Common Ground on Stem Cell Research
A Position Statement by Ken Yeh, 2011 The debate over embryonic stem cell research (ESCR) is commonly framed by pitting those who oppose the use of human embryos for research against those who seek to find new treatments and cures for diseases plaguing millions of people. But this is a misleading representation of the first position, for it implies that those who oppose embryo destructive research are not just as concerned for the possibility of helping sick people. Those who take a "pro-life" position can and should take into careful consideration the real suffering of people living with diseases, in addition to the life of the unborn. Those who take a stand against ESCR are sometimes compared to people who opposed organ transplantation when this first became medically possible. But this baseless accusation completely misses the primary point of contention of those who oppose ESCR, which is not opposition to the use of stem cells per se for research and medicine; rather, it is an objection to some of the proposed sources of embryonic stem cells. I for one have no qualms about organ transplantation—I am a registered donor myself—but what I would vigorously oppose, and so too would the majority of those who support organ transplantation, is any donation program that involved actively killing a living human being in the process of procuring organs for another person. In the same way my opposition to ESCR is primarily a stand against the active killing of human embryos—which I consider to be nascent human life—in the course of harvesting embryonic stem cells. I have no opposition to any form of stem cell research that does not involve the active destruction of human life; in other words, my position is solely against embryo-destructive research. A combined biological, medical, moral, and metaphysical case can be made for the position that the life of a human being begins at conception. In addition, refutations are readily available in response to arguments and claims that seek to dehumanize the human embryo.1 Taken together, I believe a strong reasonable basis exists for declaring that embryo destructive stem cell research should not be pursued because it intentionally ends human life in its most helpless and vulnerable form. At the very least, these arguments and evidences raise reasonable doubt against being able to claim with certainty that destroying an embryo does not end the life of a human being. Continuing with embryo destructive research without knowing for certain that these embryos are not living human beings would be as irresponsible as continuing with the demolition of a building when there are reasons to think that there may still be people inside the building who are unaware of the danger. However, I understand that not all will be convinced by these arguments for the humanity of embryos used in ESCR. There are also those who accept that these embryos are indeed living human beings, but the very real suffering of millions of people overshadows any concerns about the use of human life as a means to an end. What few in the arena of public opinion realize is that procuring treatments and knowledge through stem cells and preserving the value of human life in embryonic form need not be seen as mutually exclusive choices, as if we can only choose one or the other. The significant question is how are we going to obtain the stem cells to save and treat those with diseases: by using stem cells derived from the destruction of living embryos, or by stem cells derived by non-destructive means. It is my belief that recent breakthroughs in stem cell research mean it is possible to accomplish everything that people hope would have been possible with embryonic stem cells, but without the destruction of any more living embryos.
What I propose is a "common ground" position that I believe can be advocated by all, regardless of one's individual view of the moral worth of embryos. This solution is founded upon two relatively recent breakthroughs which promise to provide sources for pluripotent stem cells that do not involve the active destruction of embryos. The first breakthrough was the creation in 2007 of human induced pluripotent stem cells (iPSCs). Three separate teams of researchers announced that they had unlocked the means to generate iPSCs by "reprogramming" human somatic cells (taken from a small skin biopsy) back into stem cells, with the same potential for pluripotency as that exhibited by stem cells extracted from embryos. The key to cellular reprogramming was uncovered by Shinya Yamanaka just a few years earlier using mice, a discovery which will likely win him the Nobel prize. Since that time, advances using iPSCs have dramatically outpaced embryonic stem cell research due to the greater ease and efficiency of generating iPSCs compared to ESCs. Whereas only a handful of labs have the equipment and expertise to do the somatic cell nuclear transfer required to generate patient specific embryonic stem cells, hundreds of research labs are currently equipped to work with iPSCs. In the past several years, numerous studies conducted by research teams around the world have shown the efficacy of these induced pluripotent stem cells. Recent advances include increases in the safety and efficiency in producing iPSCs,2 safer ways to generate iPSCs without the application of retroviruses initially used to introduce the genes needed to do the cell reprogramming—an essential development for the formation of safely transplantable tissues using iPSCs,3 and the successful generation of diseasespecific cell lines4 to study the progression of a number of debilitating diseases, including Parkinson's disease, Huntington's disease, type I diabetes, and ALS (Lou Gehrig's disease)5. These cell lines were created from iPSCs generated from patients who had each specific disease, and they will allow researchers to study the pathology of each disease as well as test possible drugs and treatments. 