Untitled Document

Embryo and Stem Cell Research: Benefits and Controversy

By: Jeehye Kim

Biology Senior Seminar

November 24, 2003

Stan Grove

Outline

Thesis: While embryo and stem cell research may one day provide treatments for many diseases; including Parkinson's, Alzheimer's, diabetes, paralysis and cancer, ethical consideration must be addressed in order for scientist to utilize human embryos for medical research.

The purpose of this paper is to inform the reader about the stem cells and research involving embryonic stem cells and others, and to address some of the ethical and moral considerations. It is important to understand the basic concepts and terminology. The following section will give definitions, types and origins of stem cells. It will then be followed by further discussion of embryo stem cells, giving specific attention to their pluripotent characteristics and differences from adult stem cells. Finally the moral and ethical issues will be addressed from scientist and pro-life advocate's point of view. The stem cell research is still in its infancy and needs a lot of support and effort to advance further. In order to promote the advance of the techniques for the good of human kind, it is important to understand the topic and issues around the stem cell research and thus promote more stem cell research.

What are Stem Cells?

A stem cell is a special kind of cell that has a unique capacity to self-replicate and to give rise to specialized cells. There are three basic types of stem cells: totipotent, pluripotent, and multipotent. Totipotent stem cells, meaning their potential is total, have the capacity to give rise to every cell type of the body and have the potential to develop into a fetus when they are placed into the uterus (Wang, 2002). To date, no such totipotent stem cell lines (primary cell cultures) have been developed. Pluripotent stem cells, such as embryonic stem cells, are capable of generating types of cells that develop from the three germ layers (mesoderm, endoderm, and ectoderm) from which all the cells of the body arise (National Institutes of Health Department of Health and Human Service (NIH), 2001, p 2). However, pluripotent stem cells are unable to form a functioning organism. Multipotent stem cells, such as adult stem cells, can give rise only to a limited number of cell types (Wang, 2002).

In 1998, the first human embryonic stem cell lines were developed by James Thomson at the University of Wisconsin-Madison. The embryonic stem cells were derived from the inner mass of the early embryo, called the blastocyst. At the same time, John Gearhart at John Hopkins University reported the first derivation of human embryonic germ cells from an isolated population of cells in fetal gonadal tissue, known as the primordial germ cells (NIH, 2001, p 4). From both of these sources, researchers developed pluripotent stem cell lines. The pluripotent stem cell lines are capable of prolonged, undifferentiated proliferation in culture and yet maintain the ability to develop into a variety of specific cell types. The National Institutes of Health has created a Human Embryonic Stem Cell Registry, which lists stem cell lines that have been developed and can be used for research.

General Sources of Stem Cells

Stem cells can be found at different stages of fetal development and are present in a wide range of adult tissues (Wang, 2002). Stem cells can be derived from different sources and generally distinguished into four categories: embryonic stem cells, embryonic germ cells, umbilical cord stem cells, and adult stem cells. They are distinguished based on their origins and the cell types of their progeny.

Embryonic Stem Cells

Embryo stem cells are pluripotent cells taken out of human embryos and are most often donated by couples who do not wish to use them for more in-vitro fertilization processes. It is derived from the inner mass of the preimplantation blastocyst, approximately 5 days post-fertilization (NIH, 2001, p19). The embryonic stem cells are capable of self-replication and of differentiating into most all of the cells of the body, including cells of all three germ layers. A line of embryonic stem cells can be generated from a single cell under culture conditions that keep embryonic stem cells in a proliferative and undifferentiated state (Wang, 2002). The Embryonic stem cell lines can produce indefinite numbers of identical stem cells.

Embryonic Germ Cells

Embryonic Germ cells, often referred to as fetal stem cells, are derived from aborted fetal tissue. Specifically, they are isolated from the primordial germ cells obtained from the gonadal ridge of the 5-to-10-week fetus (NIH, 2001, p 2). Later in development, the gonadal ridge develops into the testes or ovaries and the primordial germ cells give rise to eggs or sperm. Embryonic germ cells appear to be similar to embryonic stem cells in their pluripotency. However, embryonic germ cells differ from embryonic stem cells in the tissue sources from which they are derived, and also differ from embryonic stem cells in their growth characteristics and their behavior in cultures. The human embryonic germ cells also have less capacity for proliferation than the embryonic stem cells.

