Ethical Concerns Regarding New Developments in Embryo Research

Testimony: Senate Appropriations Subcommittee on Labor, Health and Education

Testimony of Richard M. Doerflinger on behalf of the Committee for Pro-Life Activities. National Conference of Catholic Bishops before the Senate Appropriations Subcommittee on Labor, Health and Education Hearing on Embryonic Cell Research

December 2, 1998

I am Richard M. Doerflinger, Associate Director for Policy Development at the Secretariat for Pro-Life Activities, National Conference of Catholic Bishops. I am grateful for the opportunity to present the Catholic bishops' ethical concerns regarding new developments in embryo research.

In discussions of human experimentation, the researcher's temptation is to think that if something technically can be done it ethically should be done -- particularly if it may lead to medical benefits or advances in scientific knowledge. A civilized society will appreciate the possibilities opened up by research, but will insist that scientific progress must not come at the expense of human dignity. When this important balance is not maintained, abuses such as the Tuskegee syphilis study or the Cold War radiation experiments become a reality.

In deciding whether to subsidize various forms of human experimentation, legislators are not merely making an economic decision to allocate limited funds. On behalf of all citizens who pay taxes, they are making a moral decision. They are declaring that certain kinds of research are sufficiently valuable and ethically upright to be conducted in the name of all Americans -- and that other kinds are not. By such funding decisions, government can make an important moral statement, set an example for private research, and help direct research toward avenues which fully respect human life and dignity as they seek to help humanity.

Three kinds of experiments involving human embryos or embryonic cells have recently come to public attention. On one level, some of these experiments advance the ethical and legal debate on human cloning. They indicate that cloning is not necessary for promising stem cell research, and thus that it may be banned without endangering such research. At the same time, however, each of these experiments raises ethical problems of its own.

Currently, the drive for advances in human fetal and embryonic research is balanced against ethical considerations in three significant areas of federal law. It is important to review these to address the question: What moral principles are reflected in these enactments that can help us to make a moral judgment on new experiments that may not have been anticipated before?

Live fetal research is governed by federal regulations on the protection of human subjects first issued in 1975 (now codified at 45 CFR .46.101 et seq.). Federal regulations on fetal research treat the prenatal human being as a human subject worthy of protection, from the time of implantation in the womb (about one week after fertilization) until a child emerges from the womb and is found to be viable. Essentially the same standard is applied here as in regulations protecting live-born children: Since the unborn child is a helpless subject incapable of giving informed consent to experimentation, federally funded research involving this child is permissible only if (a) it could be therapeutic for that particular child (as with prenatal surgery to correct congenital defects), or (b) it is necessary to obtain important information and will not subject the child to significant risk of harm.1 In 1985 Congress further clarified this standard through an amendment to the National Institutes of Health reauthorization act: In assessing research on live fetuses in utero, protection from risk must be "the same for fetuses which are intended to be aborted and fetuses which are intended to be carried to term" (42 USC .289g). No matter what fate may be planned for the developing human being by others, the government must still make its own moral decision to respect life -- it cannot single out certain lives as disposable, or as uniquely fit for harmful research, simply because someone else plans to show disrespect for those lives.

Embryo research involving human embryos outside the womb -- such as embryos produced in the laboratory by in vitro fertilization (IVF) or cloning -- has never received federal funding. Originally this was because the federal regulations of 1975 prevented funding of IVF experiments unless such experiments were deemed acceptable by an Ethics Advisory Board -- and after the first such board produced inconclusive results in 1979, no Administration chose to appoint a new board. In 1994, after this regulation was rescinded by Congress, a Human Embryo Research Panel recommended to the National Institutes of Health that certain kinds of harmful nontherapeutic experiments on human embryos receive federal funding -- but the Panel's recommendations were rejected in part by President Clinton, then rejected in their entirety by Congress. Since 1995, three successive Labor/HHS appropriations bills have prevented federal funding of experiments which involve (a) creating human embryos for research purposes, or (b) subjecting human embryos in the laboratory to risk of harm or death not permitted for fetuses in utero under the regulations on protecting human subjects. Since 1997 this rider has explicitly banned funding of experiments involving embryos produced by cloning using human body cells.2

