Stem Cells

Summary

1 What are stem cells?

1.1 Totipotent stem cells

1.2 Pluripotent stem cells

1.3 Multipotent stem cells

2 Embryonic stem cells and the ethical issue

3 Adult stem cells

4 Cloning

5 Stem cells in Latin America

6 Conclusion

7 References

1 What are stem cells?

Currently, when talking about stem cells, it is almost impossible to access everything that has been written and is being written about them. And when it comes to research on such cells, it enters an extremely complex field. However, when defining what they are, there is quite a consensus. Therefore, it can be said that stem cells are undifferentiated cells, that is, non-specialized cells that have two characteristics:

1) the ability of unlimited or prolonged self-renewal, that is, to reproduce for a long time without differentiating; and 2) the ability to originate transit progenitor cells, with limited proliferative capacity, from which highly differentiated cell populations (nervous, muscular, hematopoietic, etc.) descend. (LEONE; PRIVITERA, 2004, p.165)

They can also be defined with other words: “stem cells are cells that have the ability to self-renew and divide indefinitely, in vivo or in vitro, giving rise to specialized cells” (BARTH, 2006, p.26). Therefore, self-renewal is the ability of stem cells to proliferate, generating identical cells (other stem cells). And the differentiation potential is the ability they have to, under favorable conditions, generate specialized cells from different tissues.

According to their differentiation potential, stem cells are classified into three levels: totipotent, pluripotent, and multipotent cells.

1.1 Totipotent stem cells

Totipotent stem cells are the only type capable of originating a complete organism since they have the ability to generate all types of cells and tissues in the body, including embryonic and extraembryonic tissues (such as the placenta, for example). The only examples of totipotent stem cells are the fertilized egg (zygote) and the first cells from the zygote up to the 16-cell stage of the initial morula, a very early stage of embryonic development, before the blastocyst stage.

1.2 Pluripotent stem cells

Pluripotent stem cells have the ability to generate cells from the three embryonic germ layers (primordial tissues of the early embryonic development stage, which will give rise to all other tissues in the organism. These are called ectoderm, mesoderm, and endoderm). Unlike totipotent stem cells, pluripotent cells cannot originate an entire individual because they cannot generate extraembryonic tissues. The most significant example of pluripotent stem cells is the inner cell mass cells of the blastocyst, the so-called embryonic stem cells.

Recently, scientists developed a technique to genetically reprogram adult – differentiated – cells to a pluripotent state. The cells generated by this technique are called induced pluripotent stem cells (iPS) and have characteristics very similar to pluripotent stem cells extracted from embryos.

1.3 Multipotent stem cells

Multipotent stem cells have the ability to generate a limited number of specialized cells. They are found in almost every part of the body and can generate cells from the tissues they originate from. They are also responsible for the constant cellular renewal that occurs in our organs. Bone marrow cells, neural stem cells in the brain, umbilical cord blood cells, and mesenchymal cells are examples of multipotent stem cells.

2 Embryonic stem cells and the ethical issue

Embryonic stem cells are taken from the embryo itself to be used in research. The fact that the embryo, up to the 14th day, can be divided into parts, giving rise to genetically identical individuals, led many scientists to adopt the term pre-embryo, justifying that we are not dealing with a human being but with a cluster of cells, and therefore, in this case, it can be used as a research source.

In Brazil, on March 24, 2005, the Federal Senate approved law number 11.105, which in its article 5 states that “the use of embryonic stem cells obtained from human embryos produced by in vitro fertilization and not used in the respective procedure is allowed for research and therapy purposes” (Biosafety Law). The law states that these must be non-viable embryos, frozen for three years or more. The consent of the parents is also required, and human embryonic stem cell research must submit its projects to research ethics committees. This position of the Brazilian Senate arises from the reductionist view that states that until the 14th day there is no human life in the embryo, making “it possible to use it in research and derivation of stem cells” (BARTH, 2006, p.167). Currently, many countries around the world accept and legitimize research with embryonic stem cells.

