Clarifying the Ethics and Oversight of Chimeric Research.

This article is the lead piece in a special report that presents the results of a bioethical investigation into chimeric research, which involves the insertion of human cells into nonhuman animals and nonhuman animal embryos, including into their brains. Rapid scientific developments in this field may advance knowledge and could lead to new therapies for humans. They also reveal the conceptual, ethical, and procedural limitations of existing ethics guidance for human-nonhuman chimeric research. Led by bioethics researchers working closely with an interdisciplinary work group, the investigation focused on generating conceptual clarity and identifying improvements to governance approaches, with the goal of helping scholars, funders, scientists, institutional leaders, and oversight bodies (embryonic stem cell research oversight [ESCRO] committees and institutional animal care and use committees [IACUCs]) deliver principled and trustworthy oversight of this area of science. The article, which focuses on human-nonhuman animal chimeric research that is stem cell based, identifies key ethical issues in and offers ten recommendations regarding the ethics and oversight of this research. Turning from bioethics' previous focus on human-centered questions about the ethics of "humanization" and this research's potential impact on concepts like human dignity, this article emphasizes the importance of nonhuman animal welfare concerns in chimeric research and argues for less-siloed governance and oversight and more-comprehensive public communication.

Influence of animal pain and distress on judgments of animal research justifiability among university undergraduate students and faculty.

Acceptance of animal research by the public depends on several characteristics of the specific experimental study. In particular, acceptance decreases as potential animal pain or distress increases. Our objective in this study was to quantify the magnitude of pain/distress that university undergraduate students and faculty would find to be justifiable in animal research, and to see how that justifiability varied according to the purpose of the research, or the species to which the animal belonged. We also evaluate how demographic characteristics of respondents may be associated with their opinions about justifiability. To accomplish this goal, we developed and administered a survey to students and faculty at the University of Wisconsin-Madison. Our survey employed Likert-style questions that asked them to designate the level of animal pain or distress that they felt was justifiable for each of the following six purposes-animal disease, human disease, basic research, human medicine, chemical testing, or cosmetic testing. These questions were asked about five different species of animals including monkeys, dogs/cats, pig/sheep, rats/mice, or small fish. We used the data to establish a purpose-specific pain/distress scale, a species-specific pain/distress scale, and a composite pain/distress scale that, for each respondent, averaged the extent of justifiable pain/distress across all purposes and species. For purpose, students were more likely to choose higher levels of pain for animal disease research, followed by human disease, basic research, human medicine, chemical testing, and cosmetic testing. Faculty were more likely to choose the same level of pain for the first four purposes, followed by lower levels of pain for chemical and cosmetic testing. For species, students were more likely to choose higher levels of pain for small fish and rats/mice (tied), pigs/sheep and monkeys (tied), than for dogs/cats. For faculty, order from least to most justifiable pain/distress was small fish, rats/mice, pigs/sheep, then dogs/cats and monkeys (the latter two tied). Interestingly, exploratory factor analysis of the pain/distress scales indicated that when it comes to justifying higher levels of pain and distress, respondents identified two distinct categories of purposes, chemical and cosmetic testing, for which respondents were less likely to justify higher levels of pain or distress as compared to other purposes; and two distinct categories of species, small fish and rats/mice, for which respondents were more likely to justify higher levels of pain/distress than other species. We found that the spread of acceptance of animal research was much smaller when survey questions included pain/distress compared to when only purpose or species were part of the question. Demographically, women, vegetarians/vegans, and respondents with no experience in animal research justified less animal pain/distress than their counterparts. Not surprisingly, a lower level of support for animal research in general was correlated with lower justifiability of pain/distress. Based on these findings, we discuss the role of animal pain/distress in regulatory considerations underlying decisions about whether to approve specific animal uses, and suggest ways to strengthen the ethical review and public acceptance of animal research.

The Ethics of Deliberate Exposure to SARS-CoV-2 to Induce Immunity.

We explore the ethics of deliberately exposing consenting adults to SARS-CoV-2 to induce immunity to the virus ('DEI' for short). We explain what a responsible DEI program might look like. We explore a consequentialist argument for DEI according to which DEI is a viable harm-reduction strategy. Then we consider a nonconsequentialist argument for DEI that draws on the moral significance of consent. Additionally, we consider arguments for the view that DEI is unethical on the grounds that, given that large-scale DEI would be highly likely to result in some severe illnesses and deaths, DEI amounts to a form of killing. Our thesis is that incorporating a DEI program alongside the status quo 'calibrate the curve' responses could have significant advantages at the early stages of pandemics. These potential advantages mean that, at a minimum, research into DEI would have been justified early in the COVID-19 pandemic and that DEI programs should be explored as potential additions to our overall approach to emerging pandemics in the future.

Attitudes toward animals, and how species and purpose affect animal research justifiability, among undergraduate students and faculty.

