Irving: Open Communication To Participants of the CBHD/NCCB Bioethics Stem Cell Coalition:
Setting the Record Straight Re Drs. Furton/Matthews-Roth's NCBC Website "Response" To Their Stem Cell Research Article


F. ISSUE:

The claim that certain cells in the early developing embryo are "fated" or irreversibly determined, is questioned by some human embryologists, and put in doubt by recent studies using human embryonic, fetal and adult stem cells.

-- Furton and Matthews-Roth: (quoting Pedersen et al) 'Thus outer cells can have inner descendants until the late morula/early blastocyst (32-cell stage), but cells remaining outside after the fifth cleavage division are restricted to a trophectoderm fate'. "They also state: 'The trophectoderm cells of the mouse blastocyst have descendants only in placental structures (chorion, ectoplacental cone, and trophoblast giant cells), whereas the inner cell mass cells give rise to the entire fetus, the anmion, yolk sac, and allantois, as well as to mesodermal components of the placenta." (par. 4, "Response") "... however, it should be noted that, as in the mouse, the yolk sac originates from the hypoblast, which in turn originated from the inner cell mass, not the trophoblast." (par. 5, "Response") "MM-R could find no references that trophoblast-derived cells formed any significant structures which are found in the human embryo or fetus proper." (par.5, "Response") (emphases added)

-- My response: This statement of Furton and Matthews-Roth (quoting Pedersen et al) is essentially stating that past a certain point in early human embryonic development, the cells of the developing embryo are permanently "fated" to be only involved in the development of the placental tissues or of the embryo proper and the fetal membranes. It is essentially a statement about final, irreversible differentiation.

However, alternative theories do not see these cells so "fated" and their eventual locations so irreversibly determined and "isolated". Thus, my comment suggesting that the "fates" of these two cell layers in the blastocyst is in concert with other alternative theories acknowledged in human embryology. Again, the point is to refute McCormick et al in their characterization of the blastocyst as a "pre-embryo" because of their perception of such "isolation" and "separation" between these two cell layers, and thus the lack of any permanent "developmental individuality" (i.e., lack of "personhood"). Nor is it so certain that the extraembryonic mesoderm derives from the embryo proper. In support of these statements, I quote from the following human embryology text books:

Furthermore, studies using stem cells, which until recently were thought to be permanently "fated" or differentiated (including adult stem cells), have demonstrated that this long-held dictum is no longer true. As reported in a recent article on adult stem cell research using mice:

In a bizarre experiment that demonstrates the surprising plasticity of the body's cells, scientists have converted mice's brain cells into blood cells ... [U]ntil now, the stem cells were thought to be committed to their own organ type and unable to cross over. ... A team of Italian and Canadian scientists, led by Angelo L. Vescovi ... in Milan, has now found that the neural stem cells can metamorphose into the blood-making stem cells of the bone marrow. ... The conversion of neural stem cells into blood cells is particularly surprising because brain and blood come from different germ layers created in the early embryo. ... The brain develops from the ectoderm and blood from the mesoderm. Dr. Vescovi's work defies the widely held assumption that cells in the three lineages are permanently committed to their fate. ... Dr. McKay said the new result showed that differentiation, the commitment of a cell to a specific fate, is not irreversible.4 (emphases added)

Such findings are also found in recent studies using both animals and humans, and have already been performed with human patients.5 It was also recently dramatically demonstrated in cloning experiments, e.g., as in the Dolly experiment and several other studies.

G. MAJOR MAJOR ISSUE:

The real over-arching issue in all of this is the CONSTANT AND COMPLETE CONTINUITY OF THE PHYSICAL DEVELOPMENT OF THE HUMAN BEING OVER TIME AS A UNIQUE DEVELOPMENTAL INDIVIDUAL. Once this is understood, then THERE CAN BE NO LEGITIMATE SCIENTIFICALLY JUSTIFIED ARGUMENTS FOR "PRE-EMBRYOS" OR FOR "DELAYED PERSONHOOD" -- and therefore no legitimate moral justification for using these tiny living human beings in experimental research.

I do think that McCormick and Grobstein -- as well as others -- have confused the issue by both overstating and understating in their claim that only the cells from the inner layer become the future fetus and adult, and that all the cells from the outer layer are discarded as the placenta, etc. Their POINT was philosophical, i.e., somehow, because of their own perceived "separation" or "isolation" between the inner and outer layers of the blastocyst, this translated for them into a scientific grounding for a philosophical claim -- i.e., that there was no "developmental individual" there yet -- i.e., a "person". Therefore, e.g., these early blastocysts were simply just "pre-embryos".

