What is Wrong With Embryonic Stem Cell Research?
by Rich Deem

Introduction

Stem Cell Research?

Are conservatives more concerned about a tiny clump of cells than the suffering of their fellow human beings? Is embryonic stem cell research (ESCR) really the cure-all for countless diseases? If you haven't kept up with the science involved in ESCR, this paper will jump-start your knowledge of the issues.

Rich Deem

Embryonic stem cell research is a hot topic that seems to pit anti-abortion conservatives against pro-abortion liberals. The conservatives claim that there are better alternatives to embryonic stem cells, while the liberals claim that conservatives are blocking research that will provide cures to many tragic diseases. Much of the rhetoric is designed to muddy the waters to invoke emotional responses of those within each camp. This paper is designed to break through sound-bites and go the heart of the matter - what are the scientific issues that impact the question of stem cell research.

What is stem cell research

Much of what is promoted as being news is actually an oversimplification of the issues. Many news articles about stem cell research never distinguish between the kind of stem cell research that is being promoted. For example, the media often reports of breakthrough treatment for patients without mentioning that, in all cases, the source of stem cells is adult tissues. We know this to be true, because embryonic stem cells have never been used in human patients, and won't likely be used in the near future (see reasons, below).

Where do stem cells come from?

blastocystStem cells are classified as being pluripotent or multipotent. Stem cells that are pluripotent are capable of forming virtually all of the possible tissue types found in human beings. These stem cells can only be found in a certain stage (a blastocyst) in human embryos. Multipotent stem cells are partially differentiated, so that they can form a limited number of tissue types. Multipotent stem cells can be found in the fetus, in umbilical cord blood, and numerous adult tissues. A summary of this information can be found in the Table 1.

Table 1. Stem cell types
Stem cell type Description Examples
Pluripotent Cells can form any of over 200 cell types Some cells of a blastocyst (5 to 14 day old embryo)
Multipotent Cells are partially differentiated, but can form a limited number of other tissues Fetal tissue, cord blood, and adult stem cells

A list of the sources of stem cells, along with their advantages and disadvantages can be found in Table 2.

Table 2. Sources of stem cells
Stem cell type Description Advantages Disadvantages
Embryonic Cells from human blastocysts Pluripotent Requires embryo destruction
Fetal stem cells Cells from gonads of aborted fetuses Multipotent Requires destruction of weeks old fetus
Umbilical cord stem cells Cells from the umbilical cord blood of newborns Multipotent/ Pluripotent?1 Low frequency of stem cells
Placenta derived stem cells Cells from the placenta of newborns Multipotent/ Pluripotent? Low frequency (but higher than cord blood)
Adult stem cells Cells from adult tissues Multipotent Very low frequency
Induced pluripotent stem (iPS) cells Cells from adult tissues reprogrammed to pluripotency Pluripotent Not patentable (i.e., drug companies can't make enough money)

History of stem cell research

Although the controversy of stem cell research is only recent, research first began in the 1960's. The primary source of early human stem cells was adult bone marrow, the tissue that makes red and white blood cells. Since scientists realized that bone marrow was a good source of stem cells, early transplants were initiated in the early 1970's to treat diseases that involved the immune system (genetic immunodeficiencies and cancers of the immune system). Bone marrow-derived stem cell therapy has been extremely successful, with dozens of diseases being treated and cured through the use of these adult stem cells. However, because the donor tissue type must be closely matched to the patient, finding a compatible donor can be problematic. If you haven't already done so, you should become part of the Bone Marrow Registry.

Failures of therapeutic cloning

With the advent of animal cloning, scientists had thought that patient-specific human cloning might provide cures without the tissue incompatibility problems usually associated with transplants. Specific stem cells, developed using clones genetically identical to the patient, would integrate optimally into the patient's body. Although ideal in theory, problems associated with human cloning have been quite formidable. After many years of trying to produce human clones, a South Korean group claimed to have done so in 2004,2 followed by a claim that they had produced patient-specific clones. However, subsequent questions revealed that all the research was fraudulent. Contrary to the original claims, the researchers failed to produce even one clone after over 2,000 attempts. Although a number of labs are working on producing human clones, none have succeeded - even after several years of additional attempts. At a cost of $1,000-$2,000 just to produce each human egg,3 therapeutic cloning would easily cost hundreds of thousands of dollars, if not more, for each patient. Therefore, these kinds of therapies would only be available to the wealthy, assuming the technical difficulties will eventually be eliminated.