However, “the attempt to establish this term and this phase of development for the embryo has received such criticism that few still use this term today” (BARTH, 2006, p.157). It is clear that “no modern manual of human embryology speaks of pre-embryo” (CIPRIANI, 2007, p.29).

For biology, it is currently a consensus that “shortly after fertilization, in the genome of those few cells, there is the program of a human individual at the beginning of its extraordinary intra and extrauterine journey that will make it an adult individual” (CIPRIANI, 2007, p.29).

In the understanding of the Church, it is defined that after fertilization, we are not dealing with a person, as becoming a person happens later. However, we are dealing with a human being. In this sense, the Church states that “from the moment of conception, the life of every human being must be respected absolutely because man is, on earth, the only creature that God ‘wanted for himself’” (CDF, 1987, n.5, p.14). And the same document, further on, states that “the human being must be respected as a person from the first moment of his existence” (n. I, 1, p.16), highlighting that in the zygote, which is constituted from the fusion of the nuclei of the male and female gametes, “the biological identity of a new human individual is already constituted” (n. I, 1, p.17). There are those who state that the fruit of conception, at least until a certain number of days, cannot yet be considered personal human life. However, “from the moment the egg is fertilized, a new life begins that is neither the father’s nor the mother’s, but that of a new human being developing on its own.” (JOHN PAUL II, 1995, n.60)

In this sense, it can be affirmed that

the human organism is not just a bunch of cells, but a self-organized set of cells capable of developing and fully manifesting the human being present from fertilization. This internal principle makes this embryo reach its human maturity. Prenatal life is fully human life at all stages of its development. The ontogenetic law imposes gradual differentiation and organization, but there is a unity that ensures it is always the same human being developing, from conception, through various stages, until reaching the maturity of a human person. (BARTH, 2006, p.163)

Therefore, from an ethical point of view, in the position of the Catholic Church, any intervention aimed at producing or using human embryos for the preparation and use of stem cells, seriously and irremediably injuring the human embryo, interrupting its development, is a gravely immoral act and, therefore, gravely illicit” (PONTIFICAL ACADEMY FOR LIFE, 2000, p.15). The Church makes its position clear regarding the embryo when it states that “the human being must be respected and treated as a person from its conception and, therefore, from that very moment must be recognized the rights of the person, among which, first of all, the inviolable right of every innocent human being to life” (CDF, 1987, n. I, 1, p.18).

At the beginning of 2008, in Brazil, the discussion on the subject became heated due to the unconstitutionality action of the Biosafety Law, which allowed research with embryonic stem cells. The vote held in the STF (Supreme Federal Court) ruled in favor of continuing such research.

Supporters of such research state that the embryo is not human life. According to them, after three years of freezing, these embryos are non-viable and can be used in research, and such a procedure is justified because these cells can be a potential source of cure for many degenerative human diseases. The use of embryonic stem cells requires their extraction from embryos a few days old, sacrificing them. This procedure creates an extremely delicate and difficult situation from an ethical point of view.

Both biology and medicine treatises state that human life begins at fertilization, and thereafter, the growth of the embryo is autonomous, constant, and progressive.

From a philosophical point of view, stating that human life begins after a certain number of days is an arbitrary position established based on subjective reasons. It is necessary to start from the foundational criterion, an objective fact that states that human life begins with fertilization. In this sense, it is important to bear in mind that “the beginning of human life cannot be fixed by convention at a certain stage of embryo development; in reality, it begins already at the first stage of the embryo’s development itself” (PONTIFICAL ACADEMY FOR LIFE, 2001, p.4). Therefore, when working with the embryo understood as a human being, it is necessary to grant it a morally relevant status, ensuring it individual rights that prevent it from being destroyed or put at risk. In fact, belonging to the human species involves a particular right to protection that transcends that applied to animals. Those who do not respect embryos individually but protect them as special biological material deserving respect for their use in research violate

