May 2006

Ancient Greek mythology is replete with references to part-human animals. There is the monstrous half-human, half-bull Minotaur; the Gorgon sisters (one of whom is Medusa) with hair of writhing snakes; the Sirens who are sweet singing sea nymphs each with the head of a woman and the body of a bird; and, not to be forgotten, there is the infamous Sphinx with the head and breasts of a woman, the body of a lion, and the wings of a bird. Part-human creatures are also a staple of modern science fiction, as in H. G. Wells’ The Island of Dr Moreau,¹ where animals are vivisected into part-human creatures, or George Langelaan’s The Fly, in which a scientist emerges from his disintegrator-reintegrator machine with the head and arms of a fly.²

But part-human animals are not only science fiction—they are also science fact. While not as monstrous as the creatures of lore, part-human laboratory animals raise some important ethical and societal issues.

What does it mean to cross species boundaries?

First, from a biological perspective, it is surprisingly difficult to answer the question What does it mean to cross species boundaries? This is true not only because of the number of species concepts (according to some, as many as 22),³ but also because species boundaries are not fixed.

• Species concepts: One classic definition of species is the biological species concept. This definition emphasizes the importance of reproductive isolation or lack of genetic exchange that separates species.⁴ By this account, crossing species boundaries would involve the transfer of genetic materials between populations of organisms that do not interbreed. In cases where such interbreeding can be achieved artificially, as in the laboratory, the raison d’etre of the biological species concept is undermined. Other accounts of species may be brought to bear in place of the biological species concept, but the consensus among biologists is that no single species concept will be sufficient for all situations.

• Species boundaries: One of the consequences of our evolutionary past is that genes, gene regulatory networks, epigenetic developmental processes, and features of the biophysical environment are widely shared by different kinds of creatures. The idea of fixed or rigid breaks between species plays no role whatsoever in contemporary biology. Indeed, the fluidity of species boundaries has been revealed through the techniques of comparative genomics, warning against the interpretation of species as unique types.

Given the difficulty in defining species once and for all, and also the flexibility of species boundaries,⁵ what does it mean to cross species boundaries?

When we refer to species and the crossing of species boundaries,⁵ we do so based on the following simple idea: Every individual human contains a human genome. In all likelihood, this genome will not be representative of other human genomes and will contain a lot of DNA that is contained in many other kinds of organisms, thanks to our evolution from a common ancestor. The same will be true with nonhuman organisms, such as a rose or a rat or aRhesus macaque. As such, when we refer to crossing species boundaries, we refer to the combination of genetic or cellular material from two organisms that would generally be understood, in lay terms, as belonging to different species: a human as understood by most lay people, a Rhesus macaque as understood by most lay people, and so on.⁶

Hybrids, transgenics, and chimeras

There are many types of interspecies organisms including hybrids, transgenics, and chimeras, each of which is created through different sorts of processes. Hybrids are created through breeding. Transgenics are produced through genetic manipulation and modification. Chimeras are the result of cell or tissue transplants.

• Hybrids are created by breeding across species. Hybrids are generally the result of combining an egg from one species with sperm from another to form a single embryo. Hybrids contain recombined genetic material throughout their genome and throughout all the tissues in their body.

• Transgenics are the result of gene transfer. Typically, transgenics contain transferred or manipulated genes in addition to the host nuclear and mitochondrial DNA. One exception may be a transgenic embryo comprised of the entire complement of nuclear DNA from one organism fused with an enucleated egg cell from another.

• Chimeras comprise a mixture of cells from two or more genetically distinct organisms of the same or different species. They are mosaics at the cellular level; individual cells are derived from either the host or the donor but not both.⁷

Note that chimeras and transgenics need not cross species boundaries, whereas hybrids are always interspecific.

Multiple applications

Crossing species boundaries happens all the time in nature and in agricultural settings, and it has a long history in developmental biology and immunology laboratories. Consider just a few examples:

• lateral gene transfer between bacteria, whereby genetic material is transmitted horizontally from one organism to another⁸
• the crossing of strains of wheat; the insertion of genes from a plant (or an animal) into a plant to improve crop yield and robustness⁹
• the mating of a horse with a donkey to create a mule; the fusion of sheep and goat cells to create a “geep”¹⁰
• the transplantation of cells and tissues from one species of frog to another, and of neural tissue from quails to chickens, to study the complex processes of development^11-13

Crossing species boundaries between human and nonhuman animals is also commonplace:

• Animal tissues, cells, and their derivatives are often transferred to humans, whether by using insulin produced from pig or cow pancreases, injecting flu vaccines cultured in fertilized chicken eggs, or transplanting heart valves from pigs into humans.
• Human genes and cells are often transferred to animal hosts to create humanized animal models (such as OncoMouse, which develops human cancers¹⁴), to grow humanized tissues that can be transplanted back into humans (such as sheep with human livers¹⁵), or to test the developmental potential of transplants.¹⁶

