Hum. Reprod. Advance Access originally published online on December 16, 2005
Human Reproduction 2006 21(5):1113-1116; doi:10.1093/humrep/dei461
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OPINION |
Navigating the quagmire: the regulation of human embryonic stem cell research
Department of Anatomy and Structural Biology, University of Otago, Dunedin, New Zealand
1 To whom correspondence should be addressed at: Department of Anatomy and Structural Biology, University of Otago, PO Box 913, Dunedin, New Zealand. E-mail: gareth.jones{at}stonebow.otago.ac.nz
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Abstract |
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 Top Abstract IntroductionPublic policy--identification of...Ethical consistency and...Assessing the four positionsSubsidiary positionsSummaryReferences |
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Embryonic stem (ES) cell research has garnered almost unprecedented attention. Debate over the boundaries of such research is ongoing, and the regulation of the field varies widely between countries. This article identifies and evaluates the four major positions that emanate from current international regulations. ES cell policies may ultimately impact on public health, and hence they must be both rigorous and transparent. We contend that these goals will only be achieved if policy is both ethically consistent and clinically realistic with regard to the ability to achieve therapeutic goals. We conclude that policies allowing the ongoing extraction of stem cells from spare in vitro fertilization embryos and the creation of embryos for research (within set limitations) cope most adequately with the tension between varying views on the moral status of the human embryo and the therapeutic potential inherent within ES cell research.
Key words: embryonic stem cells/ethical consistency/regulations
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Introduction |
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TopAbstractIntroductionPublic policy--identification of...Ethical consistency and...Assessing the four positionsSubsidiary positionsSummaryReferences |
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The potential of embryonic stem (ES) cells appears to be revolutionary. If this potential is even only partially realized, regenerative medicine could transcend barriers in ways only barely imagined at present.
There are two characteristics of ES cells underpinning this therapeutic potential, self-renewal (i.e. the ability of the cell to replicate for a prolonged period of time) and pluripotency (i.e. the ability to generate any cell type). It is this latter property that distinguishes ES cells from any other human material including adult stem (AS) cells (Towns and Jones, 2004a
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Although several experiments indicate that AS cells have some plasticity (Ferrari et al., 1998; Zhao et al., 2002; Johnson et al., 2005), care should be taken in interpreting these results. Claims of AS cell pluripotency are undermined by questions surrounding the accurate identification of product cells, the frequency at which such events occur and whether the observed effects are due to hybrid formation rather than transdifferentiation. Overall, there are few confirmed reports of pluripotent adult human stem cells, and even these may not stand up to serious critical assessment (Committee on the Biological and Biomedical Applications of Stem Cell Research, 2002). Additionally, the self-renewal capacity of AS cells is yet to be fully substantiated. Hence, although research on AS cells is certainly warranted, the current literature indicates that the potential of ES cells outweighs that of AS cells.
However, it is not just the scientific possibilities that are generating attention, for the use of ES cells has opened a Pandora’s box of ethical dilemmas, the primary point of contention being that the acquisition of ES cells necessitates the destruction of human embryos. Reaching a consensus has proved elusive, and regulations on human ES cell research vary widely between countries. However, four dominant positions can be identified. We outline these positions and address their adequacy in terms of ethical consistency and the consequences for realizing or retarding therapeutic potential. In addition, we will briefly assess two subsidiary positions which have not featured to date in the schemes of other writers (Fischbach and Fischbach, 2004; Knoepffler, 2004; Knowles, 2004; Wagers and Weissman, 2004; Walters, 2004). We categorize the four dominant positions as A through D (Towns and Jones, 2004b).
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Public policy—identification of four positions |
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TopAbstractIntroductionPublic policy--identification of...Ethical consistency and...Assessing the four positionsSubsidiary positionsSummaryReferences |
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Position A prohibits all human embryo research, including the utilization of ES cells. Ireland, Austria, Norway and Poland hold this position.
