Ethical Considerations For Using Stem Cells

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1 Ethical Considerations For Using Stem Cells By: David Rocheleau There are many times in one s life and career where we face ethical decisions or dilemmas. These instances may be presented to us on a daily basis depending on what fields of interest we lend ourselves to. Knowing all of the background information and pertinent facts is required to make an accurate and self-satisfying decision regarding the ethics of a situation. The topic of stem cells and stem cell research is one which forces a person to look deep at their ethical, moral as well as religious beliefs to come to a conclusion of whether or not it is acceptable to use such cells for treatment and research. What is a stem cell? Where do they come from? Is there more than one source of stem cells? If so, which is the best source to use? Is it against my religious beliefs? Is it just plain right or wrong to me? These are only some of the questions which a person faces when trying to decide if using stem cells is ethically justified. MJ is 26 year old insulin-dependent diabetic who must inject insulin several times daily to keep his blood glucose in the normal range. Despite MJ s unrelenting attitude to keep his diabetes under control, he still suffers from bouts of hypoglycemia throughout the week, which sometimes cause him to nearly pass out. Imagine a treatment that could eliminate MJ s need to inject insulin altogether. This would not only essentially cure MJ of his diabetes, but could also help millions of people around the world fight their diabetes. Billions in healthcare dollars could be saved and significant decreases in morbidity and mortality due to diabetes could be achieved. This could all be a reality with the help of stem cells. It all sounds great, right? Well, as stated before, there are many considerations one must take into account to decide if this type of treatment is ethical. If it were as simple as I made it out to be, we may be well on our way to curing many diseases and conditions. Stem cells have two important characteristics that distinguish them from other types of cells. First, they are unspecialized cells that renew themselves for long periods through cell division. The second is that under certain physiologic or experimental conditions, they can be induced to become cells with special functions such as the beating cells of the heart muscle or the insulin-producing cells of the pancreas. Stem cells are noted for their ability to self-renew and differentiate into a variety of cell types. Some stem cells, described as totipotent cells, have tremendous capacity to self-renew and differentiate. Furthermore, there have been close ties between the behavior of stem cells and cancer cells.

2 Scientists primarily work with two kinds of stem cells from animals and humans: embryonic stem cells and adult stem cells, which have different functions and characteristics. Embryonic stem cells have pluripotent capacity, able to form tissues of all 3 germ layers but unable to form an entire live being. Adult stem cells were previously thought to have a restricted capacity to differentiate; however, several reports have described their differentiation potential. Owen first recognized stem cells experimentally in 1945, when he found lifelong blood chimerism between twin cows. He postulated that an interchange of cells between bovine twin embryos occurred as a result of conjoined blood vessels and that the interchanging cell had to be "ancestral" to the terminal erythrocyte. 1 More than 15 years later, investigators formally tested for these ancestral blood cells by preventing radiation death in mice with bone marrow transplantation. These stem cells were noted for their ability to give rise to clonal colonies of differentiated blood cells in the recipient spleen and for their ability to rescue subsequent generations of lethally irradiated mice. This multilineage reconstitution by a self-renewing cell is a cardinal feature of stem cells. To this day, transplantation experiments like those performed in the 1960s that showed clonal, robust, and functional differentiation by a cell transplantable over many generations remain the gold standard in testing stem cells. 2 Many years of detailed study of the biology of mouse stem cells led to the discovery, in 1998, of how to isolate stem cells from human embryos and grow the cells in the laboratory. These are called human embryonic stem cells. The embryos used in these studies were created for infertility purposes through in vitro fertilization procedures and when they were no longer needed for that purpose, they were donated for research with the informed consent of the donor. Stem cells are important for living organisms for many reasons. In the 3- to 5-day-old embryo, called a blastocyst, stem cells in developing tissues give rise to the multiple specialized cell types that make up the heart, lung, skin, and other tissues. In some adult tissues, such as bone marrow, muscle, and brain, discrete populations of adult stem cells generate replacements for cells that are lost through normal wear and tear, injury, or disease. 3 One of the fundamental properties of a stem cell is that it does not have any tissue-specific structures that allow it to perform specialized functions. A stem cell cannot work with its neighbors to pump blood through the body (like a heart muscle cell); it cannot carry molecules of oxygen through the bloodstream (like a red blood cell); and it cannot fire electrochemical signals to other cells that allow the body to move or speak (like a nerve cell). 3 However, unspecialized stem cells can give rise to specialized cells, including heart muscle cells, blood cells, or nerve cells. Unlike muscle cells, blood cells, or nerve cells which do not normally replicate themselves stem cells may replicate many times. When cells replicate themselves many times over it is called proliferation. A starting population of Page 2 of 10

