The story for the year 1997 was the cloning controversy, the public debate over cloning human beings. Ian Wilmut, the laboratory midwife to the world famous sheep, Dolly, never intended to clone a human being. He still opposes the idea. Almost everyone opposes the idea. Yet, the cultural explosion ignited by this new scientific achievement continues to spread fallout. The prospect of gaining too much control--too much choice--over our own evolutionary future elicits anxiety, fear, suspicion. Genetic science seems to be igniting fires previously smoldering in our primordial sensibilities. Science is secular. And when secular science enters our DNA we fear it is entering a realm of the sacred. We fear a Promethean blunder. We fear that our own human hubris will violate something sacred in our nature; and we fear that nature will retaliate with disaster. To protect ourselves from a possible Promethean blunder by science, we are tempted to stop further research with the commandment: "thou shalt not play God!"
Then, during 1999, we opened the first few pages on chapter two of the cloning controversy story. I will refer to this chapter as "the stem cell debate." The debate has only begun. What is not yet clear is just what needs to be debated. Perhaps nothing. Perhaps everything. What is clear is that the fallout from the cloning explosion is still lighting fires here and there. Whether or not the public will add stem cells to the fuel to make those fires burn hotter remains to be seen.
Stem cells have become front page news in Australia, as well as in the United States and other countries. On February 4, 1999, the Australian National Academy of Science issued a position statement. Note the structure of Recommendation 1.
Council considers that reproductive cloning to produce human fetuses is unethical and unsafe and should be prohibited....However, human cells derived from cloning techniques, from ES cell lines, or from primordial germ cells should not be precluded from use in approved research activities in cellular and developmental biology
Here two things are put together. First, disapproval of reproductive cloning for the purposes of making children. Second, approval of research on human embryonic stem cells, approval even in the face of ethical squeamishness regarding embryo research. If this Australian statement is a barometer, we need to ask: what is the cultural weather forecast? What might be coming?
In what follows it will be my task to report on the fast-moving frontier of stem cell research within the field of genetics. I will try to identify the ethical questions that are relevant to what could turn out to be one of the most dramatic new chapters in medical history, a chapter just beginning and expected to continue over the next decade or longer. Then I will try to formulate questions regarding theological anthropology, agenda questions raised by science that need to be addressed by systematic theologians and public policy makers. I will ask more questions than I am ready to answer. Yet, I believe that such work invested in trying to formulate the relevant question (die Fragestellung) takes us more than just halfway toward a helpful answer.
Human embryonic stem cells (hES cells) are cells that are self-renewing--virtually immortal--and have the capacity to develop into any or all tissue types in the human body. If medical scientists could gain the ability to turn on selected genes to grow selected tissues and organs for transplantation, hES cell-based therapies would revolutionize treatment of degenerative age-related diseases such as Parkinson's disease, diabetes, and congestive heart failure.
Two recent claims of laboratory triumph are relevant. First is the isolation of human embryonic stem cells (hES cells) by James Thomson, an associate veterinarian in the University of Wisconsin's Regional Primate Research Center. Thomson began with fertilized ova--spare embryos from in vitro fertilization (IVF) not placed in a uterus--and cultured them to the blastocyst stage, about four to six days. At this point he removed the outer shell of the blastocyst, separated out the individual cells, and placed them on a feeder tray. The cells divided. They reproduced themselves. Because these cells are as yet undifferentiated--that is, they are pluripotent and able to make any part of a human body--they are the cells from which other cells stem. Because they replicate themselves indefinitely, Thomson in effect created an immortal line of embryonic stem cells.
Second, John Gearhart, a professor of gynecology and obstetrics at Johns Hopkins University School of Medicine, drew human embryonic germ cells (hEG cells) from fetal gonadal tissue. These cells, when taken from an aborted fetus, resemble in nearly all respects the pluripotent stem cells described above. I will provide more detail on the Gearhart discovery in the description that follows.