6 Describing the creation of disease-specific cell lines, Harvard Stem Cell Institute director Doug Melton stated, "The suite of iPS cell lines reported by the Daley group marks an important achievement and a very significant advance for patients suffering from degenerative diseases. These disease-specific iPS cells are invaluable tools that will allow researchers to watch the development of diseases in petri dishes, outside of the patients. And we have good reason to believe that this will make it possible to find new treatments, and eventually drugs, to slow or even stop the course of a number of diseases. In years ahead this report will be seen as opening the door to a new approach to develop therapies."7 James Thomson, the researcher whose team was the first to isolate embryonic stem cells, stated in the seminal study that produced the first human iPS cells, “The human iPS cells described here meet the defining criteria that we originally proposed for human ES cells, with the notable exception that the iPS cells are not derived from embryos. Similar to human ES cells, human iPS cells should prove useful for studying the development and function of human tissues, for discovering and testing new drugs, and for transplantation medicine. For transplantation therapies based on these cells, with the exception of autoimmune diseases, patient specific iPS cell lines should largely eliminate the concern of immune rejection.” 8 In a sense, iPSCs are like the biological equivalent of being able to turn lead into gold; why continue the effort of digging gold mines and extracting the bits of gold from rock when it is much easier and more effective to generate gold from lead? The conclusion of a significant number of researchers, including Thomson, Yamanaka, and Ian Wilmut—
who pioneered the use of somatic cell nuclear transfer to clone Dolly the sheep—is that iPSCs offer the greatest potential for actual clinical use of stem cells in therapy. 9 These researchers are focusing exclusively on developing medical treatments and research using iPSCs. But with the rapid advances being made using iPSCs, why is research using embryonic stem cells still being conducted? A detailed treatment of the reasons is beyond the scope of this essay, but it involves a complicated mix of science, money, public opinion, and even politics. In my opinion, there are sufficient responses that call into question whether these reasons provide sufficient justification for continued ESC research.10 However, the purpose of this paper is to raise consensus towards a common ground solution. It is sufficient to note that a number of researchers do believe that embryonic stem cell research needs to continue, even with the promise of iPSCs. The question then is: are there other ways to acquire embryonic stem cells that do not decrease the value of human life for those who consider an embryo to be nascent human life? In other words, can embryonic stem cells be harvested in sufficient quantity and quality for the purpose of research without requiring the additional destruction of living embryos? The common ground solution may be found in this second breakthrough, which is the discovery that embryonic stem cells may be derived from arrested development embryos.11 The seminal paper that sparked this line of inquiry was written by Donald Landry and Howard Zucker and titled, "Embryonic death and the creation of human embryonic stem cells."12 Landry and Zucker proposed a definition of death that could be applied to human life in embryonic form, much like the cessation of brain waves is currently used to establish clinical death for fully developed human beings. This definition is critical for determining when a person's organs may be rightfully transplanted into another person; too early and the risk is that the procedure to harvest the organs is actually killing the person; too late and the cells of the organs will have expired, rendering the organ useless for transplantation. Landry and Zucker clarify that the cessation of brain waves is not what actually defines death, rather, "For a developed human organism, brain death marks the irreversible loss of the capacity for all ongoing and integrated organic functioning."13 Death is therefore defined as the point at which the organism ceases to function as an integrated whole. Dr. Maureen L. Condic elaborates on this distinction in her essay, “Life: Defining the Beginning by the End,” The critical difference between a collection of cells and a living organism is the ability of an organism to act in a coordinated manner for the continued health and maintenance of the body as a whole. It is precisely this ability that breaks down at the moment of death, however death might occur. Dead bodies may have plenty of live cells, but their cells no longer function together in a coordinated manner. We can take living organs and cells from dead people for transplant to patients without a breach of ethics precisely because corpses are no longer living human beings. Human life is defined by the ability to function as an integrated whole—not by the mere presence of living human cells.14 She goes on to describe how an embryo, even though it is merely a small collection of cells, does exhibit this ability to function as an integrated whole and therefore should be considered a human life. Landry and Zucker then suggest that this definition of organismic death can be applied to distinguish between organismically dead and living embryos, thus possibly drawing a line for when it would be morally acceptable to harvest stem cells from an embryo. They conclude in this paper,
