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Embryo, stem cell and foetus

Published: 1/19/2016

Central to research ethics is the principle that a human being cannot be used solely as a tool for research. To do so would be an affront to human dignity. But does a fertilised egg have human dignity? Or can we use it in medical research? Stem cell research, which took off in the late 1990s, has brought this question to the fore. The prospect of being able to cure people of serious diseases means that we must decide whether it is permissible to harvest stem cells from fertilised eggs or foetuses. 

Definitions

When a stem cell divides, it gives rise to two new cells. One is a new stem cell, the other a cell that begins differentiation. The remarkable potential of stem cells can thus be summed up in two words: growth and precision. Stem cells can be grown almost indefinitely in the laboratory, and could in principle develop into any tissue or organ desired. Whether this will become reality in the future remains to be seen, but stem cells have already raised hopes of generating new cells and tissues for use in treating serious diseases such as Parkinson's disease, Alzheimer's disease, type 1 diabetes and heart attacks.

When a sperm cell fertilises an egg, the new cell is called a zygote. In the course of development from zygote to embryo, a blastocyst is formed. The term 'blastocyst' refers to the fertilised egg at the 5–6 day stage. When the blastocyst attaches itself to the womb, it becomes an embryo. This is the term used to refer to the future child up to eight weeks after conception. Research on stem cells taken from 'early embryos' (blastocysts) is called embryonic stem cell research, although some would reserve the term 'embryo' for a later stage. In political and ethical debate, the use of these terms is rarely very precise. But nor is it certain that it would be helpful or even possible to apply a precise scientific language to this highly charged field. When we should use the words 'foetus' and 'embryo' and whether we can use terms like 'pre-embryo' on the one hand and 'human progenitor' on the other are all subject to controversy. (A pertinent example of the debate over language can be found by looking up 'foetus' in Wikipedia and viewing the discussion over definitions.)

Distinct stem cell sources, distinct ethical challenges

The problem with stem cells is where to get them from. Or, in technical terms, which source to harvest them from. Some sources of stem cells need not pose ethical difficulties at all. Somatic stem cells can be obtained from individuals who have already been born (so-called 'adult' stem cells), or from umbilical cord blood. Given that there are sources of stem cells that do not raise serious ethical concerns, many believe that only this form of stem cell research is defensible. Ethics would in that respect dictate research. But 'adult' stem cells have a major limitation with regard to growth – they are multipotent, which means that their ability to produce new cells is limited. There is debate in academic circles over how much potential lies in these ethically unproblematic stem cell sources. If it transpired that that embryonic stem cell research would have greater potential to save lives in the future, would we not then be ethically obliged to pursue precisely this type of research? Answering 'yes' to this question would nevertheless entail an ethical evaluation of the 'costs' of embryonic stem cell research. The anticipated benefits are only one side of the story.

Stem cells from fertilised eggs: Taking lives to save lives?

In 1998, James Thomson of the University of Wisconsin in the USA managed to isolate pluripotent stem cells from blastocysts that had been generated from fertilised eggs in association with assisted reproduction. When stem cells are isolated from the inner cell mass of a blastocyst, the beginnings of a human life come to an end. This is at the heart of the major controversies surrounding embryonic stem cell research today. Is it acceptable to end a human life as part of research that aims to save lives?

There are many different approaches to this issue. Among them are three classical lines of reasoning that all argue in favour of protecting the fertilised egg/embryo (we use the terms rather loosely here), albeit on different grounds. One can claim that the fertilised egg is already a person (in the moral sense), and therefore has human dignity and a right to life. One can claim that the fertilised egg has the potential to become a person, and that everything with this potential should be afforded strong protection (Føllesdal 2008). Or one can claim that the fertilised egg gradually develops into a person, and that its moral worth and protection must be graded in line with this development. Based on the first two positions, embryonic stem cell research will be difficult if not impossible to accept. According to the latter position, the embryo's right to protection is 'graded', which implies a willingness to consider whether other (beneficial) factors could override this right.

Supporters of embryonic stem cell research will often adhere to the gradualistic view. This view 'accords with' embryological development, and many will take it for granted. This is not a guarantee that it is correct. Other positions that are actually more conducive to embryonic stem cell research are those that assume a delayed 'humanisation' – that is, the fertilised egg first becomes a person with a right to life (and thus acquires a 'soul') at a later stage of foetal development (Saugstad 1992). Another such position focuses on individuation as a necessary condition for the right to life (Smith & Brogaard 2003). Early on, the fertilised egg can divide and give rise to identical twins. Only after some 14 days can we know with certainty whether we are dealing with one human life or several. The famous Warnock Committee that first explored this issue in the UK in the 1980s arrived at this latter position. This led to a judicial regulation of research in the UK whereby research on the embryo is permitted in the first 14 days of life.

Surplus fertilised eggs: Study first, destroy afterwards?

