Bulletin of the Natural Family Council of Victoria, Volume 21
The recent news that a group of reproductive physiologists had "cloned" a human being has aroused public anxiety again and has solicited an answer to the question about the nature and dignity of the so-called "human pre-embryo". In order to judge the facts and intentions correctly we must await the forthcoming scientific paper. As far as I understand, on the basis of the best sources of information, the experimentation was not really on "cloning" but simply on "splitting" of human embryos at the cleavage stage and on the development of the separated cells. Whatever the case may be, I am really amazed at the pharisaic behavior and declarations of many scientists, and most regretfully even of some Catholic theologians as well, who have struggled in favor of, or strongly supported, the English law of November 1990. That legislation allowed the experimentation on human embryos up to the fourteenth day from conception. Some of the above scientists are still striving, in national and international bioethics committees, to impede any legislation on the subject, with the precise aim of leaving absolute freedom in this field to value-free scientists and technologists. If they were consistent they should have applauded those who, without any scientific merit, tried on human embryos what is currently done on animals.
I am sure that in the present world-wide culture, very little can be done for an inversion of route in both fields: that of assisted human reproduction and that of human embryo experimentation. However, with all sincere respect and consideration for all those who have different opinions and think they are on the right path, I believe that we, as Christian Catholics, in a spirit of dialogue and of "service to the conscience" -- in compliance with the last Encyclical Letter (Veritatis Splendor, n. 65) -- have the duty to propose those facts and arguments that might help, at least, those people who are still uncertain and are still searching for the truth in order to find a guide and motivation for adhering to the Magisterium of the Catholic Church concerning the dignity and the respect of human beings from the very first moment of their conception.
It is exactly on this perspective of a service to the conscience that I will try to summarize the scientific facts and the conclusions derived from the analysis of these facts. Facts and conclusions that, in my opinion, are the proof that every human being begins its own individual life at a point that is commonly called the "moment of conception", which coincides with the starting point of that process which is scientifically termed "formation of the zygote" at the fusion of the gametes or syngamy.
The ontological status of a human embryo has become a burning issue of contemporary bioethics since 1978, the year of the birth of the first test-tube baby. The target question may be reduced to the following: what are the essential status and value to be assigned to such microscopic things as the zygote and the embryo from the two-cell stage up to some thousands? The answer to this double question -- status and value -- cannot be the task of science alone. However, science can provide solid bases to further philosophical, theological, ethical and legal reflection, which is necessary in order to reach sound conclusions about the value and, consequently, the dignity and rights of the embryo. Indeed science, through accurate observation, appropriate experimentation for testing hypotheses, and a biological -- substantially inductive -- reasoning can establish the point in time when a given human being starts its own life cycle or,translated into metabiological terms, its existential individual reality.
It is an ordinary observation that the first step in the formation of a human subject is, in the largest majority of cases, the fusion of two highly specialized, extraordinarily endowed and teleologically structured and programmed cells: the oocyte and the spermatozoon. It should suffice to mention just a few steps of this process which follow in a fixed order one after the other:
It is important to stress that from this precise moment a new cell is active within which a highly complex cascade of processes clearly shows that the two gametes no longer work as two independent systems but, on the contrary, that a new system has been constituted which works as a unit, that is as a new being ontologically one. This new entity is biologically defined as a zygote or unicellular embryo.
Among the many extremely co-ordinated activities of this new cell I should like to remind the reader of the orderly constitution of the zygote's new genetic information through the following processes:
The above processes are followed by the replication of the new genome, that is to say of the genetic information of the new set of 46 chromosomes; and, finally, by the first-division multiplication process, leading to the production of another cell that generally remains connected with the first one to result in a two-cell embryo.
