Caption: Derived from human embryonic stem cells, precursor neural cells grow in a lab dish and generate mature neurons (red) and glial cells (green), in the lab of UW-Madison stem cell researcher and neurodevelopmental biologist Su-Chun Zhang.
Photo by: courtesy Su-Chun Zhang UW Madison
Date: 11/01


Embryonic stem cell (ESC) research is one of the most promising yet controversial issues in biomedical research today. Citing ethical concerns, the federal government through the NIH currently restricts funding for embryonic stem cell (ESC) research to 60 stem cell lines that were created before August 9, 2001. I believe this restriction is unwise because it blocks a promising field of biomedical research and unnecessary because ESC research does not pose an ethical problem. Therefore, I argue that the Federal Government should lift its current restriction on embryonic stem cell research and begin to fund research on all stem cell lines derived from human embryos left over from in vitro fertilization. To support my position, I will first examine the scientific merits of expanding ESC research. I will then discuss how the derivation of stem cells from embryos left over from IVF is not ethically problematic. Following this, I will explore how embryonic stem cells may be used to treat disease. Lastly, I will summarize my position by recommending a course of legislation to be adopted by the congress.

Generally speaking, a stem cell is a type of cell that has three general properties: 1.the capacity for sustained self renewal, 2.the ability to remain in an undifferentiated state for a long period and 3.the ability to differentiate into other specialized cell types. Currently scientists recognize three types of stem cells. Embryonic stem cells are derived from embryos at the blastocyst stage (around 128 cells). These embryos are usually left over from in vitro fertilization attempts. The inner cell mass from the blastocyst is harvested and grown on a culture dish on top of a layer of mouse “feeder” cells which allow the ESC cells to attach. The process of obtaining the ESC’s kills the embryo. Another type of stem cells, adult stem cells (ASCs) or somatic stem cells are found in small numbers in certain types of tissues including blood, bone marrow, brain skeletal muscle, skin and liver throughout a person’s life. These stem cells are thought to function in tissue renewal and repair although the exact trigger of their activation and control is still under study. The third type of stem cells is known as cord blood stem cells. They are isolated from the umbilical cord of a newborn. These cells are readily obtainable and can be stored for a decade or more to be used to treat the person from which they were obtained or a suitable donor with an immune match (NIH Stem Cell Information Website, 2006).

The Federal Government should expand funding for ESC research because ESC’s have greater medical potential than ASC’s or cord blood cells. One major difference between ESC’s and ASC’s is in their potential for differentiating into different cell types. ESC’s are pluripotent. They have the ability to form any cell type in the human body (excluding the totipotent zygote). On the other hand ASC are restricted in their developmental fate. Usually, ASC’s can only differentiate into cells in a particular tissue. For example, hematopoeitic or blood stem cells can only give rise to blood cells and not other cells like neurons or liver cells (DHHS, 2001).

The capacity for differentiation is important in medicine. Most stem cells therapies are designed against diseases caused by the death of cells that do not normally regenerate, leading to a deterioration of body function. Theoretically, injecting stem cells into the damaged tissue can fix this problem by causing the stem cells to differentiate into the type of cells that need replacement. Using embryonic stem cells is advantageous because ESC’s can differentiate into cells from any tissue and thereby treat a wide array of diseases. On the other hand, adult stem cells can only be used to repair tissues from which they are derived thus limiting their utility. In addition, adult stem cells have not been found for every body tissue, thereby raising the possibility that some tissues may not be amendable through ASC’s based therapies (NIH: Stem Cell Information, 2006).

There is, however growing evidence that ASC’s are capable of trans-differentiation, a process in which an adult stem cell like a hematopoeitic stem cell is capable of differentiating into a cell type outside of its direct lineage, such as neurons. However, the extent of transdifferentiation has not been fully established (NIH: Stem Cell Information, 2006).

A second advantage of ESC’s is their ability to renew themselves without differentiation for up to one year in cell culture. ASC’s on the other hand can replicate for only a short time outside of the body before they differentiate into a specific cell type. The ability to remain undifferentiated is important because only undifferentiated stem cells are useful for therapy. Once stem cells have differentiated they can no longer adapt to the patient’s tissue. Because ASC’s can only replicate for a short time outside the lab without differentiation, this limits the quantity of undifferentiated ASC’s that can be grown for cell based therapy. ESC’s however, can be multiplied for much longer, increasing the supply of cells available. However, in this case as last, additional research is attempting to clarify the cellular controls in hopes of finding a way to allow ASC to remain undifferentiated for longer (NIH: Stem Cell Information, 2006).

