Zygote and "Clonote" — The Ethical Use of Embryonic Stem Cells
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《新英格兰医药杂志》
The Stem-Cell Debate
The editors asked two members of the President's Council on Bioethics to address the following questions:
Research on human embryonic stem cells holds great promise for the development of therapies for chronic and debilitating diseases that are currently untreatable. Should the federal government of the United States provide funding for such research? If it does not provide such funding but effective stem–cell-based therapies are developed elsewhere, should their use be allowed in the United States?
Michael J. Sandel, D.Phil., is the Anne T. and Robert M. Bass Professor of Government at Harvard University. Paul McHugh, M.D., is the Henry Phipps Professor of Psychiatry at Johns Hopkins University School of Medicine. The opinions expressed are those of the authors and do not necessarily reflect the views of the President's Council on Bioethics.
Their responses follow.
Bioethics is a debate without rules about a future dimly apprehended — a debate that is ever in danger of slipping from judicious deliberations into secular sermons. I awoke to these facts soon after I had joined the President's Council on Bioethics, when we began to discuss embryonic stem cells. The discovery of pluripotential, infinitely self-replicating stem cells early in the 1980s had lit up a whole domain of cellular and developmental biology and suggested therapeutic approaches to chronic, debilitating, and incurable diseases such as Parkinson's disease and diabetes mellitus. But for some years, the U.S. government, knowing that harvesting the cells killed the embryos, would not fund research on stem cells that had been derived from human embryos.
(Figure)
Blastocyst opened to reveal the inner cell mass.
Courtesy of Wellcome Library, London.
On August 9, 2001, President George W. Bush made a thoughtful speech in which he proposed regulations permitting federal funding for research using stem-cell lines from human embryos that had been killed before that date. The National Institutes of Health, proceeding under this compromise, has since made 15 to 20 human stem-cell lines available for federally supported research.
But as might have been expected, few serious participants in the debate were satisfied by this compromise. Most stem-cell specialists reject what they see as an arbitrary limit on their resources and programs — and, among other substantive objections, note that a boundary date for production eliminates the chance of improving the quality of stem cells.1 People who recognize a gift of individual human life in every embryo — an "end" in itself, not to be treated merely as a "means" — recoil at its destruction, no matter when or why it occurs. All the members of the President's Council on Bioethics — whose formation President Bush announced during that same August speech — developed our views on federal funding as we gathered information and exercised (vigorously, I can attest) our human talent for disagreement.
The concern that shadows the free use of human stem cells derives from disquiet over their origins. If a source other than embryos can provide pluripotential stem cells — and harvesting them requires no killing — then this shadow vanishes. Thus, we all celebrate the discovery of stem cells in umbilical-cord blood, bone marrow, and other tissues.
But President Bush charged our council with thinking through the possibility of "cloning" as another source of human stem cells. This process, better termed somatic-cell nuclear transfer (SCNT), carries the potential of producing a living replica (clone) of the donor of a somatic-cell nucleus. It involves calling into play the genetic material and mechanisms that are latent in all somatic-cell nuclei, allowing them, under certain conditions, to recapitulate embryonic development and produce stem cells.
Ultimately, the council was unanimous in many conclusions about cloning.2 We rejected the use of cloning for human reproduction. We agreed that regulatory measures should be developed for stem-cell cloning to guarantee, among other matters, that only qualified laboratories would receive federal support for work with human SCNT.
We were divided over whether research should be put on hold until the regulations are in place. A small majority (11) of us favored a four-year moratorium on federal support to permit these regulations and oversight structures to be developed. A large minority (seven) of us believed that this work is so rich in therapeutic promise that it should proceed without delay, and regulations could catch up with it.
It seemed to me that most of our disagreements rested on different attitudes generated, interestingly, by the same view of SCNT. This view maintains that there is no ethically important difference between a blastocyst derived from in vitro fertilization and one derived from SCNT. Thus, if one holds that deriving embryonic stem cells from in vitro fertilization should be illicit, this conclusion would also apply to SCNT, and vice versa.