The analyses of these few steps of the process from the one-cell embryo to the two-cell embryo and of the structure of the main information centre leads to the recognition of two main characteristics of the zygote. The first one is that it exists as a unit. The second is that it is intrinsically oriented and determined to a strictly defined development. Orientation and determination are essentially due to the thousands of genes, contained mainly in the chromosomes, each one of them carrying a specific information for the regulation of the development of any particular zygote. Indeed, further observations and analyses show that each zygote has an exclusive set of genes of its own with the following properties: firstly, it confers to the one-cell embryo a human specific identity; secondly, it impresses on it a permanent sign of its biological singularity and, therefore, individual identity; thirdly, it represents a structure absolutely necessary -- although not sufficient -- for the rigorously and unequivocally oriented development of the new system. Indeed, by using an analogic, easily comprehensible language we could say that it is in the genome that the description and the developmental and functional programs of the new subject are engraved.
To confirm such conclusions one needs but a hint to the serious developmental disorders that occur when the genetic information is altered either by chromosomal aberrations or by a single gene mutation. The addition of one extra chromosome 21, or of a certain small portion of it, is sufficient to originate the pathological pattern of the "Down syndrome" (mongolism). Also the mutation of the gene controlling the production of a type of substance named collagen is sufficient to originate a lethal bone dysplasia defined as "thanatophoric dysplasia".
From all of the above data and their analysis only one logical conclusion can be drawn, and that is: at the fusion of the two gametes a new human cell, marked with a new and exclusive informational structure, begins to operate as an individual unit. However, at this point we cannot yet state that the zygote is actually the cell where the life cycle of a well-determined human being is initiated. In order to reach a valid conclusion on this most important point one must proceed to the examination of the development process, also called epigenesis.
Let us consider this process, from the zygote stage up to approximately the 14th day which is the most critical time span for our analysis. All the observations show that, if the environmental conditions are such that vital functions can be performed, the new human cell continues to multiply and the new cells to differentiate along the Iine established by the new informational plan.
At the structural level the epigenetic process, in the first period, is characterized by:
During compaction, the cells adhere still more strongly to each other through peculiar physical junctions, called tight junctions and gap junctions, that facilitate the intercellular transfer of ions and signal molecules. During polarization, a redistribution occurs of endocellular structures such as mitochondria, microtubules, big molecules like actin and clatrin, so that at the fourth-division cycle two types of cells can be recognized, polar and apolar, which by taking different positions -- at the periphery or in the centre respectively -- give the embryo a true morphological heterogeneity. This first differentiation has a meaning. The polar cells of the morula will give rise mainly to the trophoblastic cell line from which the embryonic membranes (amnion and chorion) and the placenta shall derive; the apolar cells will give rise to the embryablastic cell line from which the embryonic disc will develop, where the organogenesis takes place.
On the fifth day from fertilization, the differentiation increases. In the blastocyst four types of cellular sheets can be distinguished: the polar and mural trophoblast and the primitive ectoderm and endoderm. In the subsequent days, from the 6th to the 14th, the implantation of the embryo occurs, the chorion and amnion appear, the embryonic disc with two clearly distinct sheets of cells, the ectoderm and the endoderm, is formed. Finally, approximately 14 days after fertilization, at the caudal embryonal end a densely packed group of cells appears, called the primitive streak, from which a third sheet of cells, the mesoderm originates. From this moment on, the ever more complex and rapid morphogenetic process continues through histogenesis and organogenesis. To complete the picture, at the fifth week of gestation, when the length of the embryo is less than 1 cm, the primitive brain, heart, gastro-enteric and urinary tracts are present and sexual differentiation beams; at the sixth week the primordial limbs are clearly visible; and at the seventh week the bodily form is complete.
The simple analysis of the development process at the structural level, here briefly summarized, might be sufficient to reach sound conclusions when preparing the answer to the initial question. However, there are new data, provided by the incessant scientific research that add strength to the argumentation. These new data can help answer some of the questions raised by the embryologists themselves, simply by looking at the first stages of the development. The questions are the following:
Although it is not yet possible to give definite answers to these questions, two main lines of investigation have furnished data that offer some important clues to the understanding of the morphogenetic process. The first line of research, still in progress, is the analysis of the biochemical modifications that occur in single cells, in the different cell lines, in the various regions of the growing body at successive stages of the organization of the definitive form. The second line, now rapidly expanding, is the uncovering -- by the methods of classical genetics and mainly of new genetics -- of those genes involved in the many epigenetic steps from the zygote up to the acquisition of the definitive body configuration. A few very important findings that will help in our reflection are reported below.
