Abstract
14-Day Rule describes the timer of two weeks set on the development embryonic stem cell in vitro. Beyond, the 14 days cap the research is stopped and the contents are destroyed to ensure no further development occurs. After the birth of the first test tube baby in 1978, in 1979, the 14-Day rule was established, and it is currently incorporated in the laws of many countries. In the early days developing the embryo to the 14 days limit was infeasible but with current development of technology, such as pluripotent somatic cell, use of transcription factors and genetic remodeling, the embryo is being developed to a great extent within 12-13 days. This puts the 14-Day rule a subject to change, since it is not only failing to address its purpose but also, due to the vagueness in the definition of the of the embryo it has become difficult to conduct further studies. To change this rule, it is mandatory to establish proper definitions to all the embryonic stages and a new ethical consensus is required between the scientific and the general public communities. The update to the rule must be based on the embryonic stages, rather than a specific time set.
A Race that Ends in 14 Days
Sadman Shawraz
ENG 21003-E Writing for Sciences
CCNY Fall 2019
Michael Coppola
An average human body is composed of around 30 trillion of cells (Sender, 2016) but during the first stage of human development, or any other sexually reproductive species, all of it starts from one cell, the fertilized egg cell known as zygote. Later as it differentiates in three layers of cells called germ layers, all the cells of the layers are pluripotent, meaning each cell is capable of developing an entire organ or an organ system, for example cells from the mesoderm, one of the germ layers, can differentiate into connective tissues, such as bone & blood and skeletal muscles responsible for movement etc. Also known as embryonic stem cells, the research on these cells is crucial and of great value, as this can be used to produce a complete organ for transplant, fix damaged tissues or even be used heal disconnected or damaged nerves which results in paralysis in parts of the body. However, the research in this field is politically and ethically controversial as it uses early embryonic human cells, cells that form a child. Using the stem cells from human embryo, according to John (2009), “is fraught with disputes about the onset of human personhood” (p. 729). Chan (2018) points out two oppositions on this dilemma, at one side, there are those who believe embryo is a form of human life with moral status equal to that of any other living humans and on the other side, they believe it is just a collection of cells which do not possess any of the features to be called a living human. In the 1970s, the stem cell researchers wanted to tackle the ethical issue and a scientific consensus was taken in 1979 on a 14-Day Rule beyond which the embryonic stem cell must not be let to develop, by the Ethics Advisory Board of the US Department of Health, Education and Welfare (Hyun et al., 2016). In those days, growing a human embryo beyond two weeks was not feasible due to the lack of technological advancement and knowledg. However, in 2013 a research team from Oregon Health & Science University led by Masahito Tachibana discovered a completely different method of developing and studying embryonic stem cells. Instead of isolating stem cells from a developing embryo, the researchers were able to develop embryo like structure by inducing pluripotency to somatic human cell. In other words, they used regular body cells, and turned them to stem cells using transcription factors. After few days the cells formed a primitive streak (Tachibana, 2013). Primitive streak is a streak formed by cells that states the earliest possible trace of the higher vertebrate embryo after fertilization in the ovum. Reaching the 14-Day threshold the researches had to destroy the cells. Furthermore, in the following year a research team from the Rockefeller University in New York City, developed the three germ line layers from embryonic stem cells using bone growth factor, within the 14-day limit (Warmflash et al., 2014). This proved that the 14-Day rule not only has become obsolete due to the advancement in current research and technology but also a restriction to the advancement in this field of research. As a result, scientists and ethical researchers have come to the point of asking the question whether or not to change or remove the 14-Day Rule in human embryonic stem cell research. In this article, we will discuss why the 14-day rule has failed to realize its purpose for which it was established and procedures that should be followed while addressing the ethical standards when adopting a replacement for the rule.
