The public has not been presented with the full spectrum of the issue of human embryonic stem cell research (hescr). In fact, as far as the public knows, the scientific community seems united in its support for hescr. But, this is not the case.
The American Association of Anatomists (AAA) has supported hescr for many years. However, attempts have been made to promote a dialogue on hescr with this organization; but, those attempts have been summarily rejected1,2.
In the rush to promote this research, which would involve the use of early human embryos, some of the basic tenets of human embryology have been violated.
First of all, there is no such cell as a human embryonic stem cell. This term has been equated with the blastomeres (cells) of the early human embryo3. This is incorrect.
By definition a stem cell is a partially differentiated cell, but not wholly differentiated. Virtually every tissue in the human body has its stem cells. In some tissues they are extremely difficult to identify. They are there to replace damaged or lost differentiated cells. There may be multiple factors which stimulate them to divide and proliferate. When they do, two daughter cells are produced, one which moves to a pool of differentiating cells, the other remains in the pool of stem cells, available to be stimulated again.
The key words "stem cell" first appear in the literature only in the 1960s4. In fact, Goodman and Hodgson, in 1962, may have been the first authors to use the term in scientific papers, and this identified stem cells in the peripheral blood of mice5. Prior to this, these cells were known in histology, but originally were identified by the terms "reparative cells" or "regenerative cells".
In the 1977 edition of the text "Histology" the term stem cell is indexed but refers only to the life cycle of blood cells6. However, in the text in the sections on skin and the gastrointestinal tract, it is stated that regenerative cells are present. In the 1983 edition of the same text the term is, again, indexed, but refers to "stem cells" in the skin (epidermis) and gastrointestinal tract7. There is a section in this edition on development and in this section there is no mention of stem cells.
In the 1989 edition of the text "Molecular Biology of The Cell" the term "stem cell" is indexed and refers to "embryonal stem cells" derived from placing the inner cell mass in culture. The resulting cells are called "stem cells"8. However, elsewhere in this text on the section on development, there is no mention of stem cells in the early embryo.
In Carlson's 1994 text on Human Embryology the text refers to "embryonic stem cells" as the cells of the early embryo that still retain the potential to develop into any cell type in the adult9. Yet, nowhere in the text is the inner cell mass nor any blastomere equated with stem cells. In Carlson's 2004 edition it is stated: "In embryos, stem cells can be derived from the inner cell mass (embryonic stem cells) or primordial germ cells"10. He states further: "Regardless of their origin, stem cells are maintained and propagated in an undifferentiated state (my emphasis) in culture".
In Larsen's 2001 text on Human Embryology, "Embryonic stem cells" only appears in the Glossary. It states: "arise from inner cell mass during in-vitro culture of blastocysts". But, in the text neither the inner cell mass nor the blastomeres are identified as "stem cells"11.
In a current text on Histology, used in many Medical Schools today, pluripotential stem cell (PPSC) identifies the hemopoietic stem cell. But, the term stem cell does not appear for the inner cell mass or for cells of the early embryo12.
The term "stem cell" has been commandeered to be equated with early human blastomeres and probably came about in the late 1980s or early 1990s. Another term which has appeared in the public discourse on stem cells is "Master Cells". As yet, no text which I have examined has included this term in its index. These terms have been related to the kind of media hype presently endured in the sense of "curing" devastating diseases, such as Alzheimers or Parkinsons.
There are many studies being carried out on so-called "stem cells", and many adult stem cells have been identified. Two major publications attest to this13,14. In addition to this, Thomson et.al developed methods for culturing what he termed as human embryonic stem cells15. However, whenever stem cells appear during development, or beyond, they would be de facto adult stem cells. They must be identified, isolated and characterized. Additionally, it should be observed when put into culture if these cells derive two different populations, as they do in vivo. There have been many culture studies, but all seem without direction toward isolating or defining the parameters of adult stem cells16. These studies are meritorious and are extremely important because they reveal some of the events involved in defining differentiation. But, placing blastomeres from the early embryo or the inner cell mass into culture, then characterizing the resulting definitive cells does not identify either the original blastomeres or the derived definitives as true stem cells.
