Case Western Reserve researcher outlines road map for addressing ethical concerns tied to research
Insoo Hyun, PhD, associate professor of bioethics at the School of Medicine of Case Western Reserve University, has proposed a framework for addressing ethical questions surrounding potentially revolutionary research on part-human, part-animal embryos, which can be produced when human stem cells are transplanted into animal embryos.
This kind of research, which raises the prospect of growing human organs in genetically modified large animals, such as pigs and sheep, represents a possible solution to the chronic shortage of human organs available for transplantation. It also offers a way to gain better understanding of many human diseases. But last September, ethical concerns caused the National Institutes of Health to impose a moratorium on funding such research. (Private funding was unaffected.)
In an opinion piece published in the August 30 issue of PLOS Biology, Hyun suggests that most, if not all, of the concerns tied to such research can be reasonably addressed. The piece appears only weeks after the NIH announced that it may lift its funding moratorium after a 30-day comment period on proposed regulations which require heightened review of such research under certain conditions. Broadly, Hyun urges that regulation of research of these embryos should prioritize animal welfare while at the same time enabling scientific progress in areas of biomedical importance.
Hyun writes that research on part-human, part-animal creations, often called chimeras (after a Greek mythological figure with the head of a lion, the body of a goat, and the tail of a serpent), has been taking place without much debate for decades, such as in the case of mice transplanted with human cancer cells. However, apprehension has arisen about research involving human pluripotent stem cells, the subject of the current NIH moratorium. These cells are made from skin or blood cells which are genetically modified to act like embryonic stem cells that have the capacity to form any adult cell types.
Building on the current ability to grow a rat pancreas in a mouse and vice versa, some researchers are interested in growing a human pancreas in a pig by inserting human pluripotent stem cells into pig embryos whose ability to produce their own pancreases has been disabled. This line of research could serve as a foundation for growing various types of human organs such as hearts and kidneys in livestock animals for transplantation. If the pluripotent stem cells for transfer were derived from a patient's own tissue sample, then, in theory, the resulting organ would be immune-compatible with the patient.
But some researchers and bioethicists worry that a developing animal with a human organ could have at least partially human moral status, especially if the central nervous system is involved.
Hyun says that such concerns, while understandable, are over-stated because the interspecies boundary between humans and livestock makes it improbable that significant biological mixing within the resulting animal would occur. For example, mouse/rat chimeric experiments only produce about 20 percent donor chimerism outside the relevant organ niche, and the interspecies barrier is much lower between these rodents than it is between humans and livestock. Moreover, the evolutionary distance between pig and human is greater than the distance between human and mouse.
Secondly, researchers are developing a process known as "targeted organ generation." Here, transferred human stem cells would be genetically modified to prevent them from developing into human neural cells, which produce the central nervous system including the brain. Third, says, Hyun, researchers can stop their chimera experiments each time well before the full gestation cycle to examine fetal tissues for any unwanted migration and development of human cells outside the organ niche environment.
These steps are consistent with ethical standards for chimera research established by the Ethics and Public Policy Committee of the International Society for Stem Cell Research, which Hyun had helped to develop.
Additionally, Hyun says that the appearance of human-like self-consciousness is needed to elevate the moral status of a research animal. But he says that this distinctive psychological characteristic is not likely to emerge in a chimeric animal's brain, as it takes several years to develop in fully human infant brains and only under the right social and nurturing conditions. Relatedly, some people assume that simply the presence of human cells in an animal's brain might enhance its moral status, a view Hyun calls "an extreme form of anthropocentric arrogance." Instead, the much more likely outcome of neurological chimerism is an increased chance of animal suffering and biological dysfunction and disequilibrium, if past experience with transgenic animals can serve as a guide. "This is why," says Hyun, "focusing on animal welfare principles is crucial."
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