3 stem cells that proliferates for many months in the laboratory can yield millions of cells. If the resulting cells continue to be unspecialized, like the parent stem cells, the cells are said to be capable of long-term self-renewal. The specific factors and conditions that allow stem cells to remain unspecialized are of great interest to scientists. It has taken scientists many years of trial and error to learn to grow stem cells in the laboratory without them spontaneously differentiating into specific cell types. For example, it took 20 years to learn how to grow human embryonic stem cells in the laboratory following the development of conditions for growing mouse stem cells. 3 Therefore, an important area of research is understanding the signals in a mature organism that cause a stem cell population to proliferate and remain unspecialized until the cells are needed for repair of a specific tissue. Such information is critical for scientists to be able to grow large numbers of unspecialized stem cells in the laboratory for further experimentation. When unspecialized stem cells give rise to specialized cells, the process is called differentiation. Scientists are just beginning to understand the signals inside and outside cells that trigger stem cell differentiation. The internal signals are controlled by a cell's genes, which are interspersed across long strands of DNA, and carry coded instructions for all the structures and functions of a cell. The external signals for cell differentiation include chemicals secreted by other cells, physical contact with neighboring cells, and certain molecules in the microenvironment. 3 Adult stem cells typically generate the cell types of the tissue in which they reside. A blood-forming adult stem cell in the bone marrow, for example, normally gives rise to the many types of blood cells such as red blood cells, white blood cells and platelets. Until recently, it had been thought that a blood-forming cell in the bone marrow which is called a hematopoetic stem cell could not give rise to the cells of a very different tissue, such as nerve cells in the brain. However, a number of experiments over the last several years have raised the possibility that stem cells from one tissue may be able to give rise to cell types of a completely different tissue, a phenomenon known as plasticity. 3 Examples of such plasticity include blood cells becoming neurons, liver cells that can be made to produce insulin, and hematopoietic stem cells that can develop into heart muscle. Therefore, exploring the possibility of using adult stem cells for cell-based therapies has become a very active area of investigation by researchers. There are many ways in which human stem cells can be used in basic research and in clinical research. However, there are many obstacles between the promise of stem cells and the realization of these uses, which will only be overcome by continued intensive stem cell research. Studies of human embryonic stem cells may yield information about the complex events that occur during human development. A primary goal of this work is to identify how undifferentiated stem cells become differentiated. Scientists know that turning Page 3 of 10