I, however, see a distinction between the two procedures that sanctions different practices involving their products. In my view, SCNT resembles tissue culture, whereas in vitro fertilization represents instrumental support for human reproduction. Specifically, SCNT is an engineered culturing of the nucleus of a somatic cell, accomplished by implanting this nucleus into an enucleated ovum, thereby forming a new diploid cell with the genetic characteristics of the "donor" of the nucleus. This new cell begins to replicate, following a developmental program that is latent in the genes of every somatic cell but that has been suppressed since it was employed in the original embryonic development of the donor organism.
I argue that this process of SCNT, by causing the expression of an intrinsic potential for growth and replication that is found in every somatic cell, can extend and expand a donor's cellular mass into extracorporeal space, as any form of tissue culture does. The stem cells that issued from the process would, in this view, be licitly used as the donor allowed. To specify this fundamental difference between in vitro fertilization and SCNT, I suggested that, since we call the first cell produced by fertilization the zygote, we dub the combination of nucleus and enucleated ovum that launches SCNT the "clonote."
Thus, I argue that in vitro fertilization entails the begetting of a new human being right from its start as a zygote and that we should use it to produce babies rather than cells or tissues to be harvested for purposes dictated by other human beings. In contrast, SCNT is a biologic manufacturing process that we may use to produce cells but should not use to produce babies.
My distinction rests on the origin of cells in SCNT, not on the process's vaunted potential for producing a living replica (clone) of the donor, as with Dolly the sheep. My confidence in making origins rather than potential the crux of the argument rests first on a reductio ad absurdum: if one used the notion of "potential" to protect cells developed through SCNT because with further manipulation they might become a living clone, then every somatic cell would deserve some protection because it has the potential to follow the same path. But I became more sure of this opinion when strong testimony was presented to the council3 indicating that SCNT performed with primate cells produces embryos with such severe epigenetic problems that they cannot survive to birth.
I still support the call of the council's small majority for SCNT regulations that will ensure, among other things, that human ova are not wasted like cheap reagents, or women pressed into service in unsafe ovum-production lines. Also, because I see that my argument supporting SCNT as a source of cells might easily justify growing the blastocysts to more advanced stages so as to harvest organs or tissues, I support limiting the existence of the clonote to 14 days. When these regulations are in place, federal funding for biologic research on human stem cells derived through SCNT should proceed.
I continue to hold in principle — as do many Americans and governments of several Western nations — that using in vitro fertilization to generate harvestable cells and tissues represents a seriously problematic, life-disowning use of biologic science. But I also appreciate that practice with human embryonic stem cells has raced ahead of principle and that the President's compromise — restraining the practice but not banning research that could bring great benefits — was a wise one.
I'm asked what I would say if some other country's scientists, using methods unsupported in the United States, discovered a cure for parkinsonism, diabetes, or Huntington's disease. But that's easy. First, I'd celebrate. I've not spent 50 years working and praying for such a victory to meet it without a welcome.
Then, after we'd drunk all the champagne, I'd surely ask, "What price this glory?" If we could reap the benefits using adult stem cells or SCNT, I'd lose no sleep over the methods that revealed them. If the therapies depended on trophic factors that we could extract and synthesize, I'd salute them. If the only effective therapies came with cells manufactured in factories where women were treated like battery hens, vats of sperm and ova bubbled and brewed, and human embryos were chopped and diced, I'd fret — as I fret over any product made under inhuman conditions.
But, even for bioethics, such matters lie too far in the future. The method I followed in arguing for SCNT remains compelling. Know the technical features through and through when working out the rightness or wrongness of a medical procedure. "God is in the details," noted the architect Ludwig Mies van der Rohe. Never has that truth echoed more loudly in the arena of biologic enterprise than it does now.
Source Information
From the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore.
References
Gearhart J. New human embryonic stem-cell lines -- more is better. N Engl J Med 2004;350:1275-1276.
Human cloning and human dignity: the report of the President's Council on Bioethics. New York: PublicAffairs, 2002.
Jaenisch R. Testimony: President's Council on Bioethics, July 24, 2003. (Accessed June 22, 2004, at http://www.bioethics.gov/meetings.)
Related Letters:
Ethics of Embryonic Stem Cells
George R. P., Lee P., Kay G. N., Pullicino P. M., Anderson R. E., Erickson C. P., Levick S. E., Sandel M. J., McHugh P.(Paul R. McHugh, M.D.)
