20th WCP: An Evolutionary-Ecofeminist Perspective on Xeno- and Human Fetal Tissue Transplantation

Technological advances in biomedicine are occurring with increasing rapidity at this time in human history, far more rapidly than most of us have been able to comprehend and evaluate them. Yet it is imperative that we strive to do so, because we are faced with a choice of paths to pursue, paths that may lead in ever more divergent directions with regard to how we conceive of ourselves as humans and our relation to the rest of the natural world. How might ecofeminism, an approach developing within environmental philosophy, be relevant to issues of biomedical ethics, and in particular to the topics of xenotransplantation and the use of human fetal tissue? Precisely because a central strand within the ethical controversies surrounding such issues has to do with the way we differentiate between "self" and "other," and ecofeminism directly addresses the linkage that may be established between the self-versus-other distinction and dualistic thinking, the drawing of sharp binary oppositions that carry heavy value disparities, an orientation that is seen to underlie relations of domination, oppression and exploitation that abound within western culture. I have designated my own emerging view an evolutionary ecofeminist position to underscore the importance of contemporary evolutionary biology's affirmation of the continuity between human life and other forms of life, a continuity that is being disregarded when we conceptualize the self-versus-other distinction according to a dualistic pattern of thought.

Xenotransplantation, the transplantation of tissues and organs from other animal species into human beings, is conceived by some as the answer to the "organ shortage" problem: currently more than 45,000 persons are on the waiting list for organ transplantation within the U.S., far more than are able to receive human organs at the present rate of organ donation. (1) As a way of meeting this presently unmet need, and coincidentally as a potentially highly lucrative into which the biotechnology industry would very much like to expand (with profits estimated to be in the $6 billion range (2) ), plans for breeding and maintaining colonies of nonhuman animals — the pig appears to be the animal of choice at present, but nonhuman primates remain high on the list of species potentially useful for the factory organ-farm — are proceeding apace.

Xenotransplantation is not without significant human risk, however, not only to the recipient of the transplanted organ but to the human community at large, and a number of researchers have called for a moratorium on clinical trials until its risks can be more precisely delineated. (3) Xenozoonosis, the transmission to humans of pathogens producing disease in nonhuman animal species, is a very real concern. In any transplantation procedure, including allotransplantation, the transplantation of organs or tissues from one human to another, there is a significant risk of infection, since "the graft itself serves as a nidus or 'culture plate' from which organisms can spread in the human host," cells migrating from the graft may carry infection throughout the body, and the administration of immunosuppressive drugs, needed to prevent rejection of the implanted foreign tissue, diminish the response of the recipient to infection as well, potentially enabling a buildup of disease organisms to occur before clinical infection is recognized. (4)

Even a transplanted human organ, if it does not come from a genetically identical twin, will be met with a rejection response without immunosuppressive therapy, and the more distant the donor, phylogenetically, the more vigorous the rejection will be. Discordant xenotransplantation, transplantation between distantly related species, is typically accompanied by hyperacute rejection, resulting in damage to or destruction of the organ within minutes after establishing its blood supply within the recipient; "preformed natural antibodies" against antigens of distant species are present in the blood even without prior exposure or immunization of the host, and the activation of complement pathways has an immediate cytotoxic effect. Concordant xenotransplantation, transplantation between closely related species, may avoid hyperacute rejection but may still face both a delayed antibody-mediated response and a cell-mediated response that can produce rejection within a number of days unless immunosuppressive therapy is instituted. (5)

Transplantation of organs from nonhuman primates into humans would be considered concordant xenotransplantation and would bypass the problems of hyperacute rejection, but the potential for transmitting diseases that could infect a human host is thought to be high with nonhuman primate donors (HIV, for example, the virus producing AIDS in humans, is thought to be derived from a primate retrovirus that "jumped species"). Pigs, while recognized as discordant donors, offer the pragmatic advantages of longstanding domestication, rapid reproduction, and the capacity for rearing, during the first few months, in gnotobiotic (germ-free) environments that seemed to offer the hope of producing pathogen-free herds; transgenic pigs, genetically engineered so as to avoid triggering the hyperacute rejection response, are already in production. (6)

