It's Science vs. Politics in Stem Cell Research

It's Science vs. Politics in Stem Cell Research

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The Patients' Coalition for Urgent Research (CURe), a consortium of three dozen national nonprofit patient organizations, reports that over 100 million Americans suffer from illnesses, some of them terminal, which may be treated by medical advancements in the area of stem cell research (1). The list of ailments includes cardiovascular diseases, autoimmune diseases, diabetes, osteoporosis, cancer, Alzheimer's disease, Parkinson's disease, severe burns, spinal cord injuries, and birth defects. While scientists continue to look for treatments and cures for these diseases through new medicine, innovative surgical techniques, and gene therapy, perhaps the most promising research is being encountered on the frontier of human embryonic stem cell research. From the beginning of this research in animals in the early 1980's, stem cells have been celebrated for their nearly infinite potential in application towards the alleviation, and ultimately the eradication, of many branches of human illness and disease.

Animal stem cell research and preliminary human stem cell research indicates stem cells as a source of self-renewing, undifferentiated cells that have the ability to differentiate into organs, nerves, blood cells, skin, eyes, hair - basically, any tissue or cell found in an adult mammal. So far, scientists have isolated and indefinitely grown stem cells and, to some degree, demonstrated the cell's ability to differentiate into numerous tissues and cell types. From this groundwork, the scientific community envisions that research using stem cells will lead us to the ability to grow entire organs for transplant to patients suffering from kidney, liver, and heart failure; neurons for patients afflicted with Parkinson's and Alzheimer's disease; tissue replacement for patients with damaged organs or severe burns; functioning islet cells that will produce insulin for patients diagnosed with diabetes; and the list continues. Because stem cells have the ability to differentiate into every kind of cell contained in the human body, their possible therapeutic effects have the potential to help hundreds of millions of people worldwide.

However, where there is the most promise, there is also the most controversy, and the bridge between life and death relies largely on the compromise between science and politics. The case against human embryonic stem cell research rests upon the core argument that embryonic stem cells are derived from human embryos and, as such, are protected by ethical principles against human experimentation (2). Whether or not stem cells represent a viable source of human life recapitulates the same debate as the abortion controversy: the argument about when human life begins.

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However, issues surrounding stem cell research are even more complicated than abortion, given the technology's likely capacity to save the lives of millions of already living human beings. Because of this potential, even some staunchly pro-life politicians, such as Utah senator Orrin Hatch, support research using human embryonic stem cells (3). President Bush's recent decision to limit government funding of stem cell research to the use of already existing stem cell lines rides the political fence, trying to anger as few groups as possible while allowing scientists supported by the public sector to probe into stem cell research. Although neither opponents nor proponents of the research are satisfied with the decision, the door has been opened for government scientists to delve into the research already begun by the private sector.

TERMINOLOGY

Embryonic stem cells are first found five to seven days after fertilization, when the embryo forms a structure called the blastocyst. The blastocyst is a hollow, fluid-filled sphere, containing only 140 cells. The outer cells are called the trophoblast, which is responsible for the attachment of the embryo to the uterine wall and eventually forms the placenta. The inner cell mass is located at one end of the blastocyst and are the cells that will form the organism. Left in the blastocyst and allowed to differentiate further, these cells would form the mesoderm, endoderm, and ectoderm of the organism - the three layers from which all organs and tissues are ultimately derived. When harvested, these undifferentiated cells (not yet committed to becoming any particular type of cell or tissue) are called embryonic stem cells.

Because these stem cells are capable of differentiating into any cell type, they are called "totipotent." Once the cells are removed and grown in the lab (called "culturing"), they are considered "pluripotent," because, while they can still become organs and other tissues, they can no longer form an entire individual if implanted back into a woman's uterus. This is because the trophoblast is missing, without which the organism cannot form a placenta.