But scientifically, McCormick and Grobstein are incorrect when they paint this simplistic picture of the development of the early human embryo -- especially in their depiction of the blastocyst in this "isolated" way. Not only are there interchanges going on at the blastocyst stage, they are also leaving out the fact that some of the tissues and cells "outside" of, or external to the "embryo proper" -- which are also discarded after birth -- are actually derived from the inner cell mass of the embryo proper, and that some of these same cells are incorporated into the later fetus and adult. That is, if by "trophoblast layer" one is referring to all of the cells and tissues which are discarded after birth (as McCormick and Grobstein seem to be stating), then this is scientifically incorrect. Cells from the inner cell layer are also eventually discarded after birth (as Furton and Matthews-Roth have also accurately noted):

The real issue here should be the constant and unbroken developmental continuity and interaction between and among all of these cells, tissues and organs -- from the single-cell zygote to the adult human being. In order to refute the "isolationist" characterization of early human development by McCormick, Grobstein and others (and the moral philosophical claims which they argue follow from this characterization) -- even at the risk of loosing my readers -- I will end this "issue-analysis" with just a few further quotes (in addition to those above) from several human embryology textbooks which demonstrate the already known and extraordinary continuous interaction which takes place throughout all of human development:

There are other points I could raise but will not go into detail here, e.g., how Furton and Matthews-Roth simply restate my comments as if they were their own, yet to most readers unfamiliar with the science it might appear as if they were really arguing against me (I have given examples of that above). Or they simply evade my comments by distracting the readers with a totally different issue which is not even relevant to my original comments. For example, in responding to my point that there are methods of cloning other than nuclear transfer, they simply remark that parthenogenesis has never been successful in humans (par. 8, "Response")! The point was not whether or not parthenogenesis has ever been successful in humans; the point was that restricting their definition of cloning to only nuclear transfer is erroneous. I pointed this out because too many people -- even scientists who are not human embryologists -- are beginning to think that there is only one way to clone. This error has already been incorporated in several state proposed statues to ban cloning -- where "cloning" is only as defined in terms of nuclear transfer. This would leave the door open for other methods of cloning to escape legislation (e.g., twinning, pronuclei transfer, back-breeding, or the use of human chimeras -- or, when the day comes, parthenogenesis).

Again, in response to my comment that a clone is not genetically identical to the donor because of the difference in mitochondrial DNA between the donor and recipient cell (the clone), they simply played down the significance of mitochondrial DNA (par. 8, "Response"). The issue is not whether or not mitochondrial DNA plays a major role here; the issue is that the DNA of a donor cell would be different than the DNA of the recipient cell (the clone) -- and therefore they would not be, as Furton and Matthews-Roth had stated, "genetically identical". It would also cause rejection reactions in patient recipients. Besides, mitochondrial diseases that are genetically based are being discovered fairly rapidly now and are often very lethal, so it would be significant as to whose mitochondrial DNA a clone would or would not receive.

In sum, I find the manner in which Furton and Matthews-Roth have operated in this situation with regards to their posting my private e-mail -- with deletions, additions, and changes in format -- on their web site, without my permission, as well as in the oblique manner in which they have responded to my scientific comments, to be rather "disingenuous". Furthermore, much of the human embryology they used in their original article as well as in their "Response" is still inaccurate and ill-founded, and could definitely be used by others to construct a "pre-embryo"-type argument which would justify the use of early human embryos in destructive experimental research -- including human embryonic stem cell research.

It is unfortunate that this situation has arisen, but I have found it necessary to respond and set the record straight in order to at least try to diminish the damage to which Furton and Matthews-Roth are apparently oblivious. And since I have no internet web site of my own or organization to publish my response, I can only try to reach those directly interested in the human embryonic stem cell debates via this e-mail. Hopefully it will help in some way to clear up some of the confusion. I would welcome any and all corrections, comments or suggestions.


Endnotes

1  The internet web site addresses for Furton and Roth's "special" article on stem cell research are the following:

(a) For Furton and Roth's original article on stem cell research (Part I) (about which I sent comments to colleagues in a private e-mail -but not to Furton, Roth, or the NCBC): http://www.ethicsandmedics.com/specials/9908-1.html.

(b) For Furton and Roth's rendition of my private e-mail on their internet web site: http://www.ethicsandmedics.com/specials/letter1.html.

(c) For Furton and Roth's "advertisement" of their web site special to respond to "an anonymous reader": http://www.ethicsandmedics.com/specials/stemcell1.html.