Umbilical Cord Blood Stem Cells

The umbilical cords were traditionally treated as a waste material after delivery of the newborn. However, since the recognition of the presence of blood stem cells in umbilical cord blood in the late 1980s, umbilical cord blood collection and banking has grown quickly (Wang, 2002). Umbilical cord stem cells are derived from the umbilical cord blood remaining in the placenta and the blood vessels of the umbilical cord. Umbilical cord blood can be used as a source material of stem cells for transplant therapy. However, because of the limited number of stem cells in umbilical cord blood, most of the procedures are performed for young children of relatively low body weight (Wang, 2002). The advantage of umbilical cord blood and placenta as a source for stem cells is their transferability to other individuals without provoking an immune reaction. Umbilical cord blood stem cells are immuno-naive, meaning they have not been exposed to disease or allergens so they are much easier to manipulate in terms of treating patients (Stock, 2002). The current challenge is to promote the growth of umbilical cord blood stem cells in culture in order to generate sufficient numbers of stem cells for adult recipients.

Adult Stem Cells

An adult stem cell is an undifferentiated cell that occurs in a differentiated tissue, renews itself, and becomes specialized to yield all of the specialized cell types of the tissue from which it originated (NIH, 2002, p 2). Adult stem cells are mulipotent because their potential is normally limited to one or more lineages of specialized cells. To replace lost cells, adult stem cells typically generate intermediate cells called precursor or progenitor cells, which differentiate or develop into fully specialized cells. Such adult stem cells have been identified in a number of sources, including bone marrow, blood, the cornea and the retina of the eye, brain, skeletal muscle, dental pulp, liver, skin, the lining of the gastrointestinal tract, and pancreas (NIH, 2002). Yet, in all these sources, adult stem cells are rare. Like all stem cells, adult stem cells have the capacity of self-renewal; meaning they can make identical copies of themselves for the lifetime of the organism. However, unlike embryonic stem cells, it is usually difficult to expand adult stem cells in culture.

Why embryonic stem cells are controversial

Among the four sources of the stem cells, only human embryonic stem cells have been greatly discussed in moral issues for their use and method to extract the stem cells. Currently, there are four ways to extract the embryonic stem cells. The first method is extracting the stem cells from human embryos created by in vitro-fertilization as a method for overcoming infertility. These embryos are donated by couples who no longer have plans to use the embryos. The second method is extracting stem cells from human fetal tissues following elective abortion. The third method is extracting stem cells from human embryos created by in vitro-fertilization with gametes donated for the sole purpose of providing research materials. The fourth method is extracting stem cells from human (or hybrid) embryos generated asexually by somatic cell nuclear transfer (therapeutic cloning) of the adult human cell nucleus into an enucleated human or animal ovum. Therapeutic cloning involves removing the nucleus of an unfertilized egg cell, replacing it with the material from the nucleus of somatic cells (a skin, heart, or nerve cell, for example), and stimulating this cell to begin dividing (Somatic Cell Nuclear Transplant: Therapeutic Cloning, 2003). Once the cell begins dividing, stem cells can be extracted 5-6 days later and used for research.

The controversial part of the embryonic stem cell research is due to the issue of determining when the embryo's life begins. A question, "At what point does an embryo or fetus become "human"?," is at the core of today's battle over stem cell research as mentioned by Maienschein, director of the Center for Biology and Society at Arizona State University. The consideration that embryos are nascent human life, which must be destroyed in order to extract the stem cells, is a controversial matter and has provoked opposite opinions for using human embryonic stem cells from pro-life advocators (The Stem Cell Sell, 2001). Moreover, some populations are worried over the possibility of cloning using human embryonic stem cells. The controversial issues over the embryonic stem cells still remain and have affected the research process through government policies and funding. Further discussion of this topic regarding government polities and moral issues will be presented later in this paper.