4 genes on and off is central to this process. Some of the most serious medical conditions, such as cancer and birth defects, are due to abnormal cell division and differntiation. A better understanding of the genetic and molecular controls of these processes may yield information about how such diseases arise and suggest new strategies for therapy. A significant hurdle to this use and most uses of stem cells is that scientists do not yet fully understand the signals that turn specific genes on and off to influence the differentiation of the stem cell. 3 Human stem cells could also be used to test new drugs. For example, new medications could be tested for safety on differentiated cells generated from human pluripotent cell lines. Other kinds of cell lines are already used in this way. Cancer cell lines, for example, are used to screen potential anti-tumor drugs. But, the availability of pluripotent stem cells would allow drug testing in a wider range of cell types. However, to screen drugs effectively, the conditions must be identical when comparing different drugs. Therefore, scientists will have to be able to precisely control the differentiation of stem cells into the specific cell type on which drugs will be tested. Current knowledge of the signals controlling differentiation fall well short of being able to mimic these conditions precisely to consistently have identical differentiated cells for each drug being tested. Perhaps the most important potential application of human stem cells is the generation of cells and tissues that could be used for cell-based therapies. 3 Today, donated organs and tissues are often used to replace ailing or destroyed tissue, but the need for transplantable tissues and organs far outweighs the available supply. Stem cells, directed to differentiate into specific cell types, offer the possibility of a renewable source of replacement cells and tissues to treat diseases including Parkinson's and Alzheimer's diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis. For example, it may become possible to generate healthy heart muscle cells in the laboratory and then transplant those cells into patients with chronic heart disease. Preliminary research in mice and other animals indicates that bone marrow stem cells, transplanted into a damaged heart, can generate heart muscle cells and successfully repopulate the heart tissue. Other recent studies in cell culture systems indicate that it may be possible to direct the differentiation of embryonic stem cells or adult bone marrow cells into heart muscle cells. See picture below adapted from NIH website: 3 Page 4 of 10

5 In people who suffer from type I diabetes, the cells of the pancreas that normally produce insulin are destroyed by the patient's own immune system. New studies indicate that it may be possible to direct the differentiation of human embryonic stem cells in cell culture to form insulin-producing cells that eventually could be used in transplantation therapy for diabetics. 3 Although many of these ideas sound very promising, there are many technical and ethical barriers scientists must overcome to display the full potential of stem cell based therapy. Scientists have been able to do experiments with human embryonic stem cells (hesc) only since 1998, when a group led by Dr. James Thompson at the University of Wisconsin developed a technique to isolate and grow the cells. 3 Moreover, Federal funds to support hesc research have been available since only August 9, 2001, when President Bush announced his decision on Federal funding for hesc research. Because many academic researchers rely on Federal funds to support their laboratories, they are just beginning to learn how to grow and use the cells. Thus, although hesc are thought to offer potential cures and therapies for many devastating diseases, research using them is still in its early stages. Adult stem cells, such as blood-forming stem cells in bone marrow (called hematopoietic stem cells, or HSCs), are currently the only type of stem cell commonly used to treat human diseases. Doctors have been transferring HSCs Page 5 of 10

6 in bone marrow transplants for over 40 years. More advanced techniques of collecting, or "harvesting," HSCs are now used in order to treat leukemia, lymphoma and several inherited blood disorders. The clinical potential of adult stem cells has also been demonstrated in the treatment of other human diseases that include diabetes and advanced kidney cancer. However, these newer uses have involved studies with a very limited number of patients. On August 9th, 2001, President George W. Bush announced that federal funds may be awarded for research using human embryonic stem cells if the following criteria are met: The derivation process (which begins with the destruction of the embryo) was initiated prior to 9:00 P.M. EDT on August 9, The stem cells must have been derived from an embryo that was created for reproductive purposes and was no longer needed. Informed consent must have been obtained for the donation of the embryo and that donation must not have involved financial inducements. The NIH, as the Federal government's leading biomedical research organization, is implementing this policyy. The NIH funds research scientists to conduct research on existing human embryonic stem cells and to explore the enormous promise of these unique cells, including their potential to produce breakthrough therapies and cures. Investigators from ten laboratories in the United States, Australia, India, Israel, and Sweden have derived stem cells from 71 individual, genetically diverse blastocysts. These derivations meet the President's criteria for use in federally funded human embryonic stem cell research. 3 "...it is ridiculous for people who have already decided that it is moral to kill babies in the womb to show some squeamishness about destroying human embryos in a petri dish. Hell, man, once you decide to become a child-killer, their ages no longer matter. Or the numbers. Damnation of your soul is completed with the first one." Charley Reese 4 "Cal Thomas' article against stem cell research...is not particularly useful, because it does not deal with his fundamental belief that human personhood begins at conception. Similarly, articles by medical groups that promote stem cell research are not helpful, because they do not touch on their fundamental belief that embryos are not human persons. If there is to be any hope of resolving these issues, we must debate when human personhood begins. If we can reach a near consensus on this, then abortion, in-vitro fertilization, stem cell research and other debates will neatly resolve themselves." Comment letter to the Jewish World Review 5 Page 6 of 10