Countries whose policy falls into position B confine the use of ES cells to those currently in existence, in that they were extracted prior to a specified date. This prohibits the extraction of ES cells, as well as the utilization of ES cells, derived in the future. Regardless of some major differences between them, Germany and the United States fit into this category.
Position C allows for the use and ongoing isolation of ES cells from embryos surplus to the requirements of clinical IVF programs governed by the 14-day embryo research limit (Chief Medical Officer’s Expert Group, 2000), a position adopted by Canada, Greece, Finland, Hungary, the Netherlands and Taiwan, among others. Australia has also recently moved to this position (Russo, 2005).
Position D countries, such as the UK, Belgium, Israel and Singapore, also permit the utilization and extraction of ES cells from surplus IVF embryos. However, they also allow the creation of human embryos specifically for research purposes. We have not subdivided this section by method of creation as we consider such details to be of minor ethical significance.
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Ethical consistency and therapeutic potential |
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We advocate the need for ethical consistency between related policies throughout a society. For instance, for a society opposed to embryo destruction, public policy should aim to protect embryos across all reproductive areas—both in clinical and in research domains. Consequently, stem cell regulations based on the premise that embryos should not be destroyed should be mirrored by comparable regulations governing IVF.
We also suggest that regulations need to be evaluated in terms of their ability to realize therapeutic potential. Although the respective policy positions will put a varying degree of emphasis on clinical goals, they must accurately incorporate the relevant science. For example, it would be misleading for regulations to claim to promote therapeutic potential but include restrictions that compromise safety or human health.
Further, policies must acknowledge that although the potential of ES cells is great, much basic research is still needed before any clinical application can be realistically considered. Claims that clinically applicable ES cell therapy is imminent are seriously misleading. This recognition should not undermine the priority of ES cell research, but it should be incorporated into regulations and long-term planning.
ES cell policies may ultimately impact on public health, and hence they must be both rigorous and transparent. We contend that these goals will only be achieved if ES cell policy is both ethically consistent and clinically realistic with regard to the ability to achieve therapeutic goals.
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Assessing the four positions |
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TopAbstractIntroductionPublic policy--identification of...Ethical consistency and...Assessing the four positionsSubsidiary positionsSummaryReferences |
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Position A
A prohibition stance deems that ES cell extraction and utilization should be banned. Ethical justification of this stance emanates from the argument that the human embryo is a human being from fertilization onwards. The ‘potential’ of a human embryo allows it to be equated with more fully developed forms of human life. Therefore, the ethical basis of this stance is that ES cell research destroys human lives, and so, must be opposed.
If position A is applied consistently, it would be expected to have consequences in other reproductive areas. Notably, countries adhering to this position might be expected to prohibit IVF, since it results in the destruction of embryonic life. The number of embryos produced through IVF is surplus to clinical requirements, with the result that many will eventually be discarded. However, IVF is available in many of the countries where ES cell research is prohibited, including Austria, Ireland, Poland and Brazil (Andersen et al., 2005). Because embryo destruction is implicit to these procedures, it is ethically inconsistent to deny researchers the opportunity to utilise these discarded embryos. An apparent resolution to this quandary is provided by the position of Germany and Italy, where only as many embryos as are to be transferred are allowed to be created (German Embryo Protection Act, 1991; Fineschi et al., 2005). However, this creates additional difficulties, since the repetition of ovarian stimulation, the inevitable transfer of multiple embryos and the subsequent increase in multiple pregnancies endanger the woman’s health (Ludwig and Diedrich, 2003; Fineschi et al., 2005). They may also have negative repercussions for the development and well-being of children born under these circumstances.
However, even if consistency between IVF policy and the use of ES cells is attained, it may become increasingly difficult to sustain this stance. The adoption of position A should imply that no therapeutic benefit could subsequently be obtained from the results of ES cell research carried out elsewhere. Because any benefit, in terms of therapies, would only be achieved by accepting embryo destruction in other societies, an act that would clearly contradict their own ethical stance. Although human ES cell research is still in its early phases, if clinical therapies become available, nations taking a prohibitive approach could come under considerable public pressure to change their stance. This conclusion is not reached by adhering to strict moral complicity, by which material resulting from past unethical acts is itself inherently unethical. In this case, the reliance is not upon past acts, but upon present and future acts, namely the continued destruction of embryos to create further ES cell lines. Reliance on pre-existing cell lines for ongoing human applications is clinically untenable, as is discussed under position B. It is the consideration of these future issues that may render a purely prohibitive position unsustainable in the longer term.