The editors asked two members of the President's Council on Bioethics to address the following questions:
Research on human embryonic stem cells holds great promise for the development of therapies for chronic and debilitating diseases that are currently untreatable. Should the federal government of the United States provide funding for such research? If it does not provide such funding but effective stem–cell-based therapies are developed elsewhere, should their use be allowed in the United States?
Michael J. Sandel, D.Phil., is the Anne T. and Robert M. Bass Professor of Government at Harvard University. Paul McHugh, M.D., is the Henry Phipps Professor of Psychiatry at Johns Hopkins University School of Medicine. The opinions expressed are those of the authors and do not necessarily reflect the views of the President's Council on Bioethics.
Their responses follow.
Bioethics is a debate without rules about a future dimly apprehended — a debate that is ever in danger of slipping from judicious deliberations into secular sermons. I awoke to these facts soon after I had joined the President's Council on Bioethics, when we began to discuss embryonic stem cells. The discovery of pluripotential, infinitely self-replicating stem cells early in the 1980s had lit up a whole domain of cellular and developmental biology and suggested therapeutic approaches to chronic, debilitating, and incurable diseases such as Parkinson's disease and diabetes mellitus. But for some years, the U.S. government, knowing that harvesting the cells killed the embryos, would not fund research on stem cells that had been derived from human embryos.
(Figure)
Blastocyst opened to reveal the inner cell mass.
Courtesy of Wellcome Library, London.
On August 9, 2001, President George W. Bush made a thoughtful speech in which he proposed regulations permitting federal funding for research using stem-cell lines from human embryos that had been killed before that date. The National Institutes of Health, proceeding under this compromise, has since made 15 to 20 human stem-cell lines available for federally supported research.
But as might have been expected, few serious participants in the debate were satisfied by this compromise. Most stem-cell specialists reject what they see as an arbitrary limit on their resources and programs — and, among other substantive objections, note that a boundary date for production eliminates the chance of improving the quality of stem cells.1 People who recognize a gift of individual human life in every embryo — an "end" in itself, not to be treated merely as a "means" — recoil at its destruction, no matter when or why it occurs. All the members of the President's Council on Bioethics — whose formation President Bush announced during that same August speech — developed our views on federal funding as we gathered information and exercised (vigorously, I can attest) our human talent for disagreement.
The concern that shadows the free use of human stem cells derives from disquiet over their origins. If a source other than embryos can provide pluripotential stem cells — and harvesting them requires no killing — then this shadow vanishes. Thus, we all celebrate the discovery of stem cells in umbilical-cord blood, bone marrow, and other tissues.
But President Bush charged our council with thinking through the possibility of "cloning" as another source of human stem cells. This process, better termed somatic-cell nuclear transfer (SCNT), carries the potential of producing a living replica (clone) of the donor of a somatic-cell nucleus. It involves calling into play the genetic material and mechanisms that are latent in all somatic-cell nuclei, allowing them, under certain conditions, to recapitulate embryonic development and produce stem cells.
Ultimately, the council was unanimous in many conclusions about cloning.2 We rejected the use of cloning for human reproduction. We agreed that regulatory measures should be developed for stem-cell cloning to guarantee, among other matters, that only qualified laboratories would receive federal support for work with human SCNT.
We were divided over whether research should be put on hold until the regulations are in place. A small majority (11) of us favored a four-year moratorium on federal support to permit these regulations and oversight structures to be developed. A large minority (seven) of us believed that this work is so rich in therapeutic promise that it should proceed without delay, and regulations could catch up with it.
It seemed to me that most of our disagreements rested on different attitudes generated, interestingly, by the same view of SCNT. This view maintains that there is no ethically important difference between a blastocyst derived from in vitro fertilization and one derived from SCNT. Thus, if one holds that deriving embryonic stem cells from in vitro fertilization should be illicit, this conclusion would also apply to SCNT, and vice versa.