Many types of stem cells exist in the human body. All have the capacity to replicate, to self-renew; and they have the capacity to differentiate in order to produce specific body parts such as muscle cells, skin cells, nerve cells, and such. Yet scientists believe they are organized in a hierarchy according to a scale of specialization. Please watch carefully as I label the steps on the hierarchical staircase.
On the top we find totipotent (totally potent) stem cells, which are capable of forming every type of body cell. Each totipotent cell could replicate and differentiate and become a human being. All cells within the early embryo are totipotent up until the 16 cell stage or so.
Next are the pluripotent stem cells which can develop into any of the three major tissue types: endoderm (interior gut lining), mesoderm (muscle, bone, blood), and ectoderm (epidermal tissues and nervous system). Pluripotent stem cells can eventually specialize in any bodily tissue, but they cannot themselves develop into a human being.
Finally, we have tissue specific stem cells committed to making blood, muscle, nerve, bone, or other tissues. Hematopoietic stem cells, for example, are responsible for all types of blood cells, but no other tissue types. These renew themselves, yet they specialize in the tissue they produce. Their continued presence in an adult person gives the body its repairing and healing ability.
We have just made the point that tissue specific stem cells--such as those we find in the hematopoietic, intestinal, and epidermal systems--are valuable to the body because they continue to replace themselves. Yet, curiously enough, they may turn out to be even more valuable. They may be transferable. Recent experiments with mice have successfully transferred neural stems cells from the brain to the bone marrow, resulting in the production of blood. Once transplanted from the brain into the bone marrow, the neural stem cells produced a variety of blood cell types including myeloid and lymphoid cells as well as early hematopoietic cells. This shows two things. First, the neural stem cells appear to have a wider differentiation potential than is required to produce brain tissue. Second, some kind of triggering mechanism must be present in the blood system that can instruct the stem cell genes to produce blood cells. Thinking ahead medically, this brightens the prospect that neural cell transplants might be able to treat human blood cell disorders such as aplastic anemia and severe combined immunodeficiency.
Regardless of how interesting this might be, our focus here is on pluripotent cells. What Thomson and Gearhart have done is isolate pluripotent hES cells. The Thomson method is to take a human egg fertilized in vitro, which itself is a totipotent stem cell. Thomson then nurtures it to the blastocyst stage, about four to six days. He then removes the trophectoderm, the outer shell, thereby exposing the inner cell mass. He separates the cells and places them on a feeder tray and cultures them. Each cell is now pluripotent, capable of making any bodily tissue; but because the cells no longer constitute an embryo they are not thought of as potential human beings.
Gearhart arrives at pluripotent stem cells, but he takes another route. He begins with an aborted fetus at about the five to eight week stage. He removes the primordial germ cells, which at this stage still have the full complement of 46 chromosomes. Later in fetal development the gonads would otherwise become distinguished either as ova for girls with 23 chromosomes, or sperm for boys with 23 chromosomes. Prior to this stage, still at the five to eight week period after conception, the germ cells are migrating toward the genital ridge with 46 chromosomes. The Gearhart procedure catches them in this early migratory movement. Once the primordial germ cells are separated and placed on a feeder tray, they become cultured pluripotent hEG cells.
It is not yet clear whether or not hES cells are identical to hEG cells. Both are pluripotent and equivalent in function, to be sure. Yet, it may be discovered that different alleles appear in different hES cells, because hES cells could be imprinted by either the male or female source. The blastocyst stage of embryogenesis is a stage that avoids the gender imprint. What is not yet known is whether original gender imprint will matter. For the foreseeable future the two types of stem cells will be treated the same.
