This paper was written for “Public Speaking for Science & Citizenship”. Apart from the hilariously pretentious (yet accurate) name the class was very good, but as a public speaking class I didn’t produce much writing. Apart from reflections that make little sense outside of the course, and presentations that make no sense without a speaker, the only writing I produced was this paper.

Introduction

I vividly remember the excitement: my family had just gotten cable for the first time, and I had discovered the joys of CNN. Watching in August 2001, stem cells erupted into my mind (as into the public spotlight consciousness) when President Bush announced morally muddy guidelines for federal funding in stem cell research.

Federal funding could go towards research from 60 embryonic stem cell lines which had already been created, but future lines (which would require the destruction of more embryos) would not be eligible. But adult and fetal stem cells would be clear, and he promised $250 million in federal funds for this safe stem cell research. Seven years later, much has changed. We as a nation have learned more about what stem cells are and what they can do, and scientists have discovered new ways to obtain embryonic stem cells for research. This paper will serve to explain the basic science of stem cells to the reader before moving on to explore new techniques in obtaining embryonic stem cells, all while carefully discussing the ethics of the research involved.

Stem Cells in Vivo

Stem cells “are undifferentiated cells capable of both self-maintenance and differentiation into specialized cells” (Musina). An “undifferentiated” cell fulfills no direct bodily purpose: it is not a red blood cell or a bone cell or a neuron. Stem cells are self-maintaining: unlike other cells in the body they can undergo cellular division; when doing so they can differentiate into somatic cells (cells forming the body’s organs and tissues which do not reproduce) useful throughout the body. Following from this definition, all embryos are composed of stem cells. Differentiation is a slow process: stem cells first repeatedly produce less-potent stem cells, which produce “precursor cells” capable of producing only one cell after rapid cellular divisions.

As summarized in Jaenisch and Young, stem cells can be classified based on their potentiality — their ability to form different cells of the body. Totipotent stem cells can form the entire human body and are limited to no more than the first 8 cells in a human embryo. Pluripotent cells can form all the cells of the body (but not certain extracellular liquids and membranes); all embryonic stem cells are pluripotent. Adult stem cells are multipotent, meaning they can form multiple cell types from one. The fetal stem cells mentioned above are generally at a midway point between pluripotent embryonic stem cells and multipotent adult stem cells (Marcus and Woodbury).

As the body ages the stem cells become more specialized, and in post-natal humans only multipotent stem cells remain. These adult stem cells are responsible for maintaining the body and replacing dead cells, while embryonic stem cells are responsible for the creation of the human body, with all its organs and complexities.

Stem Cell Sources

Adult Stem Cells

Adult stem cells are not ethically troubling. Retrieved from willing donors, this research is comparable to research using blood or running organ transplants. The cells involved are capable of producing only limited kinds of cells and there is not a worry about cloning. Lack of concern in any area led President Bush to promise federal funding for adult stem cell research as described above.

Fetal Stem Cells

More recently, there has been increased interest in stem cells obtained from extra-fetal tissues, such as the amniotic fluid or placenta. Scientists have known about hematopoietic (blood) stem cells available in the umbilical cord since the eighties and have employed them in treatments since 1988 (Marcus and Woodbury), but there is increasing evidence of broadly multipotent stem cells in the amniotic fluid (Coppi et al) and other tissues (Marcus and Woodbury). Nonetheless, these stem cells are so far not truly pluripotent as in embryonic stem cells, and their exact nature and ease of extraction are still being determined.

Given that the tissues providing fetal stem cells are usually thrown away after birthing, there is little reason to think there will be any controversy surrounding their use.

Embryonic Stem Cells

The greatest controversy surrounding stem cell research has been about the research into embryonic stem cells. This is because of the traditional source for embryonic stem cells: the destruction of a 100 to 200-cell embryo in the blastocyst stage (President’s Council on Bioethics). Given this procedure, those who believe that protected human life begins at conception — as does the Roman Catholic Church — must condemn embryonic stem cell research as murder and profiting from murder (McLaren). There are also those who, like Anne McLaren herself, believe that human life is a continuum and that an embryo acquires human rights as it becomes more developed. In this case a moral calculus must be employed. In research, then, there is a trade: destroy the embryo and gain scientific knowledge to treat other humans in the future (expected benefits are outlined in the following section).

