on behalf of the U.S. Conference of Catholic Bishops
before the President's Council on Bioethics
June 12, 2003
Subject: Embryo Research and Related Issues
Appendix: Modern Embryology And The "Pre-Embryo"
A decade ago, many biologists (and philosophers and theologians who relied on their theories) believed there was a qualitative difference between the embryo less than fourteen days old and all subsequent stages of development.1 The early embryo was dubbed a "pre-embryo" by some textbooks.2
Today, however, this approach is largely abandoned. Some textbooks that once used "pre-embryo" have quietly dropped the term from new editions, now describing the newly fertilized zygote simply as an embryo and therefore as the beginning of a new human individual.3 Other experts openly dismiss the term "pre-embryo" as "discarded" and "inaccurate."4 Professor Lee Silver, a staunch proponent of embryo research and human cloning, has given perhaps the most startling testimony on this point:
I'll let you in on a secret. The term pre-embryo has been embraced wholeheartedly by IVF practitioners for reasons that are political, not scientific. The new term is used to provide the illusion that there is something profoundly different between what we nonmedical biologists still call a six-day-old embryo and what we and everyone else call a sixteen-day-old embryo.The early embryo was once dismissed as a mass of interchangeable and undifferentiated cells -- capable at any point of splitting into two or more embryos (hence without inherent individuality) -- and largely formless until the appearance of the "primitive streak" at around fourteen days (hence without spatial orientation).
The term pre-embryo is useful in the political arena – where decisions are made about whether to allow early embryo (now called pre-embryo) experimentation – as well as in the confines of a doctor's office, where it can be used to allay moral concerns that might be expressed by IVF patients. "Don't worry," a doctor might say, "it's only pre-embryos that we're manipulating or freezing. They won't turn into real human embryos until after we've put them back into your body."5
However, it now seems that an embryo's potential for spontaneous "twinning" is established very early, perhaps by factors determining the thickness and integrity of the zona pellucida – so that the vast majority of embryos, from the outset, do not have the active potential to produce twins spontaneously.6
Moreover, it now seems that the mammalian embryo's spatial orientation is largely determined during the first days of development, perhaps by signals in the outer cell wall or trophoblast.7 The most recent findings based on mouse embryos even suggest that "two axes of the blastocyst become specified in the single-cell embryo" -- that is, that the embryo's axes determining right and left, up and down, are determined by the point where a sperm first penetrates the egg, and that important patterning information for this event may already be present in the egg before fertilization.8
Differentiation into cells with different roles and functions also begins with the very first cell division of the early mammalian embryo. These first two cells already have different roles in embryonic development – with one largely devoted to making the embryo proper, the other to developing the support structures (placenta etc.) needed for long-term survival.9 Further development proceeds from this first differentiation along a definite plan – with one of the two cells dividing first, in accord with its distinct function, so that the embryo develops three cells, then four, then eight, and so on. At each stage this is no mere colony or aggregate of cells – much less a mere envelope full of genes – but an integrated, developing organism of our species.
So radically different are our new findings about the embryo that a major science journal notes that they were "heresy" only a few years ago. Human and other mammalian embryos were once thought to become organized and give their constituent cells definite fates only after implantation in the womb; now it is found that the embryo begins differentiation, and develops a "top-bottom axis" guiding future development almost immediately after conception. The journal notes that from now on, "developmental biologists will no longer dismiss early mammalian embryos as featureless bundles of cells."10
New discoveries suggesting the possibility of human cloning may further adjust our perceptions of the embryo. It may be that each cell of a very early embryo can artificially be induced to split off and produce a new, genetically identical embryo -- but it seems that, with some additional manipulation, so can each cell of our adult bodies. And if the embryo's cells are "undifferentiated" enough not to be permanently committed to any particular type of cell, it increasingly appears that the same is true of our adult stem cells -- and perhaps even of our completely differentiated body cells -- under appropriate conditions.11 In short, if an organism's ability to "twin," or its cells' ability to dedifferentiate, is an indication that the organism is not a human individual, then it seems none of us are human individuals.
Some ethicists have seized upon the fact that the destruction of an embryo can produce relatively undifferentiated stem cells in culture. They assume this means the cells were interchangeable and without direction when they were part of the intact embryo. This is simply a fallacy. The fact is that these cells respond promptly to changes in their environment. If they are ripped out of the developmental context in which they played a role within an organized whole, they can (as it were) lose their sense of direction and revert to a less specialized state. As the National Institutes of Health's report on stem cell research notes, however, it is probably misleading to say that pluripotent stem cells exist in the living embryo. Rather, pluripotent stem cells "develop in tissue culture after they are derived from the inner cell mass of the early embryo..."12
This ability to revert to a more versatile state seems to be an effective survival mechanism, an important reason why human embryos are so resilient in the face of threats from their environment. They can respond to a loss of one or more cells by compensating, because their progressive differentiation is not yet "locked in stone" even to the (limited) extent that adult cells are.