The establishment of the 14-Day rule was first proposed in the 1970s to address the ethical issue of human embryonic stem cell research, believing that the development a stem cell of the human embryo does not reach the level where it can be called a living being in just two weeks. After the establishment of the rule in 1979, many other countries have adopted the rule in their rules and regulations of human embryonic stem cell research. At least 12 countries have included this law, such as China’s 2003 Ethical Guiding Principles on Human Embryonic Stem Cell Research and India’s 2007 Guidelines for Stem Cell Research and Therapy (Hyun et al., 2016). Countries such as Canada, Sweden and Australia have also incorporated this law in their stem cell research. The rules apply to different stages of the embryo, in different countries, depending on how they are defined. For example, it can cover embryos produced via any means, even from somatic cells; or specifically fertilization, or the formation of the gastrulation stage with the three germline layers or the primitive streak which Tachibana et al. (2013) reached using somatic stem cells. The irregularity in definitions make it more difficult for the scientists to do their research, as Warmflash et al.’s (2014) prove, since they developed the gastrulation stage before reaching the 14-day threshold. This stage comes after the primitive streak formation developed by Tachibana et al. (2013). Both researches discarded the stem cells after 14-Day was reached but it put the rule in question as it failed to specify at what stage it is unethical to stop the research.
Before we can redefine the law, we need to understand where the law fails. Both Warmflash and Tachibana’s team reached the 14-day threshold but they both reached completely two different stages in development in the embryo. Thus, defining the stages projects a key value in renewing the 14-Day rule. Piciocchi & Martinelli (2016) analyzed the definition of the word “embryo” which is a result of the controversy in the bio-ethics, moreover, understanding the specific steps of the embryonic development is necessary when deciding on the debate of renewing the law of embryonic stem cell research. The laws regulating the stem cell research, of different countries uses the terminology “embryo” differently but all the laws bind the research to a 14 days limit. For example, in a case from Bundesgerichtshof, Federal Court of Justice in Germany, Oliver Brüstle v Greenpeace (2011), the court included the definition of the embryo as “any human ovum after fertilisation, any non-fertilised human ovum into which the cell nucleus from a mature human cell has been transplanted, and any non-fertilised human ovum whose division and further development have been stimulated by parthenogenesis”. Furthermore, The difference between the embryo in stem cell research and the same term used in the abortion laws needs to be addressed (Piciocchi & Martinelli 2016). Since words may carry different meaning when leaving the scientific field and into the general society, before articulating a new law to replace the 14-Day rule it is crucial to have a general consensus on the developing stages of the embryo, types of embryonic stem cells corresponding to their production such as in vitro from a somatic cell or sample zygotes provided by a clinic 4-5 days after fertilization. Only after developing a specific term we can redefine the 14-Day rule where instead of using the time of development as a threshold, a certain defined embryonic stage should be considered a point of intervention.
Shen (2018) identifies the lack of knowledge in the scientific community when describing and identifying the steps of a human embryo development. To understand the various developing stages, it became necessary for researches to push the research of the embryonic stem cells to its maximum limit, the 14-Day threshold. From donated embryos for in vitro fertilization (IVF) procedure, researchers were able to develop the embryo in vitro and identify the key features in the development of early human morphogenesis which include segregation of the pluripotent and extra-embryonic lineages, generation of bilaminar disc, formation of pro-amniotic cavity, appearance of the yolk sac and trophoblast differentiation (Shahbazi et al., 2016). This revolutionary step in understanding the developing stages of human embryo is crucial in human health research which will not only help us identify birth defects but also help maintain the health of both the mother and the child during the pregnancy stages. However, even though Shahbazi and her team’s feat is revolutionary, it was limited to the 14-Day rule. Furthermore, Shen (2018) also suggests genetic remodeling, such as the use of CRISPR technology, since it is difficult for scientists to find embryos for research. Thus, artificial embryos are used to explore the cellular signals and physical forces in the developing embryo (Shen, 2018).