I, however, see a distinction between the two procedures that sanctions different practices involving their products. In my view, SCNT resembles tissue culture, whereas in vitro fertilization represents instrumental support for human reproduction. Specifically, SCNT is an engineered culturing of the nucleus of a somatic cell, accomplished by implanting this nucleus into an enucleated ovum, thereby forming a new diploid cell with the genetic characteristics of the "donor" of the nucleus. This new cell begins to replicate, following a developmental program that is latent in the genes of every somatic cell but that has been suppressed since it was employed in the original embryonic development of the donor organism.
I argue that this process of SCNT, by causing the expression of an intrinsic potential for growth and replication that is found in every somatic cell, can extend and expand a donor's cellular mass into extracorporeal space, as any form of tissue culture does. The stem cells that issued from the process would, in this view, be licitly used as the donor allowed. To specify this fundamental difference between in vitro fertilization and SCNT, I suggested that, since we call the first cell produced by fertilization the zygote, we dub the combination of nucleus and enucleated ovum that launches SCNT the "clonote."
Thus, I argue that in vitro fertilization entails the begetting of a new human being right from its start as a zygote and that we should use it to produce babies rather than cells or tissues to be harvested for purposes dictated by other human beings. In contrast, SCNT is a biologic manufacturing process that we may use to produce cells but should not use to produce babies.
My distinction rests on the origin of cells in SCNT, not on the process's vaunted potential for producing a living replica (clone) of the donor, as with Dolly the sheep. My confidence in making origins rather than potential the crux of the argument rests first on a reductio ad absurdum: if one used the notion of "potential" to protect cells developed through SCNT because with further manipulation they might become a living clone, then every somatic cell would deserve some protection because it has the potential to follow the same path. But I became more sure of this opinion when strong testimony was presented to the council3 indicating that SCNT performed with primate cells produces embryos with such severe epigenetic problems that they cannot survive to birth.
I still support the call of the council's small majority for SCNT regulations that will ensure, among other things, that human ova are not wasted like cheap reagents, or women pressed into service in unsafe ovum-production lines. Also, because I see that my argument supporting SCNT as a source of cells might easily justify growing the blastocysts to more advanced stages so as to harvest organs or tissues, I support limiting the existence of the clonote to 14 days. When these regulations are in place, federal funding for biologic research on human stem cells derived through SCNT should proceed.
I continue to hold in principle — as do many Americans and governments of several Western nations — that using in vitro fertilization to generate harvestable cells and tissues represents a seriously problematic, life-disowning use of biologic science. But I also appreciate that practice with human embryonic stem cells has raced ahead of principle and that the President's compromise — restraining the practice but not banning research that could bring great benefits — was a wise one.
I'm asked what I would say if some other country's scientists, using methods unsupported in the United States, discovered a cure for parkinsonism, diabetes, or Huntington's disease. But that's easy. First, I'd celebrate. I've not spent 50 years working and praying for such a victory to meet it without a welcome.
Then, after we'd drunk all the champagne, I'd surely ask, "What price this glory?" If we could reap the benefits using adult stem cells or SCNT, I'd lose no sleep over the methods that revealed them. If the therapies depended on trophic factors that we could extract and synthesize, I'd salute them. If the only effective therapies came with cells manufactured in factories where women were treated like battery hens, vats of sperm and ova bubbled and brewed, and human embryos were chopped and diced, I'd fret — as I fret over any product made under inhuman conditions.
But, even for bioethics, such matters lie too far in the future. The method I followed in arguing for SCNT remains compelling. Know the technical features through and through when working out the rightness or wrongness of a medical procedure. "God is in the details," noted the architect Ludwig Mies van der Rohe. Never has that truth echoed more loudly in the arena of biologic enterprise than it does now.
Source Information
From the Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore.
References
Gearhart J. New human embryonic stem-cell lines -- more is better. N Engl J Med 2004;350:1275-1276.
Human cloning and human dignity: the report of the President's Council on Bioethics. New York: PublicAffairs, 2002.
Jaenisch R. Testimony: President's Council on Bioethics, July 24, 2003. (Accessed June 22, 2004, at http://www.bioethics.gov/meetings.)
Related Letters:
Ethics of Embryonic Stem Cells
George R. P., Lee P., Kay G. N., Pullicino P. M., Anderson R. E., Erickson C. P., Levick S. E., Sandel M. J., McHugh P.(Paul R. McHugh, M.D.)