The picture of the early human embryo emerging from modern science is that, from the very beginning, this is a living, organized, developing being. Many landmarks of development occur at later stages, but these are anticipated and even, to a large extent, determined by what occurs at the very beginning of human development. No such landmark provides a non-arbitrary way to divide this first stage of development from all others in order to justify harmful experimentation on the early embryo.
1. See T. Shannon and A. Wolter, "Reflections on the Moral Status of the Pre-Embryo," Theological Studies 51 (1990), pp. 603-26.
2. See K. L. Moore and T.V. Persaud, The Developing Human, 5th ed. (Philadelphia: W.B. Saunders, 1993), p. 37.
3. See K. L. Moore and T.V. Persaud, The Developing Human, 6th ed. (Philadelphia: W.B. Saunders, 1998), p. 2. Another widely used textbook notes: "Almost all higher animals start their lives from a single cell, the fertilized ovum (zygote)... The time of fertilization represents the starting point in the life history, or ontogeny, of the individual." B. M. Carlson, Patten's Foundations of Embryology, 6th ed. (New York: McGraw-Hill, 1996), p. 3. For additional citations see USCCB Secretariat for Pro-Life Activities, "What Is An Embryo?", www.usccb.org/prolife/issues/bioethic/fact298.htm.
4. Two leading experts now list "pre-embryo" among "discarded and replaced terms" in modern embryology, saying that it is "ill-defined and inaccurate." R. O'Rahilly and F. Müller, Human Embryology & Teratology, 2nd ed. (New York: Wiley-Liss, 1996), p. 12. The authors note: "Although life is a continuous process, fertilization is a critical landmark because, under ordinary circumstances, a new, genetically distinct human organism is thereby formed." Ibid., p. 8.
5. L. Silver, Remaking Eden: Cloning and Beyond in a Brave New World (New York: Avon Books, 1997), p. 39.
6. M. Alikani, et al., "Monozygotic Twinning in the Human Is Associated with the Zona Pellucida Architecture," 9 Human Reproduction (1994), pp. 1318-21.
7. R. L. Gardner, "The Early Blastocyst is Bilaterally Symmetrical and its Axis of Symmetry Is Aligned with the Animal-Vegetal Axis of the Zygote in the Mouse," 124 Development (1997), pp. 289-301; R. Beddington and E. Robertson, "Axis Development and Early Asymmetry in Mammals," 97 Cell (1999), pp. 195-209.
8. K. Piotrowska et al., "Role for Sperm in Spatial Patterning of the Early Mouse Embryo," 409 Nature (2001), pp. 517-21; R. L. Gardner, "Specification of Embryonic Axes Begins Before Cleavage in Normal Mouse Development," 128 Development (2001), pp. 839-47; R. L. Gardner, "Thoughts and Observations on Patterning in Early Mammalian Development," 4 Reproductive Biomed Online (Supp. 1) (2002), pp. 46-51.
9. K. Piotrowska, et al., "Blastomeres Arising From the First Cleavage Division Have Distinguishable Fates in Normal Mouse Development," 128 Development (2001), pp. 3739-48.
10. H. Pearson, "Your Destiny, From Day One," 418 Nature (4 July 2002), pp.14-5.
11. It is now known that any body cell's nucleus can be reprogrammed to form the basis for a new embryo by placement into an enucleated egg (somatic cell nuclear transfer cloning). There are many recent successes in redirecting adult stem cells to form other cell types -- see, for example, D. Josefson, "Adult Stem Cells May Be Redefinable," 318 British Medical Journal (1999), p. 282; E. Mezey et al., "Transplanted bone marrow generates new neurons in human brains," 100 Proceedings of the National Academy of Sciences (2003), pp. 1364-9; R. Poulsom edt al., "Adult stem cell plasticity," in 197 Journal of Pathology (2002), pp. 441-56; L. Liang et al., "Somatic Epidermal Stem Cells Can Produce Multiple Cell Lineages During Development," in 20 Stem Cells (2002), pp. 21-31.
12. National Institutes of Health (NIH), Stem Cells: Scientific Progress and Future Research Directions (Dept. of Health and Human Services, June 2001), p. ES-9 (emphasis added).