If the donation of embryonic cells from organismically dead embryos is considered as analogous to the donation of essential organs from cadavers, the result could be widespread acceptance of the use of such cells for research and development…. In sum, application of the ethical framework for essential organ donation to the harvesting of human embryonic cells from dead embryos could provide a common ground in which the imperative to safeguard human dignity and the drive for biomedical research are not in conflict. 15 Landry and Zucker followed up this initial proposal with an actual research study 16 to determine clinical criteria for establishing organismic death in embryos. They observed the development and cellular division of a statistically significant number of embryos from an established IVF clinic. From their results they concluded that there was a clearly observable and biologically significant difference in "arrested development" embryos, which had ceased to continue the normal course of development by day 5. From the study: Based on these data, we propose that hypocellularity and lack of compaction on ED5 constitute a set of criteria for diagnosing an irreversible arrest of normal development for human embryos and, in direct correspondence to the paradigm for brain death, are sufficient criteria for the diagnosis of death. The human embryo satisfying these criteria has died as an organism even if certain individual cells remain alive. The adequacy of these criteria rests on this central finding: no such ED5 embryo ever developed into a normal blastocyst with an inner cell mass.17 In follow-up studies,18 researchers determined that viable ESC lines could still be extracted from these “arrested embryos,” which had stopped the process of cleavage and development. These would not be the embryos that are still potentially viable if given the chance to implant; these would be the ones that are determined to be organismically dead. They have stopped developing, and even if inserted into a womb they would never implant and develop into a baby. This would be akin to parents of children who have died donating their organs and tissues to further research. The critical distinction is that the embryo is already dead from natural causes before its cells are harvested, rather than being killed by the act of harvesting the cells. There are still some critical questions that need to be answered regarding this technique, such as whether these arrested embryos would have actually stopped growing if they had been placed in a woman's womb rather than remaining in a petri dish, as well as concerns that these arrested embryos carry currently undetected defects that render them unusable for therapy. But it seems to me that for the purposes that have been proposed for why embryonic stem cells are still needed for research that stem cells from these already dead embryos would, in Landry and Zucker's words, "provide a common ground in which the imperative to safeguard human dignity and the drive for biomedical research are not in conflict." Suppose someone asks you not to take a certain drug from one pharmaceutical company because that company uses animal testing to produce this drug. Instead, the person asks you to use a drug that provides all the same benefits from another company that does not require animal testing to produce the drug. Would you accuse this person of caring more about the treatment of animals than about your health? Even though you may not share this person’s values regarding the treatment of animals, it would at least be fair to say that the importance that this person places on the value of animals does not impinge upon your means of obtaining relief by using this drug; that is, the beneficial result can be the same, the only distinction is in the source of that drug.
It is indeed important to conduct research that will lead to better understanding of our bodies and treatments for the diseases that many of us suffer from. At the same time, I also value the life of the unborn. If the end result is the same (pluripotent stem cells), does it matter where researchers obtain those stem cells from? For those who do not assign much value to embryos, it should not matter. But to those who do assign value to embryos, it matters a great deal. It is the difference between letting a terminally ill patient die first before using his or her body for research versus doing research on that person which actually kills the patient. Though the end result may be the same--the patient dies, and the body is used for research—there is a moral distinction to me whether that person died from his disease or was killed by the researcher. My concern is that the taking of a human life, even when it is just a small mass of cells or an embryo, in the name of research devalues the dignity of all human life. The decision to take a life, even when it may help save a life, should never be taken for granted, especially if there are alternatives that do not require the taking of life at all. I do believe that we all share a desire to respect the dignity of life; for me, this respect is expressed in my desire to protect human life when it is at what I consider to be its most fragile and insignificant stage of development, when it is just a mass of growing cells. To allow researchers to destroy embryos for stem cells will I fear prepare the way for an even greater acceptance of the use of humans in the earliest and most fragile state of development as simply a useful commodity. It seems to me that this is one of the rare moments in the history of science where we can both have our cake and eat it at the same time. That is, we can have all the benefits that can come from embryonic stem cell research but without actually requiring any more embryos to be destroyed for this research, and that is a breakthrough that I think we can all celebrate, regardless of your view about the moral status of embryos.