When the stem cells are cultured for several generations (each division being considered another generation), the resulting cells are called a stem-cell "line." Scientists place the stem cells on a layer of feeder cells, which are cells from mice that stop the differentiation of the stem cells by releasing of inhibitory chemicals. The stem cells then continue to divide without differentiating to form the cell line. These cells can then become neural cells, hematopoietic cells (precursors to blood cells), cardiomyocytes (heart-muscle cells), etc., when various differentiating factors are introduced (4). Much of the current research focuses on finding the differentiating factors that turn stem cells into differentiated cells. In some cases, stem cells themselves can be injected into tissues and are directed by signals from the tissues themselves to differentiate into the surrounding tissue type.

Other types of stem cells exist besides embryonic stem cells. These include neural stem cells, epithelial stem cells, hematopoietic stem cells, and so on. These cells are found in adults, and are responsible for the regeneration of neural, epithelial, and blood cells that occurs naturally (5). These so-called "adult stem cells" were once thought to be committed to the regeneration of the particular tissue they were associated with. However, it has recently been shown that these stem cells have the ability to differentiate into a wider range of cells than previously thought, an issue that will be addressed later in this paper (6).

PRE-HUMAN RESEARCH

Embryonic stem cells were first harvested from the blastocysts of mice in the early 1980s (7). Further studies in mice have shown that embryonic stem (ES) cells contribute to all differentiated cell types of the organism in vitro, including neural cells, blood cell lineages, and heart muscle cells. ES cells have also been transplanted into living mice and have successfully integrated both structurally and functionally into the tissues where they were transplanted (8). Neural cells, hematopoietic cells and cardiomyocytes have the propensity to develop spontaneously from embryonic mouse stem cells. Differentiation, such as the formation of embryoids (a population of cells resembling a small beating heart), or yolk sacs containing hematopoietic cells, can occur under standard culture conditions (4).

Severe combined immunodeficiency, or SCID, mice have immune systems which do not reject transplanted ES cells. When mouse embryonic stem cells have been transplanted into these SCID mice, they have developed into muscle, bone, cartilage, teeth and hair (4). A study by scientists at the National Institute of Health demonstrated the ability of stem cells to restore mobility to the hind limbs of rats paralyzed by a virus. The cells were injected into the fluid surrounding the spinal cord. Three months later, the rats were able to walk. The report admits that the disease was probably only partially corrected, as the walking observed was described as "clumsy" (10). Nonetheless, these findings give hope to humans, as the disease addressed in mice is similar to amyotrophic lateral sclerosis (ALS), a muscular disease found in humans. These findings, and others, in animal research have led patient groups to urge scientists to start research using human embryonic stem cells.

HUMAN EMBRYONIC STEM CELLS

The first accounts of derivation of ES cell lines from human blastocysts were published in November 1998. Geron Corporation (Menlo Park, CA), a private company, announced that it had funded two separate groups that had derived human pluripotent stem cells from human blastocysts and had cultured cell lines from the stem cells. Thomson et al. reported deriving the stem cells from donated embryos produced by in vitro fertilization for clinical purposes (11). The embryos used in this research were leftovers, given to researchers by individuals with informed consent after approval from an institutional review board. Thomson and his group found that the cells they derived from human blastocysts had high levels of telomerase activity. Telomerase activity is characteristic of cells with the ability for high levels of replication. Differentiated cells do not show high levels of telomerase activity. The cells also expressed certain cell surface markers that characterize embryonic stem cells, and lacked markers characterizing specific differentiated cell types. The cells were allowed to replicate without differentiating for four to five months. After this time period the ES cells still had the ability to form derivatives of the endoderm, mesoderm and ectoderm, including cartilage, bone, smooth muscle, striated muscle, gut epithelium, neural epithelium, and embryonic ganglia.