There seems to be a catch-22 associated with at least some efforts to avoid the problem of hyperacute rejection, however. Procedures aimed at knocking out the pig gene that codes for the main xeno-antigen which triggers complement-mediated lysis of porcine cells in the human body (alpha-Gal), or at inhibiting the complement cascade that destroys porcine cells exhibiting such a surface antigen, are likely to also inhibit the human body's natural defense against animal viruses (retroviruses and other enveloped viruses) that are enclosed in viral envelopes expressing the alpha-Gal antigen. "In other words, virus inactivation occurs by precisely the same mechanism as hyperacute rejection of xenografts," and therefore "modifications to make porcine xenografts resistant to hyperacute rejection may also make any enveloped viruses of pigs similarly resistant to lysis." (7) Such transgenic pigs may facilitate the adaptation of porcine viruses to infectivity in human hosts. Moreover, pigs have recently been found to harbor multiple copies of porcine endogenous retroviruses (PERV) within their genome, some of which can infect human cells in vitro. (8) Such disease agents would not be known human pathogens and would not cause any disease in their nonhuman hosts, simply remaining latent within the tissue, and thus would be difficult or impossible to screen for; when introduced into a human host, however, they would have a potential for producing disease with unrecognizable clinical manifestations, as well as for recombining with genetic material either from the host or from other infectious agents to create new pathogens.

Because xenotransplantation carries such disease risks, not only for the individual recipient who is expected to benefit from the procedure but also for the human population at large, intensive and lifelong monitoring of the health of xenograft recipients has been urged by a number of researchers, a move that would represent a major expansion of "informed consent" policy and one that would present the possibility of legal challenge on invasion of privacy and other grounds. In an age of international air travel, moreover, even if careful surviellance measures were implemented in the United States and certain other countries, an epidemic arising in any part of the world may potentially become global in short order. A significant number of biomedical researchers and other professionals agree that the disease risk is far from a "remote possibility." Virologist Jonathan Allan, who sits on the advisory subcommittee on xenotransplantation for the FDA, has been outspoken in pressing for caution; "once xenotransplantation begins," he is reported as saying, "it will no longer be a question of whether baboon and other donor animal viruses will enter the population, but how serious the effects will be." (9) The U.S. Public Health Service has, however, recently rejected recommendations for a moratorium on clinical trials and has even seemingly left open the possibility of allowing use of "virus-laden wild primates." (10)

A revealing contrast can be drawn between our society's apparent willingness to proceed with xenotransplantation and the approach many of us take toward the manipulation and transplantation of human fetal tissue. Though problems of rejection and disease are both far less 9though not nonexistent) when human tissues and organs are used for transplantation into humans, the implantation of human fetal neural tissue has shown promise in permitting repair and regeneration in cases of damage to the central nervous system, and the possibility exists for culturing large quantities of differentiated tissues for the restoration of muscles or organs from human embryonic stem (ES) cells, (11) great resistance exists to the use of human fetal tissues, and fairly restrictive guidelines have been established with respect to what sorts of fetal tissue research are and are not acceptable for federal funding in the U.S. The resistance, of course, is linked to the political weight accorded to the ongoing abortion controversy in this country, and, as I have claimed in other writings, the way those opposed to abortion frame their objections, as is the case with those who voice strong reservations over using human fetal material even at less risk and for more benefit than the alternatives, traces back to the dualistic "split" we in western culture draw between human life and all other life.

As ecofeminists Val Plumwood and Karen Warren have articulated, (12) our culture is riddled with dualisms: somewhere within a spectrum of variation in some particular characteristic, a sharp line is drawn dividing those who "have" that characteristic from those who "don't have" it, and the two groups are then thought of as being radifcally separate, different not just in degree but in kind. Such dualistic splitting underlies many of the major divisions constructed within humankind: variations in skin color come to be perceived as abrupt disjunctions between "black" and "white" races; differences in gender expectations or sexual orientation result in the construction of sharply separate "male" and "female" beings or in a normative heterosexual sphere over against a deviant homosexual one; national, cultural, and ethnic demarcations become reified as absolute boundaries that must be defended even at the price of great human suffering. Typically, after the binary opposition is created, one pole is designated as definitive of the "superior" group, and, on the basis of this presumed superiority, this group believes itself to be justified in dominating, oppressing, and exploiting the "inferior" group that is linked to the opposite pole, lacking in the characteristic marking the superior group and hence open to serving as merely a means to the superior group's ends. Ecofeminism has recognized the connections between such dualistic oppression of one human group by another and the similar dualistic exploitation of "nature" by humans: by virtue of their superior rationality, their use of language, their status as having been created in the image of God, or whatever characteristic is chosen on which to base the dualism, humans are conceptualized as uniquely different in kind from the rest of the biological world, vastly superior to other forms of life, and therefore completely justified in utilizing other species — even those who differ from us by only 1 or 2% of their DNA sequence — as nothing but instruments in the attainment of human purposes. Toward the goal of overcoming all forms of oppression and exploitation, human over other humans and human over "nature" and nonhumans, ecofeminists have called for a reexamination of our dualistic patterns of thought and ultimately a reconstruction of the way we perceive the relation between "self" and "other" so as to allow a nonhierarchical, nonexploitative appreciation of difference among living beings. (13)