Embryonic stem cell research no longer necessary?

Three separate groups of researchers showed recently that normal skin cells can be reprogrammed to an embryonic state in mice.4 The fact that these iPS cells were pluripotent was proved by producing fetuses derived entirely from these transformed skin cells. Just five months after the mouse study was published, the feat was repeated by two separate laboratories using human skin cells.5 The ability to produce embryonic stem cell-like lines from individual patients removes the possibility of tissues rejection and avoids the high costs and moral problems associated with cloned embryos. Dr. Shinya Yamanaka, one of the study leaders later commented, "When I saw the embryo, I suddenly realized there was such a small difference between it and my daughters... I thought, we canít keep destroying embryos for our research. There must be another way." The moral problem of destroying a human embryo encouraged Dr. Yamanaka to pursue a more ethical way to generate human stem cell lines. See the full report.

What diseases might be cured by stem cell research?

Stem cells have been promoted as a cure for numerous diseases in the popular press, although the reality of the science suggests otherwise. For example, claims that stem cells might cure Alzheimerís disease are certainly untrue. According to Michael Shelanski, Taub Institute for Research on Alzheimer's Disease and the Aging Brain (Columbia University Medical Center), “I think the chance of doing repairs to Alzheimer's brains by putting in stem cells is small.”  Ronald D.G. McKay, National Institute of Neurological Disorders and Stroke says, “To start with, people need a fairy tale.”6 Stem cell research is widely promoted as a possible cure for type I and type II diabetes. However, these diseases involve the destruction of islet pancreatic cells by the patient's immune system. Even if tissue-compatible islet cells can be produced, transplanting them into a patient will be a very temporary cure, since the patient's immune system will attack the transplant in short order. So, a total cure for diabetes might have to involve a total immune compartment replacement (with its risks), in addition to an islet cell transplant. Parkinsonís disease is another disease that is often mentioned as potentially curable through stem cell research. Proponents of ESCR cite studies in which embryonic stem cells produce dopamine in the brain of rats. However, only 50% of the rats had improvement of function and 25% developed brain tumors and died!7 A main problem for ESCR is that these stem cells spontaneously form tumors in virtually all studies that have been conducted to date. In addition, it seems that the number of dopamine-producing neurons declined over time, suggesting that the cure might be just temporary.8

Problems in stem cell research

According to many stem cell researchers, embryonic stem cells are the preferred stem cells for cell-based therapies. Although they tend be be more versatile than adult stem cells, other sources (including umbilical cord stem cells) have proven to be just as versatile.1 The same properties that make embryonic stem cells so versatile are also the properties that make them unusable for therapy. Unless completely differentiated prior to use in patients, these cells will migrate throughout the body to produce tumors. Experiments performed in mice and rats have shown that spontaneous tumor formation is a persistent problem.7-9 Maintaining and growing embryonic stem cell lines has also been problematic. Some of these lines have mutated, making them unusable in patients.10 The main problem with embryonic stem cell research is the problem is tissue incompatibility.11 Millions of lines must be established in order to serve a significant percentage of potential patients. The use of autologous adult stem cells (cells from the patient) eliminates the problems with tumorogenesis, mutation, and tissue incompatibility. However, since such individualized therapies could not be patented, the pharmaceutical companies have no financial incentives to pursue such therapies. In contrast, embryonic stem cell lines could be patented. Since millions of lines would be required to serve all the different tissue types of patients, pharmaceutical companies could charge a fortune for each patented line they produced. Scientists and research facilities that produced such lines would also reap large financial benefits. The highly favorable financial aspect of embryonic stem cell research is one of the main driving forces behind the push to fund this research.

