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 6th, 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.
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.