A. It is certain that the new genome, established in the zygote, assumes the control of the morphogenetic process, at least from the two-cell embryo stage. The evidence that this very early activation of the new genome occurs also in the human embryo has been obtained recently through the studies of P. Braude and co-workers (see Reference 2). Using 7 fabricated zygotes and 26 fabricated embryos -- 6 at the two-cell stage, 10 at the four-cell stage, and 10 at the eight-cell stage -- they were able to show that, at least in the transition from four to eight cells, the new genome becomes active towards controlling the production of new proteins. Surely, further research with more refined methods will show that the new genome activation begins still earlier: in fact, protein genes cannot be activated without a previous activation of many other genes, the rRNA and the tRNA genes. By pure biological induction these data indicate that the new genome, established at fertilization, is the basis and the steady support of the structural and functional unity of the embryo, which develops along a trajectory that maintains a constant direction.
B. This mere indication, however, became evidence when a large number of factors involved in the incessantly oriented development of the embryo was finally known, and the all-embracing activity of the genome was better understood. From all this new knowledge the other conclusion emerges, that the regulation of the process of development is the result of the hierarchically ordered activity of three classes of genes. They are the following:
In summary, the specific task of these regulator genes is to determine the differentiation of the cells and the gradual structuring of the different organs through the action of an enormous variety of macromolecules whose production they control. It is quite easy to imagine the complexity of interactions between the genes, at the three different levels and within the same level. Such complexity necessarily increases with the progress of the development and, therefore, implies many other regulator factors and mechanisms of self-control, especially in order to facilitate the communication between the extracellular environment and the cells, between cell and cell, and between cytoplasm and the nucleus that contains most of the genetic information.
On the basis of the facts and their correct scientific interpretation summarized here, and of a pure biological inductive reasoning, one can derive three main characteristics of the human developmental process from fertilization on, and on the logically inevitable consequences of those characteristics.
The first characteristic is co-ordination. The embryo development, from the moment of the fusion of the gametes up to the formation of the embryonic disc after around 14 days, and still more patently afterwards, is a process where there is an evidently co-ordinate sequence and interaction of molecular and cellular activities, under the control of the new genome, that is modulated by an uninterrupted cascade of signals which are transmitted from cell to cell and from the external and/or internal environment to the single cells. It is precisely this undeniable characteristic that implies and, even more, requires a rigorous unity of the being that is steadily developing. This co-ordination and the implied unity clearly demonstrate that the human embryo -- like any other embryo -- even in the earliest stages is not a simple aggregate of ontologically distinct cells, but it is a real individual where the single cells are strictly integrated in a process, in which it autonomously translates, along the many differentiating and morphogenetic steps, its own genetic space in its own organismic space.
The second characteristic is continuity. After careful analysis of the process of development of the human embryo, no one can help concluding that at the moment of fusion of the gametes a new life cycle of a new human being initiates. This life cycle viewed in its dynamic profile, proceeds without interruption. The single events, for instance the multiplication of cells, the formation of new tissues and organs, may appear discontinuous, but each one of them is an expression, at a given point in the space-time dimension, of the uninterrupted sequence of imperceptible events which are co-ordinately linked one to the other, without solution of continuity. If there were interruption, then there would be pathology or death. It is precisely this characteristic that implies and establishes the unicity of the new human being: from the infusion of the gametes on, it is always the same and identical human subject who is being autonomously built up according to a strictly defined plan, though going through stages that are qualitatively ever more complex.
