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Oocyte Cytoplasm Transfers and the Ethics of Germ-Line Intervention

Published online by Cambridge University Press:  01 January 2021

John A. Robertson
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Extract

The February 1997 announcement of the birth of Dolly, the sheep cloned from a mammary cell of an adult ewe, has drawn attention to the growing ability to select, alter, or otherwise manipulate the genome of offspring. Prior to Dolly, ethical discussion of genes in reproduction had focused on negative selection: carrier screening, prenatal diagnosis, and abortion or embryo discard. After Dolly, ethical debate will have to consider the direct or positive use of genetic selection or alteration technology.

The principal use of genetic selection techniques in human reproduction (reprogenetics) likely will be to treat or prevent disease in offspring. In the future, however, such techniques might also be used to enhance or even diminish expected characteristics of progeny. Techniques to accomplish these goals are likely to include: selection of the nuclear genome, as occurs in somatic cell cloning; chromosomal transplants; or direct insertion or deletion of specific genes.

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Article
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Journal of Law, Medicine & Ethics , Volume 26 , Issue 3 , Fall 1998 , pp. 211 - 220
Copyright
Copyright © American Society of Law, Medicine and Ethics 1998

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References

See Robertson, J.A., “Genetic Selection of Offspring Characteristics,” Boston University Law Review, 76 (1996): 421–82.Google Scholar
Dolly was not an accident. Several months after the announcement of the birth of Dolly, scientists in Hawaii succeeded in cloning several generations of mice clones, a development suggesting that cloning humans or other mammals is likely to be feasible. See Wakayama, T., “Full-Term Development of Mice from Enucleated Oocytes Injected with Cumulus Cell Nuclei,” Nature, 394 (1998): 369–74.CrossRefGoogle Scholar
Banning a procedure because it might be used for bad purposes is, as is the conclusion of most slippery slope arguments, unjustified. In this case, a beneficial procedure would be banned without any firm evidence that the problematic procedures would occur and without any comparison of the beneficial uses to the harms. For an analysis of slippery slope arguments in reproductive genetics, see Robertson, J.A., Children of Choice: Freedom and the New Reproduction (Princeton: Princeton University Press, 1994): At 163–64.Google Scholar
See Stolberg, S.G., “A Small Spark Ignites Debate on Laws on Cloning Humans,” New York Times, Jan. 19, 1998, at A1. If one were truly interested in cloning, one could engage in embryo splitting, even before nuclear transfer techniques are perfected. See Robertson, J.A., “The Question of Human Cloning,” Hastings Center Report, 24, no. 2 (1994): 6–14.Google Scholar
See Council of Europe, Draft Additional Protocol to the Convention on Human Rights and Biomedicine on the Prohibition of Cloning Human Beings with Explanatory Report and Parliamentary Assembly Opinion, 34 I.L.M. 1515 (1997) (adopted Sept. 22, 1997); Human Cloning Prohibition Act, H.R. 923, S. 1601, 105th Cong. (Mar. 5, 1997); National Bioethics Advisory Commission, Cloning Human Beings: Report and Recommendations of the National Bioethics Advisory Commission (Rockville: National Bioethics Advisory Commission, June 1997) (calling for a temporary, five-year ban) (hereinafter, NBAC Cloning Report).Google Scholar
See Robertson, J.A., “Liberty, Identity, and Human Cloning,” Texas Law Review, 76 (1998): 1371–456.Google Scholar
The NBAC Cloning Report's recommendations recognize the importance of research, but other efforts have been less protective of research. See Robertson, , id. at 1435–38 & infra notes 20–22 and accompanying text.Google Scholar
The National Institutes of Health's Recombinant DNA Committee's “Points to Consider” outlines at a more specific level a similar inquiry. See Recombinant DNA Committee, National Institutes of Health, “Recombinant DNA Research: Actions under the Guidelines,” 60 Fed. Reg. 20731-37 (Apr. 27 1995). The NBAC Cloning Report attempted a similar analysis for cloning, but, with only limited time available, did so at a much cruder level. See Robertson, J.A., “Wrongful Life, Federalism, and Procreative Liberty: A Critique of the NBAC Cloning Report,” Jurimetrics, 38 (1997): 69–82.Google Scholar
See Robertson, , supr note 6, at 1372–73, 1402–03. The procedure for answering these questions must also be resolved. At the most general level, international law could deal with the acceptability or nonacceptability of certain techniques. National or federal law or policy could also decide it. Within a given nation, issues of executive, legislative, and judicial authority will arise over genetic selection. Many questions will be studied by commissions, but many will be dealt with by the professionals and couples directly involved. Each decisional level, however, will have to deal with the substantive ethical issues raised by a technique.Google Scholar
