The biology of bioethics: uses and abuses of the scientific data

Gonzalo Herranz.
lecture Closing lecture of Master's Degree in Bioethics, University of Navarra 2010-2011.
The second part is published: Herranz G. Retraction of articles in bioethics: proposal of a paradigmatic case. Cuadernos de Bioética 2011; 22(2): 151-67. available en http://aebioetica.org/revistas/2011/22/2/75/151.pdf

I am happy to speak to people who are so convinced that biomedical science needs ethics that they have devoted many hours and efforts to study bioethics. They have now reached the Master's degree Degree . And if, from this moment on, they continue to study hard, bioethics will become, in a way, part of their identity, they will exude bioethics from their pores. Your card at presentation will be able to say with justice: So-and-so, Master in Bioethics.

He or she will be convinced that without ethics, the biological sciences and their cultivators are aimless, because what happens to them is what happens to a sailor who is guided by the bow of his or her own boat: he or she goes nowhere. He needs the financial aid of the stars, the compass or the probe, the profile of the coastline or the light of the lighthouse. A master in bioethics knows that his first task is to bring ethics to laboratory or to the hospital, so that those who do and apply biomedical sciences guide their work in the respect for life and the dignity of the human being. And they must make ethics friendly. Then they will not lose their sense of direction and good humour.

The biology of bioethics

As degree scroll announces, I am not going to refer today to the ethics of bioethics. I would like to deal with the biology of bioethics, with what biomedical science has to contribute to the study and reflection of a Master of Bioethics.

Bioethics is vitally interested in biology. In a way, biology gives bioethics its identity and character, it is part of its name and an element of its essence. This means that it is not enough for the bioethicist to master with skill and professionalism the principles, rules and procedures of the moral Philosophy . To be a good bioethicist, he/she must acquire and possess a serious, well-considered, up-to-date knowledge knowledge of biology: of its theoretical foundations, its methods of observation and experimentation. He/she also needs to be able to critically read the biological bibliography . The bioethicist must possess biological knowledge proportionate to his or her philosophical knowledge.

To be more specific: the competent cultivation of bioethics requires having learned, and continuing to learn throughout one's life, what is relevant to biomedicine; it requires skill to search for, select and evaluate for oneself the biological data that concern the issues and problems that interest and occupy one. It is a task that each person must assume with responsibility staff, making him/herself the guarantor of the truth, reliability and quality of the biological data that he/she introduces into his/her reflections. Only in this way will the bioethicist be able to correctly resolve problems and cases, and will also be able to formulate reliable norms.

It should not be forgotten that bioethics, at its very core, is interdisciplinary. It is born and grows from symbiosis, from the integration of ethics and the life and health sciences, from the dialogue they maintain with each other, from the questions they ask each other and the answers they give each other. Such interdisciplinarity has a stimulating consequence: bioethics is not easy, especially when it deals with serious issues. Because, at subject serious, there is no room for division of roles. Interdisciplinarity is in the dialogue of specialists, but it must first be in the mind, in the curiosity, in the humanistic character of each one. It would not be acceptable for bioethicists to say: let the biologists provide the data, give us their version of the facts, and we will provide the ethics. It would not be decent, because bioethicists cannot allow themselves the laziness of "believing" what biologists say with the faith of a charcoal burner; nor can they, without prudent enquiry, accept at face value that the biological data they take from more or less high quality knowledge dissemination articles, manuals, or specialised journals are always objective and solid. It would not be permissible for them to abdicate their own conscience.

And vice versa: the cultivators of biology, who are human beings, with their virtues and vices, made of the same moral fibre as everyone else, must take great care to ensure that their work, publications and statements are ethically responsible and upright. In everyday reality, there is little practical and sincere recognition among scientists that ethics is the air they breathe, the atmosphere that encompasses their entire work, that should inform their work and their ambitions. Rather, they tend to regard ethics as a hindrance, a formalism, which slows down their research. It is not easy for them to listen to ethicists, not only because they usually go about their business and live too fast, but because many are convinced to the marrow of their bones that it is from science, and not from ethics or religion, that man's salvation comes.

