Round Three—“Mixing & Matching” Biological Building Blocks: Mouse-Human Chimeras Are Here!

Gong—Welcome to round three of the human reproductive technology advances—mouse-human chimeras. Round one, framed by the praiseworthy intent of overcoming human infertility, placed human gametes, sperm and eggs, into a Petri dish to procreate at will. Round two, capitalizing on the inefficiencies within the in vitro fertilization clinic, took apart “left over” human embryos for embryonic stem cells. Round two and a half extended the logic of embryonic stem cells to make genetically matched embryonic stem cells through “therapeutic” cloning. These second rounds have an equally imperative goal of curing millions from heretofore untreatable maladies.1

Round three is driven by the accessibility of human biological building blocks for developmental biology’s toolkit. In order to learn how early life develops, developmental biologists artfully explore reproduction and development by mixing and matching biological building blocks such as genes and embryonic stem cells. The gold standard laboratory model—the mouse—is logically the place to try out these human biological building blocks. Mixing and matching genes was first. Technology allowed inserting one or two genes at a time into the germ line or genetic inheritance. More recently, artificial chromosome technology has allowed insertion of 100s of genes at a time. Both techniques create what is called a ‘transgenic.’ For twenty years now, transgenic mice containing human genes in their genetic inheritance have been scurrying about in laboratory cages.

Mixing and matching human and mouse embryonic stem cells has just begun in the last few years. Embryonic stem cells are inserted into a developing embryo with other genetically distinct embryonic stem cells. The mixed embryonic stem cells blend together and form one organism creating what is called a ‘chimera.’ A chimera, then, fuses multiple genetic life forms into one creature. An analogy for chimera is a rose graft. For example, often a rose bush has the root of one genetic inheritance with vines from another grafted together to form a single plant. They co-exist for the life of that organism, but never genetically intermingle to make genetically blended offspring.

The rationale for the latest mouse-human chimera is to make an animal model to study human brain development and disease.2 The new study injected human embryonic stem cells into the brains of fetal mice. These human embryonic stem cells went on to form human brain cells, neurons, and glia within the mouse brain. The human cells were found in many brain regions, and testing the electrical workings of the chimeric brain showed normal activity 18 months after transplantation. The scientists suggest that these hybrid animals will be a great model for studying human brain diseases and extrapolate that they may even be useful for screening drugs. (This latter statement, that mouse-human chimeras may serve as model for screening therapeutic drugs, is over-reaching at this stage. Proving that this model can predict whether drugs work for human brain cells will require a lot of complicated experimental work.)

The justification for creating mouse-human chimeras is laudatory, but can these ends justify creating these hybrid mice-humans? What is at the heart of this debate? The central issue is not whether animal models useful for overcoming human brain diseases should be made, but rather, which ways of pursing this goal are ethical and which are not. In short, is blending a mouse and human together into one creature ethical?

The President’s Council on Bioethics considered some definitive lines for the blending of human and animal in March of 2004.

“One bright line should be drawn at the creation of animal-human hybrid embryos, produced ex vivo by fertilization of human egg by animal (for example, chimpanzee) sperm (or the reverse): we do not wish to have to judge the humanity or moral worth of such an ambiguous hybrid entity (for example, a “humanzee,” the analog of the mule); we do not want a possibly human being to have other than human progenitors. A second bright line would be at the insertion of ex vivo human embryos into the bodies of animals: an ex vivo human embryo entering a uterus belongs only in a human uterus.”3

They offered two recommendations for regulating creation of human-animal hybrids.

· Prohibit the transfer, for any purpose, of any human embryo into the body of any member of a nonhuman species; and

· Prohibit the production of a hybrid human-animal embryo by fertilization of human egg by animal sperm or of animal egg by human sperm.4

Both of these recommendations were aimed at prohibiting procreation of hybrids or crossing the inheritance line. Chimeras were considered, but the similarities of a chimera to transplantation of an animal part into a human shaped their conclusion that . . . “Likewise in the context of biomedical research, we now see nothing objectionable in the practice of inserting human stem cells into animals—though we admit that this is a scientifically and morally complicated matter.”5

Another national body, The National Academy of Sciences, recommended prohibiting creating just one type of animal-human chimera—introducing human embryonic stem cells into a non-human primate embryo6. Other types of chimeras, such as human-mouse, could be allowed if they passed a review by a special ethics panel. A further recommendation was that no hybrid with human embryonic stem cells should be allowed to breed. The current project of injecting 100,000 cells into each fetal mouse brain passed review because the chimeric brain would be more than 99 percent mouse. It is important to note that while this project was limited to introducing 100,000 cells, the success of this experiment supports the scientific logic for increasing the proportion of human cell within a mouse-human chimeric brain model.

Earlier, some principles were put forth to guide Christians in formulating a response to the possibility of such animal-human hybrids.7 Christians hold a stewardship role over animals and are permitted to use them to benefit humanity. Using animals in scientific studies then can be ethical for Christians. But a more fundamental principle is at stake, the divinely created order. Species are created purposely by God. Ultimately God is the author of life with a unique value placed on man. Man’s gift of procreation is to fulfill God’s purposes, not our own. Using human procreation to fuse animal-human runs counter to the sacredness of human life and man created in the image of God.

Further, you don’t have to be clairvoyant see that chimera experiments are paving the way for round four—synthetic biology and artificial life. Conceptually, synthetic biology takes the same biological building blocks, genes and embryonic stem cells, but does not constrain the imagination by restricting the assembling of these biological building blocks into known species. This opens the door to designing altogether original organisms. Artificial life tries to make novel organisms in another way. Instead of using known building blocks such as genetic material made of DNA or RNA, this field endeavors to create novel building materials using new compounds and recreating life processes with these materials. Equally troublesome is the percolating philosophical framework called transhumanism that not only justifies but applauds pursuing artificial life and synthetic biology full force.8

Creating animal-human chimeras, as The President’s Bioethics Council points out, is a scientifically and morally complicated matter. The fact that chimeras can’t procreate blended offspring but rather co-exist for only that one life span lessens some of our moral concern. But the larger context of probing the developmental stages of human life and gaining unprecedented insight into ways to control and manipulate animal and human reproduction must be our focus. Medicine knows full well the responsibility one must bear when welding knowledge that can be used for great good or great harm. Science struggles with assuming responsibility as easily as asserting scientific freedom. Moral deliberations must go arm-in-arm with scientific investigation to ensure that our society fully considers the stated hopes, and carefully deliberates on the by-products of the “breakthroughs.” For example, in order to overcome infertility, IVF creates more embryos that can be implanted. The end has clearly blurred the means. One cannot underestimate the urgency of wrestling now with this scientifically and morally complicated morass and corporately seeking God’s wisdom.