I use the term cytoplasm transfers even though the procedure may mechanically involve the transfer of the nucleus of the recipient women into an enucleated donor egg. In fact, oocyte transfers may transfer the nucleus or the cytoplasm, with its mitochondrial DNA (mtDNA), from one woman to another; but, ordinarily, only another woman's cytoplasm is donated or used for another woman's reproduction. A case in which the donation of nucleus rather than cytoplasm occurs is discussed infra at p. 125.Google Scholar
See, for example, Zhang, J., Abstract, “In Vitro Maturation of Human Preovulatory Oocytes Reconstructed by Germinal Vesicle Transfer,” Fertility and Sterility, 68 (1997): S1.Google Scholar
As Andrea Bonnicksen notes, nuclear transfers are a warm-up exercise for cloning, providing a “relatively safe context for refining procedures that could later be used for human cloning.” Bonnicksen, A.L., “Transplanting Nuclei Between Human Eggs: Implications for Germline Genetics,” Politics and the Life Sciences, 17 (1998): At 4. The ability to interchange nuclei and cytoplasm between haploid cells would be easily applied to nuclear diploid transfers as well, the cloning technique used to produce Dolly.CrossRefGoogle Scholar
Injection into an unfertilized egg prior to meiosis is ordinarily envisaged, because that is the time at which the addition or substitution of healthy cytoplasm may prevent aneuploidy or other abnormalities from developing. It is thus unlikely that donor cytoplasm would be injected into an already fertilized egg until research shows that the cytoplasm also affected postfertilization development.Google Scholar
The diploid cell could come from an embryo, a fetus, or any born person. It could also come from a recently dead person. No fertilization is necessary, because the nucleus that is inserted into the enucleated egg cell is already diploid as a result of prior fertilization.Google Scholar
In this case, the donation is from a haploid oocyte to a now diploid cell, but only cytoplasm containing mtDNA is transferred.Google Scholar
Cloning can also occur by embryo splitting. See Robertson, supra note 4.Google Scholar
See NBAC Cloning Report, supra note 5; Robertson, supra note 4; and Robertson, supra note 6.Google Scholar
Genetic transfers affect the germ-line either because a haploid nucleus is transferred to another egg or because cytoplasm containing mtDNA, which is also part of the germ-line, is injected into a fertilized egg or embryo.Google Scholar
See Wallace, D., “Mitochondrial DNA in Aging and Disease,” Scientific American, Aug. (1997): At 40 (reporting that random accumulation of mtDNA could contribute to the common effects of aging—such as loss of memory, hearing, vision, and stamina—as well as more serious disorders that debilitate the elderly).CrossRefGoogle Scholar
See Rubenstein, D.S., “Germ-Line Therapy to Cure Mitochondrial Disease: Protocol and Ethics of In Vitro Ovum Nuclear Transplantation,” Cambridge Quarterly of Health Care Ethics, 4 (1995): 316–39.CrossRefGoogle Scholar
See Stephenson, J., “A Role for Mitochondria in Age-Related Disorders,” JAMA, 275 (1996): 1531–32.CrossRefGoogle Scholar
Although mitochondrial diseases are passed on only by women, they are not X-linked diseases. The genetic defect resides in the mitochondria, not in the X chromosome. It is thus passed on whether or not the resulting child is male or female, though only the daughters of affected women would in turn pass on the disease.Google Scholar
Only the daughter of an affected woman would pass on the mitochondrial mutation to her offspring, because the mutation resides in the cytoplasm of the egg. A son with the mutation would not pass it on to his offspring, for he transfers no mitochondria in his spermatozoa.Google Scholar
Given the defect in her mtDNA, it is unlikely that injection of donor oocyte cytoplasm into her fertilized oocytes, which would then coexist with her defective mtDNA, would be chosen to deal with this problem.Google Scholar
See U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, American Society of Reproductive Medicine, Society for Assisted Reproductive Technology, and RESOLVE, 1995 Assisted Reproductive Technology Success Rates, National Summary and Fertility Clinic Reports, Volume I—Eastern United States (Washington, D.C.: U.S. Department of Health and Human Services, Dec. 1997): At 35 (hereinafter 1995 Assisted Reproductive Technology Success Rates).Google Scholar
See Zhang, supra note 11; Zhang, J., “In Vitro Maturation (IVM) of Humanpreovulatory Oocytes Reconstructed by Germinal Vesicle (GV) Transfers,” in Kempers, R.D., eds., Fertility and Reproductive Medicine (Amsterdam: Elsevier, 1998): 629–35; and Takeuchi, T., Abstract, “Preliminary Experience of Nuclear Transplantation in Human Oocytes,” Fertility and Sterility, 70 (1998): S86. The theory animating this research is that healthier or younger cytoplasm provided prior to meiosis will prevent the aneuploidies that prevent implantation or the birth of healthy children. The germinal vesicles are transferred to a healthy enucleated egg because they are the precursors of the oocyte's nucleus prior to meiosis.Google Scholar