As members of a university community that sponsors animal research, we developed a survey to improve our knowledge about factors underlying the perceived justifiability of animal research among faculty and undergraduate students. To accomplish this objective, we gathered quantitative data about their general views on animal use by humans, their specific views about the use of different species to address different categories of scientific questions, and their confidence in the translatability of animal research to humans. Students and faculty did not differ in their reported levels of concern for the human use of animals, but women reported significantly higher levels of concern than men. Among students, experience with animal research was positively correlated with less concern with animal use, and having practiced vegetarianism or veganism was associated with more concern. Gender, experience with animal research, and dietary preferences were similarly correlated with the extent of justifiability of animal use across all research purposes and species. Faculty responses resembled those for students, with the exception that justifiability varied significantly based on academic discipline: biological sciences faculty were least concerned about human use of animals and most supportive of animal research regardless of purpose or species. For both students and faculty, justifiability varied depending on research purpose or animal species. Research purposes, ranked in order of justifiability from high to low, was animal disease, human disease, basic research, human medicine, animal production, chemical testing, and cosmetics. Justifiability by purpose was slightly lower for students than for faculty. Species justifiability for students, from high to low, was small fish, rats or mice, pigs or sheep, monkeys, and dogs or cats. Faculty order was the same except that monkeys and dogs or cats were reversed in order. Finally, confidence in the translatability of animal research to our understanding of human biology and medicine was not different between students and faculty or between genders, but among faculty it was highest in biological sciences followed by physical sciences, social sciences, and then arts and humanities. Those with experience in animal research displayed the most confidence, and vegetarians/vegans displayed the least. These findings demonstrate that, although the range of views in any subcategory is large, views about animal research justifiability can vary significantly among respondent subpopulations in predictable ways. In particular, research purpose and choice of animal species are important variables for many people. This supports the claim that ensuring purpose and species are robustly integrated into research proposal reviews and approvals should be considered to be a best practice. We suggest that strengthening this integration beyond what is described in current regulations would better meet the justifiability criteria expressed by members of our campus community.

Assessing undergraduate student and faculty views on animal research: What do they know, whom do they trust, and how much do they care?

Research using animals is controversial. To develop sound public outreach and policy about this issue, we need information about both the underlying science and people's attitudes and knowledge. To identify attitudes toward this subject at the University of Wisconsin-Madison, we developed and administered a survey to undergraduate students and faculty. The survey asked respondents about the importance of, their confidence in their knowledge about, and who they trusted to provide information on animal research. Findings indicated attitudes varied by academic discipline, especially among faculty. Faculty in the biological sciences, particularly those who had participated in an animal research project, reported the issue to be most important, and they reported greater confidence in their knowledge about pro and con arguments. Among students, being female, a vegetarian/vegan, or participating in animal research were associated with higher ratings of importance. Confidence in knowledge about regulation and its adequacy was very low across all groups except biological science faculty. Both students and faculty identified university courses and spokespersons to be the most trusted sources of information about animal research. UW-Madison has a long history of openness about animal research, which correlates with the high level of trust by students and faculty. Nevertheless, confidence in knowledge about animal research and its regulation remains limited, and both students and faculty indicated their desire to receive more information from courses and spokespersons. Based on these findings, we argue that providing robust university-wide outreach and course-based content about animal research should be considered an organizational best practice, in particular for colleges and universities.

Chimeras, moral status, and public policy: implications of the abortion debate for public policy on human/nonhuman chimera research.

Researchers are increasingly interested in creating chimeras by transplanting human embryonic stem cells (hESCs) into animals early in development. One concern is that such research could confer upon an animal the moral status of a normal human adult but then impermissibly fail to accord it the protections it merits in virtue of its enhanced moral status. Understanding the public policy implications of this ethical conclusion, though, is complicated by the fact that claims about moral status cannot play an unfettered role in public policy. Arguments like those employed in the abortion debate for the conclusion that abortion should be legally permissible even if abortion is not morally permissible also support, to a more limited degree, a liberal policy on hESC research involving the creation of chimeras.

Informed consent and federal funding for stem cell research.

A review of the consent forms signed by those who donated embryos for the NIH-approved embryonic stem cell lines reveals several problems, providing ethical as well as scientific reasons to overturn the Bush administration's restrictions on federal funding for stem cell research.

Academic freedom and academic-industry relationships in biotechnology.

Commercial academic-industry relationships (AIRs) are widespread in biotechnology and have resulted in a wide array of restrictions on academic research. Objections to such restrictions have centered on the charge that they violate academic freedom. I argue that these objections are almost invariably unsuccessful. On a consequentialist understanding of the value of academic freedom, they rely on unfounded empirical claims about the overall effects that AIRs have on academic research. And on a rights-based understanding of the value of academic freedom, they rely on excessively lavish assumptions about the kinds of activities that academic freedom protects.

Medical privacy and the public's right to vote: what presidential candidates should disclose.

We argue that while presidential candidates have the right to medical privacy, the public nature and importance of the presidency generates a moral requirement that candidates waive those rights in certain circumstances. Specifically, candidates are required to disclose information about medical conditions that are likely to seriously undermine their ability to fulfill what we call the "core functions" of the office of the presidency. This requirement exists because (1) people have the right to be governed only with their consent, (2) people's consent is meaningful only when they have access to information necessary for making informed voting decisions, (3) such information is necessary for making informed voting decisions, and (4) there are no countervailing reasons sufficiently strong to override this right. We also investigate alternative mechanisms for legally encouraging or requiring disclosure. Protecting the public's right to this information is of particular importance because of the documented history of deception and secrecy regarding the health of presidents and presidential candidates.

At the edge of humanity: human stem cells, chimeras, and moral status.

Experiments involving the transplantation of human stem cells and their derivatives into early fetal or embryonic nonhuman animals raise novel ethical issues due to their possible implications for enhancing the moral status of che chimeric individual. Although status-enhancing research is not necessarily objectionable from the perspective of the chimeric individual, there are grounds for objecting to it in the conditions in which it is likely to occur. Translating this ethical conclusion into a policy recommendation, however, is complicated by the fact that substantial empirical and ethical uncertainties remain about which transplants, if any, would significantly enhance the chimeric individual's moral status. Considerations of moral status justify either an early-termination policy on chimeric embryos, or, in the absence of such a policy, restrictions on the introduction of pluripotent human stem cells into early-stage developing animals, pending the resolution of those uncertainties.