THE SCIENTIST VOLUME 7, No. 17 THE NEWSPAPER FOR THE SCIENCE PROFESSIONAL September 6, 1993 Technology Transfer Boom Offers Scientists Rewards-And Challenges (portrait photo of Helen Blau) FREE TO STAY: Technology transfer, says Stanford's Helen Blau, allows basic scientists to see their ideas put into action without being forced to abandon academia. (begin quote box) Editor's Note: In this first part of a two-part series, academic researchers and university officials involved in technology transfer discuss its beneficial effects on academic science and society. In the second part, to appear in the Sept. 20, 1993, issue, scientists and others express concern that increasing emphasis on corporate-supported research may significantly undermine aspects of basic science on campus. (end quote box) As industry-academia deals proliferate, scientists on campus must also negotiate conflicts that arise BY FRANKLIN HOKE A boom in technology transfer activity is under way on the ill-charted ground upon which academic and industry science interests overlap. Becoming dramatically visible in the 1980s-on the heels of pivotal new intellectual property law-and continuing into this decade, the increased cooperation is bringing important changes to both sectors, say researchers and technology transfer officers. This growth in the conversion of basic research findings into marketable products or services is bringing welcome new resources into academic labs and allowing researchers to see their ideas carried through to realization, observers say. And the infusion of basic research ideas into company labs is surely stimulating the development of new products. Muting, somewhat, this growing enthusiasm for academic-corporate collaborations are traditional concerns of academicians that an increased commercial presence on campus may undermine important elements in their culture--support for unfettered, curiosity-driven work, for example. More crucial to many are the questions that arise concerning conflict of interest: When a scientist's work is simultaneously supported by a university and a private corporation, where do his or her interests properly lie? And if there are choices to be made in terms of investing time and intellectual energy, which funder comes first? Faculty and administrators involved in technology transfer say they have worked to confront these difficult issues directly and that such worries are exaggerated. "An increased presence of any kind of major [social] institution on campuses carries with it advantages and risks," says David Kipnis, Distinguished University Professor of Medicine at Washington University, St. Louis. Kipnis, a diabetes researcher, also chairs the committee overseeing the joint biomedical research program between the university and the Monsanto Co., also located in St. Louis. "For example," he says, "you could just as well substitute government for industry. Too much government on campuses has created problems, where major [agencies] attempt to overdirect and micromanage research. The same thing could be true if industrial intrusion becomes excessive. Academic institutions have to always be on the lookout. We should relate with all, but make certain that our primary roles in society are not unduly influenced or subverted by these relationships." Advocates for increased corporate involvement in basic science say (Continued on Page 6) 6 THE SCIENTIST September 6, 1993 NEWS Schools Work To Manage Technology Transfer (continued from page 1) that funding constraints in the federal government--in particular at the National Institutes of Health--necessitate such new approaches to supporting science. And they see no threat in well-managed relationships between academic labs and companies. "As the NIH budget continues to effectively shrink, there are going to have to be alternative ways to support research, and we're going to have to find mechanisms to achieve that," says Anthony Cerami, president of the Picower Institute for Medical Research, Manhasset, N.Y. "And, in my mind, the most creative research can be done in academic institutions or research institutes, away from industry, because they don't have the quarter-to-quarter pressures that a company would have, and so they can really do things that are imaginative." Before launching the Picower in late 1991, Cerami headed a lab at Rockefeller University in New York where an antibody potentially able to block the damaging actions of a cytokine called tumor necrosis factor, or TNF, was discovered (F. Hoke, The Scientist, Feb. 22, 1993. page 1). Patents based on the findings were initially licensed to Chiron Corp., Emeryville, Calif., for development and then to the United States subsidiary of % Bayer AG, Leverkusen-Bayerwerk, Germany. (portrait photo of David Kipnis) KEEPING A LOOKOUT: Universities must make sure relations with industry do not subvert their primary social roles, says Washington University's David Kipnis. Cerami has collaborated with company scientists throughout the preclinical process, and a therapeutic product is now in late-stage clinical studies. (begin advertisement) Hypothesis Accepted !! Knowledge Express TM THE source for cost effective and comprehensive technology transfer information. 