Tun-Hou Lee, an associate professor of virology at the Harvard School of Public Health, is the co-inventor of a number of Harvard-owned patents.
Several of these patents have been licensed to a biotechnology firm, Cambridge Biotech, in which Lee and his family own stock.
Since the patents are held by Harvard, Cambridge Biotech must pay royalties from the sale of those patented products to the University. And under a distribution agreement within the University, Lee, as the co-inventor, receives a fraction of the royalties.
What some may find surprising is that according to Harvard University regulations, Lee has done nothing unethical or illegal.
But many within the University say close connections like Lee's between Harvard professors and biotechnology firms is cause for concern.
By all accounts, an overwhelming majority of Harvard's biochemistry and Medical School professors have some relationship with biotech companies. That relationship can range from simply owning stock in the company, to sitting on the scientific advisory board or board of directors of the company, to even founding or running the company.
Many professors--even those who say they believe such relationships are beneficial--concede that there is a problem when company interests begin conflicting with the University's goal of educating students.
The History
Loeb University Professor Walter Gilbert, who works in the Molecular and Cellular Biology Department, says the "uneasy relationship" between the university and biotech companies go back to the 1970s and '80s.
In 1980, the Supreme Court ruled that a human-made microorganism qualified as patentable matter. The same year, Congress passed the Patent and Trademark Amendment Act, allowing universities to receive patents directly, license patent rights and collect royalties on inventions from federally-funded research without seeking waivers from federal agencies.
These changes opened the door for academic scientists and universities to pursue the commercial aspects of biotechnology, according to an article in Technology Review by MIT professor Charles Weiner in 1986.
According to Weiner, the changes transformed biology virtually overnight. Academic biologists have become consultants, advisors, founders, stockholders and contractees of new biotechnology firms, he wrote.
In his 1982 book Beyond the Ivory Tower, then-Harvard president Derek C. Bok wrote, "The great majority [of people] are concerned that programs to exploit technological development will confuse the university's central commitment to the pursuit of knowledge and learning by introducing into the very heart of the academic enterprise a new and powerful motive--the search for commercial utility and financial gain."
Bok wrote that the possibility of making money by exploiting a commercially attractive discovery was against the basic tenet of the university.
Outside Jobs
Harvard professors, even those with their own links to biotechnology firms, generally acknowledge this potential for conflict of interest, especially if a faculty member holds a job at such a firm.
"I do believe [the relationships] cause conflicts of interest and I worry seriously about these things, particularly if there is money involved," says Jerome Gross, an emeritus professor at the Medical School who sits on the scientific advisory board of Organogenesis, Inc., a biotech firm which manufactures organ replacements for transplantation.
"A director 'legally' owns the company and therefore has a major responsibility for its welfare which may be in conflict with academic responsibilities," Gross says. "For somebody to found the company and be an officer in the company and at the same time have serious academic commitments, I think, is a more serious conflict liability."
One aspect of holding a job which Dean of the Faculty Jeremy R. Knowles said he resigned his position on the scientific advisory board of Biogen when he became dean in 1990, "primarily because of time constraints." And Gilbert, who founded Biogen and said he served as its chief executive officer for four or five years in the early '80s, resigned his professorship at Harvard while he ran Biogen. Gilbert was subsequently re appointed when he stepped down as CEO. FAS regulations, as outlined in the "Principles and Policies That Govern Your Research and Other Professional Activities," require that "no more than 20 percent of one's total professional effort [during the academic year] may be directed to outside work." Money Epigen Other professors are more concerned with conflicts when a company provides research funds to a professor. "[The relationships] could be considered a conflict of interest if the professor allowed it to be a conflict of interest, namely if the research was strictly in the interest of the company providing the funds," says Warren E.C. Wacker, former director of University Health Services and a former member of the board of directors of Millipore Corporation. Gilbert says that as faculty receive company money to conduct research more frequently, the propriety of the research becomes a more critical issue. "I think research at the University should be open," he says. "Company research which has a confidential character is not good." But many professors respond that this type of conflict of interest has the most enforceable guidelines. Bjorn R. Olsen, Hersey professor of anatomy and cellular biology and a member of the scientific advisory board of Organogenesis, Inc., says he has held a stock option in the company for the duration of the time he has worked for them. Olsen says Harvard received a grant this year from Organogenesis, Inc. to support a specific project in which he participates. "I had to make a choice between receiving support for the project and not having the stock options, or have the stock option in the company but not receiving any support," Olsen says. "Obviously, I have chosen support, but I will not benefit