When does an academic researcher's work with industry conflict with the person's role as a scientist or clinician? What must a biomedical scientist do to avoid even the appearance that financial gain or prestige is distorting her research - a situation that can erode the trust of patients, institutions, and the public?

If you are a university-based researcher, you probably signed a conflict-of-interest disclosure agreement with your institution when you started. If you are about to begin a research career, you will quickly encounter conflict-of-interest policies. Universities no longer wonder whether there are potential conflicts between commercializing your work and conducting your research. Increasingly, they are acknowledging that potential conflicts are inherent in being an academic scientist. How do you and your institution work to manage those inherent conflicts and prevent them from derailing your scientific mission?

At a meeting recently held at Harvard Medical School (HMS), medical and ethical luminaries from there and from the Massachusetts Institute of Technology (MIT) explored these conflicts and suggested some new approaches. The event, "Undue Influence? Equity Interests in Biomedical Research," focused primarily on how the prospect of personal wealth could distort a university researcher's mission, in both conscious and unconscious ways. Dennis Thompson, Director of the Center for Ethics and the Professions at Harvard University and moderator of the meeting, has previously defined a biomedical research conflict of interest as "a set of conditions in which professional judgment concerning a primary interest (such as a patient's welfare or the validity of research) tends to be unduly influenced by a secondary interest (such as financial gain). Conflict-of-interest rules, informal and formal, regulate the disclosure and avoidance of these conditions" [1].

At the seminar, Thompson pointed out that financial gain is only one of many temptations that can distort a scientist's research mission. However, unlike intangible enticements, such as the drive for prestige, financial incentives can be readily measured and thus, he felt, should be measured. For example, if a researcher holds equity interest in a start-up and can profit greatly by contributing to its research, the scientist might change the direction of the lab or channel graduate students closer to the company's goals. Universities often set policies to prevent this type of conflict, or even its appearance, by limiting a researcher's equity holdings or corporate responsibilities. Conflict-of-interest policies usually cover two types of situations: a researcher who is involved with a company that is funding the academic laboratory; or a researcher with substantial interest in a company (such as a spin-off company) not formally tied to the lab, but that uses the researcher's knowledge.

As several speakers mentioned during the Harvard conference, changes in American society over the past decade or so are forcing research institutions such as Harvard Medical School to reevaluate their conflict-of-interest policies. Corporate funding of biomedical research has skyrocketed, improving research and technology transfer while offering scientists new ways to get rich - through stock, royalties, consulting fees, and other arrangements. Lita Nelsen, director of the Technology Licensing Office at MIT, suggested that some of these arrangements tempt scientists more than others do. For example, royalty agreements don't create millionaires unless the product works. Thus, there is no incentive to cheat on your research. Equity, she suggested, presents more incentive for dangerous liaisons with industry, since the chance of great wealth makes "visions of sugar plums" dance in researchers' heads.

As an academic biomedical scientist, you should carefully examine your institution's policies before making outside agreements with industry. Most institutions will permit outside work, and some will encourage it. For example, in the past 13 years, MIT has granted 1,000 licenses to industry, and enabled the start-up of 230 companies, including 20 companies in 1999. However, your institution may have very different policies and enforcement procedures, so be sure that you study them. Don't take chances; flagrant violations could cost you your career. Your institution may simply require that you disclose any conflicts or potential conflicts of interest, allowing it to investigate further if it chooses. Other policies simply establish firm prohibitions against certain types of activity instead of disclosure, while some policies combine disclosure with prohibitions.

As speakers pointed out during the Harvard meeting, institutional policies often distinguish between basic biomedical research and clinical research, requiring higher standards for the clinical work. Harvard Medical School currently makes this distinction in its policies. MIT's policies, however, do not. According to Nelsen, "we learn from our mistakes without killing people" because the university does not conduct clinical research. As she described it, MIT's policy consists of a few unbreakable rules with no loopholes.

Conflict-of-interest policies at medical research institutions are made to protect the institution's publicly stated missions and reputation. If you conduct clinical research, you are held responsible for how your work affects many groups, including patients in trials, users of products resulting from your work, students in training, your colleagues, your institution, and the public. Conflict-of-interest policies generally cover all of these areas, with particular concern for maintaining public trust. At the Harvard conference, David Blumenthal, director of the Health Policy Research and Development Unit at Massachusetts General Hospital, noted that scientists who undermine the public trust pose a greater threat to technology transfer than strict conflict-of-interest policies do. According to Blumenthal, patient protection should be the most important priority when forming policies.

John Parrish, a professor at both Harvard Medical School and MIT, agreed about the primary importance of protecting patients, stating that "patient care is a sacred trust." However, he also claimed that technology transfer is now a basic mission of academic health centers, along with patient care, teaching, and research. Parrish stated that we are underachieving in transferring science into health care, which is an ethical obligation. Arguing against strict conflict-of-policy rules, Parrish favored using good judgment and sound disclosure statements - given to both institutions and patients - to simultaneously protect patients and innovation.

Parrish, who directs three labs with over 100 researchers in each lab, believes that strategies such as strategically timing when a lab receives corporate funding could reduce the temptations that divert researchers from fundamental work into more industrially oriented projects. For example, a lab can use government grants to conduct research on a topic, and then fund the later, more applied stages with corporate funding. Finding new and complex ways of dealing with conflicts of interest, rather than simply making prohibitions, will stimulate innovation by providing a reward for the researcher's creative work.

Just as conflict-of-interest policies should be flexible enough to not inhibit creative work, they need to be broad enough to cover all situations where harm to patients, investigator bias, actual fraud, violations of privacy or secrecy, or unfair advantages may occur. When conflict-of-interest issues are discussed, it may be tempting to imagine an eminent, graying white male professor at an elitist institution who fudges on his research or uses patients as guinea pigs in order to boost his exorbitant holdings in drug companies. However, conflict-of-interest problems can occur in many situations with many types of scientists, and examples exist that defy the stereotype

Eugene Braunwald, chair of Harvard Medical School's Committee to Review HMS Policy on Conflict of Interest and Commitment, cited some of these cases at the meeting. As he explained, it is possible to be an excellent researcher and grow rich without violating trust. It is also possible that poor, struggling researchers can fall prey to temptations that offer far more dangers than rewards. In the first case, Braunwald cited Jim Black of ICI Industries and Wellcome. During his career, Black made discoveries that opened up two classes of drugs, beta blockers and H2 antagonists. There are now 14 beta blockers on the market, used for treatment of angina, hypertension, arrhythmias, and congestive heart failure. Current H2 blockers include the best-seller Zantag. Black received an honorary degree from Harvard, won a Nobel Prize, was knighted by the Queen of England, and became incredibly rich. He responded to powerful financial incentives and did all the right things without breaching ethics.

In contrast to Black's case, Braunwald described a hypothetical example of a single mother serving as assistant professor under a three-year appointment. Her income, and the support of her child, depends upon renewal of an RO1 grant. If her experiments are not going well, she may be tempted (understandably) to make false claims on the renewal application in order to survive.

The moral of these stories: researchers and institutions must be vigilant about all types of situations where financial gain, prestige, or power tempt scientists to compromise their scientific missions. Yet, you should not jump to conclude that a mix of personal and scientific interests leads inevitably to ethical compromises. With careful and considered planning, you can manage your potential conflicts of interest so that your can work can thrive when these interests converge.