Back in 1993 when Eric Lander, Mark Levin, and Raju Kucherlapati founded Millennium Pharmaceuticals, Inc., they knew that if they wanted to establish their company as a leader in the emerging field of genomics, they would need to be prepared to face new issues generated by this field. Their biotech company would need to address ethical issues raised by genetic testing, including genetic privacy, tissue ownership, and gene patenting - and it would need to be ready to respond proactively. The company founders believed it was necessary to incorporate a bioethics vision into its R and D from the outset.

To that end, soon after establishing Millennium, Levin and his colleagues hired Steve Holtzman, who, as chief business officer, would spearhead the company's bioethics initiative. "Written into my job description - literally - was a mandate to bring an awareness of sensitive ethical issues to the staff that our work would raise," Holtzman says. "The idea was that if Millennium were to become a leader in the field of genetics and genomics, we would need to help set the right tone for this work," he adds.

"Millennium's founders and board of directors believed that in order to realize the full potential of its technologies and to guarantee their socially responsible use, it was necessary to have a strong, informed public discourse within the company about issues the science was raising," Holtzman says. This meant that Millennium's entire staff - not just the management - needed exposure to the social, legal, and ethical implications of its science. Getting in on the ground floor of genomics gave Millennium a special responsibility to set what it believed was "the right tone."

Holtzman proved to be the right man for the job. Armed with a B.A. in philosophy from Michigan State University, he had taught medical ethics at the university level and had earned a B.Phil. in moral philosophy from Oxford University in the United Kingdom. Over the last few years, Holtzman has been a prime mover in integrating a bioethics vision into the biotech industry and beyond. In October 1996, he was the only biotech representative named to serve on the President's National Bioethics Advisory Commission. Even before that, Holtzman was instrumental in establishing and cochairing the bioethics task force for the Biotech Industry Organization. Recently, he was appointed to the board of directors at the Hastings Center, the preeminent bioethics think tank, located in Hastings-on-Hudson, New York.

After arriving at Millennium in 1995, Holtzman chose Philip Reilly as company advisor and staff educator. Reilly brings a unique mix of talents to the post. Director of the Shriver Center in Waltham, Massachusetts, he is an M.D. specializing in genetics, and also a J.D. As a consultant for biotech and pharmaceutical companies, Reilly is ubiquitous, dealing with a wide range of issues.

Reilly created, and now teaches to the Millennium staff, an ongoing, ever-evolving bioethics seminar. Remarkably, since 1996, some 500 of Millennium's 850 employees have elected to take part in the voluntary class, which meets each Friday at 4:00 P.M. Participants range from clinical-trial administrators to researchers to lawyers. Reilly's and Holtzman's aim for the class - which resembles the college courses Reilly teaches elsewhere, complete with primary- and secondary-source readings - is to lay the groundwork for reflecting on issues that science generates. The goal is to give the staff tools with which they can think issues through, without promoting any particular position.

Millennium's long-term bioethics initiative has given it a reputation among other companies as a place they can come to with their own ethics/technology questions. Recently, one company consulted with Millennium regarding its concern that its technology had applications in biological weaponry. A number of other biotechs use Millennium in a similar way as a sounding board for ethics matters.

What makes Millennium unique among biotech companies dealing with bioethical questions is its grass-roots approach. Some companies, such as Geron and Myriad Genetics, address pressing issues by consulting with a bioethics advisory board - but they are not bound to follow the board's advice. Other companies employ bioethicist consultants to serve on their boards (Celera Genomics, for example, employs Art Caplan of the University of Pennsylvania in that capacity), to shed light on difficult issues or provide a conceptual framework within which to consider ethics questions. Still other companies, including SmithKline Beecham and Genzyme, have established and maintain permanent bioethics committees.

Millennium stands alone among biotech companies because it has woven a bioethics vision into the corporate fabric from the ground up. Rather than ruling from "on high," or putting the onus of ethical judgments on the shoulders of one or more "experts," Millennium trains its staff to act as their own consultants - and other companies are following its lead.

In the spring of 1996, during a 10-week internal program called "Genetics, Law, and Social Policy," Reilly and Millennium personnel covered topics such as a history of the eugenics movement in the United States; legal cases pertinent to privacy issues; population screening; genetic counseling; genetic discrimination; DNA banking; new reproductive technologies; and legal issues raised by behavioral genetics.

In a shorter, four-session unit conducted this past spring, Reilly and participants covered genomic research, ethics, and public policy. The seminar focused on research using human subjects and the complex questions regarding what to do with subjects' tissues after the conclusion of a clinical trial. The class included an overview of federal regulations concerning clinical trials, the role of institutional review boards in overseeing trials, and an exploration of special issues that arise when research is conducted with a vulnerable population such as the mentally ill.

"Success of the program can be measured by whether staff forms their own conclusions; in the end, my input should not be needed," says Holtzman. It is, after all, up to Millennium employees to decide not just how the science is to be done, but how it is to be used. With a staff population drawn largely from the 1960s and 1970s, Millennium believes it neither can nor should dictate how science is applied.

With a culture of asking questions and "doing the right thing" now firmly established at Millennium, ongoing study and dialogue is encouraged outside the lab and the classroom. The company set up an internal employee Web site that provides resources beyond course readings to deepen the debate and increase understanding of related issues.

Among the concrete results of Millennium's unique bioethics culture is the employees' decision to change the consent forms used for clinical trials. After studying informed consent, the staff concluded that Millennium's forms did not disclose enough information, so they altered them accordingly. Specifically, the staff believed clinical-trial participants should be informed explicitly that the research the company was conducting would likely result in profit for the company, in which participants would not share. Such detailed disclosure is far from the norm for informed-consent policies in pharmaceutical and biotech companies. Many consent forms may not even mention that a for-profit firm is involved, but may list only its academic collaborators.

Millennium employees felt that consent forms should explicitly indicate that profit was a distinct possibility for the trial's underwriters and that any such profit would not extend to participants. An increased sensitivity to research participants, disclosure, and issues of ownership is a direct result of Millennium's staff having studied the issues, thought them through, and come up with what they can live with.