Ethics of Embryonic Stem Cell Research

Introduction
Imagine a world in which everyone in need of a new organ received one within days. The transplants are not donated from another human or animal but are accepted without a single fear of immune rejection. A world in which burns and paralysis are merely minor inconveniences dealt with as inconspicuously as a cold. Chronic illnesses such as diabetes and blood disorders are permanently healed with a single injection. And the loss of a limb is a temporary condition, laughed away as meaninglessly as a paper cut (assuming we still use paper and not an iHologram in this utopian world). This is the storybook future of human embryonic stem cell research. And surprisingly, the promise of miraculous and almost mythological medical healing is beginning to be professed by even the most skeptical scientists and experts. This possible future is what fuels the scientific passion and support for this research. But this prediction overlooks a very serious conflict in the ethical community over the sacrifices made to pursue this research. The question surrounds the moral status of the embryo. Can we as a society in good conscience destroy what can potentially be a seen as a human life, in order to benefit the sick and suffering? This paper will explore this issue and show how the acceptance and use of embryonic stem cells is no more troubling than animal testing for medical purposes and that, although imperfect, it is a necessary and acceptable moral sacrifice we must make as a society until a better alternative comes along.

Scientific Background and History

A large portion of the ethical issues currently debated in the public arises from an improperly nuanced understanding of the science behind embryonic stem cell research. The major movement started in the early 1980s, when scientists derived the first embryonic stem cell line from mouse tissue. This was heralded as a cornerstone event which would usher in a new era of scientific research and innovation.4 Then, almost 15 years later in 1998, James Thompson and his lab isolated the first human

embryonic stem cell lines. This finally brought the wondrous potential of stem cell research to the field of human treatment. In a remarkably short paper (3 pages), Thompson et. al. described the first process used to isolate 5 different human embryonic stem cell lines. The stem cells came from the excess frozen embryos from 5 out of 14 different cases at in vitro fertilization (IVF) clinics. The embryos were obtained from individuals after informed consent and approval by an institutional review board to give away their excess embryos to scientific research. These donors had sought IVF treatment to solve their fertility problems which required the artificial production of embryos for later implantation. Eggs from the mother, oocytes, were artificially fertilized using sperm from the father.18 Multiple copies of these fertilized embryos were created because IVF often fails on the first few attempts.20 The process of creating an embryonic stem cell line starts with preparations for IVF. Once an egg is fertilized, it is placed into a Petri dish with a certain growth fluid to provide the cells the proper nutrients to grow. This cell is then allowed to grow and duplicate multiple times for about 5-7 days until it reaches the blastocyst stage.7 The blastocyst at this point is small, on average about 0.194mm in diameter.15 To put this into perspective, a very common diameter of mechanical pencil lead is 0.7mm. This means that about 13 blastocysts could fit on the tip of a mechanical pencil. This is the point in which embryos are normally frozen and stored for potential IVF treatment. During a normal (non-IVF) pregnancy, the blastocyst would not yet have implanted in the uterine wall of the female, leaving a high likelihood of miscarriage. In fact, around 50% of all pregnancies miscarry before implantation.8 Researchers can now legally acquire the excess embryos from the IVF clinic and continue on with the protocol to create an embryonic stem cell line.2 In order to do this, the researcher must isolate the inner cell mass, the grouping of cells that holds the true stem cell potential useful for research. They add a series of solutions to the blastocyst in order to slowly peel off the outer layers of non-pluripotent cells, leaving behind an intact inner cell mass.14 This is even smaller than a blastocyst on average about .075mm in diameter.15 This translates to about 85 inner cell masses on the tip of that mechanical pencil.

This inner cell mass is then placed onto a bed of mouse embryonic fibroblast feeder cells which provide nourishment to the cells while they continue to grow. Then after 1-2 weeks, the inner cell mass is transferred to a new plate and allowed to proliferate at will. The embryonic stem cell line is now produced.7

Why Stem Cells?

Each individual cell in this cell line is now characterized as pluripotent. This categorization is defined as a cell which can directly differentiate into any human tissue type. The outer cells lost when peeling away at the blastocyst are the cells that can directly differentiate into the placenta. But the important point is that each of these pluripotent cells can now potentially become any part of a human body. Every organ, every blood vessel, every cell in the body can be directly traced back to one of these inner cell mass cells and potentially clinically produced from these cell lines.9 Another point that makes an embryonic stem cell line so important is its immortality. This means that no matter how much of or how often you grow these cells on a Petri dish, they will not reach an age limit. The reason for this is largely due to the high levels of telomerase activity in the stem cells.18 One of the main reasons that living organisms have an upper age limit and are prevented from being immortal is because with each mitotic division, each chromosome gets shorter. Eventually this repetitive shortening becomes a functional problem and the organism has reached its upper limit. Telomerase is an enzyme that counteracts this progressive shortening and compensates for it upon each mitotic division. Humans lose telomerase expression eventually in life. But these embryonic stem cells have consistent and sufficient expression of telomerase to ensure immortality.18 Another advantage is that the cells will not independently differentiate into any of the many cell types that they are capable of developing into without any external chemical stimulus. This all means that hundreds of years from now, scientists will still be able to use the same cells isolated by Thompson et. al. in 1998 and they will still be the same, undifferentiated cells, with the same ability to become any tissue in the human body.7