III. Current achievements of stem cell research and potential benefits

Current usage of stem cell therapy: Hematopoietic stem cells (HSC)

The most studied and practiced stem cell research studies hematopoietic stem cell that form new blood cells. The hematopoietic stem cell is an adult stem cell isolated from the blood or bone marrow. The hematopoietic stem cells are currently used in the blood stem cell transplant therapy, which is well known as bone marrow transplant therapy. Among the first clinical uses of HSCs are the treatments of cancers of the blood-leukemia and lymphoma, which result from uncontrolled proliferation of white blood cells (NIH, 2002, p 51). Another use of HSCs are the treatment of hereditary blood disorders, such as different types of inherited anemia (failure to produce blood cells) and inborn errors of metabolism (genetic disorders characterized by defects in key enzymes need to produce essential body components or degrade chemical byproducts) (NIH, 2002, p 51). Recent research indicates that bone marrow or hematopoietic stem cells can be also induced to differentiate between other types of tissues other than blood cells. Some of these include brain, muscle, and liver cells within a mouse model (NIH, 2003). This research gives a potential therapy using HSCs for cell transplant therapy for diseases such as diabetic or Parkinson's disease. However, the fundamental problems that impose on investigator are the difficulty of definitively identifying the HSCs and getting it to proliferate, or increase its number in a cultural dish (NIH, 2002, p 45).

Possible uses of embryonic stem cell research

During recent years, the discovery of stem cells in various adult tissues, stem cell plasticity, and human embryonic stem cells have brought new excitement and opportunities (NIV, 2002). Especially the ability of the human embryonic stem cells to grow human tissue of all kinds opened a great potential for developing cell therapies to treat a wide range of human diseases. Recent research indicates that human embryonic stem cells in a mouse model can be induced to form cardiac muscle or neural tissue in the brain. 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, diabetes, osteoarthritis, and rheumatoid arthritis (Wang, 2002). Human embryonic stem cells are pluripotent and able to proliferate in a cultural dish to produce enough cells to transplant to a recipient. However, more research is required to determine how to control the differentiation of stem cells so they will be therapeutically effective. It is also necessary to study the potential of immune rejection of the cells, and how to overcome that problem.

The human embryonic stem cells can be also used to test new drugs. For example, new medications could be tested for safety on differentiated cells generated from human pluripotent cell lines (Wang, 2002). There are other kinds of cell lines already used in this way such as cancer cell lines. However, the availability of pluripotent stem cells would allow drug testing in a wider range of cell types (Wang, 2002). "Treating specific cell types with chemicals and measuring their response offers a short-cut to sort out chemicals that can be used to treat the diseases that involve those specific cell types." Moreover, "ramped up stem cell technology would permit the rapid screening of hundreds of thousands of chemicals that must now be tested through a much more time-consuming process (Embryonic stem cell fact sheet, 2000)." In order to screen drugs effectively, the conditions must be identical when comparing different drugs. Scientists, therefore, will have to be able to precisely control the differentiation of stem cells into the specific cell type on which drugs will be tested (Wang, 2002).

Another application of the human embryonic stem cell research can offer insight into human developmental events that cannot be studied directly in human in utero or fully understood through the use of animal models (Embryonic Stem Cell Fact Sheet, 2000). "A primary goal of this work is to identify how undifferentiated stem cells become differentiated (Wang, 2002)." Understanding the event that occurs at the first stages of development has potential clinical significance for preventing or treating birth defects, infertility and pregnancy loss (Embryonic stem cell fact sheet, 2000). The challenges of using most stem cells and coming up with strategies for birth defect therapy 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 during the development process (Wang, 2002).

VI. Current policy, ethical issues, and opinions of embryonic stem cell research

Because of progress in human embryonic stem cell research in 1998, medical authorities foresaw possible breakthrough treatments for previously untreated diseases, given enough time, funding, and embryonic stem cells suitable for implantation. Pro-life advocates, however, immediately objected to the research because it destroyed human embryos. Sympathetic pro-lifers in Congress moved to restrict human embryonic stem cell research, setting off a legal battle of national proportions (Konsen, 2003, p 508).