Stem cell research is a step to be taken toward the improvement of transplantation therapy and toward lengthening a person's life. We will postpone discussion of life-extension, noting here the relevance to transplantation medicine. Specifically, rejuvenation through transplantation of tissue grown in a laboratory from stem cells would be of enormous value for cardiomyocytes to renew heart muscle to prevent congestive heart failure; replacement of hematopoietic stem cells for producing healthy blood in bone marrow to resist infection by the human immunodeficitent virus and to treat AIDS and possibly sickle cell anemia; cultivating endothelial cells to reline blood vessels as treatment for atherosclerosis, angina, and stroke due to arterial insufficiency; rejuvenating islet cells in the pancreas to produce natural insulin to fight diabetes; renewal of neurons in the brain to treat Parkinson's disease and victims of stroke; fibroblast and keratinocyte cells to heal skin in the treatment of burns; and chondrocytes or cartilage cells to treat osteoarthritis or rheumatoid arthritis.
The trick will be to discover just what turns which genes on and off. Once scientists have learned how to trigger gene expression, they can apply it to pluripotent stem cells and direct the growth of selected bodily tissue. Particular organs could be grown in culture. Heart tissue or entire organs such as the pancreas or liver could be grown in the laboratory. These would be healthy rejuvenating organs ready for transplantation.
In order to transplant the laboratory grown organs, however, we need to override our immune system in order to avoid organ rejection. Two scenarios lie before us. One would be to create a 'universal donor' cell that would be compatible with any organ recipient. The task here would be to disrupt or alter the genes within the cell responsible for the proteins on the cell's outer surface that label them as foreign to the recipient's immune system. This approach would be difficult. It would involve disrupting genes within the same DNA in which we are trying to express certain other genes. Exposing such cells to harsh conditions with rounds of different drugs may damage more than just the targeted surface proteins.
A preferable second scenario would be to make cells that are genetically compatible (histocompatible) with the organ recipient--that is, to make cells with an identical genotype. If the organ genotype matches that of the recipient, no immune system rejection will take place.
Enter cloning--that is, somatic cell nuclear transfer. We can imagine the following scenario for customizing organ growth and transplantation. We could begin with an enucleated human oocyte--that is, we could begin with an egg with the DNA nucleus removed. Via somatic nuclear transplantation--cloning--we could insert the DNA nucleus of the future transplant recipient. We could then turn on selected genes--that is, we could cause the stem cell to differentiate into cardiomyocytes to produce heart tissue. The heart tissue could be grown ex vivo, outside the body, and then through surgery placed within the recipient. Because the implanted heart tissue has the same genetic code as the recipient, no rejection would occur. This is in part the Dolly scenario. It differs in part because it grows only organ tissue and not an entire fetus.
Another variant on the second scenario that distinguishes it from Dolly would be one that eliminates the use of the oocyte. Instead of an oocyte, the recipient's DNA nucleus might be placed within a non-egg cell. The goal would be to accomplish laboratory organ growth in a stem cell that is not an egg. To accomplish this, we need further research on cytoplasm's role in gene expression.
What is there in the cytoplasm that programs the DNA? Could we discover this? If so, we could begin not with an oocyte but rather with an hES cell. We could enucleate a non-egg stem cell and insert the specific DNA nucleus, then reprogram the cytoplasm to cause the desired differentiation.
At this point we should see that ethical factors are beginning to influence the science. This variant on the second scenario appears to have a slight ethical advantage. The removal of the DNA nucleus from the donated oocyte might be considered the destruction of a potential human life; and the insertion of a DNA nucleus appears to be an asexual creation of a human embryo. We suddenly find ourselves in the middle of the abortion debate. By beginning with hES cells, scientists think this debate could be avoided. However, the use of hES cells does not avoid the embryo problem completely. The Thomson method relies on destroyed blastocysts as the source for hES cells; and the Gearhart method relies on aborted fetuses. Much needs to be cleared up here.