the morally relevant status of a human being. But isn’t the problem broader? The Catholic Church maintains that an embryo must be treated “as a person.” This formulation is very careful, as it does not simply state that embryos are identical to people. The Church claims that we cannot distinguish “human beings” from “persons” by attributing them two different levels because the development of a human being is a continuous and unified process. Differentiations can be established in this process, but it cannot be broken down into different phases. Indeed, the consequences for human society of distinguishing human beings based on the stage of development would be unpredictable. The inseparability of human beings also comes from the reflection that, in this condition, we cannot define others as human or not if they exist as such. The consequence of the inseparability of a human being and its development is a morally relevant status that guarantees the embryo fully valid life protection. This does not allow them to be used for research, treating them as raw material. If this status is respected, life, as the most fundamental right, cannot be weighed against other goods of high status. (MIETH, 2003, p.173)

Therefore, according to ethics, especially Christian ethics, research with embryonic stem cells cannot be accepted because the ends do not justify the means, and in this case, the good sought, which is the cure of diseases in adults, involves the elimination of human beings. Therefore, “a good end does not make good an action that is, in itself, bad” (PONTIFICAL ACADEMY FOR LIFE, 2000, p.15).

At the same time, one cannot disregard the fact that science continuously evolves, and in recent years there has been significant progress in dealing with human embryos. Several published studies show that today it is technically possible to extract only one cell from the human embryo and start its indefinite multiplication. The great advantage of this technique

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from an ethical point of view is that the embryo is not destroyed. Let’s mention the news that states: “an American company from Massachusetts claimed to have developed a way to produce human embryonic stem cells without damaging the original embryo, in a discovery that could eliminate ethical objections to this promising type of research” (O GLOBO ON-LINE, 24/08/2006). We will not delve into the technical details of this type of procedure, which would resolve the ethical issues raised by research with human embryos.

3 Adult stem cells

Adult stem cells are taken from a specific tissue of the human organism for use in the same individual or in others. Until a few years ago, it was known that these cells exist in many adult tissues and are capable of giving rise only to cells of that same tissue. However, science has advanced greatly in research with these cells, and recently, “pluripotent stem cells have also been discovered in various human tissues, that is, cells capable of giving rise to other types of cells, mostly hematopoietic, muscular, and nervous” (PONTIFICAL ACADEMY FOR LIFE, 2000, p.9-10). Because of this, recently, several scientists conducting research with embryonic stem cells have changed their position, as two discoveries have shown that it is possible to reprogram adult cells to be pluripotent.

The progress and results achieved with adult stem cells, in addition to their plasticity, present “a wide range of potential applications, presumably not distinct from the uses of embryonic stem cells, since plasticity largely depends on genetic information that can be reprogrammed” (PONTIFICAL ACADEMY FOR LIFE, 2000, p.12).

However, one cannot be naive and believe that the ethical issue weighs so heavily that research with embryonic stem cells will be abandoned. What is really happening is a kind of economic war. A lot of money has already been invested in building laboratories for research with embryonic stem cells, and there is no going back, especially since this type of research is more complex and requires more advanced technology. It should be noted that “companies do not altruistically produce cell lines to donate them for research or therapeutic purposes. Everything is patented and sold” (BARTH, 2006, 242). It is said that, in the not too distant future, the use of adult stem cells will be a very accessible procedure, requiring less complex technology and, therefore, lower cost. This type of procedure is not of interest to large laboratories that hold high technology. They invest large capital to maintain the monopoly of research and also to obtain great profits.

Research with adult stem cells has yielded good results and does not present ethical problems, as it does not require the elimination of human life and is encouraged by the Church.