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"They have their objectives, and companies have theirs." Many scientists also say a prime motive for working with companies is the strong personal satisfaction they derive from seeing useful applications developed that are based on their research ideas. They recognize, too, the necessity of contributing to that process to ensure its success. "You can have a great idea, but if it doesn't end up helping people, then it's not so rewarding," says Helen M. Blau, a professor of molecular pharmacology at Stanford University's School of Medicine. "The technology transfer process helps you have that chance. For example, I'm not going to be able to, in my lab, grow cells under the quality control and in the quantities necessary for a clinical trial. So, if there weren't companies to pick up the technology and move it to the next step, it might not get there." Blau's research at Stanford found that myoblasts (muscle cells) could be useful in gene therapy to deliver recombinant proteins in the treatment of muscle disorders and other maladies like growth hormone deficiency. She is working with the biotechnology company Cell Genesys, Foster City, Calif., to develop specific applications of these findings. "It's truly exciting to be part of this process," Blau says. "And if I'm not consulted and a part of it, then it's less likely to happen." But despite increasing interactions, academic researchers are by no means unanimous in embracing industry support, which can be accompanied by over-specific direction and, often, little scientific return. "I have been reluctant over the years to take on projects that I call "hybridomas for hire," says Alexander Karu, a professor of biochemistry at the University of California, Berkeley. "One of my concerns has been the heavy unidirectionality of the information flow [in relationships with industry]. People who've approached me want to know a great deal about our plans and what we're doing, but we get very little feedback in terms of basic science. And my mission here is basic science." Despite these misgivings, Karu is currently developing a series of antibodies with a major chemical company, in what he characterizes as a true two-way collaboration. The company's synthetic organic chemistry expertise has complemented his own lab's capabilities very well, he says. (begin quote box) UC-Berkeley biochemistry professor Alexander Karu: "I have been reluctant over the years to take on projects that I call hybridomas for hire. My mission here is basic science." (end quote box) Finding Homes For Technology University technology officers cite changes during the 1980s in the laws governing intellectual property to explain the continuing expansion of technology transfer activities. Probably the most important of these is the 1980 Bayh-Dole Act, or Public Law 96-517, which allowed universities for the first time to patent inventions based on federally funded work at their institutions. By the end of the decade, hundreds of institutions had opened patents and licensing offices to facilitate the transfer of their researchers' findings to companies where useful applications might be developed--and royalties generated. Growth in the numbers of new technology transfer offices continues to be strong. Among the institutions leading the way and providing important guidelines for others have been Stanford, the Massachusetts Institute of Technology, and Harvard University. The increased royalty income derived from licensing is an important new source of university research support, university technology officers say. But they also insist that placing research findings where they can best be developed into beneficial products is perhaps an even more important goal of the process. "This is kind of like finding homes for a lot of different technoliogies," says Katharine Ku, director of Stanford's Office of Technology Licensing. "The family that wants a child is the one that, at least theoretically, might be the best family. So, when we try to find a licensee, a company that's interested in devoting the resources [to development), the best licensee is the one that cares the most. Our biggest fear is that the licensee takes the license and just sits on it." (portrait photo of Anthony Cerami) INDUSTRY NO THREAT: Industry funding is little different from goverment funding, says Anthony Cerami, Picower Institute president and former Rockefeller University professor-each funder has its objectives. Clear patent ownership by the universities has been crucial in generating company interest in investing in academic research, too, according to technology transfer officers and researchers. "Before that time, it was very difficult for a company to be assured that it could get an exclusive license to a patent that came out of research it sponsored on campus," says Duke Leahey, director of industrial contracts and licensing at Washington University. Leahey is also president of the Association of University Technology Managers. "You're not going to