Stem cell research

In the first few years of human stem cell research, most of the ethics discussions centered on the use of human embryos as sources of stem cells. Research to derive human embryonic stem (hES) cells involves removing cells from the inner cell mass of a human blastocyst, which destroys the developing embryo. While this debate continued, further debate on the ethics of cloning to produce children, and cloning for biomedical research, emerged. This debate arose in response to claims about the anticipated benefit of future stem cell therapies using cells from cloned embryos, which would allow patients to receive transplants of cells containing their own DNA.¹⁷

While these issues remain ethically contentious, a new debate has recently emerged concerning the ethics of crossing species boundaries to make part-human chimeras. Stem cell scientists and others insist that this cross-species work is important to basic science and a necessary step on the path to regenerative medicine. They maintain that it would be unethical to involve humans in stem cell transplantation research without first having studied the safety and efficacy of the human cells in nonhuman animals.

Ethical controversy

Issues of health and safety, especially given the possibility of zoonosis, or the transfer of a disease from nonhuman animals to humans, have long been front and center in the ethics debate about cross-species work.¹⁸ In the last decade or so, with the increase in science options for the crossing of species boundaries, other ethical issues have come to the fore.

In 1997, Stuart Newman, a developmental biologist sponsored by biotechnology activist Jeremy Rifkin, sought to preclude the creation of a humanzee—a part-human, part-chimpanzee chimera. Together, Newman and Rifkin tried to patent the relevant technology so that they would be able to restrict its use and to promote a vigorous social dialogue about the desirability of such part-human beings.¹⁹ They were unsuccessful in obtaining the patent, leaving open the possibility that humanzees may soon walk among us, with or without patent protection. Examples of recent research involving the transplantation of cells and tissues into prenatal nonhuman animals (embryos and fetuses), the transplantation of cells and tissues into nonhuman animal brains, and the transplantation of cells and tissues into the brains of nonhuman primates, serve to make this point:

• Scientists at Harvard University have published their research involving the transfer of human neural stem cells into the developing fetal brain of bonnet monkeys.²⁰
• Scientists in Israel have reported that human embryonic stem cells transplanted into chick embryos differentiated into neurons.²¹
• Scientists in Nevada have reported on inserting human neural stem cells into fetal sheep to assess their developmental potential.²²
• Scientists in California have reported on the development of functional neurons in mouse brains, where the neurons were derived from human embryonic stem cells.²³

While this research is ongoing, a debate has erupted about the ethics of creating part-human beings in response to proposals from some stem cell scientists to use nonhuman primates as an assay system for testing the developmental potential of human stem cells. The fact that biologists are especially interested in transplanting human neural stem cells into the brains of nonhuman primates²⁴ intensifies the controversy about humanzee-like chimeras.

The ethics of creating part-human beings

The ethical debate has been multivocal, with moral considerations raised from many perspectives, both religious and secular. The central moral concerns with creating part-human beings include worries about the following:

• the unnaturalness and intuitive repugnance of certain kinds of creatures, such as part-human combinations²⁵

• the threat of intensified moral confusion regarding the creation of novel part-human beings who violate the pragmatically clear moral demarcation line between species upon which current institutions, structures, and social practices are based⁵

• the potential for transferring moral status to nonhuman animals by conferring on them characteristically human cognitive capacities, which may or may not threaten human dignity^24,26

• the possibility that enhanced animals would deserve to be treated as if they were human subjects but would continue being treated as if they were unenhanced nonhuman animals²⁷

• the moral status of nonhuman animals, especially primates, as experimental animals²⁸

Scientists and others who advocate cross-species work argue that the part-human animals will be useful as disease models, assay systems, or organ sources.^16,29 They dismiss the worries about repugnance, deny the potential for moral confusion, and endeavor to sidestep concerns about moral status and potential threats to human dignity. They also rely heavily on current norms for research involving humans to legitimate preclinical cross-species research in nonhuman animals.

Additionally, advocates of transhumanism, the movement to enhance humans using biotechnology, argue that the creation of hybrids, transgenics, and chimeras may be useful in the quest to radically alter humans.³⁰ They see an opportunity to improve upon human nature and to enhance cognitive and physical performance—an idea that is itself morally controversial.³¹

Toward a constructive public debate

Unfortunately, much of the public debate on the ethics of crossing species boundaries is characterized by sensationalism and political posturing. While some commentators have attempted to explore the moral dimensions of interspecies research in careful and respectful terms, many of the media reports have exaggerated the conflict, providing more heat than light. Even so, attempts at public education and public engagement have tended to reveal the persistence of the moral controversy. This suggests the need for scientists, ethicists, and others to take seriously the ethical concerns that have been raised. The voluntary guidelines for human embryonic stem cell research recently published by the National Academy of Sciences arguably are an attempt to do just this.³² As we have argued elsewhere, however, considerably more debate and discussion is needed about the fundamental underlying values.^33,34

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