personally from the success of the company." John F. Codington, an associate professor of biological chemistry and molecular, pharmacology and a senior scientist at the Harvard affiliated Boston Biomedical Research Institute, says Boston Biomed has granted the biotechnology company Epigen the commercial right to use the antigens and antibodies that he developed and the right to prepare a diagnostic test he developed for commercialization. Codington says he advises Epigen as to the conditions under which these materials can be used most effectively. "Epigen has sponsored my research in the past, and at present, they give a minimal amount of financial aid to my research," Codington says. But he says relationships does not represent a conflict of interest because "this does not influence my basic interest in studying the role of tumor antigens and the development of methods for diagnosing and preventing cancer, which are my primary interests." Codington says he has given a statement to his department regarding his connections with Epigen and doesn't see any problem with the relationship. Profits CREATIVE BIOMOLECULES Some professors say that conflicts of interest can arise in cases in which the professor profits from the research. "I think that the big trend of capitalizing fiscally on the research that we do is something that I don't approve of," says Dr. Alexander Leaf, Jackson professor of clinical medicine emeritus at Massachusetts General Hospital. Leaf says that since much of the research conducted by physicians is funded by government money, the fruits of that research should be enjoyed by society rather than used by individuals for profit. "This can be a distraction and distortion of the academic mission," Leaf says. But other professors say patents don't tend to be profitable. "I have a number of patents which have been licensed to companies, but I have never profited from any one of those," says Michael Klagsbrun, a professor of surgery who sits on the scientific advisory board of Creative Biomolecules. Lee, who owns stock in a company licensing some of his patents, says his story does not represent a conflict of interest. "I don't see any conflict of interest involved because my lab is not performing anything for the company, and we are not receiving any funding support from the company," Lee says. "In fact, there is nothing that Cambridge Biotech is doing that is related to my lab, and nothing that my lab is doing now is related to what Cambridge Biotech is doing." Clinical Trials Cambridge Biotech One final type of financial conflict, professors say, is if a professor conducts clinical trials of a drug in which he or she might have some vested interest. Both Knowles and Gilbert say there is more potential for conflict at the Medical School than in FAS because Medical School professors can help with clinical trials. In one widely reported example, Scheffer Tseng, a researcher at Harvard and Mass General Hospital, conducted clinical tests of a potential eye treatment in the mid-1980s. The treatment did not work, but it was later disclosed that Tseng had tested patients not authorized to receive the drug and reaped large profits from stock he owned in a company developing it. Non-Financial Conflicts BIOGEN A number of professors say that conflicts of interest can also exist through non-financial means, for example if a professor has some sort of intellectual interest in a company. "Even if [the professor] has some kind of an intellectual vested interest in a company and also academia, I think it's very difficult to separate responsibilities and commitments to both sides," Gross says. Gross says he is concerned about the effect of the relationships on students. "I think that when a senior faculty member is seriously involved with a commercial venture, it is very difficult not to influence the thinking of the young people in their immediate area of responsibility, such as students and post-doctoral fellows," Gross says. "Because of the increasing economic stringency of the research funds, these young people see the writing on the wall and the behavior of their mentors and they are much more likely to think of more patentable experiments and much less likely to take risks in their research, which is what scientific research is all about," Gross says. More Knowledge INTERNEURON PHARMACEUTICALS, INC. Some professors, though, say the connections they have with biotechnology firms actually help their teaching mission by allowing them to impart more knowledge to their students. Gilbert, who co-founded Myriad Genetics in 1992 in addition to Biogen, says his teaching is better because of his connections. "As a faculty member, [you] learn a whole aspect of the world that you didn't know before," Gilbert says. "You are exposed to a whole set of medical questions." "This stimulates my thinking," he says. "I am more aware of how pharmaceuticals are made." Jack L. Strominger, Higgins professor of biochemistry and former chair of the department of biochemistry and molecular biology, agrees that the impact on teaching is "positive and enormous." "I still think I get much more out of it than the company," says Strominger, who has worked on the advisory board of several biotechnology companies during the last 30 years. "The scientists present their work and I get educated," he says. "You use every bit of knowledge you have in academic teaching and this broadens your ability to teach as well as to advise students about the future." Knowles lists the general benefits of the close relationships as "intellectual stimulation, cutting-edge work, relevance to society, emergence form the ivory tower, sharing of ideas and materials, helpful contacts for students, future jobs [and] speeding the flow of basic science to helpful products." And many in the industry agree that those are the essential benefits. "I think many professors have made important contributions to