invest eight to 10 years and millions of dollars taking a product from its bench-type invention through definition of the product, clinical trials, and FDA [Food and Drug Administration] approval, to then hope the consumer buys it, unless you have some sort of proprietary position," says William Hoskins, director of the Office of Technology Licensing at UC-Berkeley. "The patent provides that, and an exclusive license to that patent goes even further." "Companies are really the only group with the financial and personnel resources to develop diagnostics and therapeutics," says Cerami. "And without patent protection, it makes it almost impossible for a company to be able to justify spending the very large amounts of money it takes to develop an idea into a viable product." Researchers also say that, besides NEWS September 6, 1993 THE SCIENTIST 7 managing university intellectual property, campus technology offices provide another vital service. In today's complex legal atmosphere, investigators who use a given firm's reagents, for example, may find that company later laying excessive claim to their research results. University technology offices have the expertise to help scientists steer clear of such ensnarement, while still being able to take advantage of important tools and collaborations. "We have been working in the area of recombinant antibodies," says Karu, "and we wanted to license some of the vectors from the Scripps Research Institute [in La Jolla, Calif.]." Berkeley's technology officer, Karu says, "was very instrumental in negotiating rational arrangements by which we could use those vectors. So, [the technology office] helps in this way, when I have a question about using somebody else's reagents or materials without becoming a de facto employee or having any claim placed upon my work by the donor." "Sometimes, when companies give you reagents, they want you to sign all kinds of forms," says Stanford's Blau. "Every time I get a reagent from someone, I run the forms through the technology office here, to make sure that whatever I'm signing does not in any way interfere with my function as a professor, that I can speak and publish freely. So the office here helps protect us." (portrait photo of Katharine Ku) ADOPTION AGENCY? Stanford's Katharine Ku says licensing a technology is like placing an adopted child in a supportive home "The best licensee is the one that cares the most. Our biggest fear is that the licensee takes the license and just sits on it." Peer-Reviewing Conflict The potential for conflicts of interest that concerns people inside and outside academia go beyond the worry that a researcher may redirect his or her research to attract more funding or to benefit a company in which the researcher may have a financial interest. They also extend to conflicts of commitment--basically, failing to reserve enough time to properly discharge university duties, such as teaching, and to exploitation of graduate students. Because the whole arena of technology transfer is complicated and relatively unexplored, say technology officers and researchers, guidelines for conduct are only just emerging on many campuses. "Universities have developed their policies in response to situations that they've been presented with," says Jim Severson, assistant director of the Office of Patents and Licensing of the University of Minnesota, Minneapolis. "Ten years ago, we couldn't have envisioned the different kinds of involvements possible." Among the most flexible and effective tools that the universities have for dealing with conflicts, they say, are disclosure and peer review. These tactics have the added advantage of tending to involve the wider community in considering these difficult issues. In most cases, researchers make disclosures to their departmental chairperson for review. On a number of campuses, faculty committees are asked to monitor individual relationships. When disputes do arise, enforcement authority often resides in a dean or other administration official. "We feel the essential first step is to have total and complete disclosure," says Stephen Sammut, managing director of the Center for Technology Transfer at the University of Pennsylvania in Philadelphia. "And then we review the cases and try to manage the conflicts of interest." The need to develop mechanisms to confront potential conflicts is seen as a high priority where technology transfer is active. (portrait photo of Steve Roth) Photo: Tommy Leonard AN ENDURING DIFFERENCE: Steve Roth says businesspeople are different from academics: "Their overriding concerns are not why a maple leaf is different "from an oak leaf, for example." "Given the complexity of commerce and academe these days," Sammut says, "if we simply put on blindfolds and made believe conflicts of interest are not going to happen, we would, number one, be fooling ourselves and, secondly, not really serving the public interest." "You shouldn't be left to your own devices when money is involved," says Washington University's Leahey. "So, you should have a conflict of interest policy and a committee that reviews things for people to remind them when