In order to make any determination about relative moral value, the alternative to embryo destruction in stem cell research must be explained. Currently, all embryos available for research are donated from fertility clinics as leftover embryos that will never be implanted into the woman whose DNA they carry. The alternatives in a fertility clinic are bleak: perpetual storage in a freezer or death by being removed from the conditions that support an embryo alone in the world (McLaren). McLaren clearly prefers useful scientific gun to pointless destruction (as does this author), but there are easy counterarguments to be made: the ethical problems of current fertility treatment programs do not excuse the ethically inacceptable destruction of embryos for scientific purposes.

Stem Cell Research Prospects

Scientists are publicly eager to conduct research on stem cells in the face of high hopes for medical treatments. Diseases and disorders including transverse melitis, amyotrophic lateral sclerosis, spinal muscular atrophy (Gross), type I diabetes, Parkinson’s disease, and spinal injuries are expected to be solved through stem cell research (Musina et al). Treatments have already been developed for various blood diseases — including leukemias and lymphomas — based on adult stem cells present in bone marrow. And Rando provocatively titles an article “Stem cells, ageing and the quest for immortality.” While it concludes that any such thing as anti-age stem cell treatments is a long way off, the very title implies that there is some hope for the distant future.

However, this research has been hampered by the federal regulations on stem cell funding. Federal funding is available only to the original 60 lines approved in 2001, and many of those have broken down or are in a form that is more difficult to use than modern lines (Gross). Funding is still available for adult stem cell research, but it holds less promise and provides more difficulties in transplant of stem cells from one individual to another (Drukker et al.).

Embryonic Stem Cell Research

In light of the ethical issues outlined above, researchers have devoted considerable effort to developing new techniques and sources that provide embryonic stem cells without the ethical issues involved in complete embryo destruction. Two of them are presented here: blastomere extraction via biopsy and somatic cell dedifferentiation.

Blastomere Extraction

Given that one of the principle issues in obtaining embryonic stem cells is that doing so requires the destruction of the embryo, an obvious attempt to work around the problem is to remove some embryonic stem cells without killing the embryo you are extracting them from. In October 2005, Chung et. al. published their article “Embryonic and extraembryonic stem cell lines derived from single mouse blastomeres” in Nature. The technique is based on biopsy procedures used in preimplantation genetic diagnosis, one of the checks by fertility clinics to ensure that embryos are healthy before implanting them in the mother.

After removing blastomeres from many mouse embryos using standard techniques, the research team had to perform two checks: ensure that the mouse embryos were unharmed, and that the blastomeres they had extracted would exhibit the proper signs of an embryonic stem cell. After implanting the embryos into mothers, they found that the embryos were carried to term. The blastomeres that had been extracted were subjected to a number of chemical tests and observed to see how they would differentiate into different types of cells, and many of them produced cells as expected from an embryonic stem cell. Not all were successful, leading the team to conclude that the position within the cell of the extracted blastomere is important, as is the exact treatment of the cells after extraction.

This procedure, once perfected, alleviates the primary concern with embryonic stem cell research: it does not require embryo destruction to obtain stem cells and increases the respect shown to the embryo for those who believe that a balance of respect is necessary. However, for those to whom an embryo is a protected human life, this is not sufficient. The procedure still amounts to forcible medical experimentation and surgery upon an unwilling patient. Abuse, while better than murder, is not ethically acceptable even for the medical benefits it brings. Moreover, the research necessary to perfect this technique will necessarily result in the destruction of embryos when errors are made, and this destruction will harm the procedure’s ethical acceptability: nobody likes to use tainted research (President’s Council).

Lastly, a blastomere extracted at the 8-cell embryo stage may still be totipotent (Denker). If this is the case, then blastomere extraction in fact creates a clone of the biopsied embryo and then proceeds to destroy that clone: an even worse ethical problem than the destruction of a single human embryo is the process of human cloning followed by the murder of that clone.