Fetal tissue transplantation research has been a matter of extended controversy. Such research could receive federal funds during the Bush Administration only if the tissue was obtained from sources other than induced abortion. The possible use of ovaries from aborted fetuses to create research embryos provoked more controversy within the NIH Human Embryo Research Panel than perhaps any other proposal; in the end the Panel decided to defer any possible funding of such research until further discussion could take place. Under current federal funding policy, human fetal tissue -- defined as "tissue or cells obtained from a dead human embryo or fetus after a spontaneous or induced abortion, or after a stillbirth," 42 USC .289g-1(g)) -- may be used for "therapeutic purposes" only if various safeguards are followed to ensure that the researcher avoids participating in an abortion and has no effect on the "timing, method, or procedures used to terminate the pregnancy" (42 USC. 289g-1(b)(2)).

In our view, current safeguards on the use of fetal tissue are inadequate. The only sure way to prevent federally funded research from collaborating in and providing legitimacy for abortion is to forbid abortion as a source for potentially "therapeutic" tissue. Certainly, it would be wrong for Congress to apply to early human embryos any policy less protective than that now applied to the later embryo and fetus. Existing law explicitly applies to human embryos, and destroying or discarding an embryo in the laboratory is the moral equivalent of abortion. As Congress has already done in the case of live fetal research, it should make clear in this area of research that the same standards apply to human embryos whether inside or outside the womb.

Current law on live fetal and embryonic research is no mere political compromise. It is a reflection of universally accepted ethical principles governing experiments on human subjects -- principles reflected as well in the Nuremberg Code, the World Medical Association's Declaration of Helsinki and other statements. Members of the human species who cannot give informed consent for research should not be the subjects of an experiment unless they personally may benefit from it, or the experiment carries no significant risk of harming them. Only by such ethical principles do we prevent treating people as things -- as mere means to obtaining knowledge or benefits for others.

Some will be surprised that such protections can exist under the U.S. Supreme Court's abortion decisions. But the Court has never said that government may not protect prenatal life outside the abortion context. It has even allowed states to declare that human life begins at conception, and that it deserves legal protection from that point onward -- so long as this principle is not used to place an undue burden on a woman's "right" to choose abortion before viability.3 Although states may not place meaningful restrictions or prohibitions on abortion under current Supreme Court jurisprudence, harmful experiments on human embryos are illegal in ten states regardless of how they are funded.4 Public sentiment also seems even more opposed to public funding of such experiments than to funding of abortion.5

Moreover, a scientific consensus now recognizes the status of the early human embryo, and the continuity of human development from the one-celled stage onward, to a greater extent than was true even a few years ago. In the 1970s and 1980s, some embryologists spoke of the human embryo in its first week or two of development as a "pre-embryo" and claimed it deserved less respect than embryos of later stages. But most embryology textbooks have now dropped the term, and some texts openly refer to it as a "discarded" and "inaccurate" term.6 The Human Embryo Research Panel and the National Bioethics Advisory Commission have both rejected the term; they describe the human embryo, including the one-celled zygote, as a living organism and "a developing form of human life."7

How is this human life treated in each of the three most recent developments in human embryo research?

University of Wisconsin: Stem cells from an IVF embryo

The University of Wisconsin proposal seems to be exactly the kind of experiment that the federal funding ban was consciously directed against. Researchers obtained 36 live human embryos from IVF clinics, grew them to the blastocyst stage, and then destroyed them for their stem cells; cells from 14 of the embryos were placed in culture, and "cell clusters" from five were successfully cultured to grow tissue. The researchers report that the inner cells were "isolated by immunosurgery" from the rest of the embryo.8 The effect is the same as if one were to "isolate" the heart and lungs from an adult human -- the being from whom the cells are taken is killed.

This kind of experiment was recommended for federal funding in 1994 by the Human Embryo Research Panel, but rejected by Congress every year from 1995 to the present. In this respect it does not present a new issue, for Congress has already decided that even so-called "spare" embryos from IVF clinics should not be subjected to destructive experiments using federal funds.9

Two new issues have been raised regarding this experiment, however.

