Stem cell research: An approach based on orthodox bioethics

It would probably not be an exaggeration to say that the ethical issues raised by research into the nature and potential of stem cells are the number one bioethical issue today, both in the media and in expert circles. In order to understand the ethical dilemma of the issue, we must delve into some technical and biological details.

Stem cells, also called progenitors, are the cells of the initial development of the embryo up to the stage of 16 to 32 cells. Such cells are also present in the umbilical cord environment, as well as in adult organisms, especially in the spinal cord. What makes them valuable in medical research is a property of theirs which in the language of genetics is called totipotency. Totipotency is defined as “the ability of a single cell to reproduce an entire individual»[1]. That is, each of these cells contains within itself the information for the further development of the entire human organism. In these cells, the process of their differentiation into specific tissues has not yet begun, which is why they are also called undifferentiated. The property of totipotency has focused the interest of scientists on unraveling the secret of differentiation, which if revealed is believed to provide the possibility of laboratory production of tissues and organs for transplantation. Also, stem cells after genetic editing can be introduced into organs and tissues where there is cell dysfunction and replace it[2]. At present (stem cells) can be used to treat many serious diseases, such as various forms of cancer, leukemia, hematological disorders, immunodeficiencies, etc. Research, which is ongoing, holds great promise for the treatment of other diseases, such as Alzheimer's disease, Parkinson's disease, diabetes mellitus, various metabolic disorders, cardiovascular diseases, liver disorders, multiple sclerosis, muscular dystrophy, spinal cord injuries and strokes.[3].

The core of the bioethical issue regarding stem cells concerns mainly the process through which they are procured by the scientific community and less so their (potential) therapeutic application.[4]Stem cells grow and multiply in cultures, which are created through three basic methods:

1. With the first method, stem cells are obtained from the inner cell mass of 5-10-day-old embryos. This method is the easiest from a technical point of view, but it has also created the most ethical dilemmas. These are what are characterized as embryonic or fetal stem cells. These embryos are usually created in the laboratory, in-vitro and are not implanted in the female uterus for the purpose of pregnancy and birth. It should be noted that even in many countries such as Germany[5], Italy etc. the creation of such embryos is prohibited. In most cases, embryonic stem cell cultures are used for the "surplus embryos» from in vitro fertilization. The set of cells obtained from the embryos are "pushed" through laboratory techniques to develop permanent undifferentiated cell lines. With appropriate manipulation through growth factors, they can theoretically differentiate into all types of tissues[6].

2. A second method of producing stem cells is by obtaining (pre)gametic cells from aborted embryos. These pregametic cells are the precursors of the subsequent sperm or egg. This method encounters serious technical problems and is probably being abandoned as an alternative solution.[7]In some European countries such as Germany it is one of the methods that is legally permitted.

3. The third method uses cloning techniques[8]. This method is similar to the first with the difference that the stem cells are obtained from the embryoblast of cloned embryos and not embryos of in vitro fertilization. They are created through the technique of somatic cell nuclear transfer, or otherwise the Dolly method, from the well-known sheep, the first product of this type of cloning. In this case, there are two possibilities: 1. To implant the cloned embryo in a human uterus and to be born normally, which is strictly prohibited by all laws or 2. to let it develop until the blastocyst stage (4^η day after cloning), from which the desired stem cells will be obtained. However, these stem cells are not completely totipotent, like the first embryonic ones, but pluripotent. That is, they cannot develop into all types of tissues and organs, but only into certain[9].

Because in the above cases we have the creation, experimental use and destruction of embryos, in most Western countries there have been strong reactions and therefore bans or moratoriums on research. The research community, in addition to its response to the bans, has made efforts with new techniques to create the necessary stem cell lines without the use and consequent destruction of embryos.

The main ones of these techniques are the following:

1. Transdifferentiation of adult somatic cells. Through genetic interventions, cells taken from adults (mainly skin) are returned to the state of undifferentiated stem cells.[10].