See Cohen, J., “Birth of Infant After Transfer of Enucleate Donor Oocyte Cytoplasm into Recipient Eggs,” Lancet, 350 (1997): 186–87.CrossRefGoogle Scholar
It is possible that some women who are carriers of nuclear genetic diseases would choose to provide the cytoplasm into which the nucleus of donor eggs is transferred to maintain at least some genetic tie with the offspring whom they gestate and rear.Google Scholar
See generally, Robertson, supra note 3.Google Scholar
In 1995, 3,352 cycles of egg donation were reported to the U.S. Centers for Disease Control and Prevention. See 1995 Assisted Reproductive Technology Success Rates, note 25, at 35.Google Scholar
A dilemma common in bioethics—the paradox of small numbers—arises here. Because so few persons are directly affected, the risk that the use of oocyte transfers will harm many others is minimized. At the same time, because so few people need to use this technique, denying it to them will cause limited harm. If not for the presence of procreative rights and the costs of enforcing a prohibitory policy, the small numbers involved would support either permission or prohibition of the practice. But see Planned Parenthood v. Casey, 505 U.S. 833, 887 (1992) (noting that the degree of burden, not the numbers affected, explains why Pennsylvania's twenty-four-hour wait for abortions is constitutionally permissible even though the spousal notification requirement, which in practice affects very few women, is unconstitutional).Google Scholar
I am referring here to the standard case of egg donation as now commonly practiced, in which the recipient woman gestates the resulting embryo, and not to the more unusual situation in which an egg donated to an infertile woman and her husband is then gestated by another woman, as occurred in the much publicized Buzzanca case. See In re Marriage of Buzzanca, 61 Cal. App. 4th 1410, 72 Cal. Rptr. 2d 280 (1998).Google Scholar
See New York State Task Force on Life and the Law, Assisted Reproductive Technologies: Analysis and Recommendations for Public Policy (New York: New York State Task Force on Life and the Law, Apr. 1998): At 339–40; Cohen, C.B., ed., New Ways of Making Babies: The Case of Egg Donation (Bloomington: Indiana University Press, 1996): At 293, 299; and Robertson, J.A., “Ethical and Legal Issues in Human Egg Donation,” Fertility and Sterility, 52 (1989): 1-11Google Scholar
See Fla. Stat. Ann. § 742.14 (West 1997); N.D. Cent. Code §§ 14-18-01 to −04 (1994); Okla. Stat. Ann. tit. 10, § 544 (1991); Tex. Fam. Code Ann. § 151.102 (West 1997); and Va. Code Ann. § 20–158 (Michie Supp. 1994).Google Scholar
See Robertson, J.A., “Legal Uncertainties in Egg Donation,” in Cohen, , ed., supra note 33, at 175–87. A few divorcing husbands have argued that they are entitled to sole custody of a child resulting from egg donation because the wife is not the genetic mother, thereby ignoring the agreement or understanding that the couple would undergo egg donation for the purpose of having a child whom they both would rear. The courts have rejected these arguments, as rightly they should. See, for example, McDonald v. McDonald, 196 A.D.2d 7, 608 N.Y.S.2d 477 (1994).Google Scholar
Even if this were not the case, it does not follow that the donor would then have rearing rights contrary to her donation agreement, for such rights do not exist in full egg donation, where it is clear that the donor is the genetic mother and the recipient ordinarily gestates.Google Scholar
See Robertson, supra note 6, at 1425. This is true both in haploid and in diploid egg cell transfers.Google Scholar
One is reminded of the rules for determining racial purity in the Jim Crow era and in Nazi Germany. Questions of ritual purity and impurity are also treated at length in the Talmud.Google Scholar
In coital reproduction, the genetic and gestational mother is necessarily the same. In egg donation, the genetic and gestational mothers are different, but one woman provides all the DNA. In nuclear transfer cloning, two different women could be providing DNA, with the source of the nuclear DNA providing more DNA than the source of the mtDNA. If we add rearing, a fourth possible maternal role is created.Google Scholar
Two peer reviewers of this article indicated that reference to a “wetnurse” is offensive to women. I use the term merely to note an additional way in which an aspect of maternal rearing—early physical nurturing—had historically been allocated to other women, and not to comment on its legitimacy or desirability.Google Scholar
