Independent Scholar
See Also: Advocacy; National Institutes of Health; University of Wisconsin–Madison.
Further Readings
Charo, R. Alta. “Body of Research—Ownership of Human Tissue.” New England Journal of Medicine, v.355/15 (2006).
Liao, S. Matthew, Pascal J. Goldschmidt, Jeremy Sugarman, for the Working Group on Ethics of Progenitor Cell-Based Strategies for Disease Prevention. “Ethical and Policy Issues Related to Progenitor Cell-Based Strategies for Prevention of Atherosclerosis.” Journal of Medical Ethics, v.33 (2007).
Regulations for the Ethical Practice of Stem Cell Research. San Francisco: California Institute for Regenerative Medicine, 2007.
Chimera Formation, Ethics of
Chimera Formation, Ethics of
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Chimera Formation, Ethics of
A chimera, in the current scientific world, is an organism composed of cells or genes obtained from two or more different species. Human-animal chimeras can be created by transplanting human stem cells into animal fetuses or human genes into the genome of animal fetuses. Thus, a human-mouse chimera may contain a human liver in a mouse or may have a liver constituted of both human and mouse cells. These kinds of experiments are relatively recent—the first interspecies chimeras were engineered in 1989 by I. J. Davis, a researcher at the University of California. His work produced the geep, a new intraspecies chimera obtained by fusing a sheep embryo with a goat embryo. Most of the ethical and scientific discussion to this point has used the term chimeras, generally considered as organisms containing cells from two or more zygotes and different from transgenic (created by the interspecies transfer of DNA) and hybrids (created by breeding animals or plants of different species or varieties).
Chimeras in myth and ancient folkloric culture were powerful gifted creatures. In ancient Greek mythology the chimera, one of the several imaginary and symbolically important monsters, was represented as a dreadful beast resembling a lion but with the body of a goat and the tail of a serpent. Like this mythical animal, the geep shows morphological attributes of different species.
The hopeful prospect and the concern of largely improving health and potentially curing some of the most fatal diseases affecting mankind often has relieved many bioethical questions related to stem cell research. The use of embryonic stem cells, on the other hand, has generated uncommon and specific ethical dilemmas, reasonably because the clinical applications obtained from this research are difficult to understand, and sometimes they are overshadowed. Scientists universally think of chimera studies as indispensable for answering basic questions in stem cell and developmental biology.
In stem cell research, human-to-animal chimera experiments normally implicate the transfer of multipotent or pluripotent human stem cells into animals in embryonic, fetal, or postnatal stages of development to study stem cell behavior. Alternative forms of human-to-animal chimera studies involve transferring into animals human stem cell derivates that are no longer pluripotent or multipotent for preclinical research. Pluripotent cells (hPSCs) are able to evolve into any type of tissue as long as stem cells can renew themselves perpetually. The contest over this type of research denotes a different perception of humanity and our place in the world.
The chimeric animals hold a huge potential for the basic research in human physiology as well as in the transplant of human tissues and even organs and in testing of drugs and medications. In May 2005, the U.S. National Academy of Science (NAS) approved guidelines that have been adopted by many scientific organizations around the world. The guidelines contain ethical directions, but few of them forbid the combinations of cells from humans and nonhuman animals and the transfer of human embryonic stem cells (hES cells) into nonhuman primate blastocysts as well as the transfer of any embryonic stem cells into human blastocysts.
Regardless of its potential, chimera research meets relevant opposition from a large portion of the society. The issues connected to the creation and use of chimeras arise from the transgression of the common ethical codes and to the rigid view of human identity and uniqueness. Chimeras diverge from the prevailing perception of “genetically modified organism.” Technically, a chimera consists of two genomes in a single individual, producing two types of cells that work together to form a viable organism. It develops from two fertilized eggs that come into contact and form a single embryo, instead of staying separate and developing into fraternal twins. Chimerism within a species happens in a natural way in almost all animals, including humans. Interspecific chimeras, on the other hand, rarely exist in nature because of the improbability of distinguishing conditions required.
Despite shared pasturing of goats and sheep, a sheep-goat hybrid–also called a geep or toast–as shown here is extremely rare. Sheep have 54 chromosomes while goats have 60 chromosomes and most offspring die as embryos or are stillborn. A large percentage of those that do survive are sterile, due to the Haldane’s rule phenomenon. (Wikimedia Commons/Judge Floro)
In August 2003, Hui Zehn Sheng and his team generated the first human-nonhuman chimera at the Shanghai Second Medical University, removing the genetic material from some of the cells of a rabbit embryo and substituting human DNA. A human-rabbit chimera was created and a new broad field of research inspired follow-on studies that confirmed the enormous potential of chimeras. In France, Nicole Le Douarine, years earlier, substituted vertebral cells in a cow fetus with human pluripotent stem cells to study the differentiation and development of the spinal cord. These results suggested new procedures in regenerative medicine for patients with severe injuries and clarified the integration between peripheral and central nervous systems in early stages of development.
Scientists are also using chimeras to study the progress and mechanism of diseases in live tissues and organs. Chimeras with human tissues offer a rather precise substitute performing as models of the real human body.
More recently, in March 2013, researchers found that implanting brain cells of human origin into newborn mice made them smarter. To lead the experiment, Han and colleagues separated specific cells of the brain (glial cells) from aborted human fetuses and transplanted them into the brains of newborn mice. When the human-mice chimeras reached adult age, they achieved better results in memory tests and various learning tasks compared to the other mice in the lab. Ten years earlier, Irving Weissman at Stanford University had theorized a similar, very confuted experiment. He wanted to genetically engineer a mouse with the entire brain repopulated by human neurons. The anticipated outcome became known as the “human-neuron mouse.”
Due to concerns over ethical issues, after reviewing the literature on human-nonhuman chimeras, a panel of bioethicists at Stanford University decided to dismiss the experiment, concluding that the main concern was relevant since repopulating the brain with human derived neurons might give rise to a chimera with aspects of human consciousness and cognitive abilities.
Most of the ethical issues related to chimeric research are not particular to the stem cell field; in some way, chimeric research is an extension of current research in transgenesis to create humanized animal models for research. But it may also be assumed as the continuity of techniques and practices established over the past centuries. The most often disputed questions against chimeras are the unnaturalness argument and crossing the species boundaries. Essentially, much of the debate about creating blends emerges from a view that