Position B
Countries accepting position B adopt a modified prohibition stance, concurring with the stance taken in position A. However, they can pursue ES cell research, as long as they use existing cell lines derived prior to a set date.
This position is an attempt to allay the fears of those who see embryo research as commodifying the human embryo while appeasing those who wish to pursue the therapeutic potential ES cells offer. As a result, this position gives the appearance of upholding an absolute position on the inviolability of the embryo whilst allowing a moderate amount of research to occur using already derived material.
However, ethical inconsistency arises from the ongoing creation and destruction of embryos produced in IVF programs existing in these countries (Weiss, 2003; Andersen et al., 2005). This position is also deeply flawed in terms of therapeutic potential. Although it gives the impression of allowing research to proceed, any ES cell work undertaken in these countries is compromised by its dependence on existing cell lines. Pre-existing cell lines will eventually be rendered unacceptable for clinical trials due to reasons relating to the accumulation of mutations and the risk of disease transfer between species (Roccanova et al., 2001; Cheng et al., 2003; Kennedy, 2003; Klimanskaya et al., 2005; Martin et al., 2005). Hence, despite first impressions, both ethical consistency and clinical goals are seriously compromised by this position. It emerges as little more than a political construct.
Position C
This can be described as a modified acceptance stance, with no pretence that absolute protection is bestowed upon the embryo from fertilization onwards. Research on human embryos is allowed but guided by both the relevance of the research for human health and the scientific rationale (Stem Cell Research Committee, 2003).
Restrictions of this nature are aimed at showing a degree of respect for the human embryo while encouraging research that may benefit patients in the future. The derivation of ES cells from embryos is consonant with this framework, since it falls well within the 14-day limit and its goal is improved understanding of developmental processes and ultimately an extension of therapeutic options. It is ethically consistent with other reproductive technologies permitted in these countries, namely, IVF, its associated procedures and post-fertilization contraception.
The use of surplus embryos is generally recognized as a moderate step in ES cell research. Except for the very small number of surplus embryos donated to other couples for reproductive purposes, they will eventually be destroyed, regardless of any research agenda. The decision to destroy embryos and the subsequent one to use embryonic material in research are separate decisions and can be procedurally isolated. This argument holds even though the act of extracting stem cells destroys the embryos concerned (Towns and Jones, 2004a). An additional attraction of position C is that it employs a model that has been developed extensively in relation to the use of aborted tissue in fetal neural grafting (Jones, 1991; Björklund et al., 2003). It is not, therefore, creating an ethical precedent.
A possible limitation of this position comes in the area of therapeutic potential. Since research is restricted to ES cells derived from surplus IVF embryos, a lack of genetic diversity may exist. Although the significance of this restriction is at present difficult to ascertain, it should be taken into account in any assessment. Perhaps more importantly, a prohibition on creation of embryos specifically for research means that cell lines cannot be produced via somatic cell nuclear transfer (SCNT) or therapeutic cloning. Thus, the possibility for creating immunocompatible cell lines is not possible under position C.
The unwillingness of this position to allow the creation of embryos specifically for research purposes demonstrates its cautious nature. It perhaps signals that these societies wish to prevent the commodification of human embryos, as those available are already in existence. For most embryos, the only choice available is destruction with or without research. But is the precautionary element at the heart of this position inconsistent? As noted, thousands of embryos are set for destruction in IVF programs (Weiss, 2003; Russo, 2005). In addition, in IVF, the number of embryos transferred to the uterus far exceeds the number of successful pregnancies. For example, in Europe, the rate of successful transfer is <37% (Andersen et al., 2005). Consequently, embryos are created and destroyed in IVF as well as in ES cell research. Although a more successful compromise than position B, this position can be criticized for circumventing the ethical issues rather than confronting them.