One final disadvantage of adult stem cells is that as the body ages, ASC’s age as well. In September of this year, researchers discovered that a gene known as P16INK4 is a key regulator of cellular proliferation. As animals age, their stem cells begin to accumulate higher levels of P16INK4 which inhibits stem cell proliferation. As a result, these animals have a lower ability to replace dying cells or to repair tissue damage. However, attempts to eliminate or reduce P16INK4, led to mice that developed cancer at a much earlier age. Scientists hypothesize that P16INK4 accumulation is a safe guard measure that preemptively shuts down stem cells as an animal ages and accumulates mutations thereby averting tumorigenesis (17). This result means that any adult stem cells that are obtained from older individuals may have less regenerative potential due to P16INK4 accumulation. Therefore therapy attempting to use ASC’s must contend with the body’s own regulatory scheme that inhibits ASC proliferation with growing age. In comparison to ASC’s, ESC’s are very young because they have undergone much fewer numbers of cell division and come from an environment which lacks aging factors like P16INK4. Thus, ESC’s do not share the problem of cellular aging as ASC’s (Wade, 2006).

Despite the above mentioned advantages of embryonic stem cells to adult stem cells, there are some who believe that ASC research also has potential advantages as well. We address there contentions now.
A chief contention of ASC proponents is that ESC therapy must overcome one major scientific hurdle before becoming useful. This critical barrier to using ESCs in cell based therapies is the problem of immune rejection which prevents the body from accepting ESC derived from a foreign embryo. Each of us is born with different major histocompatibilities complexes that serve as markers to identify self from foreign. ESC’s which have a different HLA marker than our own face attack by our immune system when injected. Therapeutic cloning, or Somatic Cell Nuclear Transfer (SCNT) promises to solve this problem. In 2004, a breakthrough was announced by Korean stem cell researcher Hwang Woo-suk who claimed to have cloned the first human embryo. However, his discovery was later proven to be fraudulent. The scientific and political fallout and resulting restrictions imposed has set the ESC research back for several years. However, additional scientists are picking up the pieces left after Hwang’s bombshell to continue the work of therapeutic cloning. Another solution proposed by some would be create a large bank of ESC’s that will contain all the possible HLA permutations thereby circumventing the problem of rejection (Check, 2005).

Scientists remain hopeful that immune rejection will be overcome as had another problem that had plagued ESC research. Previously, ESC could only survive if grown on a layer of mouse feeder cells. These feeder cells sometimes introduced into the human ESC cells contaminants what would make them unsafe for therapy. However, recently, scientists have circumvented this problem by developing techniques that allow for the growth of ESC’s on sterile plastic container surfaces (NIH Stem Cell Info, 2006).
Another key scientific objection to ESC research is that ASC research is much better explored and established. This is indeed true. ASC based cell therapy is not new, in fact, it has been in use since the 1960’s in the form of bone marrow transplants. In addition, due to the current political restrictions, the NIH spends about 5 times more on ASC than ESC research (Okie, 2006). However, just because ASC’s have had a longer history or more research funding due to restricted policies does not mean that ESC’s will have less future potential than ASC’s.

The last category of stem cells, cord blood cells face similar problems as ASC’s. Cord blood stem cells quantity is limited because the small amount of initial obtainable cells will only undergo a limited amount of division before entering senescence. In addition, as with all non-ESC, cord stem cells are limited in their differentiation ability. Finally legal issues pertaining to the ownership of the limited amount of cord stem cells complicate their usage (Kline, 2004).

Having reviewed all three types of stem cells, I conclude that despite the problem of immune rejection, ESC’s show higher potential as vehicles for cell based therapies because of their pluripotency, ability to remain undifferentiated for longer periods and their young cellular age. Currently however, federal research funding is limited to 60 stem cell lines created after August 9, 2001. There is a need to expand these stem cell lines because the limited diversity represented by this array of cells is stifling research efforts. In addition, of the 60 lines that were made available in 2001, only 22 lines remain usable today. Even these 22 lines have a variety of problems including genomic instability and contamination by mouse feeder cells on which the ESC were grown. (Havard Stem Cell Institute, 2006; Allen, 2005). Current technology has advanced far beyond what was available in 2001 and before. Thus stem cell lines derived from current methods would be far more useful and safe than past lines.

