A Cancer on ASU

Could Bob Pettit have cured cancer in his lifetime? We might never know, thanks to nasty university politics

The task of getting a cancer drug on the market is arduous. From the process of specimen collection to clinical trial, drug discovery takes at least 15 years. And that's assuming everything goes well.

Basically, after the specimens are collected, microbiologists extract useful compounds, and chemists help isolate them into a form that is testable. The compounds are tested and screened against different cancer cell lines to see how the two interact. If that step is successful, the chemists then have to try to find a way to synthesize the compound — after all, if it's only produced in one kind of sea sponge from a remote part of the world, a compound isn't useful unless it can be re-created.

If that step goes well, the compound can go into preclinical development and then on to animal studies. If there are no problems at that step, the compound can go to human clinical trials, which happen in three phases.

ASU president Michael Crow
courtesy of ASU media relations
ASU president Michael Crow

Currently, there are nine CRI drugs in some phase of human clinical trial.

Two of these drugs — auristatin and combretastatin — are especially promising.

Combretastatin has been successful in treating non-small-cell lung cancer in phase three clinical trials and has FDA orphan drug status for the treatment of thyroid cancer. It's also been shown to work well against prostate, breast and ovarian cancers, as well as proving effective against tumors. CA4 — its shorthand name — also has shown some indications of being successful in treating myopic macular degeneration, an eye disease that affects thousands of people in the U.S.

Pettit's group at Arizona State University provided national researchers with compounds, including bryostatin-1, that Dr. Peter Blumberg, chief of the NCI's molecular mechanisms of tumor promotion section, has worked with extensively. Blumberg says he's "very much impressed" by both the drug — currently in both phase one and phase two clinical trials — and Pettit's research.

"He's done an outstanding job identifying drug candidates," says Blumberg.

Pettit also provided several groups of compounds to NCI researcher Ernest Hammel, the senior investigator of the NCI's laboratory of drug discovery research and development, that showed promise in stopping blood vessel growth in tumors.

According to Paul Wender, the Bergstrom Professor of Chemistry at Stanford University, Pettit is one of the leading natural compound chemists in the country.

"Several [of Pettit's compounds] are among the more promising leads for the treatment of cancer that have been uncovered in the past three decades," he says. "It is clear we are not making the best of our national resources when laboratories with this record of success are shut down."

In spite of his successful cancer research, life at ASU was not smooth for Pettit, particularly moving into the late 1990s.

His research continued to flourish, but his career was not without conflict. Some people loved him — donors, for example, were willing to open their pocketbooks again and again (to the tune of around $25 million) thanks to his charm and dedication to cancer research.

Others say they couldn't stand working with him. His conflicts sprang up mostly surrounding patents on his drugs and inventions.

Former ASU vice president Barnhill says though he liked and respected Pettit as a scientist, there were occasional problems.

"He wasn't easy to work with, but that's not necessarily a bad thing," Barnhill says. "Faculty are trained to be entrepreneurial, and he tended to carry that pretty far. He was particularly interested in protecting intellectual property rights — again, not a bad thing, but he was more severe than most people."

Others are more blunt. Alan Poskanzer worked with Pettit in the '90s as an officer with ASU's technology transfer department, responsible for arranging licensing agreements. It was no secret around the university that the two men could not, and really did not want to, get along. Poskanzer left the university in 2002, and today operates his own licensing consulting firm based in Payson.

Poskanzer dislikes Pettit and says he went out of his way to make licensing agreements difficult. But even he says the work Pettit's group did was valuable.

"The people who support him don't have to work with him," says Poskanzer, adding that the administration really didn't feel it had much of a use for Pettit. "Milton Glick had no use for Bob Pettit. Michael Crow had no use for Bob Pettit. Jonathan Fink had no use for Bob Pettit."

And, Poskanzer adds, "I had to work with Bob Pettit." That didn't go well.

The two were fundamentally at odds when it came to the way technology was licensed at ASU. Under the Arizona Board of Regents policy, when licensing revenue comes in, the money is split up evenly among the university, the inventor and the labs.

Pettit has always been very vocal about inventors' rights. For example, when a 15 percent overhead on licensing income was established, he was one of its loudest critics. Poskanzer calls it greed, but Pettit says he was just trying to protect his intellectual property and generate as much revenue as possible to help fight cancer.

In 1997, Pettit's issue with Poskanzer and the technology licensing office came to a head.

In April of that year, Pettit discussed an option agreement with pharmaceutical company OXiGENE for his compound Combretastatin A-4 Prodrug. According to Pettit's lawsuit, which does not name Poskanzer as a defendant, the company verbally agreed to option the drug for $300,000 for two years, and promised to bring the drug to phase one clinical trials within that time period. After Pettit's original discussion, Poskanzer met separately with the same company officials and arranged a pre-license agreement with OXiGENE on the rest of the combretastatin drug family at no additional charge.

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I worked for GRP for a number of years as an ASU undergraduate and always found him to be extremely dedicated to careful and well controlled scientific research. The idea that natural products organic chemistry is somehow outdated as a possible source of cancer therapeutics reminds me of a few comments about ASU's new research efforts that came up at a recent NSF panel meeting, discussing ASU's new "Bioscienterrific Institute of NanoFictive InterConnections". Interdisciplinary "systems" work is sexy, but frankly even the agencies that fund the work are wondering if they are being had. The problem isn't that GRP's approach is timeconsuming and difficult..it was. The problem is are the proposed alternatives even science? Systems research has been consuming huge resources for almost fifteen years and frankly to date (although nobody really seems to doing research on quality of research vs. dollars invested) very modest gains have been seen, despite some flashy publications. I applaud GRP for his principled fight against both an autocratic university administration and an approach to science that may frankly add up to a big nothing. Good luck to ASU, my advice is sell the snake oil slowly, the AZ mooks might figure out that all their tax dollars aren't buying much but pretty (leaky, poorly built) research buildings.

Lynn Pritchett
Lynn Pritchett

Protocol is tedious, frustrating, and extremely time consuming. However, as Pettit's story painfully tells, it is a permanent tatoo on on the chest of every business, education, political, and research institution today. Protocol often seems an inconsequential waste of paper and energy, and when mistakes are made along the way, it magnifies the human impact ten-fold. The line crossed here, between making protocol error and choosing to bypass required procedures and/or informing all involved parties, is all too obvious. Question remain, however: "What strides in life-saving possibilities are now lost? Indeed, "What is the true price of progress?" Furthermore, "Did firing Pettit's staff, changing the institute's name, and demoting Pettit create a more focused, more efficient, more innovative and productive research environment?" Ulitimately, "Can those who made these decisions look into the eyes of a child dying of cancer, and truthfully say,"I'm sorry."

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