD Anderson would keep commercialization on-campus at least for some extended period. It was unclear when they would seek to spin off new companies or license their discoveries to established companies.

Clearly, that would create conflicts that would be hard to manage. For example, would people working for the commercial entity be paid on the same pay scale as faculty members? Would they be faculty members? Should they be faculty members? How would faculty members who work for a company carry out their obligations as teachers? Would the students and postdocs who work for these faculty members be working in the company’s laboratory? Would company work be done on state-owned university campus space? Would that be appropriate?

As Gilman saw it, much of the work done at a company is turning-the-crank sort of stuff. It needs to be done, but it doesn’t teach postdocs how to run research programs.

There are also issues of secrecy and locked doors. The whole atmosphere of a university is supposed to be open. People wander around and share ideas, discoveries and knowledge. But a company has a financial imperative and fiduciary responsibility to its investors to keep secrets secret and protect intellectual property.

By folding a pharma industry structure into an academic environment, you invite academics to wonder why they are doing all the traditional academic work while their colleagues sit behind closed doors, trying to get rich.

You magnify the potential for things going wrong, Gilman believed.

***

During the videoconference, Gilman told Chin that the work she described amounted to a large-scale research project that would need to be submitted as a multi-investigator collaborative proposal.

Though she referred to the project as an incubator, an incubator it was not. Chin was requesting money for her institute. She would then use the funds as she saw fit.

Chin sounded like the sort of person who doesn’t take no for an answer. She was obviously annoyed by Gilman’s suggestion that she submit a grant proposal like everyone else.

Chin argued that Gilman and his scientists didn’t have the expertise to review commercialization efforts and that the CPRIT budget limits were too stringent.

Gilman first noted several of CPRIT’s reviewers with commercial expertise and then replied that CPRIT had no budget limits for multi-investigator proposals.

“Yes there are,” Chin replied.

“No there aren’t,” replied Gilman, who, being the engineer of CPRIT, designed its rules for funding science.

During that video conference, while talking with Chin, Gilman sent Gimson an email, saying the Chin obviously didn’t want to apply for a grant. She just wanted the money.

Indeed, documents show that Chin’s appetite for money was gargantuan: she wanted $75 million over three years from CPRIT, to be matched by MD Anderson. Though CPRIT had no limit on such grants, $25 million a year would have been extraordinary indeed.

More importantly, handing out money without scientific justification and with no strings attached would have constituted a betrayal of public trust, Gilman believed. It would have been grossly unfair to all other Texas cancer scientists who were writing grant applications.

The conversation was unpleasant enough, but Gilman didn’t reflect on it much. He simply returned to work.

Next week: Part IV – A Nobel laureate in the crosshairs.

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

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