It is not easy to play the role of ethical conscience in front of scientists. They enjoy great prestige in today's society and are often flattered by the media on speech. Bioethics should demand one thing of them: that, overcoming any conflict of ideological, and not only economic, interests, they ensure that the information they provide to society, and especially to bioethicists, is truthful, distinguishing between what is real and what is desired or imagined.

At summary, and I insist: we cannot forget that the biology of bioethics is a serious matter. Bioethicists cannot disregard the need to take care that the biology they use is of good quality, any more than a good housewife would take care that she is not sold a pig in a poke. At subject biology, bioethicists cannot plead ignorance. They will, of course, try to be friends of biologists, but even more friends of the truth. Their lives depend on it. Therefore, an important part of the bioethicists' work is to seek dialogue with scientists, to work with them to identify, refine and validate the biological concepts and data they need for their programs of study: not as passive and acquiescent listeners, but as reflective and critical intellectuals. They have to do this on a regular, continuous basis, because they always have to update and periodically reconsider the value and meaning of the data they handle. In this way they will not run the risk of the bioethical speech degrading.

To conclude this first part of my talk, I would like to add two points.

The first point is to emphasise the idea that the in-depth study of the relevant biological data is of paramount importance in bioethics in the Catholic tradition. With enviable simplicity Cardinal Ratzinger put it: "I will never tire of repeating it: for the Church, the language of nature is also the language of morality". There can be no more expressive praise for natural science, whose typical function is to decipher as accurately as possible the language of creation, so that biotheologians and bioethicists can interpret it in the light of faith and reason. We cannot forget that, in the Catholic tradition, grace does not destroy nature, but recognises, respects and perfects it.

The second point, which is somewhat autobiographical, is to point out that what I have said so far is, in essence, self-criticism. I too, like everyone else, let myself be guided by the dominant opinions in biology, relied on them, neglected my critical duty. And it is only recently that it has become clear to me that the failure to thoroughly investigate, or neglect, the critical function of biomedical science has calamitous consequences.

In what follows, I will set out some ideas that I realised not so long ago. Perhaps, for me, a little late. That is why I am communicating them with a sense of urgency which, at times, may seem a little impassioned. I do so out of a sincere desire to open up horizons for the younger generation.

The bioethical example: the fictitious biology of the pre-embryo

For three long years now, I have been studying the foundations that biologists and doctors have laid for the now massive edifice of assisted reproduction techniques. Its cornerstone is the notion that the human embryo, in the first 14 days of its existence, is a pre-human entity, a pre-human embryo, which neither possesses biological attributes, nor claims ethical dignity, nor enjoys the legal status of human beings properly speaking: although it certainly deserves a certain measure of respect, it cannot demand for itself the respect accorded to human individuals.

This is a dominant, almost monolithic conclusion in the world. Following the path opened in 1979 by the US Ethics Advisory Board, it has been adopted by bioethics committees in practically all advanced countries. With slight variations, which do not disguise the underlying stereotype, these committees have based their reflections on the data and arguments provided by biologists. With virtually no one to contradict them, except for the Magisterium of the Catholic Church, the biologists presented as incontestable biological truths that the human neo-conceived child, during the 14 days of its existence

1. It can be divided to give rise to two or more twins;

2. It can be recombined, so that two pre-embryos merge into one chimera;

3. They are, and must be called, pre-embryos, since the internship totality of the cells that form them are destined to build extra-embryonic Structures . It is only with the appearance of the primitive streak, on day 14, that the development of the embryo proper begins in any appreciable way.

Here we come to the heart of the matter, to the biology of real-time bioethics.

We have to ask: How factually sound are these assertions? Where are the observations and experiments to support them? Today, these questions may seem anachronistic. And for many they are. But I think they are not. They still need to be answered. After critically reading hundreds of papers, I can give two. They are these:

1. That these three statements (that in the first 14 days the embryo can twin, that embryos can fuse and produce chimeras, that embryos are composed of cells of extra-embryonic destiny) have been imposed as the sole and official doctrine, so that they constitute the starting point of the vast majority of the work of bioethicists, jurists and theologians. For proof of this, one need only dive into the biomedical literature by consulting books and journals on embryology, obstetrics, Genetics, and bioethics.

2. That these three assertions have no factual basis. They are, in particular the first, striking examples, in plenary session of the Executive Council 21st century, of what Francis Bacon called idola tribus, universally accepted errors.