The primary task, as I see it, will be for scientists and ethicists to agree on the relevant vocabulary. In particular, the distinction between totipotent and pluripotent stem cells must be stipulated with sufficient clarityto permit ethical analysis. Right now it appears that only one attribute distinguishes them, namely, a totipotent stem cell has the potential for becoming an embryo and hence a human being, whereas a pluripotent stem cell does not. Yet, we must ask, why is this the case? Is it because totipotent cells have a genetic potential lacking in pluripotent cells? No. What distinguishes them is that totipotent cells have access to a placenta making them available for implantation; whereas pluripotent stem cells lack placenta access. Will this distinction hold? We will see.
One inescapable ethical question to be confronted has been formulated by Glenn McGee and Arthur Caplan, "What's in the dish?" Is an oocyte hosting a transferred DNA nucleus a person, or a potential person? Is a fertilized ovum from an IVF clinic that has been borrowed in order to make a blastocyst a potential person; or is it merely a piece of property to be donated for destruction in medical research? If the blastocyst is a potential person because its trophechtoderm makes it totipotent, is each interior pluripotent hES cell less of a potential person just because it no longer has access to a trophoblast? Would the pluripotent hES cell be considered a potential person if we could discover how to turn on its trophoblast genes and make a placenta? Would these questions apply as well to hEG cells taken from an aborted fetus? Even if pluripotent hES and hEG cells could be removed from the list of potential persons, would their respective sources in destroyed blastocysts and aborted fetuses render their utilization unethical?
These questions are essential to evangelical Right-to-Life advocates and Roman Catholics who borrow categories from earlier stages in the abortion debate. Richard Land, who heads the Ethics and Religious Liberty Commission of the Southern Baptist Convention objects to treating stem cells as property. "Human cells, tissues, and organs should not be commodities to be bought and sold in a biotech slave market." He adds, "Some researchers have established in their own minds an arbitrary lesser moral status for human beings in their embryonic stage of development."
The Roman Pontiff and the Congregation for the Doctrine of the Faith attribute full human personhood and dignity and moral status to us from the moment of fertilization on. In order to avoid any slight of ethical hand that might compromise this firm position, the Vatican uses interchangeably terms such as 'zygote'R, 'pre-embryo', 'embryo', and 'foetus'.
What is of indispensable value here for our ethical deliberation is the Vatican's unflinching resolve to protect the dignity of human personhood. Yet, the questions raised by stem cell research are more than this line of ethical deliberation is presently ready to handle. The Vatican's approach is like an ethical spray gun; whereas what we need in this instance is to paint with a fine pencil brush. We need to color within the lines, so that we avoid accidentally blotting out advances in the quality of human health and flourishing.
Although this is a quantitative question applied to a qualitative ethical concern, we intuitively sense that the public impact of such science is morally relevant. We rightly fear that if such science and its resulting technology proceed this might encourage couples to fertilize ova for the purposes of sale or donation and that it might encourage abortions for harvesting hEG cells. At this point, however, it appears that this would be an unfounded fear.
More fertilized ova are already being generated by reproductive technology clinics than will ever be implanted. It is known well in advance that many will be destroyed as a matter of course. Therefore, diverting some for scientific research purposes constitutes a potential beneficial use for tissue that would otherwise be discarded. Scientific research is not in effect preventing human births.
Let us press the question: would stem cell research lead to increased demand for fetal tissue or for IVF embryos? Probably not. Over the last four or five years of research, relatively few fetuses, less than 100, have actually been harvested for experimentation. Experiments at University of San Francisco and University of Wisconsin use less than two dozen IVF embryos per year. The hope downstream is that laboratories could generate enough stem cells in culture to preclude constant demand for more and more tissue. In sum, stem cell research as presently understood should have a negligible impact on IVF or abortion practices.
The Ethics Advisory Board of the Geron Corporation, for a case in point, has taken a position against deliberately fertilizing ova for the purpose of selling or even donating them to make hES cells. Stem cell research of this type should proceed on the assumption that it would have a sufficient supply of discarded fertilized ova that would never have had the opportunity for implantation. The Ethics Advisory Board strongly recommends that the donating women or couples provide fully informed consent, but not that they share in the financial profit. The removal of the profit motive at this stage of harvesting will be ethically helpful, because it avoids treating fertilized ova and fetuses as property.