7 Although the potential of stem cells sounds very promising, technical and scientific issues are not the only ones on the stem cell plate. Ethical concerns regarding the use of essentially what could be a living human being are prominent, especially among groups with religious affiliations. Couples undergoing in vitro fertilization treatment often have embryos that they no longer need. They have the option of just letting the embryos die, donating them to another couple, or donating them for research. For those who believe the human embryo from the one-cell stage onwards has absolute moral value, equal to that of a newborn baby or an adult, any embryo research is ethically unacceptable, as it is equivalent to murder. But life is continuous - the egg and the sperm are alive, as well as the one-celled embryo - and although a new genetic base comes into being at fertilization, many people feel that moral value develops gradually. The early embryo could be regarded as having symbolic moral value, as a potential human person, and therefore worthy of respect, but in judging whether or not embryo research is ethically acceptable, both the stage of development and the object of the research have to be taken into account. Countries with laws that allow human embryo research set a time limit for research (usually 14 days, just before the fetus begins to form, which is the start of individual human development). 6 There are no major ethical concerns about the extraction of adult stem cells, from umbilical cords, skin, bone marrow, etc., as long as the donor gives permission. However, at this time, the only way to obtain the most potentially useful stem cells is believed to be from human embryos. First, surplus embryos left over from in-vitro fertilization procedures in fertility clinics are thawed. The inner cell mass of an embryo is extracted. Stem cells are all that remain. The embryo is killed in the process. This raises the same ethical questions and conflicts that are often heard when the ethics of abortion are discussed. 5 An ovum, spermatozoon, embryo, fetus, and newborn are all forms of human life. They are clearly alive and contain human DNA. Everyone agrees that a newborn baby is not only human life, but also a human person. Pro-life advocates and prochoice advocates differ in their belief of when human life becomes a human person, and thus should have its life protected. 5 Many pro-life advocates believe that not only does human life start at or shortly after conception, but that the preembryo receives a soul. Pro-choice advocates generally believe that a definition of a human person is achieved later in gestation. Embryonic stem cell research is opposed by many pro-lifers, mainly Roman Catholics and conservative Protestants. They feel that the embryos from which the stem cells are often extracted are human persons. Since the embryos are killed when the stem cells are removed, most pro-lifers view the extraction procedure as murder and a form of experimentation on human bodies. As Gregory Koukl, president of Stand to Reason writes, "Whether it's right or not to take that life depends entirely on what it is we're killing. Let me put it as clearly as I know how. If the zygote or embryo or fetus is not a human being, no justification for either abortion of embryonic stem cell research is necessary. However, if it is Page 7 of 10