they're getting a little far afield." Leahey says, too, that while the NIH and the National Science Foundation are both struggling to develop conflict of interest policies for their grantees (NIH must publish its effort by early December this year, by congressional mandate), enforcement of those policies should remain the responsibility of the individual institution. At Washington University, officials have gone further and organized an external review committee to periodically assess the university's relationship with the Monsanto Co. According to David Kipnis, all reviewers are members of the National Academy of Sciences; molecular geneticist Daniel Nathans, a 1978 Nobel Prize winner in physiology or medicine and a former Washington University graduate now at the Johns Hopkins University School of Medicine in Baltimore, is chairman of the committee. "According to Kipnis, one of the most important concerns for their review committee is the potential misuse of graduate students. "[Review committee members] meet with graduate students, with postdoctoral fellows," he says, "to make sure that the arrangement has not distorted their research." Christina Jansen, a licensing officer at MIT, says students are also carefully protected at her institution. "Graduate students can end up working on projects for outside companies instead of doing their thesis research," Jansen says. "Activities detrimental to the academic teaching mission is one problem we watch out for." And at UC Berkeley, the faculty conflict of interest committee is also sensitive to this issue. "What they're really trying to protect," says technology officer Hoskins, "Is the relationship between the student and the faculty member, because the student is in a vulnerable position, working for the faculty member and also trying to pursue an advanced degree. And if the faculty member has an outside interest in a company, he could be using cheap labor for his own particular benefit." While they do take conflict-of-interest issues seriously, many researchers say that pressures to skew the aims of research or to lie about the results are not new in science nor unique to university-industry relationships. They also say that the issue of conflicts does not pose a larger threat to academic culture, as some fear. (begin quote box) Washington University William Hoskins: "The student is in a vulnerable position, working for the faculty member and also trying to pursue an advanced degree. [The faculty member] could be using cheap labor for his own particular benefit." (end quote box) In fact, some scientists say that, rather than undermining academia, technology transfer allows basic scientists who want to see applications result from their work to see this happen while remaining focused themselves on fundamental research. "We need that kind of dialogue, that interchange, that flow of information from the basic scientists to industry to the clinic," says Stanford's Blan, "without people having to leave academia because they want to see their ideas developed and applied toward treating human disease." Blau adds that letting companies take on development tasks can free the academic researcher to return to basic investigation. "The things that I give to companies to do are things I can't or don't want to do here," she says. Some researchers also see fundamental differences in outlook between the goals of business and of academic scientists that will tend to preserve the distinctions between industry and academia. Biologist Steve Roth's experience suggests this might be the case. Roth is a former chairman of the biology department at the University of Pennsylvania, currently on leave from the university. For now, he is vice president of research and development and chief scientific officer of Neose Pharmaceuticals Inc., Horsham, Pa., a startup aimed at developing the drug therapy potential of his more than two decades of university-based research into oligosaccharides. In another year, the university has told Roth, he will have to decide whether to relinquish his university position or to leave behind Neose; a business founded on the pursuit--albeit the product-oriented pursuit--of his scientific ideas. Despite this, and the fact that the size of the project at Neose is roughly 20 times the size of his academic lab at Penn, the choice will not be easy, he says. "I'm a biologist, and that's what I've been my whole life," says Roth. "I'm mystified by how living things are organized. It's in the core of my research." And wherever you go in the university, he says, you run into people who are similarly motivated. "In the business world," he says, "you deal all day long with people who really worry only about money. And that's not in any way derogatory--these are super-intelligent, dead-honest people, But their overriding concerns are not why a maple leaf is different from an oak leaf, for example, or why a pigeon can tell the difference. For someone who's spent his entire life with the former kind of person, it's a little odd." (begin advertisement) Multiply Your Response... Not Your Cost! 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