Another advantage comes with a new manipulation of the embryo. Somatic Cell Nuclear Transfer (SCNT) is a process that takes an egg from the female and replaces its nucleus with the nucleus from any cell in your body (since all somatic cells in the body have the same DNA). This egg is then shocked into dividing and eventually will form a blastocyst. The important point here is that the blastocyst is genetically identically to the individual from whom the somatic nucleus was obtained. This means that the blastocyst and the inner cell mass, capable of differentiating into a full body or any tissue in the body, respectively, are now capable of creating genetically and immunologically perfect organs or tissue for the individual with absolutely no fear of rejection.19 Work on SCNT is still in its infancy and has yet to become a viable research option for most research.

When Does Human Life Begin?

A large part of the debate surrounding the morality of creating embryonic stem cell lines concerns the fundamental question about when a human life starts. Many conservatives currently define the beginning of a human life as conception, the moment a sperm fertilizes an egg and produces a zygote. As a result, the creation of an embryonic stem cell line, which necessarily requires the destruction of a blastocyst, is viewed as the destruction of human life and thus immoral and unethical. Others view a blastocyst as merely a cluster of tissue, no more significant than a piece of skin.2 This section will first explore the scientific basis behind where to define the beginning of human life. Then we will discuss the views of the three major world religions, Judaism, Christianity, and Islam, as they cover a large majority of the ethical movement and influence the moral conscious of most individuals around the world. When an egg is fertilized by a sperm it becomes a zygote. For the next week, the zygote undergoes a process known as cleavage, splitting into hundreds of different cells while the entire cluster maintains fairly the same size as the original zygote. The end of that first week is when the blastocyst finally implants itself into the uterus.19 Before this point, there is still a 50% chance that the blastocyst

will be miscarried and not correctly implanted into the uterus.8 Embryos harvested for IVF are grown to the pre-implantation stage and frozen. Then they are surgically implanted into the uterus of the mother. Excess embryos not used are the ones donated to the research labs for embryonic stem cell research. Remember from earlier that the blastocyst is about 1/13 the size of the end of a mechanical pencil. To further put this into perspective, by the 14th day in a normal pregnancy, the precursor to the umbilical cord forms. After 15 days, the primitive streak begins to form, the groove that defines the orientation of embryo development (where the head will form and the right and left sides of the body). Three to four weeks into the pregnancy, the limbs and ears begin to bud, and by the fifth week they have become distinct. And finally after about 9 weeks, the fetus has a detectable heartbeat.6,19 The most premature baby ever delivered that was healthy and survived was James Elgin Gill, born just 21 weeks 5 days after fertilization.3 Thus science does not accept the possibility of suffering or personhood of an embryo just one week from fertilization. The embryo is frequently lost in a normal pregnancy, and the week-old embryo lacks many of the basic signs of personhood, including a definition as to which side of the embryo will become the head. That is of course, unless you believe that the mere potential for life affords an embryo all the protections of a full grown human and the qualification of personhood.1 The three major monotheistic religions are not uniformly clear about their views on womens reproductive health and embryo termination. However, we can find views that the majority of religious heads would agree with along with religious law that reinforces those views. In this discussion, we will generally adopt the conservative view from each religion. In that view, all of these religions reject AID (Artificial Insemination from a Donor). The reasoning is that the act of using another mans sperm (not the husbands) to inseminate the wife is akin to adultery.16 Before continuing, it should be noted that a simple appeal to our moral intuition demonstrates our innate acceptance that embryos are not equal to humans as we all would save a small child from a burning building instead of a tray of 100 embryos.1