This second answer of mine is, I have no doubt, shocking, and may make some people doubt my mental health. As there is no time for more (I want to give you a scoop in a little while), I will limit myself to showing the emptiness of the argument of monozygotic twinning.

This is based on the assertion that, during the first 14 days of its existence, the human pre-embryo is capable of splitting and giving rise to two or more twins. Although it possesses a unique and unrepeatable genome, the pre-embryo, it is said, is not yet unequivocally an individual, because it has not yet attained individual uniqueness. Thus we know man as an individual, as indivisible. Ergo, the pre-embryo cannot enjoy human status because it has not yet attained its irrevocable individuality.

The argument is typically bioethical: it has two arms. One, philosophical, revolves around the complex concepts of the individual and the person and their ethical status. It has caused rivers of ink to flow. I will not go into it. The other arm, biological, confronts us with the chronology of monozygotic twinning, which, we are told, extends to the first 14 days.

Today's academic biology asserts that the ability to twin begins the day after fertilisation, when the zygote divides into the first two blastomeres, and is extinguished on day 14, when the primitive streak appears. Within these two weeks - academic biology continues - the different structure of the foetal envelopes reveals when the cleavage took place. It is now a classic calendar, although with curious variations from one author to another: cleavage at the stage of blastomeric segmentation, days 2 and 3, gives rise to dichorionic-diamniotic twins. Excision of the inner cell mass of the blastocyst before the beginning of training of the amnion (days 4 to 8) results in monochorionic-diamniotic twins. If, as is rarely the case, cleavage is delayed and takes place between days 9 and 13, monochorionic-monoamniotic twins are formed. Finally, even later cleavage of the embryonic outline, on or after day 14, is usually incomplete and results in the production of Siamese, conjoined twins. This description is usually narrated in an assertive style, as if describing facts.

But do they correspond to true, observed, experimentally verified facts? The answer is no: we do not know if things happen like that. What is stated is a conjecture, very logical and rational, but conjecture, something imagined, not seen.

The above-mentioned calendar was born from a hypothetical model , imagined in 1922 by G. W. Corner, and published in a article on monochorionic twinning in the pig. The model related the structure of the foetal membranes (chorionicity, amnionicity) to different hypothetical moments of embryonic duplication. The author presented it as a speculative exercise, as a mere suggestion. He introduced it at the end of the discussion of his article with these words: "I am now going to indulge in a brief exercise of imagination on the morphogenesis of human monochorionic twins". He joined in his hypothesis two models of twinning: the diamniotic of the pig (studied by him in that article) and the monoamniotic of the armadillo, studied by Paterson. The hypothesis was not absolutely original. Corner was able to translate into imagined time coordinates the topographical coordinates which, before him, had been imagined by other authors to explain monozygotic twinning.

Corner's ingenious, brilliant theory became established orthodoxy over the years. It was enriched by the inclusion of dizygotic monozygotic twins (in 1922, dizygotic twins were, without exception, thought to be dizygotic). Today, Corner's model is an official icon, an undisputed paradigm, and a dogma that has not generated heretics. And yet Corner himself, 33 years later, in 1955, continued to recognise its artificial, speculative nature: "embryologists and obstetricians have constructed with pencil and paper the morphological theory of uniovular twinning, tracing the different ways that the zygote could follow to eventually develop two embryos. All this is in the textbooks. It has, however, been elaborated by mere conjecture from the structure of the placenta and the foetal envelopes...".

No one, to this day, has corroborated the theory with evidence. But it still enjoys widespread credibility. As far as I know, no one out there has had the audacity to challenge it. The consequences of such complacent conformism are, however, plain to see: there has been no research, we are where we were in 1922: at the starting line. It seems that at the origin of every research someone has to raise a doubt, ask a question, break the mould. But nobody has done so here. It is unheard of that, in a world as innovative and progressive as biomedicine, a theoretical model has not been corroborated or refuted for almost nine decades. It is as if we were in the time of Ptolemy's geocentric astronomy.