Position D
Position D is a broader acceptance stance, on account of the use of embryos produced specifically for research; aside from this additional source of embryos, positions C and D are identical.
But does the additional step of creating embryos specifically for research (and eventually therapeutic) purposes show them disrespect? Many feel that it does, since the research imperative overrides any opportunity these embryos may have had to become individuals. However, as noted, the vast majority of surplus embryos in IVF programs will never develop any further, while many (70%) naturally produced ones in the body will also succumb (Macklon et al., 2002), and only 60–70% of these spontaneous abortions are due to chromosomal abnormalities (Stern et al., 1996; Lockwood, 2000). Furthermore, Harris (2003) has commented that absolute protection of the embryo requires complete abstinence from unprotected sex.
While recognizing that vast numbers of embryos are beyond our protection during natural fertilization and subsequent gestation, such a phenomenon does not justify the destruction of embryos for research or therapeutic purposes. Consequently, there is widespread feeling that the destruction of embryos created specifically for research is premeditated in a manner not encountered in either IVF or natural reproduction. The thrust of our argument is that the magnitude of the difference between C and D is questionable as both result, knowingly, in embryo creation and in destruction. We contend, as do others (Clarke, 2004), that D is a more consistent position than C.
In terms of therapeutic potential, countries adhering to position D can maximize research opportunities. The creation of embryos specifically for research addresses the genetic diversity problem that may hamper position C and also opens the way to the benefits that may be associated with SCNT, by creating immunocompatible cells and tissues for patients undergoing transplantation. In terms of therapeutic potential, therefore, position D may be seen as the ideal.
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Subsidiary positions |
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TopAbstractIntroductionPublic policy--identification of...Ethical consistency and...Assessing the four positionsSubsidiary positionsSummaryReferences |
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These additional positions do not require any technological sophistication. Position E, adopted by Germany, upholds a willingness to import certain human ES cells while rejecting their extraction within Germany itself. In this instance, public policy disapproves of embryo research, and the extraction of human ES cells, but is prepared to allow the importation of these cells from countries that approve of embryo research. If this policy is aimed at preventing the destruction of embryonic life, consistency would demand that no use be made of cells or tissues resulting from embryos that have been deliberately destroyed—regardless of where that occurs. If German policy considers these cells to be morally tainted if produced within Germany, they are equally tainted when extracted outside Germany.
Position E has no advantage over B; both are problematic. It merely adds to the moral confusion by appearing to protect early embryos, which it, in reality, fails to do.
Position F is encountered in the United States with its segregation of public and private funding, and with the distinction between a regulated public sector and an unregulated private sector. In the United States, position B applies only to federally funded research. The ethical inconsistency within this situation is palpable, and we have no wish to argue in favour of it. Under this model, there is the potential for private sector research to be left unregulated. Furthermore, commercial interests may demand that only the most financially viable avenues of research are pursued. Although these consequences are not inevitable (Mendiola et al., 1999), they mean that any lack of central regulation is of major concern. We accept that position F allows embryo research and the extraction of human ES cells to flourish in a society with an apparently prohibitionist or near prohibitionist stance. However, it is not a position that we recommend as good policy.
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Summary |
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TopAbstractIntroductionPublic policy--identification of...Ethical consistency and...Assessing the four positionsSubsidiary positionsSummaryReferences |
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In summary, countries adhering to positions A and B show obvious ethical inconsistencies in their policies. Position A countries will not realize clinical goals, while the ability of position B countries to do so is seriously compromised. Position C countries have established a reasonable compromise but can be criticized for being inconsistent in allowing embryo creation and destruction within IVF but not within ES cell research. Nevertheless, therapeutic potential may be realized under this policy. Finally, position D countries have the most ethically consistent policies and the greatest opportunities to maximize research.
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References |
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Submitted on September 8, 2005; resubmitted on November 3, 2005; accepted on November 26, 2005.
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