The third characteristic is graduality. It is self-evident that the final form is reached gradually. This, we ought to stress, is a constant property of the gametic reproduction of multicellular beings, i.e. it is an ontogenetic law. Precisely this law of the gradual building of the final form through many steps implies and requires a regulation that is intrinsic to any given embryo and keeps the development permanently oriented in the direction of the final form. And this occurs even though the number of the previous forms happens to be considerably high. It is precisely because of this intrinsic teleological law, which begins to operate at the moment of fertilization, that any embryo -- and therefore the human embryo as well -- permanently maintains its own identity, individuality and unicity. It remains, in fact, uninterruptedly the same identical individual during the whole process of development, from the fusion of the gametes onwards, notwithstanding the ever-increasing complexity of its totality. It should be unmistakably clear that the above three characteristics, when truly impassionately considered, perfectly meet the essential criteria established by metabiological reflection for the definition of an individual.
As a conclusion, reached through the few but important data on the development of the human embryo here briefly discussed, and through the logical inductions from those data, it can be stated that the reasonable answer to the question as to when the human individual originates appears to be only one. This is: at the fusion of two hman gametes, a new human individual initiates its own existence, or life cycle, during which -- given all the conditions necessary and sufficient -- he will autonomously realize all the potentialities with which he is intrinsically endowed, although within all the limits in which every human is largely constrained, i.e. error and death.
I do believe that the insightful statements found in the Instruction on Respect for Human Life in its Origin and on the Dignity of Procreation published by the Congregation for the Doctrine of the Faith in 1987, are indeed scientifically correct. They read: "the recent findings of human biological science.... recognize that in the zygote resulting from fertilization the biological identity of a new human individual is already constituted ". Therefore, the ethical consequences are straightforward. They are clearly stated in the same instruction: "Thus the fruit of human generation, from the first moment of its existence, that is to say from the moment the zygote is formed, demands the unconditional respect that is morally due to the human being in his bodily and spiritual totality".
Under the influence of the progress in human embryology, that ended in the production of human embryos for assisted reproduction and, at present, also for research, the thesis proposed above was viewed as an obstacle to favorable legislation on the use of human embryos. Many alternative opinions were then voiced, mainly by philosophers, theologians and by a few scientists, regarding the point in time when a human embryo must be considered a human individual qualified for the attribution of rights. I shall group these opinions and try briefly to prove their inconsistencies.
1. One nowadays largely accepted opinion is that the human embryo until the 15th day from fertilization, or at least up to implantation approximately the fifth day after fertilization -- may not be considered, from the ontological point of view, an individual. Four main reasons are given in favor of this opinion:
(a) The first reason is that the embryo, in the early stages of development is simply "a mass of cells genetically human" which are each one "distinct ontological entities in simple contact with the others".
Obviously these statements, written by philosophers and theologians, who are very likely unaware of, or poorly informed about, pertinent scientific studies, are totally at variance with the data available, which is briefly reported above.
(b) The second reason was initially proposed by a well-known mouse embryologist, A. MacLaren. She thinks that until approximately the 15th day after fertilization all that happens is simply a preparation of the protective and nutritional systems required for the future needs of the embryo . Indeed, only at the 15th day after fertilization, when the primitive streak appears, there is that spatially defined entity, the embryonic disc, that "can develop directly in a fetus and afterwards in a newborn". This is exactly the reason why she introduced the term "pre-embryo", to indicate the human embryo from the moment of fertilization up to the 14th day of development.
One may simply note that the embryonic disc that can be observed around the 14th day of development is, in fact, a structure deriving from a further differentiation of the embryoblast which, actually, is already present when the embryo as a whole provides, under genetic control, for a faster differentiation of the trophoblastic envelopments, which are extremely needed for the correct and smooth progress of the body-building process. As a matter of fact, the trophoblast and the embryoblast, both deriving from the zygote, simultaneously make their own way as a whole according to a finely and teleologically directed program.
(c) The third reason is the monozygotic twins phenomenon. This phenomenon, according to the objectors, is the proof that the zygote cannot be an ontologically human individual. Indeed this phenomenon shows that this very zygote has the potentiality or the capacity to become two human individuals. This is probably the strongest reason why the philosophers deny the zygote the quality of individual, until at least the moment of the separation of the co-twins. A brief reply to this only apparently strong objection is in order.