4 Cloning

Another area of stem cell research that is opening up to science is the production of embryos by cloning. The advantage of cloning, according to scientists, is that it avoids the problem of rejection, as the clone is produced from cells taken from the individual himself. When talking about cloning, we are faced with two possibilities: so-called therapeutic cloning, which aims to produce clones to extract stem cells for use in therapy with the individual himself, and so-called reproductive cloning, which aims to produce clones to develop as human beings. This second type of cloning faces great resistance from most scientists, as it would be merely a scientific curiosity and a monstrosity. In this sense, it is important to say that human cloning is “in its method, the most despotic and, at the same time, in its purpose, the most enslaving form of genetic manipulation” (JONAS, 1997, p.136). A Brazilian moralist, who is also trained in zootechnics, states that “reproductive human cloning has become one of the most radical forms of genetic manipulation; it is part of the eugenics project and, therefore, is subject to all ethical and legal observations that widely condemn it” (COELHO, 2015, p.50). This is certainly the best book in Portuguese dealing with the issue of human genetic manipulation and its ethical and social implications. Therapeutic cloning has the acceptance of a large number of scientists. Some say we need to “enjoy the potential medical applications of therapeutic cloning. Let’s responsibly use the new powers of cloning, exclusively for therapeutic purposes” (PEREIRA, 2007, p.88). However, with human cloning, “not only is the process controlled, but the entire genetic heritage of the cloned individual is selected and decided by human artisans. A big step towards eugenics that does not happen by the causality of nature but by a deliberate human decision and manipulation” (COELHO, 2015, p.51-52).

Those who defend therapeutic cloning claim that it involves producing, from a cell, several other cells, that is, simple cell multiplication. In fact, “from the moment any cell begins to give rise to a ‘self-organized vital unit,’ we are in the presence of a new biological individuality” (BARTH, 2006, p.105). Therefore, therapeutic cloning, from an ethical point of view, falls into the same problem, that is, producing embryos as a source of stem cells that are then destroyed and eliminated.

5 Stem cell research in Latin America

Considering the theme of stem cell research and its use in seeking the cure for diseases, it can be said that not only in Latin America but worldwide, the issues raised are practically the same. This is true from an ethical, therapeutic, and social standpoint. After all, everything done anywhere in the world, especially what emerges as new, is immediately published and widely disseminated. We should highlight once again that the best results in stem cell research and its therapeutic application in humans have been achieved with the use of adult stem cells. The news that emerges shows this, as in the case of the report that states that

millions of diabetics may soon forget insulin injections if the successful result of the first stem cell implant in the pancreas, performed by Argentine doctors dedicated to finding a cure for the disease, is confirmed. It is an unprecedented method free of rejection risks, without prolonged mediation, and can be performed by any medical specialist with skill and experience in catheterizations, explained Argentine cardiologist Roberto Fernández Viña. (AVALOS, AFP, 21/01/205)

We can also mention this other news, which states:

in Colombia, a paraplegic man walks again after a stem cell transplant. Colombian senator Jairo Clopatofsky, 44 years old and paraplegic for 24 years, said on Tuesday that he started taking his first steps alongside his eight-month-old son. A year ago, the politician underwent a stem cell transplant. (Efe, Bogotá, 18/07/2006)

There are texts published in Brazil that are also available online in Latin American journals. We recommend the article “Bioethical implications in embryonic stem cell research” (BARBOSA et al., 2013). We also recommend learning about the research of Dr. Bratt, a professor in the stem cell therapy program at the Federal University of Zulia (Venezuela) and a pioneer in Latin America in the use of autologous bone marrow stem cell therapy for treating degenerative diseases such as Parkinson’s, diabetes, osteoarthritis, and spinal cord injuries.

Regarding legislation, comparing Brazilian biosafety law with that of neighboring countries, it can be said that Uruguay is the country that most closely aligns with Brazilian legislation. In that country, research is permitted, but it does not impose any restrictions on surplus embryos. Argentina, despite having very advanced bioethics, also has no legislation on the destruction of surplus embryos. Paraguay has no legislation (cf. BARROS, 2011, p.270-275, online book).