Abstract philosophical reasoning about when life begins need not come into close contact with the laboratory. But when considering the ethics of embryonic stem cell research, it can be useful to know the background for how fertilised eggs can become a source of stem cells. At the heart of the matter is assisted reproduction. When egg and sperm cells are combined in the laboratory with the aim of providing infertile individuals with children, there is often an excess of fertilised eggs. Today ethically conscious fertility clinics implant only a single embryo inside a woman to reduce the risk of multiple pregnancies. The remaining embryos are frozen. When a couple have had their desired children, any fertilised eggs remaining in the freezer are said to be 'surplus'. These surplus fertilised eggs have conventionally been destroyed.

The question is whether or not such a scenario has any bearing on the issues described above. Is it not better for a 'surplus' fertilised egg that will be destroyed regardless to be put to good use in research? This question highlights a challenging aspect of the ethics of medical applications of biotechnology: It is difficult to be consistent. Assisted reproduction is in essence about giving life. But it also creates 'surplus' lives, which in turn leaves us with choices regarding the 'usage' of such lives. President Bush once said that there is no such thing as surplus fertilised eggs. In the USA, private adoption agencies exist to deal with surplus fertilised eggs to ensure that none goes to waste. There is consistency in this if one believes that the embryo has a right to life. But this view has not caught on in the restrictive environment of Europe. Here it can seem as though the use of embryos (for research) is a more sensitive issue than that of their destruction per se.

Religion has an important role in these debates. But religion may itself be subject to more fundamental cultural constraints. The 'religion argument' in the USA was used to advocate a ban on stem cell research because fertilised eggs went to waste. The Council of the Church of Norway has supported stem cell research using surplus fertilised eggs because this is better than letting them go to waste.

Is the intention behind embryo creation ethically relevant?

Some who defend the use of surplus fertilised eggs in stem cell research wish to draw a distinction between the use of surplus fertilised eggs and the production of 'new' fertilised eggs exclusively for research. The latter scenario does not involve a fertilised egg that was produced in order to become a human being, and then proved superfluous. Instead, a human life was deliberately created solely for research. Does this constitute an ethically relevant difference? The embryo's moral status should seemingly be the same regardless of the intention behind its creation. But those who argue in favour of this view will often draw another ethical consideration into the debate. The production of fertilised eggs exclusively for research objectifies the embryo more than the use of surplus embryos does. The embryo has not had the chance to fulfil its purpose (Gr. telos), it is claimed, but has been made solely for instrumental reasons (that is, purely as a tool).

A number of stem cell scientists have expressed concern over the need to be dependent on surplus fertilised eggs from assisted reproduction. Women may feel under pressure to donate fertilised eggs. Consent may become illusory (a debt of gratitude). Doctors may feel under pressure to fertilise more eggs than necessary (in order to be able to offer these to researchers – who are often themselves...) and thus expose women to stronger hormone treatments. These ethical challenges would be avoided if we were not dependent on surplus fertilised eggs. On the other hand, we would then need to recruit other women to act as egg donors, and would probably need to compensate them for the considerable stresses involved. This is not without ethical problems either. In the USA, which allows paid egg donation for assisted reproduction, women receive between five and ten thousand dollars to donate eggs (figures from 2008). The large sum is compensation for the risks and stresses associated with egg collection. But is it right for research to be dependent on women undergoing risky and invasive procedures of no benefit to themselves and motivated primarily by the prospect of financial gain?

Is the embryo's context ethically relevant?

Another position that regards the laboratory and the circumstances around fertilisation as ethically relevant is the view that there is a distinction between embryos that are intended for implantation in a womb and those that are not. Human DNA is necessary for becoming a person, but it is not sufficient. Only when the embryo is implanted in a womb do we have the conditions required to produce a human being. Seen in this manner, the embryo's context is therefore ethically relevant.

But this position is also controversial. It is easy to come up with conditions that were once thought to be sufficient, and show that they are in fact only necessary. Today a woman who does not want to bear a child can choose in many countries to have an abortion. As such, some would argue that the woman's intention to bear the child is a necessary condition for becoming a person. But what if the woman wavers? One day she wishes to continue the pregnancy, the next she does not. Will the moral status of the foetus then change back and forth accordingly? This example shows that a 'context-based' position on moral status also poses many challenges.

Therapeutic cloning

If stem cells are harvested from fertilised eggs, and made to successfully differentiate into tissue with the potential to help a person suffering from a serious disease, one well-known challenge still remains: The patient may reject the tissue as a result of so-called tissue incompatibility. One solution to this problem, and also to the issue of using fertilised eggs from assisted reproduction, is a technique called therapeutic cloning. In common with 'ordinary' cloning, this technique involves cloning a human being by transferring the nucleus from a patient's body cell into an egg cell from which the nucleus has been removed. However, the cloned embryo (the patient's clone) that is 'initiated' with an electrical impulse will not develop into a person. Instead it will be used solely for therapeutic purposes to harvest stem cells that, in a sense, are the patient's own.

