Recklessness without rigor: Disturbing Science and the Lack of Oversight in Human Stem Cell Research

If science isn’t rigorous, it’s reckless. This statement was, in 2015, the rally cry of the National Institute of Health (NIH) as it called for the implementation of rigor and transparency to scientific research receiving NIH funding (Hosfeth, 2018). It appears, however, that those days are over. The recent International Society for Stem Cell Research (ISSCR) decision to remove the longstanding “14-day rule” limiting experimentation on human embryos beyond two weeks of their creation calls into question rigor and smacks of recklessness.

Not without limits

The International Society for Stem Cell Research (ISSCR) promotes global collaboration among stem-cell scientists and physicians. They play a catalyzing role in the development of new medical treatments utilizing human stem cells from aborted babies. Beginning with its founding in 2002, the ISSCR has overseen guidelines which set standards for directing stem-cell research.


Disturbingly, the ISSCR and its bevy of influential scientists and ethicists recently advocated for and

established new guidance that removes the longstanding “14-day rule.” The “14-day rule” limits research on intact human embryos to this period because after this 14-day period the central nervous system begins to develop.

The rule was meant to provide researchers with the opportunity to conduct experiments within the early stages of embryonic development, but not without limits. With embryonic research occurring throughout the world, some countries, although not the United States, have codified the “14-day rule” into law. Lack of Oversight and blurred lines

For years, the boundaries of the “14-day rule” were not pushed by researchers, not only for legal and ethical reasons but for technical ones as well. The primary reason for the seeming status-quo was that human embryos could not be kept growing in lab dishes beyond that limited period. However, technological advances in cell-culture techniques have surpassed that limit and scientists are ready to move beyond the rule.

New techniques in the world of stem-cell research have exploded. Scientists now create embryo models which transform cells into what resembles early embryos, creating chimeras, animals or animal embryos that have some cells from human or a differing species, and the development of organoids, cell-derived in vitro 3D organ models that allow the study of biological processes that mimic endogenous cell organization and organ structures. All in an environment where…

What is at stake?

Since its inception, consensus for the development of the “14-day rule” has been divided. Some within the scientific community feel that the rule was never meant to represent a firm moral boundary but instead a practical limit (Hyun et al, 2016), while others observe that since its creation, the rule has attributed moral significance to the process and experimentation (Nuffield Council on Bioethics, 2017). Such a division leaves the outcome of an open-ended rule recommended by ISSCR ambiguous, giving decision-making authority to arbitrary societies, boards and scientists who have an interest in extending the rule for specific research purposes. A clear conflict of interest.


The 14th day is significant for several reasons. First there is gastrulation, the development of multiple layers of cells. The development of multiple layers creates the embryo’s significance as a distinct individual. A developmental step which some claim gives moral standing to the embryo. Equally important is the potential for the embryo’s development of sentience after the 14th day of development. Sentient, being associated with perceptions, awareness, and the possibility of response, further establishes the individuality of the embryo, making it even more important to consider the limitation of stem-cell growth beyond the 14th day.


These are important points that are currently debated in the scientific community. Technological advances do not minimize the need for consideration of the outcome for these cells and the aborted babies that provided the cells.


Developing awareness of the inherent creation of life within embryonic stem-cells, one can acknowledge the slippery slope created by an ever-increasing time window for the use of these cells in research. And while, for some, this slippery slope may not be an issue, the possibility exists that continued research without limits and oversight facilitates the development of research technologies which remain incompatible with a respect for the distinct individual inherent in the embryo. Continued research using embryonic stem-cells beyond the “14-day rule” allows for the unapproved, unregulated, and frightening sphere of germline gene editing. A technology responsible for China’s gene-edited babies (“Germline Gene-Editing Research Needs Rules,” 2019).

Read the article here: Nature: Germline gene-editing research needs rules


Accountability and governance

The primary consideration of the moral implications of stem-cell research gives way to a broader crisis of confidence and trust among the public in the ways in which scientific communities create and implement science policies and regulations (Appleby & Bredenoord, 2018). While ISSCR panel members responsible for developing the new guidelines establish that these new guidelines are a starting point for new debate within the scientific community (Lanese, 2021), others are more cautious.


