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September 3, 2016

NIH human-animal chimera research under debate, experts weigh in

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  • Genetics/Genomics

Outsourcing-Pharma – As stem cell and gene editing technologies become more advanced, researchers are increasingly interested in growing human tissues and organs in animals – but what are the implications of human-animal chimeras?

Human-animal chimeras are created by introducing human pluripotent cells into early animal embryos, and their existenceis “certainly not new,” Carrie D. Wolinetz, Ph.D., associate director for science policy, National Institutes of Health (NIH), told Outsourcing-Pharma.com.

“For example, animal models have been used to validate and characterize different types of human stem cells by introducing the human cells into mice,” Wolinetz said.

However, recent scientific advancements have prompted the NIH to reexamine its Guidelines for Human Stem Cell Research and the proposed scope of certain human-animal chimera research. The institute is currently seeking public comment on the proposed changes, which it will consider in its review.

“In the interest of moving the field forward, while preserving the NIH’s opportunity to provide continuing assessment andoversight of this emerging area of research, the NIH has decided to make two policy changes in this area,” explained Wolinetz.

NIH was not previously funding such research, but has instituted a funding pause in order to consider whether new policy or guidelines were needed to guide this area of research.

Wolinetz said the moratorium on funding such research will stay in effect until NIH issues a final policy. “After the 30-day public comment period closes, NIH will consider all comments and finalize the policy,” she added. “Changes to the instructions to grant applicants require approval by the White House Office of Management and Budget.”

NIH is aiming to have revised instructions available in time for applications with receipt dates of late January 2017.

Keeping pace with transformational research Kent Lloyd, DVM, PhD, professor, Department of Surgery, School of Medicine, Director, Mouse Biology Program, University of California Davis, told us that the NIH’s plan to revise policy and guidelines on derivation of human-animal chimeras “is a thoughtful, rational, and appropriate response to the need for maximizing the scientific value of translational research using human iPS cells.”

“Science has made tremendous progress to date in reprogramming fully-committed adult somatic cells into a state of induced pluripotency that can then be induced to undergo targeted differentiation into specific cell types,” he said. “But these activities have for the most part taken place in vitro.”

However, Lloyd explained that in order to gain a better understanding of human biology and disease processes, these cells must be placed into an in vivo context.

“Thus, placement of h-iPS cells into animal chimeras will transform research into understanding mechanisms of human disease, validating and testing drug therapies in an environment that mimics a whole body environment, and testing new paradigms in transplantation biology,” said Lloyd.

Lloyd, who has previously been involved in an advisory capacity to the NIH on high-profile bioethical issues, said he has full faith and confidence that NIH leadership will proceed judiciously when making its revisions.

“This will be an iterative process based on evidence and data, and further revisions will be based on informed decisionmaking, with full consideration of public input,” Lloyd concluded.

The scientific benefits of human-animal chimeras

“At this point, such human-animal chimeras will be the subject of quite basic research to understand what is possible and what can be learned,” Jeremy M. Berg, Ph.D., editor-in-chief, Science Family of Journals at the American Association forthe Advancement of Science (AAAS), told us.

Over time, however, the organisms could be developed into tools for industrial research through the creation of organisms that have some human-like features. For example, Berg said it is possible that such organisms could be created with tissues and organs that might be less susceptible to immunological rejection by human hosts. “In developing certain human-animal chimeric models, some scientists hope the human cells will develop into specific tissues or organs for potential transplant purposes, or for drug testing,” added NIH’s Wolinetz. “Other researchers are exploring the developmental nature of particular types of human cells, which may yield important insight into human biology and disease development.”

As another example, animal models with human cells in the brain can be used to study many human brain diseases, including Parkinson’s, Alzheimer’s, and schizophrenia, and may be useful models for testing new drugs. “Furthermore, these animal models could be used to study whether introduction of therapeutic human cells can improve outcomes for diseases that are caused by the death or dysfunction of neural or other brain cells, prior to testing the cells in people,” said Wolinetz.

However, Berg explained, “there is still much basic research to be done and such potential applications will only beobtained over time.”

The ethical issues of creating animals with human cells

While these potential applications hold “tremendous promise,” Wolinetz said, “we do not know if the human cells will contribute to and affect off-target organs.” This knowledge gap is one which raises ethical and animal welfare concerns, specifically if there are significant alterationsto an animal’s cognitive state. Berg echoed these concerns and explained that the primary ethical considerations relate to “the sources of the humancells and the potential for creating animals with unwanted human-like qualities.” However he said the ethical considerations regarding the sources of the cells are largely avoided by using inducedpluripotent stem cell (iPS cells), which can be derived from adult cells as opposed to embryos.

“The concerns about generating animals with unwanted human-like qualities can be addressed by policies such as appropriate oversight structures and restrictions on generating chimeric organisms capable of reproduction and these are part of the proposed NIH policy,” Berg added.

“With that said, I am pleased that NIH is approaching this new area of research deliberately with opportunities for public input since these are potentially sensitive issues.”

Image citation: Sailko, CC BY-SA 3.0