2. Another method of obtaining stem cells is to collect them from umbilical cord blood during pregnancy. This method also gave rise to the well-known issue of stem cell banks. However, these stem cells are not particularly "pliable" and suitable for research. [11].

3. Obtaining stem cells from adults is indicated for regenerative medicine-type treatments, where after special gene editing the cells are introduced into the type of tissue from which they originated. In this direction, sufficient progress has been made to the point that it is estimated, based on very recent announcements, that the medical community is very close to their clinical use[12]However, this type of stem cells cannot satisfy all research requirements, mainly due to the technical difficulty of obtaining sufficient quantities.[13].

            As has already been seen from what has been stated so far, the main bioethical issue that arises concerns the moral status of embryos. It is a central issue of bioethics that is the subject of study and reflection by biology, medicine, philosophy, theology and law. Each of these disciplines, which usually make up the bioethical dialogue, has a particular perspective.

            The view that the embryo acquires substance from the moment of fertilization, that is, from the moment it is in the state-stage of the zygote, is based on its consideration as a potential person, a view which constitutes a philosophical principle (potentiality principle). In short, this principle dictates that "Since the zygote has the potential to develop into a human person, this potential requires that it be treated as if it were already a person. Therefore, it is not ethically acceptable to use it for the production of human embryonic stem cells, regardless of any potential benefits that might arise. »[14].

            At an important meeting of scientists from the fields of genetics, medicine and bioethics, which took place in Berlin on April 19-20, 2007, on the topic: "Ethical considerations regarding stem cell research in Europe" this principle became the main subject of bioethical discussions. It was considered necessary to examine its background, its significance and ultimately its validity, since many ethical arguments and legislation based on it prevent the development of stem cell research. For example, "…in Germany the embryo enjoys the protection of the law and an embryo is considered to be any zygote, as well as any pluripotent cell that is separated from it. Thus, it is a criminal offense to use pluripotent cells for any intervention that does not aim at treatment or, more generally, the good of the embryo»[15]So here we observe the beginning of the dynamic view of the fetal status in full force.

            There were scientists from the field of genetics at this meeting who argued that the results of recent research shake or even refute the principle of considering the embryo as a potential person. They stated that a dynamic view of the zygote without an environment for development means nothing. This view was greatly strengthened by the results of the Takahashi and Yamanaka group, which demonstrated that the overexpression of a specific combination of genes can transform fibroblasts (differentiated cells) into stem cells, equivalent to embryonic ones. This is the process of redifferentiation, which until now was considered ethically unobjectionable. The “redifferentiated” stem cells can develop into complete embryos after their introduction into tetraploid blastocysts[16]This means that in biological terms, the principle of dynamic consideration also applies in this case, so these redifferentiated stem cells can also be considered embryos, i.e. persons.

            The general conclusion that is drawn is that the dynamic view in its true dimensions is a variable state, which can apply to any cell through interventions and modifications in a certain set of genes. Given this, it is a tragic irony that research efforts aimed at reprogramming cells from adults, in order to circumvent the ethical problems of stem cells, overwhelmingly undermine the basic ethical argument on which most of these ethical problems were based, namely the dynamic view of the embryo.

«If the principle of dynamic vision were to be applied consistently, then any future creation of stem cells through the reprogramming of adult somatic cells would have to be prevented. Just as this unlikely conclusion attests to the ethical implications of research into the reprogramming and redifferentiation of cells. In other words: if, through the manipulation of selected genes, a differentiated cell can be reverted to a state of pluripotency, this transitional state cannot claim any moral status. It would be simply one of many states in which a cell can exist inside or outside the human body.»[17].

