Introduction: the challenge of nanomedicine human subjects research: protecting participants, workers, bystanders, and the environment.

T he growing capacity to build and manipulate materials at the nanoscale is both thrilling and challenging. Engineering at the level of atoms allows much needed problem-solving and innovation, but also raises questions about how to assess the effects and safety of the materials created. The promise and the challenge are especially acute in the domain of nanomedicine. Nanotherapeutics and in vivo nano-diagnostics (diagnostics used within the human body) have the potential to solve long-standing problems, including how to ferry drugs across the blood-brain barrier to treat brain tumors, how to find and destroy tiny micrometastases before cancer progresses, and how to transport corrective genes into human cells without the dangers of viral vectors. But none of these applications is possible without first testing the safety and efficacy of these interventions in human beings. And human subjects research in nanomedicine raises fundamental questions. First, there are a host of questions about how to protect the human participants themselves. Many of these questions are the familiar ones that arise when testing interventions in any area of emerging technology. But answering those questions can be difficult when more work is needed to specify the attributes of concern that characterize various nanomaterials, familiar toxicological testing methods may not be adequate, and the long-term fate of nanoparticles in the human body is still under study. These uncertainties complicate decisions about when to authorize first-inhuman trials of a new intervention, how to assess the risks of a proposed protocol, and how to obtain consent to participate in the face of significant unknowns. Making ethical judgments under the federal regulations governing human subjects research — the Common Rule 1 and the Food and Drug Administration's equivalent 2 — can be difficult. The challenges, however, go beyond the question of how to protect human participants. A growing literature addresses the occupational risks of exposure to nanoparticles. This can raise questions about the safety of a nanomedicine protocol not only for the human participant, but also for laboratory workers and clinicians who may be exposed to the nanoma-terials. Beyond the occupational concerns, there can be questions of bystander exposure, when protocols potentially involve exposure of family members and close contacts. Lastly, there are environmental questions. Excretion and shedding by the human participants and disposal of laboratory waste may involve release of nanomaterials into the environment. The human subjects concerns are challenging enough. If nanomedicine trials were only a …