Currently, it is only legal in the United States to create embryonic stem cell lines from excess IVF embryos. Since the source of the embryos is IVF, we must first examine the religious views on IVF. Jewish law is nearly unanimous in allowing therapeutic insemination using sperm from the husband. The main issue with Jewish law is the loss of identity of the father of each embryo created for IVF. As long as precautions are taken to not lose the paternal identity, the creation of embryos for IVF is permissible.13,16 The Roman Catholic Church is explicit in forbidding IVF. In 1956, Pope Pius XII declared assisted reproduction as immoral as it separates human procreation from sexual intercourse. In fact, most assisted reproduction techniques are rejected by the Catholic Church. On the other hand, almost all Protestant churches allow IVF with the stipulation that the gametes come from the couple and no embryos are wasted.13,16 This means that following a traditional Protestant view, excessive embryos would not even be created to allow for embryonic stem cell research. In Islam, assisted reproduction is allowed, under many of the same stipulations as Protestant law. However, Islam views reproduction as a duty of the marriage, and thus sees curing of infertility using IVF almost as a necessity.13,16 So as it stands, Catholicism is the only major following in which IVF is explicitly forbidden as it views reproduction without sexual intercourse as immoral. The other religions put a higher value on reproduction and thus allow IVF under certain traditional conditions such as a restricted parentage. However, the creation of the embryo is only one half of the ethical puzzle for embryonic stem cell research. The other half is the destruction of the embryo. In Jewish law (Halakha), a fetus is not considered a person (Nefesh, soul) until after parturition. Furthermore, for 40 days after conception, the embryo is just considered a fluid.11,16 Christianity has undergone a change since the days of St. Thomas Aquinas. The traditional Christian view of an embryo is one of respect and protection. However, this view does not equate a zygote with a human life until about six weeks after conception. The traditional view assigns moral rights to the embryo but does not equate the sin of its destruction with that of homicide. 11,16 However, in 1995, Pope John Paul II condemned the destruction of an

embryo at any stage as an act that cannot be legitimized, essentially equating the death of an embryo with the death of a human. As he wrote in his encyclical letter, The Gospel of Life, the use of human embryos or fetuses as an object of experimentation constitutes a crime against their dignity as human beings who have a right to the same respect owed to a child once born, just as to every person.11,12,17 Islam rejects the destruction of a fetus after quickening, the first movements by a fetus in the womb. In addition, the Islamic view is that the fetus does not have a soul until 120 days after conception.11,16 With respect to abortion, the conservative view of all of these religions outwardly rejects it in cases other than rape or when the mothers life is in danger. But the main application of this idea is whether or not research scientists can ethically destroy an embryo for research.

Moral Status of the Embryo

The common theme of each major religion is a traditional acceptance that embryos are not mere tissue but also are not fully human (the Catholic Church has only recently accepted a zygote as a full human life). In Judaism, embryos are merely part of a fluid until 40 days after conception. Traditional Christianity views six weeks as the time it takes for an embryo to gain human rights. And Islam defines an embryos ensoulment after about four months.11,12,13,16,17 This assigns each embryo a certain intermediate moral status, more significant than tissue but less significant than full humans.1,2 In this view, an embryo is deserving of a certain amount of respect since it does have the full capabilities and potential to become a human, given adequate care and nutrition. While this intermediate moral status does not afford the embryo full protection against destruction for research purposes (as does basic human rights), it does imply a certain level of protection against careless and prolific destruction. The issues here come in three parts. Each embryo must necessarily go through the moral course of creation, use, and destruction, in order to be useful for embryonic stem cell research. This issue of creation is being sidestepped in many cases, including the United States, by prohibiting the explicit creation of embryos for embryonic stem cell research. Instead, lawmakers have

mandated that only the excess embryos created for the purposes of IVF, can be used in this research. One of the main advantages of creating unique embryos for research would be an ability to control the genetics behind each cell line, explicitly outlining what disease needed to be studied instead of adapting the study based on embryo availability, as is the case today.10 The first question is whether specifically creating a human embryonic stem cell line for the purposes of destruction is immoral. The cell lines created would be immortal, thus never lose their life saving potential.18 Since the blastocyst is also only a week old, the embryo has almost no human characteristics, and thus lacks basic personhood.19 And in a normal pregnancy, there would be a 50% chance that the embryo at this stage would be lost regardless of scientific intervention.8 So the problem with rejecting the act of explicitly creating embryos for research is that logically, one must reject natural procreation because for every successful pregnancy one or two embryos will have died, statistically speaking.1,8 The issue with this line of reasoning is that in pregnancy, there is the possibility that the pregnancy will not result in the death of an embryo if it happens to be successful the first time. Also, in pregnancy, the embryos are created for the purposes of granting life not death, a necessity in research. And if we assign an embryo an intermediate moral status, then this rejection is strong. If explicit creation is rejected, then the use of excess IVF embryos can be examined. IVF embryos are created for the purposes of life. However, since they are often created in excess, it is estimated that there are over 400,000 excess embryos in freezers in the United States.2 These embryos will meet three possible fates. The first is their indefinite storage in freezers. This is a resource drain and does not solve the problems of the issue. The next is their typical disposal by allowing them to thaw and then be disposed of. This way is morally problematic as the embryos were created and destroyed, but their lifespan served no purpose. Finally, they can be donated to scientific research. Here, their initial purpose is unachievable, and instead of being destroyed, they are being used to cure illness in others. This gives their existence a purpose. And with 400,000 extra embryos in need of an ethical