            So what does all this have to say to those seeking an ethical way out of stem cell research? That the search for ethically unacceptable ways of producing stem cells is a futile effort for the scientific community. Based on the principle of the dynamic view of embryos, none of these methods can be considered ethically unacceptable, since for each cell there is the technical possibility of restoring it to a state of omnipotence. So theoretically there is the possibility of an embryo, a potential person, coming from it. This means that from a biological point of view the principle of considering the embryo as a potential person is refuted. In other words, the fact that a zygote has the potential to develop into a human does not mean that we should treat it as a human person.

            The scientists involved in the debate were critical of the validity of this principle.[18]They pointed out that the natural law on which ethics and legislation are often based changes according to scientific discoveries and social forces. This raises the question of why this principle of the potential person continues to govern bioethics and legislation in many cases.[19];

            To what has been said, we must add that the efforts that took place in the USA to create stem cells that, while retaining the property of all-power, would have been technically deprived of the possibility of further development into embryos have been scientifically refuted. These were the ironically called "politically correct vote cells", which in a "meticulous" way tried to provide a solution to the problem of the potential person. Geneticists tried to technically cancel the possibility of further development of the embryo, through the removal of a gene crucial for its development[20]More or less the logic of the whole project can be summarized as: "I will take away your ability to develop in advance, because it is immoral to destroy you from the moment I allow you to have it.».

Orthodox Viewpoint

As we have already said, the core of the whole problem is the status of the embryo (as a zygote here, as a completely initial form of embryo) and the principle of its dynamic consideration, that is, of its consideration as a potential person. The positions of individual orthodox bioethicists (e.g. HT Engelhardt[21], J. Breck[22], Patriarch of Mesogaia and Lavreotiki[23]) but also the official texts of the local Orthodox Churches (Greece, Russia, Romania[24]) clearly advocate the principle of dynamic perspective. The big difference, of course, is that although the reasons for its formulation from an Orthodox perspective are taken from the field of biology, its foundation is on a theological and not philosophical or biological basis. It would be interesting to see all the relevant texts and compare them, however, we quote in fragments as the most comprehensive and representative of all, the text of the Church of Greece on assisted reproduction, in which a thorough reference is made to the status of the embryo:

«Τthe efetus eHello,I ἀrcor MsI perspectiveor ἀnthώpin. Ta κύtarά of, thethe geneticthe ἀlickό of, or morphologicalίa and bI or physiologistίa of eἶYes theLa ἀnthώPina. Ms.I or strongόttά of na ἀto grow῿ σὑ τέsmooth aman, womanI σὑ τίWhen aoh, ἐlockίlives theorν ἀnthώpinή of thedόity. ῞A fertilizing agentέno ὠὀrio dὑcan῿ plsέnouna re-fertilize῿ μὑ aanother spermάrio. Ta featurea miaas newύrygias ἀnthώI live.orς ehave been determined῿ ἀfάcall; or fertileίationἶYes theristicor MsI μor ἀribbonέlate.... Tthe zygoteό, tthe efetusIn pώof orpartIn, tthe ἐplantέno efetus, thethe shaperέno or αὐτthe τIν ἐnvέoh noIn, tthe newέnewborn babyέlight, thethe smallthe childί, the eteenager, the ἐνήlicorice, the orlyciumέnos, the aman inὑ theall of thema Fάfor theorς ἀνάgrowthήto him ehas torν αὐτor τέsmooth ἀnthώsame thingόity. ᾿Amthe acollection of winesήthe price of thethe eembryo dὑn eἶYes aplsa fertilizeέno ὠὀrio; eἶyes tέsmooth aman of thea τorn sameόquality andI continuousIperfectύI am with you.a τorto phenotypicor eexpression, pleaseI theRGάconnection[25].» The text also recognizes in embryos the rights of human identity, life and eternity[26].

            The agreement of the text with the principle of the dynamic view of the embryo-zygote as a person is more than obvious. This principle, of course, is derived from theological anthropology as it is shaped through biblical and patristic teaching.