First, could the embryonic cells that are removed from these human embryos, once isolated, be seen as human embryos themselves? The question arises because these inner cells are often described as the cells that would ultimately form the "embryo proper" as development continues. If removed from the original embryo but transferred to the nurturing environment of the womb, would each cell or each cluster of cells begin to develop as a new organism? Is a special environment provided by researchers to suppress such development and divert it toward undifferentiated growth as tissue instead? Certainly such diversion of embryonic development by use of molecular signals has been proposed by some researchers.10 If that were at work here -- if the experiment creates new embryos and then suppresses their development -- funding such an experiment might also violate the current ban on creating human embryos for research purposes.

Second, what of the prospect of funding research that would use this tissue for supposedly therapeutic purposes after it has been grown in culture? Here, the ethical principles reflected in current law on fetal tissue argue against funding the research. One must refer here to the principles rather than to the exact letter of the law because, while it applies to embryos as well as fetuses, it speaks of induced abortion rather than of destroying embryos by dissection. But there seems to be no reason why the same ethical standard should not apply. Human embryos are destroyed precisely to obtain this tissue, and the timing and manner of the destruction are tailored to obtaining this kind of tissue. An effective separation between the destructive act and the harvesting of the tissue, which federal law requires in the case of tissue from an induced abortion, does not seem to exist here.

One positive development, however, is that this line of research has put to rest the claim made last year by some biotechnology companies that production of human embryos by cloning (somatic cell nuclear transfer) is necessary to develop therapies based on embryonic stem cells. Such claims assumed that adults could not be treated with such cells unless the embryos were produced by cloning to create a genetic "match" and avoid tissue rejection. But in his commentary on the Wisconsin experiment, John Gearhart has cited three other avenues, some of which were also cited by the National Bioethics Advisory Commission last year: Stem cells can be banked from multiple cell lines to prevent such reactions; they can be genetically altered to produce a universal donor line; or they can be customized using the relevant histocompatibility genes from the intended recipient.11

Whatever else may be said of this research, then, it means that proposed federal bans on human cloning need no longer be held hostage to the debate on stem cell research. But the experiment itself is unethical and should not be funded. Instead, as the National Bioethics Advisory Commission has already observed,12 avenues should be explored for creating stem cell lines without creating or destroying human embryos.

Johns Hopkins: Stem Cells Based on Primordial Germ Cells From Induced Abortion

Presumably the Johns Hopkins University study could not be funded unless it follows the provisions of current law regarding fetal tissue from induced abortions. We wish to reiterate here that we find the existing policy inadequate and would support federal funding only if the cells can be obtained from sources other than induced abortion.

The new question raised here is this: Are the primordial germ cells obtained from abortion victims being used to create human embryos, which are then destroyed or suppressed to provide tissue. Even the NIH Human Embryo Research Panel did not recommend funding such an experiment, and it would clearly be forbidden by the current embryo research ban.

There is some ambiguity in current reports of the new research, because the researchers speak of collecting "embryoid bodies" from these cultures and finding "derivatives of all three embryonic germ layers" in the culture. They add that some of these bodies form "complex structures closely resembling an embryo during early development," and that they "appear to recapitulate the normal developmental processes of early embryonic stages and promote the cell-cell interaction required for cell differentiation."13

However, if this research is now conducted -- or could be conducted -- to establish useful cell lines without creating early human embryos, it would avoid some of the serious ethical problems associated with other experiments in this field. In that case the only remaining ethical problem is the use of cells from induced abortion, which does not seem necessary to the nature of the research. We urge that the use of cells from spontaneous abortions, ectopic pregnancies or other sources be explored instead.14

Advanced Cell Technology: Human Cloning Using Cows' Eggs

While this third type of experiment has not been fully reported in the medical literature it seems to pose a relatively new question -- that of human/animal hybrids -- as well as an old one, that of somatic cell nuclear transfer (cloning) to make human embryos for research purposes. Even the Human Embryo Research Panel opposed funding the former; the current ban on embryo research rightly forbids funding the latter.