There is, however, an excuse, an explanation: no one has observed, and probably never will be able to observe, in vivo, the process of embryo cleavage that takes place in the woman's tube or uterus. Nevertheless, hundreds of thousands of human zygotes, morulae and blastocysts have been examined in vitro in the clinical field of assisted reproduction at internship . No one has ever provided any results. And no one has provided any reliable data, let alone data , on the timing of twinning, even though IVF causes an increase in monozygotic twinning by mechanisms that remain to be elucidated B . There are many articles published on this phenomenon and its possible causes. But none of them have been proven. In particular, no progress has been made in clarifying the moment at which embryo cleavage occurs.

I am hopeful that Corner's venerable model will gradually fall apart. It does not take into account the spatial complexity of the embryo. Perhaps a law similar to that of crystallography also operates in human embryology, which states that, above a certain level of complexity, crystal twinning is no longer possible. It is more logical to suspect that twin cleavage occurs in the first, or in the first few blastomeric divisions. We know that the early embryo already has poles and planes, that it is asymmetrical, that the first blastomeres are not equivalent. This new image contrasts with that of the "amorphous" embryo, homogeneous, made of elements equal to each other and totipotent, which could separate into casual groups, each capable at any moment of establishing two new and complete systems of bodily symmetry, two sets of axes in the three directions of space. We know that, in the embryo, molecular decisions are made long before their morphological effects are manifested. It is in the first days, while the embryo is still inside the pellucida, that it makes molecular decisions about the axes and planes of the body, and we know that their formal consequences only become visible after hatching.

If, as it is reasonable to think, twinning is already present in the first division of the zygote, many ontological problems would be solved and we would recover a simple morphogenesis for the embryo. Twinning would be a phenomenon that occurs during fertilisation and not afterwards. It begins with the penetration of the sperm and is accomplished with the first cell division of the zygote. Normally, this division gives rise to the first two blastomeres. But in monozygotic twinning, this division produces two zygotes. Each twin then continues its own development: each one decides its own development.

This theory removes the theoretical model of cleavage at different stages (two blastomeres, morula, early blastocyst, late blastocyst, embryonic disc), and puts in its place a theoretical model of membrane fusion. I hope that, in the not too distant future, someone will be able to map a molecular marker map showing us that from the very beginning there are two embryos generated ex-ante, at fertilisation.

In conclusion: The chronology of the orthodox model designed by Corner remains today a mere hypothesis, never proven. It is not permissible to turn it into a factual account. It is abusive to wield it in the bioethical discussion in support of the tremendous assertion that the beginning of human life should be delayed to 14 days after fertilisation. It is, I insist, a disproportionate, despotic inference.

This is the end of the bioethical example and we move on to the biotheological example.

The bio-theological example

The obligation to critically read the biology of bioethics becomes especially important when biological data enters into dialogue with moral theology in what it has to say about human life. Theologians need to know, unravel and evaluate the data that biologists and researchers are establishing in their research. They have to dignify their theological speech with noble materials, with purified biology. They must not contaminate it with dross, with false trash.

I will try to show how important it is to go deeply into the biomedical data when important moral evaluations depend on them. And I will use an example which, I believe, is very demonstrative, and which is part of a study that has not yet been completed. The data of this section is already sufficiently refined, even if there are still a few points to be made at fill in. The conclusions, although provisional, cannot vary much.

The study refers to the public denunciation of natural methods of birth control following the publication of the encyclical Humanae vitae, which was accused of being the cause of many abortions, malformations and chromosomopathies. Today no one talks about this any more: it was a false alarm, which was sounded in the 70s of the last century.

The case, which could be called the case of untimely fertilisation, began, as a bio-theological problem, in the deliberations of the famous Pontifical Commission for the Study of the Problems of Population, Family and Birth. In the "Medical and Psychological Section" of report of its 4th session in March 1965, attention was drawn to a risk that made the internship of natural methods of birth regulation questionable: these methods, in order to avoid fertilisation, restrict conjugal relations to the so-called infertile periods, and thus distance them from the time of ovulation. When these methods fail, the resulting fertilisation involves immature or hyper-ripe gametes. This has worrying biological and moral consequences.

The aforementioned report read as follows:

"Moreover, Professor Thibault makes some very important observations about the fact that the moment of fertilisation and the age of the sperm and egg are far from being irrelevant to the fate of the conceived being (Malformation, Mongolism). This leads one to think that the contact of sperm and egg should take place 'at the right time', that there is an optimal procreation. If this fact were to be fully confirmed and, in particular, if ways were found to determine it for practical purposes, a moral problem would then arise. The problem for husband and wife of choosing the time of fertile intercourse, and, moreover, the need to be able to avoid fertilisation outside that time.