At question is the openness, transparency, and informed nature of the development of standards and guidelines that regulate continued embryonic stem cell research. A process as grave as stem-cell research requires oversight. There need to be standards that provide for the consideration of not only the use of embryonic stem cells, but also for the life manipulated when using such cells. Such a process must be regulated, and that regulatory process should not be left in the hands of a professional society that promotes stem-cell research and holds a clear conflict of interest.


Regulatory scrutiny provides a means of oversight. While some countries have established specific laws and maintain a rigorous regulatory framework, others do not. The UK has the Human Fertilisation and Embryology Act 1990, and a regulator, the Human Fertilisation and Embryology Authority—the HFEA, for licensing embryo research within the first 14 days (Appleby & Bredenoord, 2018). Currently, the HFEA only permits research with a clear purpose, and it must be licensed (Appleby & Bredenoord, 2018). Such a model could be extended to any new standard to ensure rigor, consistency, and morally acceptable processes.


For the common good… Really?

Balancing the risk/harm of scientific research against its potential benefit to individuals and society has long been a consideration in clinical research. Importantly, we can all identify past studies involving vulnerable populations that illustrate the way in which self-interest and blurred lines related to research standards increased ethical misconduct in clinical research. Notably, consider not only unethical Nazi human experimentation during the Holocaust, but also the Tuskegee study, the natural history of syphilis was studied in poor, black male sharecroppers, the Willowbrook Hepatitis Study, which lasted from 1963 to 1966 and required mentally deficient children be enrolled in a research study to gain placement in a residential facility, and the 1963 Jewish Chronic Disease Study, in which older and senile patients were injected with cancer cells to examine cell rejection (Jairath, et al, 2006).


It is noteworthy that while currently deemed unethical, at the time each study was conducted, they were deemed ethical and consistent with the standards of the time. And while each study arguably advanced clinical understanding, they clearly did not advance the common good (Jairath et al, 2006).

The “14-day rule” arose after the birth of the first “test-tube” babies in the 1970s. With the breakthrough research and the knowledge that embryos could be grown outside of the womb made the world aware that such research needed rules. Josephine Johnston, a scholar with the Hastings Center, a nonprofit bioethics organization, noted that the early rules were “…a political decision to show the public there is a framework for this research, that we aren’t growing babies in labs.” (Regalado, 2021).


As rules regulating stem-cell research are being called into question, communities, and individuals, notably unborn children, need the same reassurance and framework given after earlier breakthroughs. Rigorous scientific research is the groundwork for continued innovations. Scientific rigor means applying the highest standards and best practices of the scientific method to research. It is all about discovering the truth.


Claiming outcomes for the common good, scientists must apply rigor and seek the truth with honesty, not an outcome tainted by self-interest. Working for the common good includes protecting the vulnerable. Blurring ethical lines not only marginalizes but also harms and maims. Overlooking the effect and giving such treatment the name of research method or advanced technologies continues to lessen the understanding of the value and sanctity of life. Children and the vulnerable deserve better and their muted voices will forever cry for the common good.


References

Appleby, J. B., & Bredenoord, A. L. (2018). Should the 14-day rule for embryo research become the 28-day rule?. EMBO Molecular Medicine, 10(9), e9437. https://doi.org/10.15252/emmm.201809437


Germline gene-editing research needs rules. (2019). Nature, 567(7747), 145–145.

https://doi.org/10.1038/d41586-019-00788-5


Hofseth L. J. (2018). Getting rigorous with scientific rigor. Carcinogenesis, 39(1), 21–25.

https://doi.org/10.1093/carcin/bgx085


Hyun I, Wilkerson A, Johnston J (2016) Embryo policy: revisit the 14‐day rule. Nature 533: 169–17

Jairath, N., Donley, R., Shelton, D., McMullen, P., & Grandjean, C. (2006). Nursing and the common good [Journal]. Health Progress; Catholic Health Association of the United States.

https://www.chausa.org/publications/health-progress/article/november-december-2006/nursing-and-the-common-good


Lanese, N. (2021, May 26). Influential panel recommends removing “14-day rule” on lab-grown embryos [News]. Livescience.Com. https://www.livescience.com/14-day-rule-extended.html


Nuffield Council on Bioethics (2017) Human embryo culture. London, UK: Nuffield Council on Bioethics


Regalado, A. (2021, March). Scientists plan to drop limits on how far human embryos are grown in the lab [News]. MIT Technology Review. https://www.technologyreview.com/2021/03/16/1020879/scientists-14-day-limit-stem-cell-human-embryo-research/

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