The scientific evidence clearly supports expanding federal funding to allow for the creation of additional lines of stem cells. However, the main objection to ESC research is not a scientific but an ethical question of whether it is morally acceptable to destroy embryos to create stem cell lines. I believe that ESC research on embryos left over from IVF is acceptable. Since these embryos would be destroyed anyways if not used for research, there is no sense to not use them to advance our knowledge of biology. I do believe however legislation should be passed that would prevent the creation of embryos solely for the purpose of experimentation.

However, recently, this key moral objection to ESC obtainment may have been removed. Scientists working at Advanced Cell Technologies in Worcester, MA have discovered a way to obtain embryonic stem cells without the need to destroy the embryo through a process first pioneered for IVF pre-implantation genetic diagnosis (PGD) (Okie, 2006). Those who oppose ESC research because it destroys a potential for life should be contented since the above technology obtains stem cells while preserving the potential for life of the original embryo.

Many people ask, why can’t those who favor stem cell research be content with private funding. Why should does who do object to ESC pay for its research through taxes? The answer to this question is that current research into stem cells is still at a very basic and fundamental level. Potential profits from applications of ESC’s are still decades away. Thus, few individuals or companies have the capital for such long term investment. On the other hand, such long term basic research is exactly what the federal government funds. Without such basic research, especially through the NIH and NSF, we would not have current products like AIDS drugs or the internet. Although State funding such as that proposed by California is a step in the right direction, it is simply not enough for this important and costly an endeavor.

Turning to the second question, the basis of our government is that while we may not support each and every measure the government endorses, we agree with the majority of the government’s position and continue to support it. No government could function if each citizen could pick and chose how exactly their tax dollars were spent. For example, while some may not support the war in Iraq, their tax dollars continue to fund it.

On another level, opposing stem cell research is driving away much of our scientific talent to other nations that support such research resulting in valuable economic opportunities lost for this nation. At the same time, lack of federal funding is causing more private funding of stem cell research which may not stay within publicly accepted moral standards. Thus in order to prevent the occurrence of a stem cell “prohibition,” and associated underground research of ESC’s, the federal government should fund stem cell research and at the same time carefully scrutinize its research methods.



Caption: Culture trays containing human embryonic stems cells being viewed under a microscope and studied by developmental biologist James Thomson's research lab.
Photo by: Jeff Miller UW Madison


In conclusion, I believe that stem cell research is moral and the federal government has a responsibility to the future health of its citizens and the competitiveness of this country’s industry to fund ESC research.
Stem cells would not be such a contentious issue was it not for the fact that many people feel it holds great promise for medicine. Thus, having examined the scientific and moral basis of supporting ESC research, we now examine the potential for its dividends. Since the isolation of ESC’s in 1998, the driving force behind ESC research has been the potential use of ESC in so called cell based therapies (CBT) to regenerate lost or damaged tissue. Due to its debilitating effects on the patient and the lack of any alternative cures, neurological diseases have been a focus area for cell based therapies (CBT).

Parkinson’s Disease (PD) affects about 250 out of every 100,000 individuals in North America (Lai, 2001). Patients with PD are characterized by rigidity, tremors and general loss of motor controls. PD is caused by a gradual loss of nigorstriatal dopamine containing neurons. Current PD treatments are effective only for the symptoms of the disease but are unable to affect disease progression. Clinical trials have shown that transplantation of human fetal dopaminergic neurons (HFDN) have led to improvements in some patients with PD. However, generally speaking, survival of these transplanted neurons has been poor. In addition, there has been no evidence showing that transplanted HFDN cells are able to reinvervate the striatum which is required to cure PD. Lastly, transplanted HFDN must be localized to the area with the most nerve damage and spread out in such a way as to create even invervation. Yet, none of these requirements have been met so far in research casting doubt on the likelihood of a cure for PD any time soon. However, a potential first step being investigated attempts to transplant human stem cells that release neuroprotective molecules which can prevent nerve cell death if not lead to regeneration of new cells (Lindvall, 2006).