For example, in response to the "Acorn and Oak tree analogy" read Robert P. George and Patrick Lee, “Acorns and Embryos,” published in The New Atlantis, Fall 2004-Winter 2005, http://www.thenewatlantis.com/publications/acorns-and-embryos
"Highly Efficient Reprogramming to Pluripotency and Directed Differentiation of Human Cells with Synthetic Modified mRNA," Cell Stem Cell (30 Sept. 2010) http://www.cell.com/cell-stemcell/retrieve/pii/S1934590910004340 "Safer Way to Make Induced Pluripotent Stem Cells Developed," ScienceDaily (2 Feb. 2011), http://www.sciencedaily.com/releases/2011/02/110201172907.htm “Disease specific induced pluripotent stem cells” Cell (Volume 134, Issue 5, 877-886, 5 September 2008), http://www.cell.com/abstract/S0092-8674%2808%2901001-5
5 4 3
"Induced Pluripotent Stem Cells Generated from Patients with ALS Can Be Differentiated into Motor Neurons," Science (29 August 2008), http://www.sciencemag.org/content/321/5893/1218.abstract "A Stem Cell Revolution," Technology Review, (27 Aug. 2008) http://www.technologyreview.com/biomedicine/21307/?a=f
"Using iPS cells to create disease models," Harvard Stem Cell Institute, http://www.hsci.harvard.edu/newsroom/using-ips-cells-create-disease-models-0
Science (21 December 2007), http://www.sciencemag.org/cgi/content/abstract/1151526
See the following online article from the May 2010 issue of Scientific American magazine for a detailed summary of the research being conducted using induced pluripotent stem cells: http://www.scientificamerican.com/article.cfm?id=your-inner-healers. You can also view an interactive multimedia presentation of the article here: http://www.scientificamerican.com/article.cfm?id=interactive-yourinner-healers
For example, one of the most common reasons given by those who continue advocating for ESCR is that embryonic stem cells remain the “gold standard” by which all stem cells should be measured against, and that without embryonic stem cell lines to compare researchers would not be able to judge the efficacy of other forms of stem cells. However, upon closer consideration, this does not seem to provide sufficient justification for continuing to create new embryonic stem cell lines. It would be odd if automotive journalists rated the quality of a particular car on the basis of how precisely it duplicates a Mercedes Benz. A Mercedes may indeed be an example of a fine automobile, but only insofar as it measures up to various independent criteria for establishing the quality of a car. Similarly, the proper measure of the value of induced pluripotent stem cells and other alternatives to embryonic stem cells is not how closely they resemble ESCs, but rather how efficacious they are in realizing the full potential uses of stem cells. Considering that iPSCs have already advanced beyond ESCs in the progress towards viable medical treatments and better understanding of diseases, it seems to me that maintaining ESCs as the “gold standard” for stem cells is a step backwards. The true goal of stem cell research is achieving these medical breakthroughs, not duplicating embryonic stem cells. ESCs may have been the first derived pluripotent stem cells, but this does not mean that they are the best. If the actual forms of treatments that provide the means to cure and help people look nothing like embryonic stem cells, that would not be considered a loss at all. "Naturally dead embryos yield stem cells," Nature (21 Sept. 2006) http://www.nature.com/news/2006/060918/full/news060918-10.html
Landry, Donald, and Howard Zucker, "Embryonic death and the creation of human embryonic stem cells,"The Journal of Clinical Investigation (Volume 114, Issue 9, 1 Nov. 2004), http://www.jci.org/articles/view/23065
ibid. p. 1185.
Condic, Maureen L., “Life: Defining the Beginning by the End,” First Things (May 2003), http://www.firstthings.com/article.php3?id_article=485
Landry and Zucker, p. 1186.
Landry, Donald, Howard Zucker, Mark Sauer, Michael Reznik, & Lauren Wiebe, "Hypocellularity and absence of compaction as criteria for embryonic death," Regenerative Medicine (May 2006), http://www.ncbi.nlm.nih.gov/pubmed/17465791
ibid. p. 373.
Gavrilov S, Prosser RW, Khalid I, MacDonald J, Sauer MV, Landry DW, Papaioannou VE, "Non-viable human embryos as a source of viable cells for embryonic stem cell derivation," Reproductive Biomed Online, (2009 Feb;18(2):301-8), http://www.ncbi.nlm.nih.gov/pubmed/19192355