disposal or use, this provides an acceptable way to deal with the issue. Even some religious intuitions, such as in Judaism, encourage the use of excess IVF embryos for research purposes, demonstrating its possible public support.13 The potential for the embryo to grow into a human is the basis for the rejection to its destruction. However, that potential to become a human does not entitle it to the full protections of personhood. If a man has the potential to run faster than the competition, it does not entitle him to the right to actually claim the prize until he runs faster than the competition.1 The United States had the potential to beat the Soviet Union to the moon. However, before actually landing on the moon, the USA had no rights to be called the winner. Thus, the embryos moral status as a person is not fully realized until it actually becomes a person. Having this potential does not give it full protections. As a result, the destruction of the embryo is not protected by basic human rights because it is by itself not a human.

Animal Research Testing

We have arrived at the conclusion that granting the embryo an intermediate moral status protects it from the inhumanity of explicit creation for research purposes. However, we have also concluded that the 400,000 unused embryos from IVF treatments (many of which are currently in need of an ethical disposal) can be destroyed for research because it gives their existence a purpose.2 Since human embryonic stem cell research is still in its infancy, we must examine an analogous situation to further explore the ethical implications of the research. The question that comes up is: What other entity has an intermediate moral status and is used for research purposes? The answer is animal research testing. Animals are regularly tested on, are entitled to similar but unequal rights as humans, and are created, used and destroyed for the purposes of medical research. Few can argue the drastic benefits to science, medicine, and humanity that have come as a result of animal testing. Regularly animals are created, used, and destroyed for the explicit purposes of furthering basic science research and medical benefits. Animals are unquestionably creatures to be

treated with ethical respect as they have a capacity for pain and feelings. Thus, they are much higher than simple tissue on a significance scale.2,5 However, as a society we have placed human rights above animal rights, especially when considering our carnivorous nature. Despite this, a massive infrastructure is in place to limit the amount of suffering that these research animals endure. But they do suffer, sometimes as a required result of the experiment (although responsible scientists would rather this not be the case). The existence of the suffering of the animals is the one major separation factor between animal testing and embryonic stem cell testing. Embryos have not developed, scientifically, the abilities to feel pain in their current pre-implantation state.19 And thus, on the scale from mere tissue to full human rights, embryos fall much further to the left than animal testing. In order to be legally allowed to test on animals, scientists must demonstrate a clear scientific and clinical significance to the work. This stipulation by most countries around the world eliminates the legality of cosmetic testing on animals, which is a superfluous use of animal testing and causes unnecessary harm and suffering. Similar restrictions can be put into place for embryonic stem cell lines, hopefully limiting any major spiritual suffering the embryos may endure.1,2,5

Alternatives
Alternatives to the destruction of embryos exist. However, these alternatives have not yielded as promising results as embryonic stem cell lines. Adult stem cells and induced pluripotent stem cells that are derived directly from living humans would solve almost all the ethical problems that people have with embryonic stem cell research. However, it is important to note that all (embryonic stem cell research, adult stem cell research, and induced pluripotent stem cell research) are still in their infancy. The promise of one does not preclude the unique successes of the other.10 Thus, as scientists have been able to manipulate adult stem cells as a potential replacement, embryonic stem cell research must be maintained as an independent and viable research method. The previously described Somatic Cell Nuclear Transfer (SCNT) similarly holds much promise. However, much like adult stem cell research,

SCNT has not proven successful enough to replace embryonic stem cell lines.1,2,5 Thus, if our interests are the quickest path to truly significant medical benefits, we must tolerate the moral problems with embryonic stem cell research until the alternatives become viable enough to replace it.

Conclusion
If we as a society have accepted animal testing as a tolerable method for research, little should prevent our acceptance of embryonic stem cell research. Both require the use and destruction of their respective entities. However, use of excess IVF embryos instead of explicitly creating for the research them begins the separation of stem cell research from animal research testing. The next point that is that animals are known to have feelings and sense pain from research but embryos do not.5,19 Thus, if anything, embryonic stem cell research should be less controversial than animal research testing. Thus, if society is willing to accept the proliferation of animal use as a research tool, then there should be no problem with accepting embryonic stem cell research. New stem cell lines are needed because the current ones are becoming outdated. Also, the relatively few numbers of stem cell lines may provide a statistically insignificant result to research. Ethically problematic research such as animal testing and embryonic stem cell testing are never perfect and most scientists would jump at an opportunity to use a nondestructive alternative. But until that alternative becomes at least equally as viable as the current opportunities, we are stuck with dealing with our issues with the current methods. And in the future, the alternatives that we are exploring may give rise to the next revolution in scientific and medical treatment. As a result, maybe the utopian world previously described will be as laughably unbelievable as instantaneous worldwide communication and global transport of people and goods was to the Romans.

Bibliography
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