Alzheimer’s disease (AD) is another disease that has been targeted for cell based therapy (CBT). AD is characterized by neuronal and synaptic loss leading to progressive memory loss and impairment of cognition. As with PD, current treatments are only able to treatment symptoms leaving the mechanism of the disease untouched. AD represents a grave challenge for CBT because of the widespread death of neurons in the brain. The lack of neurons means that stem cells introduced as a treatment will not receive the cellular signals that will induce them to divide, differentiate and integrate into the existing neural network. However, if the AD patients are diagnosed early, stem cells could be introduced that will release neuroprotective factors that prevent further neuron death and disease progression (Lindvall, 2006).

In summary, from the above two cases we can conclude that even if the basic science of these neurological diseases can be clarified (which they have not been), there are still many problems that remain before cell based therapies can become a reality. First, the FDA approval process for any cell based drug is likely to be extremely stringent, even more so than the seven to ten year process that is required for current pharmaceuticals. This is because unlike chemicals, cells are biological entities that change, mutate and decay over time. Thus, any cell based therapy must ensure a minimal level of standardization across different cell lines. Quality control methods that attempt to sort cells through flow cytometry are too slow to generate the millions of cells required for therapy. Secondly, the stem cells need to be delivered to the correct site and stay at that site, a feat not consistently achievable today. Lastly, because stem cells are by nature extremely proliferative, the threat of cancer or differentiation into undesirable cell types remains to be solved. (Parson, 2006)



Caption: Microscopic 10x view of a colony of undifferentiated human embryonic stems cells being studied in developmental biologist James Thomson's research lab. The embryonic stem cell colonies are the rounded, dense masses of cells. The flat, elongated cells in between the embryonic stem cell colonies are fibroblasts that are used as a "feeder layer" on which the embryonic stem cells are grown. (Source: University of Wisconsin-Madison.)


Thus, despite the great promise of cell based therapy, a real cure for any disease is at least a decade off. As such, the greatest use for stem cells at the current moment is as a model for research. However, in the fight over stem cell funding, supporters of stem cell research have often made hyperbolic comments regarding stem cells’ potential. The “Missouri Coalition for Life Saving Cures” states “ES cells could provide cures for many currently incurable or common diseases and injuries that cannot be cured with adult stem cells, or more effective treatments than adult stem cells may provide.” (Okie, 2006) In another ad supporting ESC, a mother with a daughter with type 1diabetes is shown saying “When a Washington Politician like Mark Green says he’s going to outlaw stem cell research, I say ‘tell it to my daughter. ’” (Okie, 2006) The only result of such hype can only be a set back for ESC research since the reality of the science is that any cures based on ESC research is still years if not decades away. By promising such miracles, over eager proponents of ESC’s risk a public backlash when stem cells are unable to deliver the expected in the short term. A more rationale case for ESC research would point out that although great results are possible, they are far off. However, the only way to obtain those results is to start researching ESC today.

Having established the rationale for federal funding for ESC research, we know examine what specific legislative actions can be taken to expand such funding. We first examine the history of legislation on stem cells. The first US federal policy concerning embryonic research was the 1995 Dickey Amendment which was signed into law by the Clinton Administration. The Dickey Amendment prohibited federal funding for any research that would result in the creation of embryos for research or the destruction of a human embryo regardless of the source of that embryo (Bioethics.gov 2003). The Dickey Amendment has remained law since.

On November 5th, 1998, researchers at the University of Wisconsin first isolated stem cells from human embryos. Because the protocol necessitated the destruction of an embryo to retrieve the cells, the research was done only with private funding (Weiss, 1998). However, due to the excitement generated by this discovery, there was mounting pressure from patient advocacy groups and scientists to reverse the Dickey Amendment which banned all research on ESC. During, 2001, the newly established Bush Administration attempted to reconcile the potential of ESC with the ethical concerns of destroying an embryo with the August 9, 2001 announcement of policy. In his announcement, President Bush permitted unrestricted federal funding for ASC research but limited federal funding for ESC research to 60 cell lines that were already established by private funding at that time. The rationale for this decision came from the fact that to establish a cell line, an embryo had to be destroyed, but to continue to propagate a cell line required no such destruction (The White House 2001). Thus, the Bush Administration created a temporary loophole to the Dickey Amendment by grandfathering in 60 stem cell lines but prohibited all future research resulting in future embryo destruction.