The second group funded by Geron Corporation, headed by John Gearhart at Johns Hopkins University, took embryonic germ cells (precursors of egg and sperm cells) from fetuses five to nine weeks old that were aborted for therapeutic reasons (12). When these embryonic germ cells were grown on a "feeder-layer", they behaved like ES cells, growing without differentiating for over seven months, retaining normal chromosomal structure, and differentiating into specialized cell types when properly stimulated. There is more political opposition to using this form of cell line derivation because of the use of aborted embryos. However, this method does not encounter many of the problems of IVF embryo research. Problems encountered by Thomson's group, but not by Gearhart et al., include the sometimes poor quality of the leftover embryos from IVF, as the best embryos are implanted into the mother's uterus. IVF human embryos are also difficult to develop to the blastocyst stage. Despite these problems, both groups have met with great success in culturing human embryonic stem cell lines.

Around the same time as Geron Corporation's announcement, Advanced Cell Technology, Inc. (Worcester, MA) described another method by which their scientists had produced human stem cells (13). Their technique did not use human embryos, but it still aroused quite a controversy by using nuclear transfer technology - the same technology used to clone the sheep Dolly. Using a cow egg whose nucleus had been removed, scientists at Advanced Cell Technology fused the enucleated cell with a human somatic cell (the term for any body cell that is not sperm or egg; in this case, a cell from the inside of the cheek). At the time of the announcement the company claimed that this method could provide unlimited stem cells for research, although they had not yet performed the tests routinely used to characterize stem cells (such as looking for telomerase activity or cell-surface protein markers). Besides the skepticism the scientists encountered for using nuclear transfer techniques, this research was further rejected because it combined human and non-human cells.

These three publications gave further hope to patients suffering from diseases such as Parkinson's and Alzheimer's. Public sentiment became an even stronger force pushing for government funding of human stem cell research, as research in the private sector is subject to many limitations to be discussed later in this paper. Many political and religious groups have continued to reject the use of human embryos for research. These groups argue that adult stem cell populations can provide enough differential flexibility to use in medical research, while avoiding the use of human embryos. Still, many scientists maintain that embryonic stem cells are the best source of potential medical breakthroughs, as they are totally uncommitted to any path of development.

OTHER STEM CELLS

Research on adult stem cells continues, as many of these populations have demonstrated an ability to do more than regenerate damaged tissue in their spatial region of origin. It was previously thought that many adult stem cell populations were developmentally committed to differentiation into cells of their own type and incapable of differentiating into any other cell type. However, it has now been shown that under conditions of tissue damage and regeneration, some adult stem cells can undergo metaplasia, a change in state of developmental commitment (14).

Bjornson et al. isolated neural stem cells from the brains of mice, propagated the cells in vitro for several generations, and then showed the cells could be differentiated into neurons, oligodendrocytes, and astrocytes (all cell types in the nervous system). The surprising finding, however, was that these cells could also change their developmental commitment and become hematopoietic cells when injected into other mice (6). Another study, essentially a reverse of the Bjornson et al. study, injected hematopoietic stem (HS) cells into the brains of mice. They found that the HS cells differentiated into various neural cells in the brain (14). While these studies show that adult stem cells are not necessarily irreversibly committed to differentiation into their own cell type, the differential range of these cells is narrower than that of embryonic stem cells (13). Additionally, it is more difficult to propagate large cell lines from adult stem cells. Limiting research to these stem cell types thus eliminates many cells of medical interest.

ETHICAL DILEMMAS

Numerous scientists in various scientific journals have debated the pros and cons of embryonic stem cells for medical research. The scientific community largely supports the use of ES cells because of the promise they hold for millions of Americans. While opponents of ES cell research usually question the morality of using what they consider to be potential humans for scientific research, there is a flip side to the coin. Arthur Caplan, a prominent bioethicist at the University of Pennsylvania, instead questions the morality of refusing to use tissues for research that may lead to cures for debilitating diseases, when these tissues will be destroyed even if they are not used (13). Sharon Begley, journalist for Newsweek magazine, states, "By banning [ES cell] research, we uphold the most extreme view of the sanctity of life, but at a price: foreclosing the possibility of doing all we can to improve the lot of the living" (3). Ultimately, the choice seems to be whether or not we hold a symbol of human life (IVF embryos) in higher esteem than life that already exists and stands in urgent need of our medical help.