Somatic Cell Dedifferentiation

A far more desirable method of obtaining embryonic stem cells would be one that does not actually require embryos. Surprisingly, this method has appeared. Somatic cell dedifferentiation is a technique in which somatic cells (organ or tissue cells) or less potent stem cells of the body are induced to dedifferentiate back into a pluripotent state, first published by Takahashi and Yamanaka. Research has long made it clear that the process of differentiation does not destroy DNA sequences within the genome, and it was theoretically possible that under the right conditions a cell would dedifferentiate back into an earlier higher-potential state. In fact, this has been observed in living organisms. By employing retroviral activation of certain gene sequences responsible for RNA known to influence potentiality, the team was able to create induced pluripotent stem cells from mouse fibroblasts (fibroblasts are connective tissue cells; they are well understood and a typical cell to use in such experiments). The resulting cells did not mimic embryonic stem cells precisely, but they displayed many of the same markers. Further research by a variety of teams has gone on to create induced pluripotent stem cells that are indistinguishable from embryonic stem cells (Jaenisch and Young).

Ethically, this procedure is difficult to worry about. The stem cells involved are donated by a conscious, willing adult subject and, in their natural habitat, would die in a relatively short amount of time. Because they are induced to their pluripotent state (and not to a totipotent state), there is no concern that use of such cells constitutes the destruction of an otherwise healthy individual or the cloning of a living human. Moreover, this method of stem cell production is ideal for therapeutic treatments: each patient can be given stem cells produced from their own genetic material.

Stem Cells in the Future

Stem cell research is becoming increasingly accepted among the American public (Heath) and the ethical issues involved are rapidly being sidestepped and made irrelevant thanks to positive scientific advances. We can look forward to embryonic stem cell research providing our society great benefits without the use of embryos. As a result, it is likely that the ethical debate over stem cell research will probably disappear in the relatively near future.

Works Cited

Anne McLaren. 2007. A Scientist’s View of the Ethics of Human Embryonic Stem Cell Research. Cell Stem Cell 1, no. 1:23-26.

Chung et al. 2005. Embryonic and extraembryonic stem cell lines derived from single mouse. Nature 439:216-19.

Coppi et al. 2007. Isolation of amniotic stem cell lines with potential for therapy. Nature Biotechnology 25, no. 1:100-106.

Drukker et al. 2006. Human Embryonic Stem Cells and Their Differentiated Derivatives Are Less Susceptible to Immune Rejection Than Adult Cells. Stem Cells 24, no. 2:221-229.

Erin Heath. 2005. Will Stem Cell Policy Evolve? BioScience 55, no. 12:1040.

H.W. Denker. 2006. Potentiality of embryonic stem cells: an ethical problem even with alternative stem cell sources. Journal of Medical Ethics no. 32:665-71.

Jaenisch, Rudolf and Richard Young. 2008. Stem Cells, the Molecular Circuitry of Pluripotency and Nuclear Reprogramming. Cell 132, no. 4:567-82.

Liza Gross. 2007. Stem Cell Promise, Interrupted: How Long Do US Researchers Have to Wait? Public Library of Science Biology 5, no. 1:6-9.

Marcus, Akiva J. and Dale Woodbury. 2008. Fetal stem cells from extra-embryonic tissues: Do not discard. Journal of Cellular and Molecular Medicine Postprint. http://www.blackwell-synergy.com/action/showPdf?submitPDF=Full+Text+PDF+%28862+KB%29&doi=10.1111%2Fj.1582-4934.2008.00221.x (Accessed April 25, 2008).

Musina et al. 2004. Stem Cells: Properties and Prospective Medical Applications. Molecular Biology 38, no. 4:469-81.

Takahashi, Kazutoshi and Shinya Yamanaka. 2006. Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell 126, no. 4:663-76.

The President’s Council on Bioethics. 2005. Alternative Sources of Human Pluripotent Stem Cells. http://www.bioethics.gov/reports/white_paper/alternative_sources_white_paper.pdf (Accessed April 21, 2008).

Thomas A. Rando. 2006. Stem cells, ageing and the quest for immortality. Nature 441:1080-1086.