Natural methods are thus suspected of causing serious biological and moral side-effects. If they fail, they may result in fertilisation that is not only unwanted, but also overshadowed by the risk of premature death of the embryo or serious disruption of the embryo's development development. If the risks were confirmed, using such methods with the knowledge that they may cause harm would be seriously wrongful. In insects, fish, amphibians, amphibians, birds and mammals, comparative biologists have studied fertilisation by immature or old gametes, and have seen how frequent are the failures of development (early embryonic death, later miscarriages, malformations, chromosomal anomalies).

The final report of the Pontifical Commission, the famous report of the majority, delivered to Paul VI in June 1965, did not, however, make reference letter on this point. There was no evidence at that time that such adverse phenomena occurred in the followers of natural methods: but it could be conjectured that such a risk was real, and not just possible. It was only later, in 1968, that Guerrero noted in his doctoral thesis that couples following the rhythm method had more boys than girls, a fact he attributed to the "anomalous" timing of fertilisation. Someone sent a copy of Guerrero's thesis to the Pope, but no one knows if the Pope paid any attention to it.

When Humanae vitae was published in July 1968, it gave rise to the strong movement of disagreement within and outside the Catholic Church with which we are all familiar. The encyclical condemned artificial contraception and accepted only the rhythm method as a licit alternative. Biologists, doctors and moralists who disagreed with Paul VI thought that an effective way to disavow the Pope's doctrine was to discredit natural methods. It was then that the argument of untimely fertilisation became topical.

The story of the argument is complex and has several characters. For the sake of simplicity, I will confine myself to the main character, the famous moralist Bernhard Häring, and the arguments he put forward in a relatively late article, published in 1976 in the journal Theological Studies, graduate "New Dimensions of Fatherhood manager". It is not an improvised study, like so many others that appeared in the stormy summer of 1968, as an immediate reaction to the encyclical.

In my opinion, this article sample shows paradigmatically how the biological data can be embedded in the theological-moral speech and merge with it. But it also shows how necessary it is in biotheology to read critically, to scrutinise the biological arm of the arguments. There is no other way, if one does not want to be led to wrong conclusions. "New dimensions..." reveals to us that even the greats of biotheology can select data - show some and hide others - they can misinterpret them and make them say more, or different, from what they actually say.

In order to refute Humanae vitae's teaching on natural methods, Häring puts forward four arguments thesis :

1. There is an undeniable link between the frequency of miscarriages and the over-ripening of spermatozoa and especially oocytes. Does this not mean that, when it allows fertilisation with aged gametes, the rhythm method often acts more as a means of "birth control" than as simple contraception?

2. It appears that the rhythm method as used so far causes a considerable loss of zygotes, similar to that attributed to the IUD and the morning-after pill. What is the subject obligation to avoid, or not cause, such loss?

3. What is the status of the zygote before implantation?

4, The relatively high frequency of foetal chromosomal abnormalities following fertilisation of aged gametes raises new issues of awareness, especially, but not exclusively, for those using the rhythm method. How to address this issue?

I will leave aside point 3. As we can see, approaches 1, 2 and 4 are bimodal: they start from a biological premise and conclude with a moral question. Basically, they are telling us that certain biological data arouse well-founded suspicions that the rhythm method may be seriously immoral.

An aside: the average reader tends to read in a descriptive way, so to speak: he or she takes notes, underlines, mentally photographs what the author says. Out of respect for the printed word, for the author's authority, out of intellectual affinity with him, or for lack of dialectical resources, the common reader records what he has read and stores it on report. In contrast, the critical reader demands that the author convinces him, enters into an active dialogue with him, does not hesitate to verify the data and the ideas that the author conveys to him. Often, he gets up from his seat or moves around the Internet to check the veracity and strength of the bibliographical support on which the author bases his arguments, and to see how faithfully the author transcribes or accommodates them. He or she must judge their value and strength for him or herself. A critical attitude is essential in bioethics. The section ends.

