This Bulletin reminds us that research on human subjects poses old yet vexingly elusive questions.

Worse, because of the evolving context and culture of research, new issues trouble human subjects and those who conduct, fund, or oversee research.

As Joal Hill observes, many constituencies—including taxpayers—collaborate in research. Indeed, research is increasingly a financial venture. Funding reductions have fostered an entrepreneurial mind-set that engenders public suspicions: are investigators ultimately governed by financial self-interest, the advancement of knowledge to help future patients, or the protection of current patient-subjects?

Paul Root Wolpe asks whether participation in research should and, in general, does conform to appropriate norms of voluntariness, informed consent, and altruistic motivation. Does our research system truly encourage—or permit—subjects to consent freely, knowledgeably, generously? Indeed, can it do so?

And what of the anguishing questions raised by the participation of children in research? According to Denise Angst and Joal Hill, federal regulations and guidelines of professional organizations emphasize the assent or dissent of the child-patient in addition to the permission or refusal of the parents. But is determining the child's preference a must? What if the child's wishes conflict with parents' desires? Researchers must indicate no guarantee of direct therapeutic benefit from research participation—yet might that very language suggest the unexpressed optimism of an investigator who is also the patient's physician? How hard should physician-investigators work to dispel this "therapeutic misconception" if even the placebo effect might help to heal?

Research subjects and their loved ones are not the only ones at risk. Institutions and colleagues can suffer because of a researcher's alleged malfeasance. R. Stephen Warner's first-person account raises more questions: Do tighter regulations and enforcement address problems sufficiently? Might they inadvertently create new problems, especially when applied unreflectively to social science research?

Application of research results can also raise questions. How should physicians respond to claims of positive correlations between spiritual practice and health? Larry VandeCreek asks whether spiritual inquiry—even intervention—is appropriate for the physician. If so, when? What if the research itself is controversial? Should physicians wait for better data or begin now to address spirituality with the proviso that new data may teach new duties?

Clearly, more questions are raised than answered in this Bulletin. The research norms envisioned in the 1960s and 70s by such luminaries as Paul Ramsey and Hans Jonas remain at risk. Not only are the sacredness of the vulnerable human subject and the holiness of that subject's free participation at issue; so are the integrity of the research enterprise and its potential to help patients in this new century.