Ethical Oversight of Chimeric Research
Chimeric research, which involves inserting human cells into animals, could lead to new therapies for humans. Investigators offered ethical guidance for oversight of this area of science.1
The motivation for the report was a funding moratorium imposed by The National Institutes of Health (NIH) for research of human pluripotent stem cells inserted into pre-gastrulation stage embryos of vertebrate nonhuman animals.2 “Concerns had been raised about the effect human pluripotent stem cells might have on a chimeric animal’s central nervous system or migrating to their brain,” explains Karen J. Maschke, PhD, a researcher scholar at The Hastings Center and one of principal investigators on the project that produced the report.
At this time, the funding moratorium remains in effect. “The NIH’s funding decision led us to develop a project to examine the ethical issues that chimeric research raises,” Maschke says.
Maschke and colleagues also wanted to examine oversight approaches regarding chimeric research. Based on interviews with stem cell scientists and members of relevant oversight committees, the three-year research project identified the central ethical considerations:
• Focus on the welfare of nonhuman animals used in chimeric research. “Researchers should consider whether existing methods for assessing welfare will be sufficient for detecting and assessing the impact of the presence of human stem cells in nonhuman animals, especially human neural cells or their derivatives, that might have a significant effect on the chimeric animal’s central nervous system,” Maschke says.
• Carefully address what constitutes sufficiently strong scientific justification for chimeric studies. “Identifying and describing the components of a strong scientific justification for chimeric research is a complex undertaking,” says Maschke, noting this may require input from a broad range of scientific and other experts.
A key concern about chimeric research is whether evidence will emerge indicating significant functional changes in the cognition and behavior of nonhuman animals that contain human cells. If so, says Maschke, “it may be difficult to resolve ethical issues regarding the moral status of those chimeric animals.”
Another important concern is whether rights-based considerations and protections would need to be in place. This issue might be addressed differently, depending on the type of nonhuman animal involved. Most chimeric research involves the use of laboratory mice.
“Considerations about moral status and rights might be different for those nonhuman animals than if the research involves the use of nonhuman primates,” Maschke explains.
Some people are opposed to research involving the use of human embryonic stem cells; some are opposed to any research with nonhuman animals. “There are some who oppose any research that involves what they view as crossing species boundaries,” Maschke adds.
IRBs will weigh in if proposed chimeric research involves the collection of cells, gametes, or embryos from identifiable human donors.
“As with other research that involves the use of these identifiable human biological materials, IRBs will focus on ensuring that researchers obtain voluntary informed consent from the donors,” Maschke says.
IRBs might ask researchers, “Will individuals who donate these types of biological materials for research be informed that their materials might (or will) be used for chimeric research studies?” IRBs and oversight committees should seek outside expertise when members are reviewing protocols for chimeric studies. “Oversight committees may need assistance to know what to look for in determining whether the presence of human cells could lead to novel harms for the nonhuman animal,” Maschke says.
Maschke and colleagues suggested including an animal behavioralist in the oversight process could help address animal welfare concerns.
Further, research institutions, oversight committee members, and scientists should discuss chimeric research in a centralized forum. This would help identify emerging ethical challenges for this type of research and facilitate consistent approaches across institutions.
“This could assist IRBs and stem cell and animal research oversight committees to prepare for future chimeric research developments,” Maschke says.
1. Johnston J, Hyun I, Neuhaus CP, et al. Clarifying the ethics and oversight of chimeric research. Hastings Cent Rep 2022;2:S2-S23.
2. NIH research involving introduction of human pluripotent cells into non-human vertebrate animal pre-gastrulation embryos.
A key concern is whether evidence will emerge indicating significant functional changes in the cognition and behavior of nonhuman animals that contain human cells. If so, it may be difficult to resolve ethical issues regarding the moral status of those chimeric animals.
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