The National Bioethics Advisory Commission, in its November 20 letter to President Clinton commenting on this experiment, rightly draws attention to the special ethical problems raised by combining human and animal cells to initiate embryonic development. On the one hand, this experiment does not create a hybrid in the sense of a being that is half human and half cow. All the nuclear genetic material comes from a human body cell; the cow egg contains some mitochondrial DNA, but this seems to be quickly taken over and directed by the human nucleus. On the other hand, proteins from the cow egg must be directing the remodeling of the chromosomes and thus the very earliest stages of development in this new being, and the ultimate effect of this is not known.

However, even if this experiment in one sense does not create a human/animal hybrid, it presents a new twist on the use of cloning to create human embryos for research purposes. Oddly, defenders of such an experiment must simultaneously argue that it is promising because it can produce genetically matched, fully human tissue for transplantation -- and that it is not covered by the ban on embryo research because fusing a human nucleus and a cow egg does not really produce a human embryo.

Cows' eggs are apparently being used not to make hybrids as such, but to avoid one of the remaining practical obstacles to unlimited mass production of identical human embryos by cloning: the fact that human eggs are difficult to obtain in large numbers, and cannot be harvested in quantity without posing health dangers to women. Therefore this experiment not only poses ethical problems in its own right but could set the stage for further mistreatment of human life as an object of experimentation on a large scale. Funding for such an experiment should be, and is, banned by current law, which forbids creating a new organism from "one or more" human gametes or body cells by fertilization or cloning.

In its new letter the Commission seems very uncertain as to whether this experiment creates an embryo. But this is partly due to the Commission's own truncated approach to what constitutes an embryo. Its assumption seems to be that the new being is an embryo only if it can be proved capable of growing and developing into a new "human being," by which it means a live-born infant. But this is too narrow a standard. In many circumstances -- especially those involving laboratory manipulation of new life -- embryos are created in such a fatally damaged condition that they will not survive to live birth.15 This does not mean that they were never embryos. One might as well say that an infant born with a fatal disease, who will not survive to adulthood, was never an infant. This strange standard seems to grow out of the Commission's earlier attempts to propose that no "human cloning" has taken place so long as any human embryos created by cloning are ultimately discarded or aborted instead of being implanted to attempt a live birth. We believe the relevant question here is whether the new one-celled entity with a human nucleus begins, even for a brief time, to grow and develop as an early organism of the human species. If so, the experiment should be seen as involving the creation and destruction of human embryos and, as such, should not be funded.

Each of these new developments poses ethical questions, and none should be pursued by the federal government unless and until ethical questions have been satisfactorily answered.

A remaining question involves the other avenues for advancing stem cell research, or for advancing the medical goals to which this research is directed, without exploiting developing human beings. Last year, for example, we proposed to Congress that there may be nine promising alternatives to the use of cloning to provide stem cell lines -- and eight of these seem to involve no use of embryonic stem cells at all.16 In the same few weeks that these embryo experiments garnered such national attention, significant advances were reported in two of these areas: The use of growth factors to help hearts grow new replacement blood vessels, and the use of stem cells from placental blood to treat leukemia and other illnesses.17

It would be sad indeed if Congress's attention were to focus chiefly on those avenues of research which garner front-page news precisely because they are ethically problematic. Instead, Congress has an opportunity to use its funding power to channel medical research in ways which fully respect human life while advancing human progress. None of the new proposed experiments change in any way the ethical principle grounding current restrictions on human embryo research: In trying to serve humanity we should not support actions that are fundamentally wrong. Even a good end does not justify an evil means.

