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by Sadhana Bala '17  Human embryonic stem cells. [image via] In the United States, the biomedical significance of human embryonic stem cells (hESC) is recognized by Democrats and Republicans alike. Every passing month brings reports of the newest successful application of embryonic stem cells to a specific medical cause. hESC therapy has been used to further research on a wide variety of ailments – including spinal cord injury, multiple sclerosis, infertility and even hearing loss (1) – and it has generated largely promising results. The controversy with hESC research does not center on the results but the methods – a moral dilemma that has been greatly debated in the media for years. Embryonic stem cells are derived from four- to five-day-old blastocysts, hollow balls of cells that represent the beginning stage of human embryo development. The extraction procedure often results in the destruction of a human embryo, usually one that has been voluntarily donated in a fertility clinic. But the huge potential of these cells has caused scientists, politicians, and the general public (2) to come to terms with this fact. Over the last two to three years, embryonic stem cells have, more or less, crawled off the agenda of the general media. Government-sponsored research for embryonic stem cells is currently at a pinnacle, yet it remains hindered due to one small piece of decade-old legislation After years of vetoes from President Bush and disapproval from factions of Congress, President Obama issued an executive order (3) in 2009 that expands funding from the National Institutes of Health for research on embryonic stem cells that come from an NIH-approved list of existing stem cell lines (lineages of stem cells that are derived from a common embryo) (4). While this policy change has definitely opened up opportunities for scientific advancement, it still restricts hESC research in one crucial way: it prohibits government funding for the creation of any new stem cell lines. Every year since 1996, Congress passes a mandate in the form of the Dickey-Wicker Amendment (5) – a clause attached to the yearly budget appropriations bill for the Department of Health and Human Services. This 17-year-old act explicitly disallows funds for research that involves the destruction of a human embryo (the main way hESC lines are created). Consequently, only a select group of already extensively researched stem cell lines is available for federally funded research.  Rep. Jay Dickey (R-AR) originally proposed the amendment. [image via] The list of approved stem cell lines is publicly available in the NIH Human Embryonic Stem Cell Registry (6). The registry reveals that there are currently 261 eligible hESC lines for which the government will fund research. While 261 may seem like a decent number, the number of useable cell lines is not as great. Some of these stem cell lines have been frozen, thawed, and refrozen for years on end, and are not good for research. Since many of the stem cell lines have deliberate mutations and were created for a specific research project spearheaded by a specific institute, they may not be useful to the average researcher. Curiously enough, a small number of institutes, including Harvard and a private Australian cell bank called Genea, have created a large proportion of the approved stem cell lines. Other entities, like the Reproductive Genetics Institute, have never had one of its many submitted cell lines approved. The same database shows the list of stem cell lines that are pending NIH approval. Some of these lines have been under review for nearly four years, confirming that the rate at which the NIH approves more fundable cell lines is sluggish. So what is the big deal with publicly funded researchers working on only a restricted assortment of existing stem cell lines? Firstly, a singular stem cell line that is constantly passed down between laboratories and researchers has a high likelihood of accumulating genetic mutations or chromosomal aberrations. Although hESCs can divide indefinitely, their utility decreases after years of experimentation. The risk of contamination is also present, and this could lead to poor results and misguided conclusions. Next, though hESC lines share common characteristics, such as the abilities to differentiate and to rapidly reproduce, they also differ in many other regards. Some lines respond better to certain types of cell media, while others show little success rate in differentiation. Swedish scientists have found that at least 3% of expressed genes differ in a collection of 25 – seemingly identical – stem cell lines (7). Therefore, researches who can only use a limited variety of stem cell lines are not able to explore the full potential of stem cell therapy, for they lack the most crucial resources. Since biomedical disorders are complex and multifaceted, these limited resources are a great setback. The last issue with the small number of stem cell lines available for research is not as well-known but is highly consequential. A University of Michigan research team (8) analyzed 47 of the most commonly used embryonic stem cell lines and found that a majority of these were derived from donors of northern and western European ancestry. None of the lines came from donors of other ethnicities. The therapies and medical treatments that are results of hESC research may react differently to various ethnic and racial groups, due to genetic or epigenetic (environmental) factors. Therefore, it is necessary for researchers to experiment with hESCs that are derived from donors of all types of ancestry. Otherwise, advancements made with stem cell research may be applicable to only a small subset of the US population. This, in the words of one of the University of Michigan researchers, is a “social justice issue.” The Dickey-Wicker Amendment, though only a small legislative rider to an executive agency’s appropriation bill, has and will have long-term effects on human embryonic stem cell research. There is a need for researchers to expand the number of stem cell lines they work on, but, under current legislative restrictions, the list the NIH offers is not extensive. The question that ultimately arises is complex: do the costs of creating human embryonic stem cells, outlined in the Dickey-Wicker Amendment, outweigh the benefits of a more comprehensive, useful, and thriving field of stem cell research? The research that is being done currently to find methods of hESC creation that do not destroy embryos is one way out of this dilemma, but will not yield conclusive results any time soon. The way forward, then, is to perhaps bring the Dickey-Wicker amendment back to the negotiations table after 17 long years.
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