Hilary Bok

Safety issues in cell-based intervention trials

We report on the deliberations of an interdisciplinary group of experts in science, law, and philosophy who convened to discuss novel ethical and policy challenges in stem cell research. In this report we discuss the ethical and policy implications of safety concerns in the transition from basic laboratory research to clinical applications of cell-based therapies derived from stem cells. Although many features of this transition from lab to clinic are common to other therapies, three aspects of stem cell biology pose unique challenges. First, tension regarding the use of human embryos may complicate the scientific development of safe and effective cell lines. Second, because human stem cells were not developed in the laboratory until 1998, few safety questions relating to human applications have been addressed in animal research. Third, preclinical and clinical testing of biologic agents, particularly those as inherently complex as mammalian cells, present formidable challenges, such as the need to develop suitable standardized assays and the difficulty of selecting appropriate patient populations for early phase trials. We recommend that scientists, policy makers, and the public discuss these issues responsibly, and further, that a national advisory committee to oversee human trials of cell therapies be established.

Public Stem Cell Banks: Considerations of Justice in Stem Cell Research and Therapy

If stem cells fulfill their therapeutic promise, moving them from the laboratory into the clinic will raise several concerns about justice. One concern is that, for biological reasons alone, stem cell-based therapies might not be available for every patient who needs one. Worse, depending on how we address the problem of biological access, they might benefit primarily white Americans. We can avoid this outcome—although at a cost—by carefully selecting the stem cells we make available.

CELL-BASED INTERVENTIONS FOR NEUROLOGIC CONDITIONS: ETHICAL CHALLENGES FOR EARLY HUMAN TRIALS

Background: Attempts to translate basic stem cell research into treatments for neurologic diseases and injury are well under way. With a clinical trial for one such treatment approved and in progress in the United States, and additional proposals under review, we must begin to address the ethical issues raised by such early forays into human clinical trials for cell-based interventions for neurologic conditions. Methods: An interdisciplinary working group composed of experts in neuroscience, cell biology, bioethics, law, and transplantation, along with leading disease researchers, was convened twice over 2 years to identify and deliberate on the scientific and ethical issues raised by the transition from preclinical to clinical research of cell-based interventions for neurologic conditions. Results: While the relevant ethical issues are in many respects standard challenges of human subjects research, they are heightened in complexity by the novelty of the science, the focus on the CNS, and the political climate in which the science is proceeding. Conclusions: Distinctive challenges confronting US scientists, administrators, institutional review boards, stem cell research oversight committees, and others who will need to make decisions about work involving stem cells and their derivatives and evaluate the ethics of early human trials include evaluating the risks, safety, and benefits of these trials, determining and evaluating cell line provenance, and determining inclusion criteria, informed consent, and the ethics of conducting early human trials in the public spotlight. Further study and deliberation by stakeholders is required to move toward professional and institutional policies and practices governing this research.

The role of animal models in evaluating reasonable safety and efficacy for human trials of cell-based interventions for neurologic conditions.

Progress in regenerative medicine seems likely to produce new treatments for neurologic conditions that use human cells as therapeutic agents; at least one trial for such an intervention is already under way. The development of cell-based interventions for neurologic conditions (CBI-NCs) will likely include preclinical studies using animals as models for humans with conditions of interest. This paper explores predictive validity challenges and the proper role for animal models in developing CBI-NCs. In spite of limitations, animal models are and will remain an essential tool for gathering data in advance of first-in-human clinical trials. The goal of this paper is to provide a realistic lens for viewing the role of animal models in the context of CBI-NCs and to provide recommendations for moving forward through this challenging terrain.

What's Wrong with Confusion?

We might be confused about the status of such interspecies beings, and this might create social disorder. As Robert and Baylis note, many people are confused about many things, for example, the moral status of children produced by two nuclear genetic donors and a different mitochondrial donor, gestated by a different surrogate, and raised by different surrogate parents. People have been confused about the moral status of clones, claiming they lack autonomy. People are confused about the moral status of embryonic stem cells—some have argued they should be treated like embryos. We should not base social policy and law on such confusions, especially when such policies harm people (making them worse off than they could have been). Racists were confused about the moral status of race. The social costs of acceding to irrational confusion are, at least historically, much greater than the costs of clearing it up and reforming society. People are confused about the moral signiacance of genetics and biology in general. Our job is to clear this up (as philosophers such as McMahan have tried to do), not to perpetuate it or allow it to persist or base social policy on it. In the future, cyborgs and artiacial intelligence will throw up even greater challenges to our conception of what matters. No doubt many people would and the introduction of animal genetic material into human beings more repugnant and bestial than the introduction of nonbiological material. But the scope for change and enhancement is limited in the plant and animal kingdoms by the range of genes that occur naturally. The scope for radical differences in artiacial life are far greater. Unless we begin to understand what is good and ought to be promoted and what is bad and ought to be prevented, we will be in no position to evaluate these rapidly advancing scientiac possibilities. ■

The Implications of Advances in Neuroscience for Freedom of the Will

SummarySome neuroscientists argue that advances in neuroscience threaten to undermine our freedom. The argument here is that those concerns are instances of a more general concern about the compatibility of freedom with causal determinism, and that denying that our choices are fully determined under causal laws presents a different set of problems for the claim that we have free will. An alternative account of freedom is presented, consistent with determinism in general, and with advances in neuroscience in particular.