More MS news articles for Jan 2002

When Big Pharma Courts Academia

Academic alliances with pharmaceutical companies create ethical challenges that some institutions learn to manage

http://www.the-scientist.com/yr2002/jan/prof_020121.html

Jan. 21, 2002
The Scientist 16[2]:48
By Joseph Paone

Norman Greenberg tests AstraZeneca compounds on mice he genetically engineered to develop prostate cancer. He supplies the animals and the system for verifying the effectiveness of chemotherapy treatments while the company provides the compounds and testing costs, and gives Greenberg ample opportunity to prove just how well his system works.

Together, the scientist from Baylor College of Medicine in Houston and his corporate partner warily straddle the barrier between academia and industry, and in the process, develop new treatments that may someday save lives. "Our situation with AstraZeneca is very focused on a number of targets, discrete compounds, and what they do in a specific system," says Greenberg, an associate professor of molecular and cellular biology. "It really helps us in the long run because we're going to make better models, we're going to know more about them, and how to use them. AstraZeneca benefits too, because they learn more about what their compounds do."

Observers of such academic-industry alliances say the agreements can create ethical minefields distort or corrupt the mission of academic science or result in the commercialization of university research departments and the exploitation of students as a de facto labor force. "There are conflicts of interest when an academic researcher's primary commitment to the use of sound procedures in the unbiased search for truth is placed in competition with other [financial or personal] interests that might eclipse the primary commitment," says Virginia Ashby Sharpe, integrity in science project director for the Washington, D.C.-based Center for Science in the Public Interest.

Over the past decade, these conflicts have become more difficult to manage because the universities that oversee them juggle conflicts of their own, Sharpe asserts. The 1984 Bayh-Dole Act, which allows universities to garner profits from federally financed research, opened the door to such commercial alliances. The burgeoning biotechnology industry also has provided the musical accompaniment to the academic-business dance. The related emergence of academic entrepreneurs and contract research organizations, the increase in unregulated, industry-sponsored research, and the dependence of academia on restricted support, makes universities more vulnerable to exploitation by commercial interests, Sharpe says. "The perils are real. Academic-industry relations can meet, or fail to meet high standards of integrity."

Thomas Murray, president of the Hastings Center for Bioethics, maintains that pharma-academic alliances create rifts between two distinct cultures—with that of the corporate partner often dominating. "One effect of increased industry funding in academia has been more secrecy," he says. "Industry is protective of intellectual property and desires secrecy, while openness, the ability to publish and make public, is what academic science really desires."

The stakes are high and growing. The University of California at San Francisco, for example, receives around $400 million a year from corporate relationships, 10% of its overall funding, says Christopher Scott, assistant vice chancellor for research at UCSF. In addition, some government funding is now predicated on the university's willingness to work with certain commercial interests. "These corporate agreements are nothing new," Scott observes. "But some of the larger ones call into question whether it is in the mission of academics to do this. People are worried that these agreements may change the direction of science, causing a shift in the way science is being done. Will innovation continue? There is a very good argument that serendipity is what moves science forward."

Caution and Creativity

Baylor approached the alliance with AstraZeneca as it has others—with a healthy dose of caution, according to Greenberg and others. The institution leads some other US medical schools in federal research funding even as it cultivates money-generating relationships with numerous companies, which requires a balancing of interests. "We're in the early stages of working this out," says James Patrick, Baylor vice president and dean of research. "We're still feeling our way through how the structure of these relationships ought to be."

Nevertheless, Baylor's AstraZeneca partnership, in place for nearly a decade, is notable for its breadth, its organization, and its longevity. The umbrella agreement calls for funding of three to six 2-year projects each year. AstraZeneca submits compelling research directions, and Baylor scientists are encouraged to submit proposals that match up with those interests.

The alliance generates less than 1% of the college's overall funding for research, says Addison Taylor, associate dean for clinical research and professor of medicine, pharmacology and physiology. Taylor dismisses concerns about turning academia into a corporate subsidiary. "I don't think the college is concerned at all that investigators are somehow prostituting themselves, or that their work is tainted in any way," he says. Still, academic investigators must not lose sight of why these relationships exist, Taylor says. "Our investigators had to learn early on that the reason AstraZeneca is in business is to develop drugs and make money."

