NIH to chimera researchers: Let's talk about this...

by Chris Yarosh

When we think about the role of the National Institutes of Health (NIH) in biomedical research, we often think only in terms of dollars and cents. The NIH is a funding agency, after all, and most researchers submit grants with this relationship in mind. However, because the NIH holds the power of the purse, it also plays a large role in dictating the scope of biomedical research conducted in the U.S. It is noteworthy, then, that the NIH recently delayed some high profile grant applications related to one type of research: chimeras.

Chimeras, named for a Greek mythological monster composed of several different animals, are organisms that feature cells that are genetically distinct.  In the lab, this commonly refers to animals that contain cells from more than once species. Research into chimeras is not new; scientists have been successfully using animal/animal (e.g. sheep/goat) chimeras for over 30 years to learn about how animals develop. Human/animal chimeras are also a common research tool. For example, the transfer of cancerous human tissue into mice with weakened immune systems is standard practice in cancer biology research because it allows researchers to test chemotherapy drugs in a system that is more complex than a dish of cells before testing them in human subjects. These experiments are largely uncontroversial, save for individuals who fall into the anti-animal testing camp (and those who dispute the predictive power of mouse models in general). Why then, has the NIH decided to pump the brakes on this line of research?

Like many things, the answer lies in the timing. The temporarily-stalled research involves injecting human pluripotent cells—undifferentiated cells that can develop into any number of different cell types—not into mature animals, but instead into animal embryos. Unlike the tumor-in-a-mouse research mentioned above, this kind of experiment is specifically trying to get normal human cells to develop as an animal matures and remain, well, normal human cells. One idea is that someday we could grow an organ (liver, pancreas, etc.) in an animal, such as a pig, that is still a human organ. This would lower the barrier for successful transplantation, meaning that somebody in serious need of a new liver could receive one from livestock instead of waiting for a human donor from a transplant list. Another thought is that chimeric animals will better model human physiology, making subsequent clinical trials more accurate.

If you read the last paragraph and felt a bit uneasy, you’re not alone. For some, this type of research crosses the invisible line that separates humans from animals, and is therefore unacceptable. Others find this research troubling from an animal welfare standpoint, and still other worry about unanticipated differentiation (e.g. “we wanted a liver, but we found some human cells in the pig’s nerves, too”) or unethical uses for this type of technology.

The NIH hears these concerns, and wants to talk about them before giving scientists the go ahead to use public funds on this type of research. Some researchers have reacted negatively to this, fearing broader restrictions in the future, but I think this is an important part of the scientific process. We live (and for scientists, work) in an era of unprecedented ability to modify genomes and cell lineages, and human/animal chimeras are just one example of a type of research destined for more attention and oversight. It is important to get the guidelines right.

The NIH will convene a panel of scientists and bioethicists to discuss human/animal chimera research on November 6^th, so keep an eye out for possible policy revisions after then. Given the promise of this type of research and the potential concerns over its use, this surely is only the beginning of the deliberative process.

UPDATE (11/05/2015): Scientists from Stanford University have posted an open letter in Science calling for a repeal of the current restrictions in this field. The full letter, found here, argues that there is little scientific justification for the NIH's stated concerns. Over at Gizmodo,  the NIH has responded by claiming that the true purpose of the stop order and review is to "stay ahead" of current research and anticipate future work. This is consistent with the NIH's views as articulated on the Under the Poliscope blog. All things considered, the workshop tomorrow, and any guidelines resulting from it, should be very interesting for people who wish to develop and use these tools.