Therapeutic cloning has proven technically difficult and has already given rise to one of the greatest cases of scientific fraud the world has seen, with South Korean scientist Woo Suk Hwang playing the lead role. But in ethical terms, therapeutic cloning raises both new and old questions. The new is of course the issue of cloning: Should we base therapeutic interventions on human cloning while simultaneously opposing reproductive cloning? The old relates to the moral status of the fertilised egg and embryo. We must assume that an embryo generated as a result of therapeutic cloning is also a human embryo with the potential to become a person. In other words, the harvesting of stem cells from this embryo makes the aforementioned concerns over the production and destruction of embryos for research purposes a reality.

However, there is a paradoxical relationship between these issues that gives rise to yet another concern. If we emphasise that embryos have (a certain) entitlement to protection, then avoiding destruction of embryos ¬– or destroying as few as possible – must be a good thing. This must also apply to embryos that are the result of therapeutic cloning. But if we maintain that cloning humans is a threat to human dignity, then any possibility of a cloned embryo developing into a human being must be seen as potentially dangerous. This restrictive form of ethics thus argues both for and against embryo destruction simultaneously. This paradox has probably contributed to a ban on therapeutic cloning in a number of countries worldwide. But several countries in our part of the world have chosen to perform further research on this technique. The UK and Sweden are among them. This gives rise to yet another challenge for research ethics: How should we deal with the fact that therapeutic cloning is prohibited in Norway, but permitted in other countries? Can we send our researchers to Sweden? Could we accept any future therapies that result from such research?

'Human progenitors' that cannot become human

Biotechnology is known for its ability to create entirely new forms of life, and this has driven some researchers to seek not just to identify, but rather to create, ethically defensible stem cell sources. ANT or Altered Nuclear Transfer is one such approach. This technique builds on the aim of therapeutic cloning, namely to develop a stem cell source that avoids problems with tissue incompatibility. At the same time the goal is to create an embryo, or rather an 'embryo', which lacks the potential to become a human being. By making changes to the cell nucleus that is inserted into the empty egg, it is possible to avoid creating an embryo that could become a person.

It was the American William Hurlbut, a member of The President's Council on Bioethics, who in 2005 proposed this solution to the ethical challenges of stem cell research (Hurlbut 2005). The technique would appear to offer the best of both worlds. It overcomes the biggest objection to stem cell research in American public opinion, namely that it involves the destruction of human life. However, in Europe, as previously discussed, the focus has been more on the instrumentalisation of embryos than on their destruction. Viewed in that light, it is not clear that a technique which contributes to further manipulation of human heredity will be regarded as a solution to existing ethical challenges. Other objections raised against ANT include the difficulty of showing beyond doubt that the 'embryos' created do not have the potential to develop into human beings. ANT will also face the same challenges as therapeutic cloning with respect to obtaining eggs from women. It will be necessary to depend on egg donors, who again will require substantial compensation for the risks and stresses involved.

Aborted foetuses – uncomfortable but not unethical?

The final source of stem cells that we will discuss is the aborted foetus. The same year that Thomson published his results on stem cells from fertilised eggs, another American, John Gearharts, reported that he had isolated pluripotent stem cells from 5–9-week old aborted foetuses. Harvesting stem cells from induced abortions is probably so controversial today that it hardly seems likely to become the stem cell source of the future. However, let us take a look at the ethical considerations involved.

One of the most common arguments against 'using' aborted foetuses in medical research is that doing so may give the impression that abortion is desirable from society's perspective. This may mean that women who are in doubt about abortion will decide in favour of it because the 'usefulness' of the abortion will count as an additional supportive argument. If we acknowledge that the debate around abortion reflects a conflict between the foetus' right to life and the woman's right to decide over her own body (which we need not do), then it may seem as though a society which makes itself dependent on access to aborted foetuses can hardly also believe in the importance of safeguarding the foetus' right to life.

On the other hand, it must be remembered that biological material from abortions exists as a result of a woman's autonomous decision to terminate a pregnancy. That decision will, at least in principle, be taken irrespective of any potential future use of the material for research. An analogy can perhaps illustrate why this need not be problematic: We transplant organs from people who have suffered serious accidents resulting in brain death. The organs in such cases become available 'by chance' and not as a result of any intention to subject the person to an accident in order to harvest their organs. Of course in some such incidences, the death may indeed be the result of an evil act, but as long as this does not have any connection with removal of the organs, we do not consider any potential organ donation to be 'defiled'. Provided there are guaranteed watertight boundaries between a woman's decision to have an abortion and use of the resulting material, it could be argued that the use of aborted foetuses is treated as more controversial than it needs to be. At the same time, many will argue that it is safest to keep this type of medical research separate from the practice of abortion.

What is ethical stem cell research?

A review of different stem cell sources thus reveals that each has its own associated ethical challenges. Stem cell research is particularly controversial because it touches on issues that many societies do not believe it is possible to reach agreement over, such as the moral status of the embryo or foetus. What is fascinating from a research ethics perspective is that rarely has the development of a new field of research been so closely entwined with ethical debate.