Let us now look at the scientific support for Häring's arguments and, in particular, whether or not it is strong evidence to support his reprobation of the encyclical.

Argument 1.

Häring, a biologist, states as an undeniable fact that fertilisation with aged gametes causes miscarriages more frequently than usual, as recent research in various animal species has shown. Häring, a moralist, concludes that choosing certain days for conjugal intercourse before or after ovulation entails an increased risk to the life and health of the embryo. And that we simply cannot escape moral responsibility for these foreseeable consequences.

The critical reader wonders: What research does Häring invoke? From which springboard does he make the leap from animal experimentation to human reproductive reality? The references Häring quotation in the footnotes deal with experiments on aged gametes of hamsters, rabbits, xenopus. One of the authors suggests the possibility that similar phenomena of embryonic death or malformation may occur in the human species. quotation also to Hellegers, who, in a theoretical essay , drew attention to such a possibility. Häring speaks of Guerrero's thesis which was sent to the Pope. Further on, quotation a work by Marshall, who observed no relationship between the age of the spermatozoa and the appearance of anomalies, but Häring rightly considers Marshall's study to be of very weak methodology.

His strong support for this argument is a new work by Guerrero and Rojas, an extension of the above-mentioned thesis , published in N Eng J Med, 1975, on miscarriage linked to oocyte and sperm ageing. For Häring, this work is very illuminating. But the authors are more modest: they acknowledge in their work certain important methodological limitations, they consider that their results strongly suggest the association between old sperm and early and late miscarriages. But they do not draw firm, let alone undeniable, conclusions.

Guerrero y Rojas' article is accompanied by a publishing house, which Häring quotation supports thesis . Häring tells us: "In a publishing house published on the occasion of the above-mentioned important study by Guerrero and Rojas, three doctors came to this unequivocal conclusion: they called for further research, for "if it were proved to be true, one can intuitively imagine that such defects would be prevented by teaching the public to juxtapose fertilisation and ovulation as closely as possible in time".

But Häring does not make reference letter to other comments made by the three doctors in their publishing house, when they point out the serious limitations of Guerrero and Rojas' work in their design and in the populations studied; above all, their main conclusion is considered unfounded. The editorialists say: "It is a long leap in the dark to believe, without data, that oocyte overmaturity leads to the genesis of abnormal human embryos and children with Down's syndrome and the like. The hypothesis that overmaturity of gametes can cause congenital malformations and mental retardation needs careful testing". And, only then, they add that "if this were proven to be true, one can intuitively imagine that such defects should be prevented by teaching the public to juxtapose fertilisation and ovulation as closely as possible in time".

In substance, Häring's argument 1 is biologically an empty argument.

Argument 2.

Häring says: "It seems that the rhythm method as used so far causes a considerable loss of zygotes, similar to that attributed to the IUD and the morning-after pill. What subject obligation is there to avoid, or not to cause, such a loss?

From a moral-theological point of view, Häring's proposal aspires to include natural methods in the same moral species as early abortifacients (IUDs, pdd), which would be tantamount to their absolute moral condemnation. Indeed, as Häring points out, "Catholic moral theology has affirmed that there is a qualitative difference between contraceptive methods in the strict sense (those that eliminate the possibility of fertilisation) and means of birth control that allow fertilisation to occur but hinder or prevent implantation".

From a biological perspective, Häring states that "many programs of study on animal fertility, and a issue of recent programs of study on human fertility such as that of Guerrero and Rojas, force us to accept that the rhythm method, as traditionally practised, not only causes a relatively high frequency of miscarriages, but even more frequently leads to the loss of fertilised oocytes and to visually unnoticed miscarriages that take place very soon after implantation. Blastocysts from overmature gametes often lack the vitality necessary for successful implantation in the endometrium.

This is a very serious accusation with enormous moral consequences. Häring insists that we cannot look the other way, that we have to face up to uncomfortable facts. If natural methods involve the loss of zygotes before implantation, we must have the courage to change the moral assessment of such methods and not try to justify the embryo loss involved with evasions.

From agreement. But where are these biological data ? In a footnote to grade , Häring points out that among the various publications that make this conclusion highly probable, if not entirely compelling, one should consult Guerrero's thesis , cited above; a article by Guerrero and Lanctot, another by Mikamo (both published in 1970 in Am J Obstet Gynecol), and a Lancet publishing house from 1975.