With regard to the practice of using aborted fetuses as a source for hEG cells, it would pass a strict Roman Catholic moral test if it meets one condition. If the fetuses are the result of spontaneous or natural abortion, then harvesting hEG cells would be licit. If they are the result of elective abortion, then it would not be licit. Similarly, Jewish ethical principles are likely to yield approval on the grounds that medical science is drawing something good out of an otherwise tragic situation, drawing good out of a respectful use of a dead body. Apart from the question of when life begins in or beyond the womb, the appeal here is to the moral value of the dead providing something life-giving for those who come later.
No matter how relevant such traditional deliberation might be, many more questions remain to be formulated and attended to.
Does it help us ethically to distinguish scientifically between totipotency and pluripotency? Is it accurate to attribute the status of embryo to totipotent stem cells and deny it to pluripotent stem cells? Even if we are successful at removing pluripotent stem cells from the category of embryos--and, thereby, exempting them from legal restrictions on embryo research--have we really dealt sufficiently with the ethical issues?
Let us review the proposed scientific distinction. Why is it that pluripotent stem cells are one step down the embryonic staircase? Totipotent stem cells are capable of producing all tissue, including the trophoblast necessary for implantation. Totipotent stem cells have the potential of becoming embryos. Pluripotent stem cells have every capability of the totipotent stem cells minus one, namely, they have no trophoblast. Minus the trophoblast, pluripotent cells cannot for this reason develop into a full human being. In this limited sense, pluripotent cells are not potential embryos.
It may turn out that the difference between totipotency and pluripotency is little more than a verbal distinction. The genetic code remains the same. The potency for making all bodily tissues remains the same. When using the blastocyst as source, the trophechtoderm is removed; and this denies to the internal hES cells access to what is necessary for implantation. What distinguishes the pluripotent stem cells is their loss of the blastocyst environment and the potential for sharing in the benefits of implantation. In sum, it is not nature but rather the laboratory procedure that demotes cells from totipotency to pluripotency.
Relevant here is the question: would a pluripotent stem cell under optimum conditions be able to produce a trophoblast and eventually a placenta for implantation? Why not, if the genetic code is complete and if it has the potential for making any tissue? Already experiments with mice have successfully shown that it is possible to form a fetus from a stem cell. It is the pre-differentiated state of the ES cell that, in principle, makes it capable of producing not only any bodily tissue but also of becoming an embryo.
This forces us to ask: would all ethical concerns previously pertaining to the use of embryos in research now apply to pluirpotent hES cells? It would seem that this is the case. But, there is more. We now need to ask just what is being covered up by the totipotent-pluirpotent distinction and also ask about the implications of possible totipotency in normal somatic cells.
The distinction between totipotency and pluripotency covers over the question of derivation. Those who advocate U.S. government funding to support stem cell research wish to avoid the problems associated with restrictions on embryo research; so they exempt stem cells through definition. If stem cells are pluripotent and not totipotent, then they escape prohibitions against the destruction of the embryo for purposes of research. The term "derivation" is brought in to reinforce this move.
In a December 1999 draft of the National Institutes of Health (NIH) "Guidelines for Research Involving Human Pluripotent Stem Cells," the Department of Health and Human Services (DHHS) is reported to have concluded that "the Congressional prohibition does not prohibit the funding of research utilizing human pluripotent stem cells because they are not embryos." It further reports that appropriations law (P.L. 105-277, section 511,112 STAT, 2681-386) prohibits funds "for the creation of a human embryo or embryos for research purposes; or research in which a human embryo or embryos are destroyed, discarded or knowingly subjected to risk of injury or death." The problem, of course, is that the human embryonic stem cells are derived from early embryos. So, what to do? The proposed NIH answer, approved by DHHS, is to permit funding for pluripotent stem cell research but deny it for deriving these stem cells from embryos. "DHHS funds may not be used for the derivation of human pluripotent stem cells from early human embryos."
