Weighing Ethical Gains against Scientific Costs

We live in an exciting time for modern medicine. In the last 20 years, scientists have mapped the human genome, discovered how to efficiently modify our genes, and unlocked the secrets of reprogramming and redefining our somatic cells. Undoubtedly, these discoveries will be remembered as milestones for our understanding of complex life. Furthermore, they will have major implications for how we practice medicine in the effort to thwart disease and physical injury. But perhaps more inconspicuously, these discoveries force us to confront how we ultimately define the human being. With each step forward in the long march of scientific progress, we are faced with new ethical concerns and moral debates regarding how we incorporate scientific discovery into standard practice.

Unlike normal adult stem cells commonly found in blood and bone marrow, embryonic stem cells (ES cells) remain a particularly controversial realm of research in America. Primarily, the disputes come from the “onset of personhood” dilemma, which also leads to division on the subject of abortion (Lo & Parham, 2009). From fertilization to birth, a complex dynamic unfolds inside the womb transitioning a single cell into an embryo, an embryo into a fetus, and a fetus into a baby. At what point during development do we assign human rights to the growing individual? This question lies at the heart of the personhood debate. At the five-day pre-implantation stage of the embryo, isolated ES cells are “capable of dividing without differentiating for a prolonged period in culture, and are known to develop into cells and tissues of the three primary germ layers” (NIH, 2016). This capacity for extended periods of division, known as the cell’s potency, is a characteristic that makes ES cells such an attractive area of medical research. The undifferentiated potential and capacity for replication brings forth a promising application in the field of regenerative medicine (National Academies Press, 2002).

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Image from the NIH: showing healing capacity of normal adult stem cells

And yet, research involving ES cells has been stalled by policy over the years. During the Bush Administration in 2001, the government denied the NIH funding for “the derivation or use of additional embryonic stem cell lines” (Lo & Parham, 2009). But in 2006, a breakthrough in the lab of Shinya Yamanaka of Kyoto Japan ushered in a new era of stem cell research. He and his team investigated 24 genes thought to be important for ES cells and, using a retrovirus, delivered the genes to mouse fibroblasts. Remarkably, the mouse cells were dedifferentiated, showing potency similar to ES cells. They were thus deemed induced pluripotent stem cells (IPS cells), as these new cell types were capable of becoming any other cell type in the body. Subsequently, the researchers were able to identify and isolate the important “factors” contributing to the transformation (Yamanaka, 2006).

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Image from Nature: demonstrating applications of IPS cells

Since then, research involving IPS cells has spread around the globe. In a mouse model of spinal cord injury, researchers compared hind limb function and body weight support in mice that received ES cells, IPS cells, saline solution, or a fibroblast solution in the injury site. They demonstrated that mice receiving both stem cell types showed support of body weight using the hind limbs, while those injected with saline did not. Furthermore, the stem cells exhibited a markedly greater healing capacity when compared to fibroblasts, the collagen and extracellular matrix producing cells thought to be critical in wound healing. (Tsuji, Miura, Okada, Fujiyoshi, et al., 2010). Additionally, IPS cells can function to produce new in vitro models of organismal systems in the laboratory. In one study, researchers tested the effects of oxygen-glucose deprivation on a brain-derived microvascular endothelial cell line produced from an IPS cell line (Kokubu, Yamaguchi, & Kawabata, 2017). Clearly, IPS cells have been invaluable in recent biological research.

As it stands, there have been relatively few clinical trials involving ES cells in America (NIH, 2016). Consequently, our understanding of embryonic development and cell differentiation in utero has been slow to advance. All of this must be understood in context, however. In Barack Obama’s State of the Union speech of 2016, the president said, “let’s make America the country that cures cancer once and for all” (Obama 2016). Then, in the following summer, at Howard University, Vice President Joe Biden announced the National Cancer Moonshot Initiative. This program is intended to craft a partnership between government agencies, corporate partners and medical experts to accelerate the search for a cure for cancer. Generally, most of the informed public understands the problem of cancer: a subset of cells inside our bodies replicates rapidly and can even move to regions outside of the cell’s origin. Therein lies the key concept: rapid replication. How could a developed understanding of exponential cell replication at life’s inception contribute to our fight against cancer?

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Image from Lawrence Livermore National Laboratory

In 2009, 22 human ES cell lines were eligible for NIH funding, but many were deemed unsafe for transplantation because long-standing lines were shown to accumulate mutations and serve as precursors to cancer (Lo & Parham, 2009). Indeed, even at our earliest moments of life, the threat of cancer can cast a dark shadow over our future. Here, we arrive at a rather difficult question. Do the ethical gains of unaltered embryonic stem cells outweigh the potential for a developed understanding of cell replication? Is a cancer moonshot that conducts ES cell research any less admirable if it can help the roughly 7.5 million people who die from cancer every year?

These are questions all of us must consider as scientists, as public policy makers, as students, as working class citizens, and as human beings. It is easy to feel as though you have no voice in the discussion, especially if you have no experience with cancer. Yet in truth, disease, aging, and eventually death are universal experiences that we all inevitably encounter. Unequivocally, our mortality serves as a birthright to engage in discourse on our death-right. IPS cells have given us the chance to sidestep the ethical concerns of ES cells, but only temporarily. Being induced themselves, they bypass the need to manipulate the embryo. But there comes a time when the ethical gains of an action must be weighed against the scientific opportunity cost. In doing so, we move toward a future where all people benefit from the advances of hard earned, intellectually refined medical progress.

Sources:

Committee on the Biological and Biomedical Applications of Stem Cell Research, Commission on Life Sciences, National Research Council, Board on Neuroscience and Behavioral Health, Institute of Medicine (2002) Stem cells and the future of regenerative medicine. Washington, D.C.: National Academies Press

Lo, B., & Parham, L. (2009). Ethical Issues in Stem Cell Research. Endocrine Reviews, 30(3), 204–213.

National Institutes of Health, U.S. Department of Health and Human Services. (2016) NIH Stem Cell Information. Bethesda, MD.

President Obama: State of the Union Address. (2016, Jan)

Robinton, Daisy A & Daley, George Q. (2012) The promise of induced pluripotent stem cells in research and therapy. Nature, 481, 295–305

Stark, Anne M (2016) Lab’s high performance computing will play major role in Cancer Moonshot initiative. Lawrence Livermore National Laboratory.

Takahashi, Kazutoshi & Yamanaka, Shinya. (2006) Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined Factors. Cell, Volume 126 , Issue 4 , 663 – 676

Tsuji, O, Miura, K, Okada, Y, Fujiyoshi, K, et al. (2010). Therapeutic potential of appropriately evaluated safe-induced pluripotent stem cells for spinal cord injury. Proceedings of the National Academy of Sciences, 107(28), 12704-12709.

Yasuhiro Kokubu, Tomoko Yamaguchi, Kenji Kawabata. (2017) In vitro model of cerebral ischemia by using brain microvascular endothelial cells derived from human induced pluripotent stem cells, Biochemical and Biophysical Research Communications, Volume 486, Issue 2, 29, Pages 577-583

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