I have already pointed out that I have not been able to obtain Guerrero's thesis from 1968. Guerrero, however, published two papers on the same subject from his thesis : one in 1974 (N Eng J Med) and one in 1975 (Stud Fam Plan). In these two papers he makes no allusion to the occurrence of embryo loss linked to natural methods. In the discussion of the results included in the 1974 article , he points to the possibility that the observed deviation in the proportion of boys and girls could be due to "a selective loss of embryos of one or the other sex before implantation or during early gestation"; and he notes that there is an extremely high loss of embryos in the initial phase of conception, but without referring to natural methods, which are not mentioned at any time in that work.

Guerrero and Lanctot's article addresses the question core topic: Age of fertilising gametes and miscarriage (Am J Obstet Gynecol, 1970). This is a work which attempts to apply a more refined study methodology, but acknowledges the notable technical limitations which weaken its findings and conclusions. The results suggest that the likelihood of miscarriage tends to be higher leave when conjugal intercourse or insemination takes place in the days close to ovulation, but the authors acknowledge that the differences observed are not statistically significant, as the issue of cases involved in the study was too small to allow any firm conclusions.

Mikamo merely notes that "Cases where the time of conception was known strongly suggest that in human reproduction delayed ovulation and delayed fertilisation may be of great importance in the pathological development ". Mikamo turns to bibliography to support his suggestion, but there is no work reference letter at the time of fertilisation, which he did not know, and he preferred to classify spontaneously aborted embryos in relation to the period of development embryo, not to the apparent duration of gestation. In any case, Mikamo emphasises the prevalent importance of intrafollicular oocyte hypermaturation in the genesis of development anomalies. But such delayed ovulation is unrelated to the timing of the conjugal relationship.

Finally, the Lancet's publishing house on "Miscarriage" does not say a word about natural methods and, therefore, about the relationship that miscarriages may have with them.

Häring's argument 2 turns out to be a biologically empty argument.

Argument 4

It says: "The relatively high frequency of foetal chromosomal abnormalities following fertilisation of aged gametes raises new issues of awareness, especially, but not exclusively, for those using the rhythm method. How to address this issue?"

Häring points out that "well-documented publications state that fertilisation with hypermature gametes is frequently the cause of chromosomal abnormalities and other damage". And quotation an extensive review by Lanman (1968) in N Eng J Med, a article by Guerrero in Studies in Family Planning (1975), a book by Jongbloet on hypermaturity ovopathy and mental and physical handicap (1971), a issue by Population Report on Periodic Abstinence (1974), a new article by Mikamo in Cytogenetics (1968), a article by Ingalls in Lancet (1972), the aforementioned article by Mikamo in AJOG in 1970, and, finally, a new article by Guerrero in N Eng J Med together with the accompanying publishing house .

Lanman's very thorough review deals with gamete ageing. And he devotes a lot of attention to chromosomal disorders. But he says nothing about natural methods causing them. Of sperm he says: "An important and critical issue for human subjects remains unanswered: whether fertilisation of an oocyte by a casually aged sperm in the female tract has deleterious effects. Such effects have been observed in drosophila and birds". On oocyte ageing he summarises: "The question has been raised whether oocytes fertilised at the end of their fertilisation period are more likely to produce poor offspring. At the moment, there is no valid evidence that this is the case. Couples practising the rhythm method with purpose contraception are perhaps the most suitable group in which to find a higher rate of defective offspring, but no reports have been published".

Guerrero's 1975 article in Stud Fam Planning is a new version of his thesis on the proportion of boys and girls born in relation to subject and the time of insemination. It fixes some of the methodological mismatches of that one and increases the issue of observed cases. But it does not say a word about chromosomal disorders linked to the rhythm method.

I have not been able to obtain Jongbloet's book. In Häring's opinion, Jongbloet offers the strongest argument for the causal relationship of natural methods and mental deficiency in offspring. To show this, he includes a very long quotation of Jongbloet's observations: in his experience the frequency of Down's children is twice as high among Catholics who use natural methods as in the population that does not use these methods. And, this is a strong test , when Catholic couples abandon these methods, they have offspring that are indistinguishable from the rest of the population.