Greenberg explains that his project with AstraZeneca is not the basic, hypothesis-driven investigative research that the National Cancer Institute (NCI) or National Institutes of Health would normally fund. Instead, the research follows a focused, analytical pre-clinical protocol. This intermediary phase of discovery, a step between hypothesis and clinical testing, is of great interest to Greenberg. He sees the alliance as bridging the gap between formulating ideas at the bench and delivering actual treatment at a patient's bedside. "Projects like these really do facilitate translational biology," Greenberg says. "They come at the critical decision point where a company may have to decide whether they should put $100 million dollars into [one] compound and take it to clinical trial, or $100 million into [another] compound. We're trying to establish a paradigm to help make better decisions, using what we believe to be more appropriate animal models."

AstraZeneca views its relationships with academics as key supplemental resources to its in-house research efforts. The company maintains about 150 discovery projects at any given time, and at some point its scientists decide they need access to external scientists and technology at institutions such as Baylor College of Medicine, and others. "We focus on academic collaborations as a way of tapping scientific expertise that lies outside of our four walls," says Christopher Yochim, associate director of the global discovery alliance at AstraZeneca.

Greenberg and his colleagues at AstraZeneca keep in touch via e-mail and telephone, and most of the alliance members from both sides meet twice a year to deliver progress reports—once at the college and once at the AstraZeneca facility in Boston. Both Greenberg and Yochim prize the open dialogue. "The hallmark of a successful academic collaboration is directly correlated to the amount of collaboration between our scientists and the scientist at the institution," Yochim relates. "That way, if something is invalid, we can refocus and look into something else. We can determine which of our projects are valid."

Scott at UCSF views corporate-academic alliances as an exciting and necessary development. "Many of the corporate-funded studies are tremendously interesting from a scientist's point of view," he says. Companies benefit by getting a "gold standard research imprint," paving the way to faster FDA approval, for example. The institution, meanwhile, gains access to technology and materials that it could not otherwise afford. "The entire Silicon Valley was built on the backs of these types of relationships," he says. "Where the danger comes in is when universities try to become too corporate in their approach, aggressively taking equity positions in companies."

Managing Dual Cultures

Supervising these corporate relationships is important, however, Scott notes. UCSF maintains numerous thresholds and firewalls to shepherd these agreements, he adds. The institution closely monitors—and in some cases forbids—stock purchases from companies with whom a researcher works through a university alliance. Consultancies also attract administrative attention. "We're going through some rigorous looks at how these things are constructed," says Scott. "Managing these relationships is the big thing that is facing us."

Disclosing competing interests protects the best interests of the scientists, according to Sharpe. "Administrators should establish procedures to review disclosures and to determine which conflicts are unacceptable," she says. Such management "may involve directing financial gain away from a researcher and into a trust; taking a researcher off a project; requiring that a researcher give up a consultancy; or restricting stockholding by a researcher."

Murray, from the Hastings Center, says university administrators should publish strict and clear conflict-of-interest policies, establish small groups to specifically monitor such conflicts, and ensure that investigators submit a statement of financial interest at least once every year.

Greenberg says he remains watchful of the boundaries between his and the company's priorities. The AstraZeneca project comprises only 5-10% of his research efforts, he estimates. Most of his projects attract funding from the NIH, the NCI, and other long-term sources. By separating the public from the private projects, he can ensure that students and postdoctoral staff work only on government funded research.

If students were to work on an industry-supported project, they could be taking a serious risk, Greenberg worries. "Anything that constituted material for their thesis would have to be looked at very carefully," he says. "If they were to do an experiment with [a company's] compounds, and ultimately the company says, 'You can't publish that.' I wouldn't put a student into that situation."

Such a stance means Greenberg works on the company dime, accompanied by technicians and postdoc fellows hired specifically for the AstraZeneca research. Even after taking these precautions, he says, he remains wary of corporate-academic relationships, in general. "We look at every one of these things as an individual, standalone, let's-not-make-any-generalizations kind of situation."

Joseph Paone is a freelance writer in Philadelphia, Pa.
 

© Copyright 2002, The Scientist, Inc