(d) For Furton and Roth's "Response" to the "anonymous reader": http://www.ethicsandmedics.com/specials/response1.html. [Back]

2 John M. Haas, taken from his review of The Human Development Hoax: Time To Tell The Truth!, University Faculty For Life Pro Vita, VI.1 Fall 1995. [Back]

3 Richard McCormick, S.J., "Who or what is the preembryo?", Kennedy Institute of Ethics Journal (1991), 1:1:3. [Back]

4 Nicholas Wade, "Cell experiment offers hope for tissue repair", The New York Times, Jan. 22, 1999, A21. See Christopher R.R. Bjornson, et al, "Turning brain into blood: A hematopoietic fate adopted by adult neural stem cells in vivo, Science (Jan. 22, 1999), 283:534-537. [Back]

5  For adult human stem cells studies describing their change to a different organ system, see, e.g.: (adult human cancerous gonadal cells become nerve cells in adult human patients) Daniel Q. Haney, "Scientists try to grow brain parts:, APNews, May 1, 1999; (fetal human neural stem cells put into mice become mice neural family cells) "Human neural stem cells advance distant prospect of reseeding damaged brain", Science Daily Magazine, Jan.26, 1999 (Source: Harvard Medical School). For adult animal stem cells studies describing their change to a different organ system, see, e.g.:(adult mice neural stem cells become mouse blood family cells) Christopher R. Bjornson et al, "Turning brain into blood: A hematopoietic fate adopted by adult neural stem cells in vivo", Science (Jan. 1999), 283:534-537; Deborah Josefson, "Adult stem cells may be redefinable", British Medical Journal, (Jan. 1999), 318:282; "Adult cells undergo identity switch reported in Science", Science Daily Magazine (Source: American Association For The Advancement Of Science); (adult rat bone marrow stem cells become rat liver cells and pancreatic cells) B.E. Petersen et al, "Bone marrow as a potential source of hepatic oval cells", Science (May 1999), 284:1168-1170 [bone marrow to liver cells only]; Paul Recer, "Cell used to make new liver tissue", The Washington Post, May 13, 1999 [bone marrrow to liver cells and pancreatic cells]; (adult vertebrate neural stem cells become neural family cells and other family cells , e.g., skin melanocytes and mesenchymal cells in the head and neck) M. Murphy et al, "Neural stem cells", Journal of Investigative Dermatology Symposium Proceedings 1997 (Aug.), 2:1:8-13.

For studies demonstrating adult human stem cells which differentiate to the same family of cells, see, e.g.: (adult human mesenchymal stem cells in bone marrow change to multilineage family cell line cells in vitro) Mark F. Pittenger, et al, "Multilineage potential of adult human mesenchymal stem cells", Science (April 2,1999), 284:143-146; Nicholas Wade, "Discovery bolsters a hope for regeneration: Biotechnology firm converts basic cells into bone and cartilage", New York Times, April 2, 1999, A17; August Gribbin, , "Stem-cell breakthrough offers hope; Baltimore team hailed for efforts", The Washington Times, April 2, 1996, A1.

For studies demonstrating adult stems that have been identifies in humans and animals, see, e.g.: (adult brain stem cells identified in monkeys and humans) "Rodent brain stem cells regenerate after stroke", UniSciScience and Research News, Feb. 8, 1999; (adult mouse brain stem cells identified) A. Gritti et al, "Multipotential stem cells from the adult mouse brain proliferate and self-renew in response to basic fibroblast growth factor", Journal of Neuroscience (Feb. 1996), 16:3:1091-1100; (adult mammalian neural stem cell identified) Clas B. Johansson et al, "Identification of a neural stemc cell in the adult mammalian central nervous system", Cell (Jan. 1999), 96:25-34; (adult mammalian forebrain neural stem cell identified) S. Weiss et al, "Is there a neural stem cell in the mammalian forebrain?", Trends in Neuroscience, (Sep. 1996), 19:9:387-93; (adult mammalian brain stem cells identified) O. Brustle and R.D. McKay, "Neuronal progenitors as tools for cell replacement in the nervous system", Current Opinions in Neurobiology, (Oct. 1996), 6:5:688-695.

For studies demonstrating the use of adult human stem cells in human patients, see, e.g.: Mark Moran, "For cell transplants, is one brain better than two?", American Medical News, May 3, 1999, p. 29; "Stem cells move closer to treating patients", UniSci, April 2, 1999; Laura Johannes, "Adult stem cells have advantage battling disease", The Wall Street Journal, April 13, 1999, B1; "The future of placental-blood transplantation", Editorials, The New England Journal of Medicine (Nov. 1998), 339:22:1628-1629; Alan W. Flake and Esmail D. Zanjani, "In utero hematopoietic stem cell transplantation", JAMA (Sept. 1997), 278:11:932-937. [Back]

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