When discussing these studies of scientists and researchers, it can be said that the 14-Day rule has failed to realize its purpose for which it was established. It was established to ensure that the human embryo is not developed to a sentient stage in vitro. However, using stomatic cell, genetic remodeling, growth factors and other technologies scientists has reached deeper stages into the embryonic development before reaching the 14 days cap. Though there were no evidence showing that the developed embryo reached the stage where it can be said that it perceives feelings, all the development came to an abrupt stop at 12-13 days. This proves that the 14-Day rule has become obsolete.
In the year 2016, International Society of Stem Cell Research has provided new guidelines regarding all forms of stem cell research. The guidelines provided pathways for research in the fields of embryonic stem cell, such as, human embryo research, procuring human eggs, formulation of human-animal hybrids or chimeras and induced pluripotent stem cells. Furthermore, these guidelines tackle the clinical challenges and provide ethical standards when translating the researches into applications in health and medicine. In the article 21.1.3.3 Category 3, the 14-Day rule is established as, “In vitro culture of any intact human preimplantation embryo or organized embryo-like cellular structure with human organismal potential, regardless of derivation method, beyond 14 days or formation of the primitive streak, whichever occurs first”. Kimmelman (2016) finds the new guidelines as a well-stablished ethical standard in regulating stem cell research since the guidelines were established on professional standards via extensive research by scientists in the corresponding fields. Since the guidelines are not actual laws, they provide opportunities for countries when establishing new laws regarding the matter of stem cell research and its clinical application. However, regardless of the guidelines’ ethical standards and extensive description on stem cell research, the 14-Day rule was described in only one section with one paragraph. Not only, the rule was not updated but also no other alternatives were provided regarding the human stem cell research. The ISSCR’s acknowledgment of the 14-Day rule describes, the current standard of embryonic stem cell research up to 14 days are to remain as it is, due to the lack of our understanding of the human embryo to the extent where we can successfully establish a replacement rule.
To ensure further development in the embryonic stem cell research the 14-Day rule needs to be changed and a new rule needs to be set, not based on time rather based on a precise developing stage of the human embryo. To identify that particular stage, more research is needed into understanding the embryonic development. This also create a dilemma as there is a necessity to remove the 14-Day rule to understand the human embryo development, and there is a requirement to understand the developing stages to abolish and change the 14-Day rule in the first place. To work around the dilemma researchers can set up a temporary rule which replaces the 14-Day rule to establish an understanding the stages of the embryo so that a new defined rule can be placed, even though, it can create ethical concerns on which of stage the development of the human embryo is stopped.
When the 14-Day rule was established, first and foremost it addressed the issue of studying the human embryo which raised multiple ethical flags during the early stages of research. The 14-Day rule was able to derive a consensus of both the scientific and social communities. Changing the rule can undermine the relation of the two communities which can not only create concerns in the public but also redirect funding in this crucial research. If the 14-Day rule is changed based on the time, for example to 21 or 28 days, there is a ethical dilemma; if the rule is changed then what are the chances that the 21 or 28 days will hold in the future when there is a new requirement to change the rule and if there is any guarantee that whether or not the rule will be completely abolished leading to future creation of artificial human beings. Chan (2018) agrees to this dilemma, as she writes that even after 28 days a human embryo is far from sentience and new ethical approach is needed to understand the issues that the artificial developing embryos might create. She also points out, it was only recent when the first baby born from mitochondrial replacement transfer was announced, and asks the question, how far we are from the announcement of a child born by ectogenesis or from synthetic embryo, though far away in future, but requires paradigm shift in our ethical understandings (Chan, 2018). In conclusion, there is an essential requirement to update the 14-Day rule to develop our understanding of the field of embryonic development and to change the rule extensive research is required in the consensus of both scientific and social communities. It is also crucial to update the rule not based on the time of development, rather the stages. This will not only ensure a better system of embryonic stem cell research but also provide guidelines for researchers regardless of their initial point of embryonic development, either from a donated egg or induced pluripotent stomatic stem cell.
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