Table 3. Problems in Stem Cell Research
Stem Cell Cost Tissue rejection Mutation Problems Ethical Problems Works for genetic diseases
Human Embryos Low(?) (IVF leftovers) Yes Yes Human embryo destruction Yes
Human Clones High None No Cloned human embryo destruction No
Adult Autologous Low None No None No
Adult Donated Low Yes No None Yes
iPS (Adult Reprorgammed) Low None No None No

The problems involved with embryonic stem cell therapies are so formidable that renowned neurosurgeon Dr. Keith Black remarked in 2004 (during California's Proposition 71 stem cell campaign) that his lab would pursue only adult stem cell research. In fact, his group (the Maxine Dunitz Neurosurgical Institute at Cedars-Sinai) recently announced that they had converted adult stem cells into neural stem cells.12

Conclusion Top of page

Human embryonic stem cell research has been promoted as being the best way to pursue cell-based therapies for a number of diseases. Although embryonic stem cells are the most versatile type of stem cells, they are unacceptable for therapy because they spontaneously form tumors when transplanted into a compatible host. Embryonic stem cells also suffer from the usual tissue compatibility problems associated with donor transplants. The proposed solution to tissue compatibility problems, therapeutic cloning, is technically challenging (i.e., it hasn't been accomplished yet) and fiscally prohibitive (costs on the order of hundreds of thousands of dollars per patient). In contrast to embryonic stem cell technologies, adult stem cells have been used to treat dozens of diseases, with the list growing every year. Pursuing this technology would eliminate the tissue rejection problems associated with embryonic stem cells, and the high cost associated with therapeutic cloning. A new technique involving reprogramming of adult skin cells (iPS) has proved feasible, producing pluripotent ESC-like stem cells, potentially from individual patients. However, because individualized adult stem cell therapies cannot be patented, this research does not appeal to biotech companies and scientists and research centers seeking royalty payments for patents. With the announcement that embryonic stem cell-like lines can be produced by reprogramming adult human skin cells, the potential usefulness of embryonic stem cell research has been lost for many stem cell researchers, as they are now pursuing the new technology, which will be cheaper and provide fewer problems for use in patient-directed therapies.



References Top of page

  1. KŲgler, G. et al. 2004. A New Human Somatic Stem Cell from Placental Cord Blood with Intrinsic Pluripotent Differentiation Potential. Journal of Experimental Medicine 200: 123-135.
  2. Hwang, W.S., et al. 2004. Evidence of a Pluripotent Human Embryonic Stem Cell Line Derived from a Cloned Blastocyst. Science 303: 1669-1674.
  3. Mombaerts P. "Therapeutic cloning in the mouse." 2003. Proceedings of the National Academy of Science 100:11924-5.
  4. David Cyranoski. 2007. Simple switch turns cells embryonic Technique removes need for eggs or embryos. Nature doi:10.1038/447618a.
  5. Gretchen Vogel 2007. Researchers Turn Skin Cells Into Stem Cells. ScienceNOW Daily News 20 November 2007
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    Takahashi et al. 2007. Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors. Cell doi:10.1016/j.cell.2007.11.019.
  6. Rick Weiss. Stem Cells An Unlikely Therapy for Alzheimer's. Washington Post Thursday, June 10, 2004; Page A03.
  7. Bjorklund, L. M., R. Sanchez-Pernaute, et al. 2002. Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proceedings of the National Academy of Sciences 99: 2344-2349.
  8. Carson, C. T., S. Aigner and F. H. Gage. 2006. Stem cells: the good, bad and barely in control. Nature Medicine 12: 1237-1238.
  9. Bjorklund, L. M., R. Sanchez-Pernaute, et al. 2002 "Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model." Proceedings of the National Academy of Sciences 99: 2344-2349.
  10. Draper, J.S., et al., "Recurrent gain of Threadlike "packages" of genes and other DNA in the nucleus of a cell. Different kinds of organisms have different numbers of chromosomes. Humans have 23 pairs of chromosomes, 46 in all: 44 autosomes and two sex chromosomes. Each parent contributes one chromosome to each pair, so children get half of their chromosomes from their mothers and half from their fathers.chromosomes 17q and 12 in cultured human embryonic stem cells," Nature Biotechnology December 7, 2003, advance online publication.
    C. Cowan et al. 2004. Derivation of Embryonic Stem-Cell Lines from Human Blastocysts. New England Journal of Medicine 350: 1353-1356.
  11. E. Phimister and J. Drazen. 2004. Two Fillips for Human Embryonic Stem Cells.Ē New England Journal of Medicine 350: 1351-1352.
  12. Stem Cells Cultured from Human Bone Marrow Behave Like Those Derived from Brain Tissue from Cedars-Sinai Medical Center, 2/2/07.

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Last Modified March 31, 2009

 

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