Häring's lengthy description of Jongbloet's observations coincides almost verbatim with the corresponding text included in report on Periodic Abstinence published in 1974 by the Population Information Program of the George Washington University, although with one significant difference: Häring omits the final lines containing an important conclusion of Jongbloet: "A much more extensive research is needed on this problem".

In any case, Häring points out generically that other programs of study on topic are not so conclusive. But, curiously, this does not prevent him from proclaiming that, in his opinion, "children born with chromosomal defects as a result of the rhythm are only a small iceberg behind which we can now see the enormous waste of zygotes and early, noticed or unnoticed miscarriages". This apparently voluntarist conclusion is not supported by any bibliographical references.

Mikamo's work on anatomical and chromosomal alterations in miscarriages speculates on the possibility that aged sperm may act as a teratogenic factor, although he attributes more teratogenetic responsibility to aged oocytes, especially those that have hypermatured within the follicle. But delayed ovulation is an issue that has nothing to do with natural methods. Mikamo is content to state that "Cases where the time of conception is known strongly suggest that, in human reproduction, delayed ovulation or late fertilisation could be of great importance for the abnormal development ".

Ingalls' article , "Maternal health and mongolism", full of 'Framingham' brand enthusiasm, points to "the hypothesis that trisomies, especially G (21 we now call it), monosomies and polyploidies [...] could be due to natural causes acting during the fertile years of the female. Ingalls highlights among the factors to be investigated the chronological ageing of the ovaries and their follicles, and the ageing of the newly ovulated oocyte. The former is measured in years, the latter in days. [...] There are suspicions that human factors as diverse as religious beliefs, and the circumstances and timing of the marital relationship may be causally related to the aetiology of mongolism. Even the role of temperature charts, used to conceive or to prevent conception, needs to be re-evaluated". We do not leave the realm of suspicion and intuition.

Guerrero's 1974 reference letter to article tries to support Häring's idea that "several scientists are looking for an explanation suggesting a relationship between gamete hypermaturity, sex ratio, and the frequency of chromosomal abnormalities related to sex chromosomes". There are no demonstrations on Guerrero's work : only discussion of three hypotheses to explain the observed differences and the need for more research.

Häring expresses his agreement with this necessity, because he thinks that the subject is of ardent interest for a fully-fledged parenthood manager. But he goes on to say: "It seems to me that those who consider that there is still a gap between the data collected on the fertility of animals and the conclusion reached on humans, may well be that they have not studied the bibliography available and all the arguments. No scientist thinks that we are dealing with arbitrary hypotheses or false alarms". And Häring calls as witnesses Hecht, Pernoll and Mccaw in his publishing house in N Eng J Med. But they say that "a lot of work has been done to test this hypothesis [that of gamete hypermaturity] in different animals, in which it seems to be generally tenable. In humans, however, relevant data are scarce".

Argument 4 is as biologically empty an argument as arguments 1 and 2.

This is the end of this exhausting tour through the pages of Häring's article . He does not seem to be an expert in the critical reading and understanding of the scientific bibliography . Nor does the use he has made of it in support of his theological thesis seem academically acceptable. I have the impression that the theologian Häring, instead of using the moderating and critical function of the relevant biological data for his reasoning, has used it as a screen for his prejudices. His way of citing the bibliography seems to be aimed at dissuading, at disinviting, his readers from visiting these works. It seems somewhat paternalistic, as if to assure us that he has already studied them for us so that we can spare ourselves the work of judging them for ourselves.

Before concluding: I am reading, slowly, Stephen Shapin's book, "Never Pure" "Never Pure: programs of study of history of science as if it had been produced by flesh and blood people, situated in time, space, culture, society, and struggling to achieve credibility and authority". It is a story of how scientists, past and present, have been building science without ever being able to free themselves from the sticky conflicts of interest between the permanent ideal of seeking scientific truth and the no less permanent reality of human lusts: money, fame, ideology, rivalry, power. Let us not forget that we are also flesh and blood people who try to do Bioethics.

In conclusion: it is not possible to work in many areas of bioethics without an intense, critical, dispassionate, patient study of the biomedical literature. This is what I wanted to convey in this closing session of the Master.

Please listen to me. Thank you very much.