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Correspondence

Altered Nuclear Transfer

N Engl J Med 2005; 352:1153-1154March 17, 2005

Article

To the Editor:

Altered nuclear transfer is a procedure that has been proposed as a morally acceptable means of procuring human embryonic stem cells.1 In their Perspective article, Melton et al. (Dec. 30 issue)2 appear to misunderstand, and therefore prematurely dismiss, the promising possibilities of this proposal.

The proposal for altered nuclear transfer, which was developed in wide consultation with leading scientists, moral philosophers, and religious authorities, represents a “third option” — a technological solution to the current moral impasse regarding the destruction of human embryos to obtain embryonic stem cells.

Using the techniques of somatic-cell nuclear transfer, but with the intentional alteration of the nucleus before transplantation, we could construct a biologic entity that, from its very inception, lacked the attributes and capacities of a human embryo. Studies with mice already provide evidence that we may be able to generate functional embryonic stem cells from a system that is not an organism but is biologically (and morally) more akin to tissue or cell culture. There is a natural precedent for entities that lack the characteristics of organisms, yet are capable of generating embryonic stem cells or their functional equivalent. Teratomas are germ-cell tumors that generate all three primary embryonic germ-layer cell types, as well as more advanced cells and tissues. Yet these chaotic, disorganized, and nonfunctional masses entirely lack the structural and dynamic character of an organism.

Most of the objections raised by Melton et al. are based on a mistaken identification of altered nuclear transfer with silencing of the gene CDX2, but — as was clearly stated in my presentation to the President's Council on Bioethics — there are many potential approaches involving the alteration of genes that are necessary for early intercellular signaling, cell differentiation, or integrated patterning of development.3 The exact gene or combination of genes will depend on the level of disorganization deemed essential to fulfill the moral criteria of this project.

Many Americans believe that a decent society should not build the foundations of its biomedical science on the intentional creation and destruction of human embryos. Such a view is consistent with the enduring traditions of our profession, encoded in the Hippocratic oath and extended in the 1948 Declaration of Geneva, which explicitly states, “I will maintain the utmost respect for human life, from the time of conception.” Altered nuclear transfer is not a “distraction” or a “diversion of resources” as stated by Melton et al., but a morally reasonable and technologically feasible proposal that honors the important human goods being defended by both sides of this difficult debate.

William B. Hurlbut, M.D.
Stanford University, Stanford, CA 94305

3 References
  1. 1

    Hurlbut WB. Altered nuclear transfer as a morally acceptable means for the procurement of human embryonic stem cells. Washington, D.C.: President's Council on Bioethics, December 2004. (Accessed February 24, 2005, at http://www.bioethics.gov.)

  2. 2

    Melton DA, Daley GQ, Jennings CG. Altered nuclear transfer in stem-cell research -- a flawed proposal. N Engl J Med 2004;351:2791-2792
    Full Text | Web of Science | Medline

  3. 3

    Chawengsaksophak K, de Graaff W, Rossant J, Deschamps J, Beck F. Cdx2 is essential for axial elongation in mouse development. Proc Natl Acad Sci U S A 2004;101:7641-7645
    CrossRef | Web of Science | Medline

Author/Editor Response

We did not misunderstand Hurlbut's proposal. We focused on CDX2 because this is the example that Hurlbut offered, but our point was more general. To repeat: “We see no basis for concluding that the action of CDX2 (or indeed any other gene) represents a transition point at which a human embryo acquires moral status.”

Hurlbut now acknowledges that “the exact gene or combination of genes will depend on the level of disorganization deemed essential to fulfill the moral criteria of this project.” Deemed essential by whom? In retreating from his earlier argument (a pseudoscientific one, in our view) that CDX2 meets these moral criteria, he implicitly concedes our point that there is no scientific basis for resolving this issue, or for determining the moral status of embryos disrupted at different stages by different mutations. We, therefore, remain unpersuaded that Hurlbut's proposal will quell the public debate. Moreover, we completely reject his implication that embryonic stem-cell research aimed at understanding fundamental human biology and curing serious diseases threatens to undermine the foundations of a decent society.

Douglas A. Melton, Ph.D.
George Q. Daley, M.D., Ph.D.
Charles G. Jennings, Ph.D.
Harvard Stem Cell Institute, Cambridge, MA 02138

Citing Articles (7)

Citing Articles

  1. 1

    J. Suaudeau. (2011) From embryonic stem cells to iPS - an ethical perspective. Cell Proliferation 44, 70-84
    CrossRef

  2. 2

    Guangming Wu, Luca Gentile, Jeong Tae Do, Tobias Cantz, Julien Sutter, Katherina Psathaki, Marcos J. Araúzo-Bravo, Claudia Ortmeier, Hans R. Schöler. (2011) Efficient Derivation of Pluripotent Stem Cells from siRNA-Mediated Cdx2 -Deficient Mouse Embryos. Stem Cells and Development 20:3, 485-493
    CrossRef

  3. 3

    Svetlana Gavrilov, Donald W. Landry. 2011. Ethics in Regenerative Medicine. , 401-408.
    CrossRef

  4. 4

    Giuseppe Testa. (2008) Stem Cells through Stem Beliefs: The Co-production of Biotechnological Pluralism. Science as Culture 17:4, 435-448
    CrossRef

  5. 5

    Philippe Taupin. (2007) Stem cells engineering for cell-based therapy. Journal of Neural Engineering 4:3, R59-R63
    CrossRef

  6. 6

    JOHN R. MEYER. (2006) EMBRYONIC PERSONHOOD, HUMAN NATURE, AND RATIONAL ENSOULMENT. The Heythrop Journal 47:2, 206-225
    CrossRef

  7. 7

    Michele Boiani, Hans R. Schöler. (2005) Developmental cell biology: Regulatory networks in embryo-derived pluripotent stem cells. Nature Reviews Molecular Cell Biology 6:11, 872-881
    CrossRef