starting the biotech [industry] in Massachusetts," says Janice G. Pero, former associate professor of biology and current president of Omni-Gene Bioproducts, Inc. "I don't think this has detracted from their role at the University," she says. "It has been a win-win situation for all parties." Benefits Outweigh Costs Organogenesis Inc. Despite the concerns, nearly all of the professors interviewed still say they believe the benefits of biotech relationships outweigh the costs. One significant benefit is the ability to develop drugs that are of practical use to society. Sometimes, not patenting the drug can actually have disastrous consequences. As a case in point, Dr. Richard J. Wurtman, an MIT professor who serves as professor of neuroendocrine regulations at the joint Harvard-MIT Health Services and Technology Division, is the co-founder and a director and adviser of Interneuron Pharmaceuticals. Wurtman says he and other MIT professors discovered in 1971 an amino acid called But Wurtman says that since MIT did not patent the drug, no one else was allowed to do so, since only inventors can patent a product. A consequence of the lack of a patent, Wurtman says, was that no one could perform safety studies on the amino acid. Wurtman says health food stores began selling tryptophan as a nutritional supplement and sold it for 15 years without approval from the Food and Drug Administration (FDA). In 1988, Wurtman says, a Japanese company made a new bacteria to synthesize tryptophan, but the bacteria also produced a new toxin. Thus, when the drug was sold in health food stores about a month later, 45 people were killed by a disease caused by the new toxin. If MIT had patented the drug, some company would have developed it and it would have needed FDA approval, Wurtman says. Then, when the manufacturer changed to the Japanese company, the FDA would have done new tests on the drug. "The fact that we didn't patent it makes us responsible," Wurtman says. Wurtman says he therefore founded the company Interneuron in 1988 with MIT as a part-owner for the sole purpose of licensing drugs for which MIT owns the patent. "If a university patents discoveries, it doesn't go any place unless a company licenses it," Wurtman says. "To my knowledge, there are only one or two drugs ever to come out of Harvard teaching hospitals." "I agreed to set up the company to license MIT patents to do clinical testing," Wurtman says. But he adds this is not a conflict of interest because the company must compete for MIT patents; the company does not automatically receive patents. "Very few professors are really involved in developing products," Wurtman says. "Great research is done in the university, but very little of it is applied. There are two goals: knowledge for knowledge's sake and solving problems. I don't see them in conflict." The Regulations MILLIPORE Nearly all professors interviewed say they avoid issues of conflict of interest by fully following disclosure rules. "There is always a possibility of conflict of interest," Wurtman says. "The way I deal with it is I always tell everybody everything--more than they want to know." Each arm of the University has different policies dealing with outside professional activities and the possibilities for conflict of interest, but for the most part, the regulations are all similar to those of the FAS. New government regulations require recipients of grants from the National Science Foundation (NSF) or the National Institutes of Health (NIH) to file a disclosure form with the Committee on Professional Conduct's subcommittee on conflicts of interest, according to Bertrand I. Halperin, Hollis professor of mathematics and natural philosophy and chair of the subcommittee. The disclosure from requests that the researcher disclose whether the annual income from the outside company is above or below $10,000, the basis for the payments, the nature of ownership interest, the value of ownership interest and the percentage of ownership. Halperin says the committee will look at all forms on which the income exceeds $10,000 and decide if the committee needs more information. If the committee determines that there is a conflict of interest, Halperin says, it will recommend to the investigator that he or she take certain steps to manage the research project or financial interest. "We may decide that the conflict of interest is so severe that the investigator would have to divest the financial interest, or we may decide that the conflict of interest can be adequately dealt with simply by public disclosure," Halperin says. But Halperin says the forms apply only to those professors receiving NSF or NIH funds and not to all faculty. Before this year, FAS regulations required professors or staff members to notify relevant officials if there was a potential conflict of interest, according to Halperin. "If there is a potential conflict of interest, then there is a Committee on Rights and Responsibilities which will look into potential conflict of interest and will decide whether something has to be done," Halperin says. These regulations remain in effect for many of the professors within the FAS, he says. Medical School regulations generally do not allow professors to perform clinical research on a drug that is contractually obligated to a company in which the professor or anyone in the professor's family holds stock or has a financial interest, according to the Medical School's "Faculty Policies on Integrity in Science." A professor is also not allowed to accept research money from a business in which the professor or anyone in the professor's family holds stock or has a financial interest. Certain exceptions to these regulations allow a professor to perform the above actions with the approval of the Dean of the Medical School and the Medical School's standing committee on conflicts of interest and commitment.
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