What, then, should be the source of hES cells? Laboratory created embryos? No. They should come from IVF clinics, where the original intent was to fertilize ova for implantation. U.S. government funds can be used "only if the cells were derived from early human embryos that were created for the purposes of infertility treatment and were in excess of clinical need of the individuals seeking such treatment."
With regard to hEG cells, the NIH is more lenient. "Unlike pluripotent stem cells derived from early human embryos, DHHS funds may be used to support research to derive pluripotent stem cells from fetal tissue, as well as for research utilizing such cells.
Reading between the lines, perhaps we can see Roman Catholic or right-to-life logic at work here. The use of fetal tissue for research is licit when the fetuses result from spontaneous abortions; but it is not licit when elective abortions are involved. Roman Catholics want to avoid any direct or indirect support for elective abortion. Yet, a hint of moral wiggle room seems to exist when deriving stem cells from fetal sources. No wiggle room seems to exist presently in right-to-life thinking regarding the deliberate destruction of embryos. One might surmise that, without saying it, these proposed government guidelines are responding to such concerns regarding the moral inviolability of what is perceived to be the integrity of the embryo, an integrity that goes as far back as the fertilized zygote. Governmental response to this is most appropriate, and welcomed. My only plea is that, if this is the operative thinking, it should be stated clearly as an ethical concern and not hid it under an alleged scientific distinction between totipotency and pluripotency.
Now, though still quite hypothetically, we might engage in further ethical speculation regarding the possible totipotency inherent in any pre-differentiated pluripotent cell. Recall the yet to be discovered role that cytoplasm and other nonnuclear factors play in gene expression. One significant research task lying before molecular biologists is to determine just how the cytoplasm interacts with the DNA nucleus, and to gain the ability to reprogram cytoplasm to make specific tissue. Once this ability to reprogram is achieved, then in principle it could be used with any cell. We would not necessarily at that point have to rely on oocytes or fertilized ova or, perhaps, even blastocysts as the source. Somatic cells might become the source for pluripotent cells.
Then we would experience a shift in ethical ground tantamount to an earthquake. Initially and naively, we could breathe a sigh of relief. If laboratory scientists are no longer tempted to harvest stem cells from IVF products or aborted fetuses, then it appears that our fears are over. Human dignity is no longer threatened, because potential babies will no longer lose their potential lives in laboratory procedures. After all, nature (or God) has given us one source for making babies--fertilized ova--and this source will be protected. We could brush off our hands and thank the alliance of scientists and ethicists for solving this sticky problem.
However, the relief will be only momentary. At this point we will begin to feel the ground under our feet starting to shift. The needles on our ethical seismograph will begin to dance furiously. Would we begin to think of each cell in our body as an embryo? Would this mean that, in principle, we could make a baby from any cell in our body? Here is what we need:
1. The full genetic code to make every tissue available in every somatic cell;
2. The ability to return our DNA nucleus to quiescence and then to its pre-differentiated state, as in the case of Dolly; and
3. The ability to reprogram the cytoplasm to cause selected genetic expression and, along with this, to initiate embryonic development. This is all it takes. The first two are already in the well. Nature has given us a full complement of genes in every somatic cell. The cloning experiments at the Roslin Institute have given us the technology of quiescence for returning an already differentiated somatic nucleus to its pre-differentiated state and, hence, pluripotency. Only the third scientific task remains to be accomplished; and this would demonstrate the principle that babies can come from anywhere.
Now, we find ourselves in a most fascinating ethical situation. Let us ask: does every cell in our existing body have the same moral status as that of a pluripotent hES cell? Or, the same status as a totipotent fertilized ovum or blastocyst? What have we done? Have we sent the moral status of common somatic cells up the ethical staircase? Or, have we brought pluripotent hES cells down a few steps? Or, have we done both?