Using the framework supplied by ecofeminist analysis, it is evident that xenotransplantation appears, at least to most people living within western culture, morally unproblematic because it presents just another case of exploiting an "other" group — nonhuman animals can be genetically engineered and maintained on highly regimented organ farms simply to meet the human "demand" for organs because they are perceived as radically "not-us," merely a form of disposable life to be used by humans and then discarded. The possibility of creating an entirely new industry based on the exploitation and commodification of other highly sentient beings, an industry which does not exist at present, is not found to be troubling because the template for such exploitation is already present in our culture and other manifestations of the dualistic pattern are widespread. Human fetal tissue, on the other hand, is perceived as "us," something on the favored side of the great divide, and so our dualistic numbing to the manipulation of an "otherized" group is not readily available. The fact that a close look at embryonic development graphically demonstrates phylogenetic continuity across all classes of vertebrates — a fact that comprised one of Darwin's strongest lines of evidence for the "theory of common descent" in his argument for evolution by natural selection — (14) is stubbornly disregarded, even by many scientists, because of our commitment to this dualistic way of thinking.

One concern that has been raised in discussions of transplantation is that what has heretofore been the conceptualizing of organ donation as a "gift" one human can give another may not withstand the growing pressure toward commodification even where human organs are at stake, and it is likely to be eliminated altogether with the arrival of xenotransplantation. (15) As Val Plumwood has pointed out, "person/property" dualism is becoming as rife within our culture as is human/nonhuman dualism, and we face the choice of constructing not only nature but ourselves according to such a "commodity model." (16) One of the hazards, she notes, of embracing a "centrism," a perspective distorted by dualistic thinking, as exemplified by such positions as eurocentrism, ethnocentrism, androcentrism, and anthropocentrism, is that those who believe themselves to be the "superior" group suffer from a serious set of blind spots: "a framework of perception and reason designed for subjugating and denying the other is not a good framework for attentive observation and careful understanding of that other, and even less is it one for evolving life strategies for mutual benefit." (17) Is it because we are so blinded by our anthropocentrism that we are willing to run the substantial risks posed by the implementation of this new technology, unable to see that the oppresor group is often injured as much or more by the very act of oppression, whatever it may be — while the alternative, respectfully giving and utilizing, but not commodifying, that which is understood as "self," in the form of organs and tissues from living or deceased human donors and human fetal and embryonic tissue, is by far the more beneficial choice for all concerned?

From an evolutionary-ecofeminist perspective, as we stand on the threshold of embarking on the very risky path toward xenotransplantation while demurring from the use of embryonic human tissues, ostensibly on "ethical" grounds, the fork in the road is clear: we are choosing to continue the pattern of abusing an "out-group" while simultaneously refusing to take responsibility for getting our "own" house in order. While many recognize as an ethical principle that, other things being equal, "those who derive benefits should sustain commensurate burdens" — a principle that, within environmental philosophy, leads to such judgments as "those who benefit most from the production of [toxic] waste should shoulder the greatest share of burdens associated with its disposal," and an opposition to environmental racism (18) — the idea that human benefits should be secured by undertaking human burdens (or, more often, not even burdens but simply alterations in our habits and thought patterns) seems, strangely, to elude us. Since only around 40% of potential cadaveric organ donors actually contribute to organ donation, (19) an intensive effort to increase the rate of human organ donation could go a long way toward making xenotransplantation unnecessary; so could a serious societal commitment to preventing heart disease and cancer by dietary and lifestyle changes and the elimination of cigarette smoking. But we seem unwilling even to consider such actions that would constitute helping ourselves by changing ourselves — it's far easier, the lazy man's way out, to let "science" solve all our problems for us while we examine our own lives not at all. Appeal to the religious dictum that "God created us in His image" while giving us "dominion over the rest of Creation" is often used to help us justify exploiting other beings while fearing to alter what is "us" at all — but does this not just amount to a game of "Father may I?" interpreted to mean that all things are permissible when done to the "other" groups (no responsibility there) while nothing should change with humanity except as Father orders it (thus no room for taking responsibility there either)?