If the donation of mtDNA were considered reproductive, then the resulting child would have two genetic mothers, as well as a gestational and social mother. However, this should not change the legal relations among the parties. As in full egg donation, the donor's agreement to relinquish mtDNA should specify that she relinquishes all rearing rights and duties growing out of her mtDNA to the recipient, who takes them on. Because the recipient would provide nuclear DNA and gestation, it is likely that the agreement between her and the donor for her to exercise all rearing rights and duties in resulting children would be upheld. Whether the child should be informed that she has two DNA genetic mothers is another issue. Also to be considered is whether mtDNA has a special role in forensic identification or in the human genome diversity project's use of sampling of mtDNA to trace the evolution of various ethnic populations.Google Scholar
See Kolata, G., “Soaring Price of Donor Eggs Touches Off Debate on Ethics,” New York Times, Feb. 2, 1998, at A1. The ethical guidelines of the American Society of Reproductive Medicine prohibit payment for eggs as such but do allow payment of expenses. See Ethics Committee of the American Fertility Society, “Ethical Considerations of Assisted Reproductive Technologies,” Fertility and Sterility, 70, Supp. 3 (1998): 6S.Google Scholar
See Kolata, G., “Young Women Offer to Sell Their Eggs to Infertile Couples,” New York Times, Nov. 10, 1991, at A1; and Hoffman, J., “Egg Donations Meet a Need and Raise Ethical Questions,” New York Times, Jan. 8, 1996, at A1.Google Scholar
Sperm donors and embryo donors also reproduce genetically tout court, and ordinarily have no contact with resulting offspring.Google Scholar
One donor could serve for several recipients, with some receiving the full gamete and some only the cytoplasm. Or a single donor could then transfer her cytoplasm to several different recipients. On commodification of reproduction and women, see generally Overall, C., Ethics and Human Reproduction: A Feminist Analysis (Boston: Allen and Unwin, 1987); and Radin, M., Contested Commodities (Cambridge: Harvard University Press, 1997).Google Scholar
See Calvert v. Johnson, 5 Cal. 4th 84, 19 Cal. Rptr. 2d 494, 851 P.2d 776 (1993). However, some states, such as New York, specifically prohibit payment to surrogates. See N.Y. Dom. Rel. Law § 123 (McKinney Supp. 1998).Google Scholar
See National Organ Transplant Act of 1984, § 301, 42 U.S.C. § 274e (1994).Google Scholar
An important aspect of this disclosure is informing donors of the extent to which medical injuries and lost wages suffered as a result of medical procedures will be covered. Many egg donor programs require that the donor have health insurance. In some cases, the program has bought a health insurance policy for the donor for a limited period. Neither, however, covers lost wages. At the very least, the extent to which there will or will not be coverage in the event of injury must be fully disclosed. See Robertson, supra note 35.Google Scholar
See Bonnicksen, supra note 12.Google Scholar
See Walters, L. Palmer, J.G., The Ethics of Human Gene Therapy (New York: Oxford University Press, 1997).Google Scholar
However, different progeny than would have existed result when germ-line gene therapy occurs. One cannot say that the resulting progeny are harmed, for those particular individuals would not have existed if the germ-line intervention had not occurred. Although this point may not hold for every germ-line intervention, for example, single-gene alteration, it holds for many, and must be confronted in claiming that a germ-line intervention harms resulting progeny. See Robertson, supra note 6, at 1405–09; and Heyd, D., Genethics: Moral Issues in the Creation of People (Berkeley: California University Press, 1992).Google Scholar
See, for example, Bonnicksen, supra note 12, at 5–6; Universal Declaration on the Human Genome and Human Rights, U.N. GAOR Res. 68, 29th Sess., U.N. Doc. 29 C/21 (1997) (draft available at <www.unesco.org/ulis/gctd.html>); and Council of Europe, supra note 5.);+and+Council+of+Europe,+supra+note+5.>Google Scholar
This argument appears to say that we should not treat disease in the most effective way now, because the disease gene is being removed from some of the genetic pool. Putting aside the fact that future progeny will not get the disease, the technology that can alter or remove disease genes should be able to replace them if they are ever needed again.Google Scholar
See Recombinant DNA Committee, supra note 8.Google Scholar
This statement thus rejects Rubenstein et al.'s proposal to have the acceptability of germ-line interventions turn on the precise kind of germ-line intervention. See Rubenstein, supra note 20, at 320.Google Scholar
See discussion of the numbers issue supra pp. 215–16.Google Scholar
For discussion of the European situation, see Bonnicksen, supra note 12, at 5–6.Google Scholar
See Act of Oct. 4, 1997, ch. 688, 1997 Cal. Legis. Serv. 3790 (West) (emphasis added).Google Scholar
See, for example, Mich. S.B. 864 & H.B. 4962 (enacted June 3, 1998); and R.I. H.B. 7123 (enacted July 7, 1998).Google Scholar
See Robertson, supra note 6, at 1433–39. A similar assessment applies to the legal barriers to oocyte transfer research that arise from state bans on embryo research.Google Scholar