We have little remorse at going to the barber for a haircut or clipping our finger nails. Nor do we feel immoral at donating blood or even a kidney to save the life of someone who might die without our bodily gifts. We tend not to think of our cells or limbs or body parts as themselves potentially whole persons with full dignity. Our body parts have a level of dignity, to be sure, but it is a dignity borrowed from ourselves as whole persons.
Nor do we feel compelled morally to exhaust our potential for reproduction. Despite the millions of ova in a woman and sperm in a man, we do not feel a compulsion to see every one individually contribute to the making of a new human person. Despite the Onan incident (Genesis 38:8-10), we recognize that God's creation begins with an excess of ova and sperm in the reservoir of potentiality within which some individual persons become an actuality. In natural sexual processes, only a fraction of ova become fertilized by only a fraction of sperm. And, of the resulting zygotes, the majority are flushed naturally out of the mother's body before implantation. If this natural parsimony is already operative with germ cells, might it relieve us of moral pressure to treat every pluripotent stem cell as an embryo, as a potential individual person?
What's in the petri dish? A person? No, I don't think so. Even if we can say in principle that what's in the petri dish is genetically a potential person, this does not in itself warrant putting an end to stem cell research. The genetic potential for making persons is virtually ubiquitous. In principle, it lies in every cell of every human body. Yet, we have no ethical warrant to actualize all this potential. No warrant exists to make babies out of every available germ cell let alone every already differentiated somatic cell; nor do I think it is required of every pluripotent stem cell.
This is a safety-in-numbers argument. In itself, it may not be persuasive in ethical deliberation. This I grant. Yet, it gains persuasive strength when combined with the argument from beneficence.
What I find decisive is the related argument from beneficence: stem cell research carries with it promise of significant advances in medicine. The potential for reducing human suffering and improving human health and well-being is enormous. If it cannot be shown conclusively that individual human dignity is violated at the source of stem cells, then it seems to me that the argument from beneficence should be decisive in providing ethical encouragement to proceed with such research.
 "The Roslin Institute and PPL Therapeutics have made it clear that they regard the idea [of human reproductive cloning] as ethically unacceptable." Ian Wilmut and Donald Bruce, "Dolly Mixture," in Engineering Genesis: The Ethics of Genetic Engineering , edited by Donald Bruce and Ann Bruce (London: Earthscan Publications, 1998) 75. See also: Ian Wilmut, "Cloning for Medicine," Scientific American, 279:6 (December 1998) 58-63. For a theological discussion see: Human Cloning: Religious Responses, edited by Ronald Cole-Turner (Louisville: Westminster/John Knox Press, 1997)
 James A. Thomson, Joseph Itskovitz-Eldor, Sander S. Shapiro, Michelle A. Waknitz, Jennifer J. Swiergiel, Vivienne S. Marshall, and Jeffrey M. Jones, "Embryonic Stem Cell Lines Derived from Human Blastocysts," Science, (Nov. 6, 1998) 282:1145-1147.
 On Human Cloning, A Position Statement, 4 February 1999, Australian Academy of Science, GPO Box 783, Canberra, ACT 2601, Australia.
 James A. Thomson, Joseph Itskovitz-Eldor, Sander S. Shapiro, Michelle A. Waknitz, Jennifer J. Swiergiel, Vivienne S. Marshall, and Jeffrey M. Jones, "Embryonic Stem Cell Lines Derived from Human Blastocysts," Science, (Nov. 6, 1998) 282:1145-1147.
Michael J. Shamblott, Joyce Axelman, Shunping Wang, Elizabeth M. Bugg, John W. Littlefield, Peter J. Donovan, Paul D. Blumenthal, George R. Huggins, and John D. Gearhart, "Deriviation of Pluripotent Stem Cells from Cultured Human Primordial Germ Cells," Proceedings of the National Academy of Sciences, (November 1998) 95:13726-13731.