8 a human being, no justification for taking his or her life is adequate. This single, succinct ethic is adequate to cover contingencies on both sides of the question." 7 In the case of embryonic stem cell research, it is a zygote which is killed in the process of extracting its stem cells, not an embryo or fetus. It is, at this point, a mass of undifferentiated cells; they haven't developed into bone, skin, heart, liver and any of the other 216 cell types in the human body. If cell differentiation has already occurred, then they zygote would no longer have any usefulness in embryonic stem cell research. 5 Lawyers from the NIH, and others, argue that stem cells are incapable of growing into a complete person. They may be coaxed to develop into nerve cells or heart cells. But, at most, they can become an organ, not a complete living person. They cannot be considered a form of human life, even within the definition of pro-life supporters. This exempts stem cell research from the Congressional ban on embryo research. Those regulations were created to prevent experiments with embryos that had the potential to develop to the fetal and newborn stages. The rules simply do not apply to stem cells. 5 Stem cells can propagate themselves so that researchers can use cells that are many generations removed from their origin. Stem cells can be replicated and may be useable in a large number of studies. Stem cells have an enormous promise to benefit mankind -- to save lives and cure or treat diseases. This generates a very strong moral obligation to explore their potential. Almost all spare embryos in fertility clinics will eventually die, due to operator error or equipment malfunction. Spare embryos are also routinely destroyed by flushing them down a drain, by incinerating them, or by thawing them out and allowing them to die. They might as well have their stem cells extracted so that they can be of some use to humanity. 5 If one traced the history of an embryo stem cell back however many generations needed to get to its origin, one would find that an embryo was murdered. Since the extraction of the initial stem cells was a violation of NIH policy, any subsequent experimentation using those cells or their descendants is not only immoral but also in violation of government regulations. 8 Those taking a pro-life stance generally believe that an embryo is a human being with a soul. Thus, the act of extracting stem cells from an embryo is murder. Stem cell research has been compared to lampshades made of human skin during the Nazi holocaust. They may be very attractive and useful lampshades; but a person was murdered during their construction. 5 Linda Bevington, director of research for the Center for Bioethics and Human Dignity has stated: "A lot of proponents of the stem-cell research are saying these embryos are extras, and they'll never be implanted, and they're doomed/destined for destruction anyway, so we might as well just take their cells Page 8 of 10

9 and create some therapies and some good. However, it is possible to adopt those embryos. It's often termed 'rescue surrogacy,' and so those embryos aren't necessarily destined for destruction. They can be implanted, and a healthy baby can be born." 9 A few embryos are "adopted" in this way in the U.S. every month. But many more frozen embryos are being created each month, and there are hundreds of thousands in storage. Robert George, a professor of moral and political philosophy at Princeton notes that embryos possess the epigenetic primordial for internally directed growth and maturation as distinct, self-integrating, human organisms. Because of this, he regards an embryo as being already, and not just potentially, a living member of the human species. 10 It is obvious that there are many differing views regarding the use of stem cells, primarily those derived from embryos or zygotes. It seems there is much less ethical debate regarding the use of adult stem cells for research, which may induce scientists to spend more time with such cells. The only problem with these stem cells is, as stated previously, not as much research has been done with these cells and the factors that differentiate them still remain to be found. It is unlikely that there will ever be complete resolution to the ethical debate of using embryonic stem cells for research and treatment. There will always be people who view a stem cell as a potential life, and as such killing it would constitute murder. On the other hand, there will always be those who view a few undifferentiated cells as nothing more than just that; cells with no characteristics of human life. Therein lies the beauty of such an ethical dilemma; there is no clear-cut right or wrong way to go. Where the future of stem cell research takes us, only time will tell. Page 9 of 10

10 References 1. Owen RD. Immunogenetic consequences of vascular anastomoses between bovine twins. Science. 1945;102: Cogle CR, Guthrie SM, et al. An overview of stem cell research and regulatory issues. Mayo Clinic Proceedings. 2003;78(8): (Accessed 12/10/05) 4. Charley Reese, "Liberals are making hell on Earth," Orlando Sentinal, 2001 JULY 22, at: (Accessed 12/8/05) 5. (Accessed 12/7/05) 6. Robertson J. A. Human embryonic stem cell research: ethical and legal issues. Nature Rev. Genet. 2001;2, Gregory Koukl, "Call to Action," Solid Ground newsletter, 2004 SEP/OCT. 8. John Morgan, "NIH and human embryo research," at: (Accessed 12/5/05) 9. Laura McGovern, "Heart Association backs stem-cell research," Focus on the Family. (Accessed 12/8/05) 10. Chuck Colson, "Embryonic Enigma," 2001-OCT-2, at: (Accessed 12/9/05) Page 10 of 10

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