Growing clamor for a loosening of the restrictions set by President Bush led the house and then the senate to pass HR 810 on July 18th, 2006. HR 810 authorizes the Secretary of the Department of Health and Human Services to conduct research on any ESC provided they:

(1) have been donated from in vitro fertilization clinics;
(2) were created for the purposes of fertility treatment;
(3) were in excess of the needs of the individuals seeking such treatment and would never be implanted in a woman and would otherwise be discarded (as determined in consultation with the individuals seeking fertility treatment);
(4) were donated by such individuals with written informed consent and without any financial or other inducements. (HR 810)

Despite enjoying bipartisan support, including by some congressmen who oppose abortion, HR 810 was immediately vetoed by President Bush, the first and to date only veto of his term on July 19th, 2006 (White House 2006). Attempts to override Bush’s veto failed to gain the two thirds majority required and the bill remains in congressional debate.

I believe that the correct action under the current circumstances is for President Bush to reverse his stance and signal for the congress to submit a bill similar to HR810 to him again for signing into law. Failing that, the congress should attempt to override the president’s veto with a 2/3 majority vote. In addition to being the scientifically correct thing to do, it is also wise politically as evidenced by the strong support ESC enjoyed in congress, and poll numbers indicate that a majority of Americans support ESC (PollingReport.com), especially so after a technique was found to extract ESC without killing the embryos. Given the new progressive majority in the congress currently, I believe there is a good chance that such legislation like HR810 can be passed which will expand funding for ESC research and open up a broader avenue for the pursuit of this important field of biomedicine.



Works Cited

The Administration's human Embryonic Stem Cell Research Funding Policy:
Moral and Political Foundations. September, 2003 http://www.bioethics.gov/background/es_moralfoundations.html

Weiss, Rick. “A Crucial Human Cell Isolated, Multiplied.” Washington Post November 6, 1998. http://www.washingtonpost.com/wp-srv/national/cell110698.htm

President Discusses Stem Cell Research. 8/9/2001. http://www.whitehouse.gov/news/releases/2001/08/20010809-2.html

“Frequently Asked Questions.” Harvard Stem Cell Institute. http://stemcell.harvard.edu/faq

Allen, Mike. “House Defies Bush on Stem Cells. Washington Post. 5/24/2005. http://www.washingtonpost.com/wp-dyn/content/article/2005/05/24/AR2005052400938.html

“H.R. 810: Stem Cell Research Enhancement Act of 2005” GovTrack Us. http://www.govtrack.us/congress/bill.xpd?tab=main&bill=h109-810

Bush’s Speech Vetoing HR 810. July 19, 2006. http://www.whitehouse.gov/news/releases/2006/07/20060719-5.html

Poll Numbers on Stem Cell Research. http://www.pollingreport.com/science.htm#Stem

Check E. “Where now for stem-cell cloners?”
Nature. 2005 Dec 22;438(7071):1058-9.
National Institutes of Health: Stem Cell Information [World Wide Web site]. Bethesda, MD: National Institutes of Health, U.S. Department of Health and Human Services, 2006 [cited Monday, October 23, 2006] Available at http://stemcells.nih.gov/info/basics/defaultpage

Okie, S. “Single Cell Storm” N Engl J Med. 2006 Oct 19;355(16):1634-5.

Okie, S. Stem Cell politics N Engl J Med. 2006 Oct 19;355(16):1633-7

Kline, M. “Whose Blood is it anyways.” Sci Am. 04/01/2004.

Wade, N. “Gene Called Link Between Life Span and Cancers” NY Times. 9/7/2006. http://www.nytimes.com/2006/09/07/science/07stem.html?ex=1161662400&en=3e8ca75192cd5fdd&ei=5070

Lai, Benjamin C.L.MD. “Epidemiology of Parkinson’s disease” BC Medical Journal Volume 43, Number 3, April 2001, 133-137 http://www.bcma.org/public/bc_medical_journal/BCMJ/2001/april_2001/PDEpidemiology.asp#Prevalence

Lindvall O, Kokaia Z. “Stem Cells for the treatment of neurological disorders.” Nature. 2006 Jun 29;441(7097):1094-6.

Parson A. “The long journey from stem cells to medical products.” Cell. 2006 Apr 7;125(1):9-11.

Stem Cells: Scientific Progress and Future Research Directions. Department of Health and Human Services. June 2001

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