It is not known when during human development stem cells first appear. Some may be differentiated (partially so) during the embryo age (before the end of the 8th week of development) or may appear during the fetal age (9 weeks or beyond), or after birth. No one knows. On this basis, no human embryonic stem cell has been identified; at least, not yet.
The most fascinating aspect of true stem cells is that they are partially differentiated, then are arrested in their resident tissue. The controls of this arrest are not known. They would undoubtedly involve identifying embryonic genes, such as Nanog17,18, and others, transcription factors, surface receptors, along with embryonic or fetal proteins, internalized activators or inhibitors, and other controls not yet known. Identifying these controls is a formidable task, but which must be done.
The promotion of using early human embryos as "stem cells" or to obtain so-called "stem cells" has led to the public debate over obtaining these wrongfully labeled blastomeres by killing human embryos; in fact, killing human life. Thus, to buttress the arguments for using early human blastomeres, for example, the many spare embryos preserved in IVF laboratories, stem cell research advocates have reduced the significance and value of human life to somewhat ridiculous levels, such as the small size of the early human embryo19,20, or, as some pundits claim, that life does not exist unless the embryo is implanted in the uterus21. Such claims have no scientific merit.
However, virtually every human embryologist states that the life of the new individual human being begins at fertilization22,23. This is the beginning of the continuum of life, and ends only with death, whenever that may occur. The failure of human embryologists to affirm these facts (they are not beliefs) has led to serious errors in the public discourse, such as a recent New Jersey Supreme Court decision on an abortion case, in which it was stated: "the court will not place a duty on doctors when there is no consensus in the medical community or among the public on when life begins"24.
Every human embryologist in the American Association of Anatomists ought to rise up in indignation at this court's statement, if for no other reason than there is consensus of virtually all human embryologists [22, 23].
The tenets of human embryology should be publicly endorsed. Political parsing of those tenets has been rampant and happening all too frequently for many years. But that is separate and apart from the scientific truths which are taught to all of our medical students by lecture and text. It is time to reclaim those tenets before it becomes too late.
The AAA should allow for a fair and balanced dialogue on hescr. It further should accept the fact that a true human embryonic stem cell has not been identified, at least, not yet.
C. Ward Kischer, Ph.D. is an emeritus professor of Cell Biology and Anatomy, specialty in Human Embryology, and former adult stem cell researcher, University of Arizona, College of Medicine, Tucson, Arizona. E mail: email@example.com
2 Kischer, C. W. 2006. The American Association of Anatomists and Stem Cell Research. Linacre Quarterly, 73:164-171. See also: Kischer, C.W.:Quid Sit Veritas, Revisited. Website: Life Issues.net. Posted: 2005. [Back]
3 Gilbert, S.F., A.L. Tyler and E.J. Zackin. 2005. Bioethics and The New Embryology. Pps. 8, 17, 144. Sinauer Associates, Inc. Sunderland, Mass. Many others, e.g. see Bodnar, M.S., J.J. Meneses, R. T. Rodriguez and M.T. Firpo. 2004. Propagation and Maintenance of Undifferentiated Human Embryonic Stem Cells. Stem Cells and Development. 13:243-253. Also, from Encyclopedia of Cancer and Society [currently in development], under a heading of Stem Cell Research: "Embryonic stem cells are defined as the inner cell mass of the blastocyst, or 3 to 5 day old embryo". Stated by J. Hellawell, Cornell University, School of Medicine. [Back]
15 Thomson, J.A., J. Itskovitz-Eldor, S.S. Shapiro, M.A. Waknitz, J.J. Swiergiel, V.S. Marshall and J.M. Jones. 1998. Embryonic stem cell lines derived from human blastocysts. Science, 282:1145-1147. [Back]
18 Chambers, I., D. Colby, M. Robertson, J. Nichols, S. Lee, S. Tweedie and A. Smith. 2003. Functional Expression Cloning of Nanog, a Pluripotency Sustaining Factor in Embryonic Stem Cells. Cell, 113:643-655. [Back]
20 Turley, Jonathan. 2006. "The case for macroscopic humans". USA Today, July 18th. Turley is a constitutional lawyer, yet, wrote as some sort of aficianado of stem cell research. He described the early human embryo as "barely perceptible" and, invoking a religious aspect, as "a type of holy dot". [Back]