History and current government policies

In order to debate the moral issues or ethical issues evolving around the human embryonic stem cell research (ESCR), it is important to understand the government funding policies in regards to ESCR. One might wonder why government funding is such a big issue. It is because through the government funding the ESCR can be regulated and can also be sustained effectively since the research cost is pretty high

On November 1998, "the text of Congress's current ban on federally funded human ESCR lines in a 2000 amendment to the department of Labor, Health, and Human Service, and Education, and Related Agencies Appropriations Act of 1999, an act which president Clinton signed (Konsen, 2003, p 512)." On January 15, 1999, "the General counsel argued that because pluripotent stem cells obtained from destroyed embryos were not morally equivalent to embryos themselves (in other words, the cells were not totipotent), ESCR was exempt from the federal funding ban (Konsen, 2003, p 514)." On August, 9, 2001, president Bush decided to restrict federal funding for ESCR to the roughly 60 existing stem cell lines where the life and death decision has already been made. He also approved federal funding for research on non-embryonic stem cells, and signaled the formation of a president's council to monitor stem cell research (Konsen, 2003, p 518). Currently no scientist facilities are allowed to destroy new embryos to extract the embryonic stem cells if they receive government funding.

Questioned moral issues and ethical issues

One might also wonder why the government put regulation on ESCR. Embryonic stem cell research is an extremely controversial prospect to the religious right and anti-abortion advocates because it uses cells from embryos spawned by in-vitro fertilization. So is embryonic stem cell research morally wrong? Konsen give a good picture of current situation over the moral issue. She says, "Congress still thinks ESCR is morally wrong, the president agrees but wants to allow it for already dead embryos. Meanwhile, NIH researchers think it is acceptable and the court lies somewhere in between. The fifty states have yet to reach a consensus, laws from overseas offer little guidance, and public opinion seem to wander depending on whose opinion polls and public pronouncements one believes (Konsen, 2003, p 529)." Overall it is difficult to make a decision whether ESCR is morally wrong based on abortion issues.

Thus I will present the two very different opinions from pro-life advocates and scientists regarding the ethical issues of ESCR. The first argument says that ESCR is ethically wrong by presenting three definitions of the pre-born (embryos) and killing of the pre-bone (embryos) in order to extract stem cells are act of murdering and therefore unethical. Initially the argument reasons that intentionally killing an innocent human being is morally wrong and if ESCR requires the intentional killing of an innocent human being, we must then conclude that such research is a serious moral wrong (Konsen, 2003, p 530). Thus the argument gives reason why pre-bore (embryos) is human. First, human parents only produce human offspring, which means the pre-born is a member of the human community. The embryos are genetically unique and possess the inherent capacity to develop into an adult. They reason using the scientific law of biogenesis by Louis Pasteur that living things do not change from one kind of being into another over time. They only change their form. What they are stays the same. The pre-born, therefore, is not a potential human but a human with great potential (Konsen, 2003, p. 530). Second, the differences between the pre-born and the newborn are morally irrelevant. They reason that the pre-born and the new born are only different in size, level of development, environment, and degree of dependency. They give explanation that the pre-born is smaller in size like a three year old is smaller than an adolescent boy. The pre-born lives in mom's womb in stead of in the world and they are less developed than the newborn like baby is less developed than child. The pre-born is depended on mom's womb as like some of cardiac patients are depend on pacemakers. Third, they argue that the pre-born are human people because they have a human nature, not because they perform certain functions. In conclusion, the pro-life advocates argue that embryos are human and killing of those embryos in order to extract the stem cell is morally wrong and unethical.

The second argument is the NIH researchers' stand on ESCR, highlighting the fact that ESCR is great benefit to biology and biomedical field, which can save a lot of people with currently incurable diseases. Therefore, they believe that there are overwhelming medical and humanitarian justifications to expand the research (Porter, 2002). Scientists also give explanations that most embryos from in vitro fertilizations are thrown away unless used in the research and at the same time it can give a great potential benefit for medical therapy. They also point out that the therapeutic cloning, one of the methods to extract stem cells, is different from the reproductive cloning because the therapeutic cloning cannot produce fully developed organism.

The scientists say that stem cell science is still in the very early stage. Much more research is required to understand the biological mechanisms that govern cell differentiation and to identify factors that direct cell specialization. They point out that future cell therapy will depend largely on advances in the understanding of stem cell biology and the ability to harness the process of stem cell growth and differentiation (Wang, 2002). They argued that only through exploration of all types of stem cell research, especially including ESCR, will scientists find the most efficient and effective ways to treat diseases. Therefore, human embryonic stem cell research should receive continual funding from the government and should not be too restricted in the research process.