Firstly, this phenomenon is a real exception: 99 to 99.6% of the zygotes develop as a unique subject. That logically means that the zygote is per se determined to develop as a unique subject.
Secondly, very recent studies on the mechanism that leads to twinning support the hypothesis that in some part of the embryoblast, because of some error occurring between the fourth and seventh day after fertilization, a new and independent plan of development is formed so that a new individual initiates its own life cycle. It seems, therefore, very reasonable to state that there is one first human being from whom a second human being originates or, in other words, that from the first system a second system stems. On the contrary it appears incorrect to state that one undetermined system becomes two determined systems.
Thirdly, the statement that there is a first human being who continues its own way, and a second human being who originates from the first, and then continues its independent course, finds strong confirmation -- one might say a proof -- in many observations. Most striking are those cases in which one of the monozygous twins has a karyotype with 47 chromosomes and is affected by Down syndrome, while the co-twin has a normal karyotype with 46 chromosomes. A number of studies suggest that mostly the first subject, and therefore the zygote is the trisomic one; the second, originating from it, is the normal one. It is evident that the first, the trisomic one, continues its own course of development, while the second starts its own life cycle as soon as the new plan becomes independent from the first.
(d) The fourth reason for denying the status of individual to the zygote until at least the implantation is that the co-existence of the embryo with the mother is a necessary condition for an embryo belonging to the human species to acquire the character of a human individual and to become a member of the human community. Now, according to the objectors, this condition can be attained only at implantation.
This argument has no foundation. It is well known that the co-existence of the embryo with its mother starts very early, a long time before implantation, since the time it makes its way along the tubes. Moreover, many new findings show that this co-existence is convenient, and wisely pre-arranged, but not necessary. As evidence it would be sufficient to recall the development of human embryos in vitro well beyond the stage of implantation, and of mouse embryos under the male renal capsule up to the complete formation of the fetus.
2. A second opinion is that no human embryo can be considered a human individual -- and still less a person -- until the central nervous system is sufficiently formed, that is approximately until the sixth to the eighth week of gestation.
No doubt, a functional brain has an essential role as a centre of unity when the human subject is completely formed: in this condition, as soon as the brain is totally dead then the unity of the system is lost; hence death. However, the situation is totally different in the embryo. There is, in fact, an intense relationship -- and therefore unity -- between cells, tissues and organs, upheld by a continuous, ordinate and co-ordinate increase of nervous cells. Such increase gains momentum between the fourth and sixth week of gestation, when the cranial nerves and the brain cortex start to organize. During the embryonic stage there is no interruption whatsoever of the dynamic, brain-controlled unifying process nor is there the consequent disintegration of the individual; on the contrary, we are faced with a highly dynamic process, where the ontogenetic law requires a gradual organization of the whole body and, therefore, of the nervous and cerebral structures as well.
My aim in defending the thesis I have proposed here, which I deem to be the only biologically correct one, and the purpose of discussing the different opinions, is simply to contribute to a deeper reflection on a topic of great importance not only for the search of the truth, but for the true well-being of human society. Without any doubt, science and medicine have opened new, large and great ways for a better understanding of the human being, from the very first moment of its existence, and for new enterprises leading to the cure and/or the prevention of diseases. Perhaps science and medicine, in their enthusiasm to know and make within an empiristic perspective, have reduced the value of a human being to a pure biological value. It follows that observing human development, one could be led to attribute different values to the zygote, to the pre-implantation embryo, to the post-implantation embryo, and so forth, up to the fetus at different weeks of gestation. These, however, are quantitative values, based only on the structural complexity of the human being. Such value judgments would represent, in respect to man a biological reductionism. My hope is that both philosophers and theologians are able to resist, on the grounds of the true facts of science, such biological reductionism, and recognize in the human being, from the very first moment of its existence, i.e. from syngamy, the glory with which he was crowned by God the Creator.