PRIVATE VS. PUBLIC RESEARCH

Some may question the necessity of government funding of human embryonic stem cell research when private companies have already commenced such research. There are four answers. First, private companies are not subject to the overview of the government, which upholds federal laws concerning the ethical principles of scientific research. Second, research carried out by private companies is not subject to the system of intense peer review, required of government-funded research. Third, the private sector is strongly influenced by profit, and is therefore more likely to rush through experimentation and forego critical evaluation of results in order to market a product that would without doubt be welcomed and consumed by the public. Finally, private companies focus most of their funds on product development and marketing, and can consequently afford to spend limited amounts of money on basic research (13).

CONCLUSION

President Bush's decision to allow government funding for research on previously existing stem cell lines may not be the answer wanted by scientists and millions of Americans who stand to benefit from the research, but it is a start. Because of their enormous pluripotent capabilities, ES cells hold within them the ability to regenerate damaged or injured tissue, to replace entire failing organs, and even serve as an alternative to animal research in testing the safety and efficacy of new drugs. If stem cells live up to their theoretical capabilities, we may see enormous advances in research within the next ten years.

Stem cells have the ability to divide indefinitely, and, therefore, unlimited research using the cell lines already established is theoretically possible. If, however, more cell lines become needed, it is morally imperative that we permit the use of IVF embryos donated under informed consent for this purpose. Leaving the propagation of cell lines up to private companies poses several concerns, not the least of which involves a slower than necessary establishment of cures and treatments for millions of suffering Americans. Research has already been impeded for more than a decade as the concerns of those holding extreme views on the definition of human life have influenced the political sector and disabled public involvement in research. In the meantime, both public and private research has shown the efficacy of animal stem cells to differentiate into various cell types in response to in vitro stimulus and in vivo developmental signals. Preliminary research into human ES cell capabilities indicates that these cells have the same capabilities as their animal complements. In the end, it is the voice of the patient that serves as the best argument for stem cell research: "No life will ever come from these [spare embryos], except perhaps mine and more than 100 million other Americans suffering from fatal and chronic diseases" (13).

Works Cited

1. Perry, Daniel. 2000. Patients' voices: the powerful sound in the stem cell debate. Science 287(5457):1423.

2. McGinley, L. and Fawcett, A. June 21, 1999. Research supporters, abortion foes clash over research on stem cells. The Wall Street Journal.

3. Begley, Sharon. July 9, 2001. Cellular divide. Newsweek. 22-27.

4. Wright, Shirley. 1999. Human embryonic stem-cell research: science and ethics. American Scientist. 87(4):352-61.

5. Watt, F. and Hogan, B. 2000. Out of Eden: stem cells and their niches. Science. 287(5457):1427-30.

6. Bjornson, C. et al. 1999. Turning brain into blood: A hematopoietic fate adopted by adult neural stem cells in vivo. Science. 283(No.):534-7.

7. Evans, M. and Kaufman, M. 1981. Nature. 292(No.):154.

8. Gearhart, J. 1998. New potential for human embryonic stem cells. Science. 282(5391):1061-3.

9. Vogel, G. 2001. NIH review outlines 'enormous promise.' Science. 293(5529):413.

10. Thomson, J. et al. 1998. Embryonic stem cell lines derived from human blastocysts. Science. 282:1145-7.

11. Shamblott, M. et al. 1998. Derivation of pluripotent stem cells from cultured human primordial germ cells. Proceedings of the National Academy of Sciences. 95:13726-13731.

12. Jones, P. 2000. Funding of human stem cell research by the United States. Electronic Journal of Biotechnology. 3(1):30-39.

13. Slack, J. 2000. Stem cells in epithelial tissues. Science. 287(5457):1431-1433.

14. Eglitis, M. 1997. Hematopoietic cells differentiate into both microglia and macroglia in the brains of adult mice. Proceedings of the National Academy of Sciences. 94:4080-4085.
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