Christopher R.R. Bjornson, Rodney L. Rietze, Brent A. Reynolds, M. Cristina Magli, Angelo L. Vescovi, "Turning Brain into Blood: A Hematopoietic Fate Adopted by Adult Neural Stem Cells in Vivo," Science 283:5401 (22 January 1999) 534-536.
Evelyn Strauss, "Brain Stem Cells Show Their Potential," Science, 283:5401 (22 January 1999) 471.
"Carrying the potential to allow the repair of any failing organ by the injection of healthy youthful cells, this breakthrough may ultimately impact health care more broadly than the discovery of anesthesia or the development of antibiotics." Thomas B. Okarma, "Human Primordial Stem Cells," Hastings Center Report, 29:2 (March-April 1999) 30.
This is the published research agenda of the Geron Corporation, Menlo Park, California.
Roger A. Pedersen, "Embryonic Stem Cells for Medicine," Scientific American, 280:4 (April 1999) 68-75.
 Glenn McGee and Arthur L. Caplan, "What's in the Dish?" Hastings Center Report, 29:2 (March-April 1999) 36-38. One insightful point made by these two authors which we will not take up thoroughly here has to do with context. Whether protoplasm is in the dish or in the womb matters. Is its moral status different when in the womb where it can be brought through pregnancy to term than when it is in the petri dish? Is the interaction between an hES cell and its environment morally decisive?
Cited in "Embryo Research Contested," by Denyse O'Leary, Christianity Today, 43:6 (May 24, 2999) 27.
Donum Vitae or "Instruction on Respect for Human Life in Its Origin and on the Dignity of Procreation; Replies to Certain Questions of the Day," in Bioethics , 3rd ed., edited by Thomas A. Shannon (Mahwah, N.J.: Paulist Press, 1987) 591.
Karen Lebacqz, Michael M. Mendiola, Ted Peters, Ernlé W.D. Young, and Laurie Zoloth-Dorfman, "Research with Human Embryonic Stem Cells: Ethical Considerations," Hastings Center Report, 29:2 (March-April 1999) 31-36.
The National Bioethics Advisory Commission employs the distinction as introduced by Harold Varmus, then NIH director, at a hearing in January 1999. Totipotent cells have "unlimited capacity. Totipotent cells have the capacity to differentiate into the embryo and into extra-embryonic membranes and tissues. Pluripotent cells "can generate all of the cell types in a fetus and in the adult that are capable of self-renewal. Pluripotent cells are not capable of developing into an entire organism." Ethical Issues in Human Stem Cell Research (September 1999) by NBAC, 6100 Executive Boulevard, Suite 5B01, Rockville, Maryland 20892-7508; www.bioethics.gov.
Andrŕs Nagy, Janet Rossant, Rčka Nagy, Wanda Abramov-Newerly, and John C. Roder, "Derivation of completely cell culture-derived mice from early-passage embryonic stem cells," Proceedings of the National Academy of Sciences, 90 (September 1994) 8424-8428.
U.S. Department of Health and Human Services, "Draft National Institutes of Health Guidelines for Research Involving Human Pluripotent Stem Cells (December 1999)," www.nih.gov/news/stemcell/draftguidelines.htm. The American Association for the Advancement of Science supports both public and private funding for stem cell research derived from all sources; yet the AAAS recognizes that many religious traditions that take a developmentalist view of personhood will be at odds with those opposing use of embryos for anything other than pregnancy. Despite such unsettled religious differences, says the AAAS, these concerns need not exclude publicly-funded research activities on cell lines that have already been established. See: Audrey R.Chapman, Mark S. Frankel, and Michele S. Garfinkel, Stem Cell Research and Applications (November 1999). http://www.aaas.org/spp/dspp/sfrl/projects/stem/main.htm.