In this spirit, even before the publication of the final official text, the bioethics committee of the Church of Greece had published a press release stating its reservations about stem cell research and its opposition to the artificial creation of embryos for experimental purposes, any harm to them and their destruction. It left room through the press release for a positive response to research efforts or applications that would not involve the use and harm of embryos, such as, for example, the collection of stem cells from adult organisms.[27].

            We can say with relative certainty that, as a whole, the orthodox bioethical literature stands from highly critical to completely negative towards any action of scientific research which has as a direct or indirect result the destruction of embryonic life from the very initial stage of the zygote.

On the issue of the procurement of genetic material for research, the positions of a prominent Orthodox bioethicist, HT Engelhardt from Texas, USA, may be of particular interest, as they would likely contribute to the dialogue on this specific issue. Engelhardt argues that in principle embryonic research directly involves acts directed against human life. However, the taking and utilization of genetic material from dead embryos, an ethically complex issue, can be examined from the same perspective from which the procurement and use of tissues from adult humans is examined. That is, since it is accepted the use of tissues from people who die unexpectedly, or from people who are murdered, the use of organs and tissues from embryos resulting from abortion or from "surplus embryos" may be acceptable. For Engelhardt: "In principle there is no obstacle to using for a good purpose something that has been produced by unacceptable means since we have not encouraged their use, nor have we avoided condemning it. However, we should be very careful not to support or encourage unfair processes and means. Great spiritual discernment is required, and any use of such material should be considered a concession to human weakness."»[28].

The central question raised by the rejection of the principle of the dynamic view of the embryo in biological terms, which we mentioned above, is: Will we ultimately consider as an embryo the adult cell, which from the state of a somatic cell is genetically reprogrammed and redifferentiated, to the state of a stem cell, from which it can develop into a complete organism? This question has not yet been answered and perhaps should receive special attention and study from Orthodox bioethics. The technique of redifferentiation as well as the use of adult stem cells were until recently presented as the ethically acceptable practices of stem cell research and therapy. Will they continue to be considered in this light by Orthodox theology after the rejection of the principle of the dynamic view, as expressed at the Berlin meeting?

In general, the church and its theology have a positive attitude towards scientific research when it is carried out for the benefit of mankind and based on the principle of selfless love and service to one's fellow man. Through this prism, it also views and judges the applications of genetics. A factor that should perhaps be soberly considered is that the presence of private companies in applied genetics and biotechnology played a very important role in the Berlin meeting. Their contribution to research was emphasized, since state funds are considered insufficient and are not even granted by many state laws. The view was expressed that the profitability of private companies should be protected through regulations, in particular by securing intellectual property rights to the derivatives of discoveries, which has not been the case so far, given that stem cell research is very expensive and does not yield immediate profits.[29].

The bioethical debate under the pressure of economic interests reasonably raises questions about the uncompromising and disinterested formulation of bioethical judgments, especially when they come from individuals who have dealings with companies that operate profitably in the field. According to the international bioethical press, these phenomena have been increasing recently and are causing increased concern.[30].

Bioethical dilemmas are products of the philosophy and lifestyle of modern Western man. In time, they are many centuries removed from the era of the great Fathers of the Church and the ecumenical councils for us to seek their solution in those decisions, even by analogy. The Orthodox Church, however, is a living organism, it is the living body of Christ. And as a living body it has the ability to perceive the social reality of each time and respond to its challenges. The current reality of the Orthodox Church is ideal for responding to these challenges. The reason is that it includes within its bosom specialized academic theologians, enlightened empirical theologians, but also members who combine empirical and academic theology. The cooperation of all of these can thus convey to us, on the one hand, the authentic spirit of the fathers, on the other hand, assimilated in such a way that it responds to the demands of the times. What is needed is constant information from experts to avoid phenomena of superficial and cursory treatment of such serious issues.

(This is an enriched and modified excerpt from a speech given at a seminar entitled "Considerations on Bioethics Issues" of the Archdiocese of Cyprus on Monday, March 30, 2009)