There once was a time (or at least so goes the mythology of modern medicine) when physicians and other scientists tried out experimental procedures first on themselves to determine their safety and propriety; now we look to the least powerful, least advantaged groups, be they human or nonhuman, to saddle with the burden of our risks and to appropriate as commodities for our own advantage. I think it's time to return to the time of shouldering what is properly "our" responsibility, even if it means breaking away from this seductive religious heteronomy. With respect to addressing thoroughly the risks of xenozoonosis, Jonathan Allen has remarked, "Xenotransplant researchers haven't done their homework." (20) Is it too much to ask that we all begin to "do our homework" on what it really means to be a human being at the end of the twentieth century, and consider what kinds of choices we are making as we select our fork in the road?

NOTES

(1) The figure is attributed to the United Network for Organ Sharing, as of March 1996, and hence is likely to be even higher now; see, e.g., AAron Spital, "Mandated Choice for Organ Donation: Time to Give It a Try," Annals of Internal Medicine, 125 (1996): 66-69, 66.

(2) See Frank Morgan, "Babe the Magnificent Organ Donor?: The Perils and Promises Surrounding Xenotransplantation," Journal of Contemporary Health Law and Policy 14 (1997): 127-60, 156.

(3) See, for example, Declan Butler, "Last Chance to stop and Think on Risks of Xenotransplants," Nature 391 (1998): 320-24.

(4) F. H. Bach et al., "Uncertainty in Xenotransplantation: Individual Benefit Versus Collective Risk," Nature Medicine 4 (1998): 141-44, 142.

(5) For a thorough introduction to the problems facing discordant and concordant xenotransplantation, see D.K.C. Cooper, E. Kemp, K. Reemtsma, and D.J.G. White, eds., Xenotransplantation: The Transplantation of Organs and Tissues Between Species (New York: Springer-Verlag, 1991), chapters 1 and 3, with continued discussion in a number of subsequent chapters.

(6) See, for example, Shuji Hayashi, "Xenotransplantation with Special Reference to Genetic Engineering," Microbiology and Immunology 41 (1997): 751-56.

(7) Robin A. Weiss, "Transgenic Pigs and Virus Adaptation," Nature 391 (1998): 327-28, 328.

(8) See C. Patience, Y. Takeuchi, and R. A. Weiss, "Infection of Human Cells by an Endogenous Retrovirus of Pigs," Nature Medicine 3 (1997): 282-86.

(9) Frank Morgan, "Babe the Magnificent Organ Donor," 154.

(10) Declan Butler, "Last Chance to Stop and Think," 324; see also A. S. Daar, "Xenotransplants: Proceed with Caution [correspondence]," Nature 392 (1998): 11.

(11) Declan Butler, "Alternative Ways of Meeting Demand," Nature 391 (1998): 325.

(12) See, for example, Plumwood, Feminism and the Mastery of Nature (New York: Routledge, 1993), and Warren, "The Power and the Promise of Ecological Feminism," Environmental Ethics 12 (1990): 125-46.

(13) See Plumwood, "Nature, Self, and Gender: Feminism, Environmental Philosophy, and the Critique of Rationalism," Hypatia 6 (1991): 3-27, 17.

(14) See, for example, Ernst Mayr, The Growth of Biological Thought (Cambridge: Harvard University Press, 1982), 426-76.

(15) See A. S. Daar, "Ethics of Xenotransplantation: Animal Issues, Consent, and Likely Transformation of Transplant Ethics," World Journal of Surgery 21 (1997): 975-82, 977-79.

(16) See Plumwood, "From Rights to Recognition: Ecojustice and Non-Humans," manuscript available at the international Environmental Justice conference, Melbourne, Australia, October 1997, 14-16.

(17) Plumwod, "Androcentrism and Anthrocentrism: Parallels and Politics," Ethics and the Environment 1 (1996): 119-152, 142.

(18) Peter S. Wenz, "Just Garbage," in Laura Westra and Peter S. Wenz, eds., Faces of Environmental Racism: Confronting Issues of Global Justice (Lanham, MD: Rowman & Littlefield, 1995), 59, 62. Wenz notes, however, that "This is exactly opposite to the predominant tendency in our society, where poor people [who benefit least from waste generation and the goods produced thereby] are more proximate to toxic wastes dumped illegally and stored legally" — since poor people are often the exploited "out-group" in intrahuman dualisms.

(19) Spital, "Mandated Choice for Organ Donation," 66.

(20) Declan Butler, "Last Chance to Stop and Think," 322.