5 Conclusion

We can conclude that whenever a society accepts that human life can be negotiated, bought, sold, or destroyed, such a society dangerously marches towards discrimination against its members, opening a eugenic perspective. Granting legal power to those with more power is allowing such subjects to decide who should live and who should die. Moreover, law and rights emerged to organize relationships in society, and for the sake of those with less power and fewer conditions, for the most vulnerable. The law emerged to protect the weakest, and in this case, the embryo is the most defenseless and vulnerable of human beings. The legal perspective is one aspect of society, which is composed of other areas such as anthropology, sociology, philosophy, etc., and especially bioethics, which also has something to say about human life. It is necessary to “revitalize the original language of bioethics, which is not predominantly that of law, of what is demanded of others, but that of duty, of what is fulfilled concerning others: ‘what should I do?’ is the question that inaugurates bioethics in the

face of ‘what can I do?’ to which technoscience responds” (NEVES, 2000, p.218).

For the ethical human being, their life has a value that is above the other beings of nature, and for the Christian, in addition to the ethical value, man (man and woman) was created in the image and likeness of God and, therefore, life must always be respected from its origin to its end and never be used as a means to be destroyed for the benefit of others, whoever they may be.

Celito Moro. Faculty of Palotina, Santa Maria (Brazil). Original text in Portuguese.

References

BARBOSA, A. S. et al. Acta bioethica. Santiago, v.19, n.1 Jun. 2013. Available at: https://dx.doi.org/10.4067/S1726-569X2013000100009. Accessed on: 15 May 2018.

BARROS, R. F. Destino dos embriões excedentes: um estudo dessa problemática nos países do Mercosul. Online book, 2011.

BARTH, W. L. Stem cells and bioethics, biomedical progress and ethical challenges. Porto Alegre: Edipucrs, 2006.

CIPRIANI, G. The human embryo, at fertilization the mark of life. São Paulo: Paulinas, 2007.

COELHO, M. M. Aparecida, SP: Editora Santuário, 2015.

CONGREGATION FOR THE DOCTRINE OF THE FAITH. Donum vitae. On the respect for human life in its origin and on the dignity of procreation. Petrópolis: Vozes, 1987.

JOHN PAUL II. Evangelium vitae, on the value and inviolability of human life. São Paulo: Paulinas, 1995.

JONAS, H. Cloniamo un uomo: dall’eugenetica all’ingegneria genetica. In: ______. Tecnica, medicina ed etica. Torino: G. Einaudi, 1997 p. 122-154.

LEONE, S.; PRIVITERA, S. Nuovo dizionario di bioética. Roma: Cittá Nuova Editrice, 2004.

MIETH, D. Stem cells: the ethical problems of using embryos for research. In: GARRAFA, V.; PESSINI, L. (orgs). Bioethics: power and injustice. São Paulo: Centro Universitário São Camilo; Edições Loyola; Sociedade Brasileira de Bioética, 2003. p. 171-178.

NEVES, M. C. P. Bioethics and its evolution. The World of Health, year 24, May/Jun, 2000. p. 211-222.

PEREIRA, L. V. Cloning, from Dolly the sheep to stem cells. 2nd ed. São Paulo: Moderna, 2007.

PONTIFICAL ACADEMY FOR LIFE. Declaration on the production and scientific and therapeutic use of human embryonic stem cells. Vatican City: Libreria Editrice Vaticana, 2000.

______. On the recent publication of an article on the cloning industry. L’Osservatore Romano (Portuguese edition), 8 Dec 2001, p.4.

Consulted sites:

AVALOS, S. Available at: https://noticias.uol.com.br/ultnot/afp/2005/01/21/ult34u115802.jhtm

EFE in Bogotá. Available at: https://www1.folha.uol.com.br/folha/ciencia/ult306u14875.shtml

O GLOBO ON-LINE, Available at: https://esclerosemultipla.wordpress.com/2006/08/24/celulas-tronco-sem-destruir-embrioes/

PRESIDENCY OF THE REPUBLIC, Biosafety Law, law no. 11.105. Available at: www.planalto.ov.br/ccivil_03/_ato2004-2006/…/lei/11105.htm