ISSCR Comments Regarding Proposed Changes to the U.S. National Institutes of Health Guidelines on Human Stem Cell Research

  • 7 September, 2016

ISSCR Comments Regarding Proposed Changes to the NIH Guidelines for Human Stem Cell Research and the Proposed Scope of an NIH Steering Committee’s Consideration of Certain Human-Animal Chimera Research

The International Society for Stem Cell Research (ISSCR) supports the continued assessment of the U.S. National Institutes of Health (NIH) Guidelines for Human Stem Cell Research. We applaud the proposed end to the current moratorium on U.S. federal funding of human-animal chimera research involving the introduction of human pluripotent cells into early stage animal embryos. Historically, the study of animal models containing human cells has produced valuable insights into human biology and disease. Ongoing research using chimeras will allow scientists to gain a better understanding of human development and disease as well as generating disease models that can be used to test new therapies. Chimeras could also potentially be used to develop human organs that can be used for transplantation.

The ISSCR supports research using human-animal chimeras conducted under appropriate review and oversight (Hyun et al., 2007; ISSCR, 2016). An advisory report from the ISSCR Ethics Committee (Hyun et al., 2007) outlines considerations for evaluating research involving the transfer of multipotent and pluripotent human stem cells into animal systems. These recommendations build on and are consistent with current ethical standards for biomedical research, including the application of animal welfare principles. The ISSCR’s 2016 Guidelines for Clinical Research and Translation (ISSCR, 2016) include a section on human-animal chimera studies (Recommendation 2.1.5), that calls for specialized oversight of research that entails incorporating human totipotent or pluripotent cells into animal hosts to achieve chimerism of either the central nervous system or germ line. This specialized oversight is particularly important when chimerism occurs in closely related primate species. The ISSCR’s 2016 guidelines recommend that animal chimeras that incorporate human cells with the potential to form gametes should not be bred with each other (Section

The ISSCR is concerned with the blanket prohibition of U.S. federal funding for research involving early stage primate embryo chimeras that is retained in the proposed changes. The ISSCR agrees that early stage primate embryo chimeras raise particular concerns about the potential for high levels of human cells in the primate brain. However, we believe such studies should be evaluated on a case-by-case basis. Study details, such as how long the animals would be allowed to develop, could alleviate such concerns. The ISSCR encourages the NIH to provide a special review process for areas of early stage primate embryo research that have a compelling scientific justification and are culturally sensitive.

The prohibition of funding for research involving early stage primate chimeras in the NIH’s draft guidelines appears to be more restrictive than the ISSCR Guidelines and the position taken by the United Kingdom’s Guidance on the use of Human Material in Animals. In both cases, the research is allowed to move forward with oversight and review. We would urge the NIH to carefully review the positions of the ISSCR and the United Kingdom in this area and to remove the current prohibition (proposed IV.A.) and expand the scope of the steering committee to allow for the consideration of such research on a case-by-case basis, based on its merits. This approach would also be similar to positions taken in the past by the NIH for other areas of culturally sensitive research.

Hyun, I., Taylor, P., Testa, G., Dickens, B., Jung, K. W., McNab, A., Roberston, J., Skene, L., and Zoloth, L. (2016). Ethical standards for human-to-animal chimera experiments in stem cell research. Cell Stem Cell 1, 159–163.

International Society for Stem Cell Research Guidelines for Stem Cell Research and Clinical Translation (2016).