The debate over the embryonic stem cell research is a heated topic. The pluripotent embryonic stem cell has a lot of potential uses for transplant therapy, study of cell biology, and testing new drugs. However, the embryonic stem cell research has also provoked pro-life advocates because the research destroys the embryos. Currently, President Bush has made compromises between pro-life advocates and scientists through his decision on August, 2001. However, these compromises have not satisfied many on either side of the debate.

Personally, I have come to believe that the embryonic stem cell research should be continually funded by the government and also should be given more freedom to expand the research. The research can potentially help a lot of people suffering from diseases like Parkinson's, Alzheimer's, diabetes, paralysis and cancer. I agree that the research should not promote destroying or selling the embryos for the research purpose; however, using left over embryos from in-vitro fertilization is justifiable and should be allowed.

1. Embryonic Stem Cell Fact Sheet. (1998, November). Retrieved October 13, 2003, from University of Wisconsin, Office of News and Public Affairs web site: http://www.news.wisc.edu/thisweek/Research/Bio/Y98/facts.html.
2. Konsen, A. H. (2003). Are we killing the weak to heal the sick?: Federally funded embryonic stem cell research. (Note) EBSCO Publishing as web document
3. National Institutes of Health Department of Health and Human Service. (2001, June). Stem Cells: Scientific Progress and Future Research Direction. (report).
4. Porter, Jean. (2003, February 8). Is the embryo a person? : arguing with the Catholic traditions. Commonweal. 129 (3). 8, 3p.
5. Somatic cell nuclear transplant: therapeutic cloning. (2003). Retrieved November 13, 2003 from Association of American Medical Colleges web sites: http://www.aamc.org/advocacy/library/research/res0003.htm
6. Stock, Peter. (2002, January). Curing without killing. Newsmagazine (Alberta Edition) 29, (2). P 49
7. The stem-cell sell. (2001, August 17). Commonweal. 128 (14). 5, 2p
8. Wang, Chen. (2002, Dec.). Stem cells. Retrieved November 4, 2004, from Assess Science web cite, the online encyclopedia of science and terminology site, from http://www.accessscience.com/server-java/Arknoid/science/AS/Search/.

IX. Additional References

1. Adult mouse bone marrow stem cells can become cells of the nervous system. (2003, September 11). Blood weekly, p 46, 2p
2. Dart, John. (2003, January). Bush's bioethics panel begins discussions. Chistian Century. 119 (3). 14, 1p
3. Lauritzen, Paul. (2002, February). Broadening the debate on cloning and stem cell research. America. 186 (3).
4. Martin, Patrick. (2001, July). Bush, the Pope and the stem cell research. Retrieved October 1, 2003, from World Socialist Web Site: http://www.wsws.org/articles/2001/jul2001/stem-j27.shtml.
5. Mcilroy, Anne. (2003, June). Stem cells trigger organ regeneration. Retrieved October 1, 2003, from The Globe and Mail web site: http://www.globeandmail.com/servlet/ArticleNews/TPStory/LAC/20030623/USTEMM/Health/Idx.
6. Mcilroy, Anne. (2003, April). Baby teeth prove rich stem-cell source. Retrieved October 1, 2003, from The Globe and Mail web site: http://www.globeandmail.com/servlet/ArticleNews/TPStory/LAC/20030422/USTEMN/National/Idx.
7. Montminy, Judith. & Neal, Robert. (2001, June). Stem Cell Research, the Law, Ethics and Common Sense. Retrieved October 1, 2003, from Daily University Science News web site: http://unisci.com/stories/20012/0601016.htm.
8. Philipkoski, Kristen. (2001, January). When god and genes are mixed well. Retrieved October, 1, 2003, from Wired New web site: http://www.wired.com/news/technology/0,1282,41052,00.html.
9. Philipkoski, Kristen. (2003, February). House votes to outlaw all cloning. Retrieved October, 15, 2003, from Wired New web site: http://www.wired.com/news/medtech/0,1286,57854,00.html.
10. What are stem cells and what are they for? Retrieved October 1, 2003, from How Stuff Works web site: http://www.howstuffworks.com/question621.htm.