Endnotes

1. 45 CFR .46.208(a). Such research may only pose a "minimal risk," which means that "the probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests." 45 CFR .46.102(i).
2. The current funding ban is Section 511 of the Labor/HHS appropriations bill for Fiscal Year 1999, enacted as part of Public Law 105-277, the Omnibus Consolidated and Emergency Supplemental Appropriations Act for Fiscal Year 1999 (p. 399).
3. Webster v. Reproductive Health Services, 492 U.S. 490 (1989).
4. See testimony and documentation provided by Lori Andrews, J.D., to the NIH Human Embryo Research Panel, February 3, 1994. Ms. Andrews cites ten states whose laws on fetal research generally prohibit experiments on human embryos ex utero: Louisiana, Maine, Massachusetts, Michigan (which in 1997 also enacted a ban on creating human embryos by cloning), Minnesota, New Hampshire, North Dakota, Pennsylvania, Rhode Island and Utah.
5. A national Tarrance poll in 1995 showed 18% support for using tax dollars for experiments that would involve destroying or discarding live human embryos in the first two weeks of development. Seventy-four percent of the Americans in the survey opposed such funding, with 64% strongly opposed. Press release, "Poll Shows Strong Opposition to Embryo Research Funding," United States Catholic Conference, July 25, 1995.
6. See Ronan O'Rahilly and Fabiola M,ller, Human Embryology and Teratology, 2nd edition (New York: Wiley-Liss 1996) at 8, 12. Professor Lee Silver of Princeton University, a proponent of cloning and embryo research, recently declared that the term "pre-embryo" was embraced by IVF researchers "for reasons that are political, not scientific" in an effort to "allay moral concerns" about their research. Lee M. Silver, Remaking Eden: Cloning and Beyond in a Brave New World (New York: Avon Books 1997), 39.
7. See: National Bioethics Advisory Commission, Cloning Human Beings (June 1997), appendix-2 ("embryo" as "the developing organism from the time of fertilization"); National Institutes of Health, Report of the Human Embryo Research Panel (September 1994), at 2 ("the preimplantation human embryo warrants serious moral consideration as a developing form of human life").
8. James A. Thomson et al., "Embryonic Stem Cell Lines Derived from Human Blastocysts," 282 Science 1145-7 (6 November 1998) at 1147 n. 6.
9. On July 11, 1996, an amendment was offered by Rep. Nita Lowey (D-NY) to drop the ban on funding research involving "spare" embryos, while retaining the ban on special creation of "research embryos"; the amendment was defeated 256-to-167.
10. See Lee M. Silver, supra note 6, at 128 (such molecular signals can be used as a way of "tricking" an early embryo into expanding as undifferentiated tissue, instead of undergoing normal growth and differentiation as an organism).
11. John Gearhart, "New Potential for Human Embryonic Stem Cells," 282 Science 1061-2 (6 November 1998) at 1061.
12. National Bioethics Advisory Commission, supra note 7, at 30-31. See NCCB Secretariat for Pro-Life Activities, "Would a Ban on Human Cloning Block Stem Cell Research?" (Fact sheet, 4/20/98; www.usccb.org/prolife/issues/bioethic/fact498.shtml).
13. Michael J. Shamblott, et al., "Derivation of pluripotent stem cells from cultured human primordial germ cells," 95 Proceedings of the National Academy of Sciences 13726-13731 (November 1998) at 13726, 13729.
14. See Peter J. Cataldo and Albert S. Moraczewski, O.P. (eds.), The Fetal Tissue Issue: Medical and Ethical Aspects (Braintree, MA: Pope John Center 1994).
15. For a critique of this approach see Testimony of Cardinal William Keeler before the House Commerce Subcommittee on Health and Environment, February 12, 1998; reprinted in 27 Origins 597-601 (February 26, 1998).
16. See NCCB Secretariat for Pro-Life Activities, supra note 12.
17. See: "Gene Therapy Helps Mice Grow New Blood Vessels," Business Wire, November 20, 1998; "Injected Genes Help Grow Heart Bypasses," Washington Post, November 10, 1998 at A3; "Stem Cells 'Grow' in Value: Potential Benefits of Umbilical Cord Banking Further Validated," PRNewswire, November 27, 1998; Pablo Rubinstein et al., "Outcomes among 562 Recipients of Placental-Blood Transplants from Unrelated Donors," 339 New England Journal of Medicine 1565-77 (November 26, 1998); Robertson Parkman, "The Future of Placental-Blood Transplantation," 339 New England Journal of Medicine 1628-9 (November 26, 1998). In light of some researchers' zeal for use of cloning by nuclear transfer to ensure an exact genetic match between tissue and recipient, it is worth noting that placental blood transplants seem to be more effective in treating leukemia if they are not too close a genetic match. Rubinstein et al. at 1573.