The following article originally appeared in the Spring 2017 issue of the MCFL member magazine, a perk of membership mailed out quarterly to all members.
On Aug. 4, 2016, the National Institutes of Health (NIH) proposed changing regulations to support expanded research into the development of chimeras, experimental genetic combinations of human beings and animals. The new regulations would allow funding for research that inserts human cells into very early animal embryos. Researchers hope to overcome the lack of organs available for life-saving transplant surgery by growing human organs and body parts in animals. Ethicists are troubled by certain aspects of chimeric research: the possibility of creating animals with human consciousness and the intentional creation and destruction of human embryos.
A fact sheet from Kansas Right to Life defines chimeras. “In medical terminology a chimera is an organism or tissue that contains at least two genetically distinct types of DNA,” it says. “An animal or human chimera is formed from the fusion of two or more zygotes, or when two individuals exchange cells during embryonic development, and the resulting individual carries at least two different types of DNA.” Human-animal chimeras can be created in several ways: by transplanting human stem cells into animal fetuses or by inserting human genes into the genome of animal fetuses. For example, a human-mouse chimera may contain a human liver in a mouse or may have a liver composed of both human and mouse cells.
The fact sheet describes different types of chimeras. “Dispermic chimeras are formed when two eggs that have been fertilized by two sperm fuse together, producing an individual originating from four gametes, or sex cells. Blood chimeras occur when blood connections form between the placentas of fraternal twins, enabling the transfer of stem cells between embryos. Microchimeras are formed when a few fetal stem cells or maternal cells cross the placenta. It is a common occurrence that after a baby is born, the mother still has some fetal cells in her body, and these cells can remain for decades.”
Dr. David Prentice, vice president and research director for the Charlotte Lozier Institute (CLI) says, “Some forms of chimerism occur naturally, as when two zygotes fuse or when two individuals exchange cells during embryonic development. This can happen with twins developing in the womb, for example.”
NIH regulations currently prohibit chimeric experiments involving pluripotent stem cells (cells which are capable of developing into any organ or tissue in the body.) Guidelines prohibit introducing human pluripotent cells into nonhuman primate blastocysts (an early embryo possessing an inner cell mass and an outer layer) and the breeding of animals into which human pluripotent cells may have contributed to the germ line (egg or sperm cells.) A moratorium on research includes funding for any experiments involving the introduction of stem cells from human to animal before the stage of gastrulation (the formation of the three germ layers in the early embryo.)
On Sept. 6, the Charlotte Lozier Institute submitted comments to NIH Director Dr. Francis Collins, recommending that NIH not change research funding guidelines. Dr. Prentice specified the ethical objections to taxpayer funding of chimeric research. “The proposed changes would allow, and approve taxpayer funding, for creation of human-animal chimeras that would produce human gametes within the chimera’s body and the proposed changes would also allow for creation of human-animal chimeras that would have substantially or completely human cell-derived brains,” Prentice wrote. “The primary demarcations of species identity, especially in the case of humans, revolve around reproductive genetics and conscious thought. The types of chimeras proposed for creation in these proposals thus cross significant ethical lines directly related to questions of species boundaries, the most important of which is the question of what it means to be human.”
Prentice said that expanded chimera creation would also involve the destruction of human embryos. “Expanding federal funds to this chimera research using 'pluripotent cells' or 'pluripotent stem cells' could lead to additional efforts to create and destroy human embryos to obtain those cells for this chimera research. Construction of some chimeras under these proposals may actually lead to creation of human embryos, which would be a violation of federal statute. Further, there is no scientific or ethical necessity that validates NIH approval or taxpayer funding of experiments creating the proposed human-animal chimeras.”
Not all research involving animal-human cells is problematic. “To clarify, chimeric research does not refer to therapies like a mitral valve replacement using a pig’s heart valve or other mammalian tissue,” says cell biologist Fr. Tad Pacholczyk. “This procedure does not involve the admixture of DNA or the potential for the creation of a genetically new or altered animal-human combination. For decades, scientists have engaged in noncontroversial practices involving intermixing animal and human cells such as growing human cancer tumors in mice to study disease processes and evaluate treatment strategies.”
He notes the concerns (which also govern debate about the safety of genetically modi ed organisms) that undesirable genes may grow along with the desirable ones. Says Pacholczyk, “The science of growing entire human organs in pigs or other animals is still in its infancy, and researchers have yet to figure out how to make human cells co-exist in a stable fashion with animal tissues. There are abundant concerns about the possibility of transmitting animal viruses to humans especially considering how readily other viruses like avian u have been able to jump from birds to humans.”
In May 2016, NPR's Rob Stein reported on the work of Pablo Ross, a reproductive biologist at the University of California. Ross hopes to create a pancreas that could be transplanted into a patient with diabetes. He uses the gene editing tool CRISPR-Cas9 to delete the gene needed to make a pancreas and then injects human induced pluripotent stem cells (iPS) into the pig embryos. Stein said, “The researcher's hope is that the human stem cells will take advantage of the void in the embryo to start forming a human pancreas. Because iPS cells can be made from any adult's skin cells, any organs they form would match the patient who needs the transplant, vastly reducing the risk that the body would reject the new organ.”
The embryos are injected into a sow's uterus and are allowed to develop to the time when organs start to form. The chimeric embryos are dissected and examined to see whether the human stem cells have started to form a pancreas and other types of tissues. Stein notes, “The uncertainty is part of what makes the work so controversial. Ross and other scientists conducting these experiments can't know exactly where the human stem cells will go. Ross hopes they'll only grow a human pancreas. But they could go elsewhere, such as to the brain.”
Stein's article exposes the antagonism towards those who hold that chimeric research may undermine what it means to be human. He quotes Jason Robert, a bioethicist at Arizona State University who says, "One of the concerns that a lot of people have is that there's something sacrosanct about what it means to be human expressed in our DNA. And that by inserting that into other animals and giving those other animals potentially some of the capacities of humans that this could be a kind of violation — a kind of, maybe, even a playing God."
In a Sept. 2 letter to NIH Deputy Director Lawrence A. Tabak, Dr. Marie Hilliard, representing a consortium of health care providers, ethicists, and advocates for persons with disabilities, wrote, “We have significant concerns for an increasing eugenic societal mentality that in the long run puts, not just individuals at risk, but all of humanity at risk. The chimeric research under consideration laudably aims to better understand and push forward therapeutic frontiers for a number of devastating diseases. Such research could potentially lead to an immunologically tolerated and readily available source of human organs and body parts for transplantation. Even with these good intentions and solid scientific potential, research involving human-animal chimeras must be carefully designed to protect human dignity and to avoid serious ethical pitfalls, many of which were recognized as the basis for the recent NIH moratorium on human-animal chimera research.”
Dr. Prentice further noted, “In one of H.G. Wells’ dystopian novels, a man is rescued at sea and brought to an island where he encounters a mad scientist, played by Marlon Brando in a movie adaptation, who has spent 17 years creating “animals fused with human genes.” “The Island of Dr. Moreau” ends tragically with death abounding.
“The NIH proposal, in turn, begins with death abounding amidst the hubris that scientists can foresee, and forestall, every harm their manipulations of the human-animal boundary will cause. To play God is to put power before knowledge. For this reason alone, the NIH funding moratorium on this type of research should continue while ethical alternatives are explored and fully funded.”
The National Institutes of Health, a part of the U.S. Department of Health and Human Services, is the nation’s medical research agency charged with making important discoveries that improve health and save lives. With the confirmation of pro-life Congressman Tom Price as secretary for Health and Human Services it is hoped that NIH will reconsider changing policies on human-animal chimeras.