To kill or not to kill, that is the question. [Unknown]
The correlation between chromosomal errors and their phenotypic
consequences is sufficiently well established to allow us to decipher, however
partially, the destiny of an individual just by looking at his chromosomes. For
example, if we know that a subject will be developing from a fertilized egg
carrying an extra chromosome 21, we know for sure that the individual will
exhibit later all the characteristics of the 21-trisomy syndrome, including,
among other abnormalities, severe mental deficiency. Hence the very practical
point has been repeatedly advanced that if early detection of a chromosomal
condition could be achieved (such as made possible by analysis of the cells
floating in the amniotic fluid), a decision could be taken whether such a
pregnancy would be allowed to go to term or would be interrupted by an induced
abortion. Such a problem is so close to us and so obviously important that it
has become one of the possible immediate consequences of recent advances in
theoretical knowledge and technical capabilities. Without proposing to
elaborate a new philosophy of the human condition, it seems appropriate that
human geneticists realize that the question "to kill or not to kill," is by no
means purely practical or technological. I will deliberately leave out of the
discussion the ethical aspects, because I think human geneticists are no better
qualified in ethics than are any other scientists. On the contrary, I would
focus our attention on the biological aspects related to a mere ob-servation:
"What do we know about the time at which a new human being comes into
existence?"
Such a query is not new, and here the geneticist is very similar to
Diogenes coming out of his barrel and looking for a man. The only difference is
that our lantern has been modernized into a microscope, and I would propose
that we consider this quest for a man in the light of cytogenetical
findings.
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The karyotype of mankind
Our first statement is such a commonplace observation that we
generally do not pay enough attention to it. All human beings now living on
this planet share the same karyotype. More precisely, apart from the XX and XY
sexual dimorphism, every chromosomal pair is morphologically identical in all
of us within the degree of uncertainty inherent in present methods. On the
other hand, the continuous recurrence of "de novo" chromosomal rearrangements
(like trisomies, monosomies, or various kinds of translocations) exemplifies
the tremendous mutational pressure exerted upon the human karyotype.
Furthermore, the heavy and painful tribute paid by each generation to meiotic
or mitotic mistakes shows at what cost the constancy of the human karyotype is
preserved.
If karyotypes other than the standard human chromosomal constitution
were equally good or even better, human races should have split from each
other, forming multiple karyotypic systems. This has not happened in our
species although many examples can be found in other mammals. Conversely,
fortuitous convergence of other karyotypic constitutions toward the human-type
pattern becomes exceedingly improbable. We are then left with the interesting
but academically uncomfortable conclusion that speciation in plants and animals
is a very different process from human race formation, and we are obliged to
use quotation marks when we speak about "Darwinian evolution of man".
No matter how we tackle the problem, it follows from the actual
findings that the present-day human karyotype must have appeared first in an
extremely small group, even as small as one couple, and must have maintained
itself constant, simply because it was the very best solution. It follows also
that mankind is a biological unit of which races are variations with no precise
boundaries. Hence the old idea that human beings are brothers is not an ethical
hypothesis or a purely moral goal, but simply a correct expression of plain
reality. The recognition of such brotherhood is very comforting, but increases
our concern as human geneticists for the destiny of those unfortunate children
who do not share equitably our chromosomal heritage.
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The disinherited children
As we first noted, a question is thus raised: Should these variants of
the human condition be allowed to live?
Here, to try to simplify the problem, we could first dismiss the
problems raised by grown-up individuals or even newborns. No doubt exists, I
suppose, that to suppress the life of an adult, an infant, or even a newborn,
is to be classified as homicide, no matter how severely affected the patient
should be.
Indeed it could be remarked that some conditions like 13 trisomy, for
example, are not compatible with a prolonged extrauterine life. An argument
could thus be presented that their suppression would be only equivalent to
premature euthanasia. Without discussing the particular topic of euthanasia, a
very strong difference must be stressed here: the purpose of euthanasia is to
spare seemingly unnecessary suffering to the patient, while the goal of the
suppression of a disabled child is to prevent suffering to his family and to
society.
If we definitely are not concerned about the finished individual, what
about the beginning of life? When the future human being is still a
conglomerate of cells, apparently not yet differentiated, should we consider
him as a human being or not? Should we reject this cell mass if it does not fit
our specifications, or should we respect him and protect him in all possible
ways? Such a question, directly raised by the possible detection of a
chromosomal error in a young embryo, has to be faced by human geneticists.
Surely the answer must be based upon scientific grounds and be as free as
possible from emotional or opportunistic reactions.
The necessity of assuming this duty is imperative. Geneticists cannot
play Pontius Pilate and wash their hands, saying, "The parents will choose."
Parents are generally not cytogeneticists, but are always deeply emotionally
involved. How then could they judge?
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The technical approach
Challenged with this problem we can try a "technical" approach. Just
for a moment let us suppose that the question of being a man or not is either
irrelevant or already solved, and look for a "technical" solution. Although the
matter seems, and indeed is, considerably simplified by such a bold statement,
not all difficulties have vanished. We must first consider that the phenotypes
determined by chromosomal aberrations cover an extremely broad spectrum.
At one extreme we can locate-apart from the 13 trisomy already
mentioned-the 18 trisomy, the pure triploidies, and a few other conditions
which are practically incompatible with prolonged extrauterine life. A second
category includes severe conditions like trisomy 21 or Cri du Chat syndrome,
which are entirely compatible with a long life expectancy but inflict severe
physical impairments and a mental deficiency, although varying appreciably from
subject to subject. In technical terms, we must stress that our predictions are
quite accurate but are only negative. For example, the presence of an extra
chromosome 21 in a fertilized egg gives us the following information: the
children who will develop from this egg will never attend a high school and
will not be able to live independently. Remarkably enough, we do not know
whether the affected individual will be able to read, write, or count and
achieve a mental age of seven or eight years, or whether he will have an
extremely poor development, with an IQ below 20. Obviously the human
geneticists looking at chromosomes have not yet reached the cleverness of the
fairies who could predict everything just by looking at a baby in his cradle.
However, our "misfortune-telling" is precise enough to know that the child will
never be self-supporting in everyday life.
The other extreme of the spectrum is much more troublesome. For
example, an XO woman, although sterile and slightly physically abnormal, can
spend an interesting life found worthwhile by herself as well as by others. I
have in mind the case of an excellent technician I met years ago in a
laboratory of human biochemical genetics. The case of an XXY Klinefelter is
still more ambiguous. Apart from sterility, a kind of built-in permanent
contraception, an XXY subject can have a quite normal life and even can become
a highly reputable surgeon-to cite another individual case.
Finally we find quite normal conditions, like triplo-X mothers,
fortuitously detected, or XYY individuals who can enjoy a perfectly decent and
respectable life. Indeed we know, statistically, that the XXX condition is far
more frequent among inmates of institutions for mentally retarded persons, and
we are quite convinced that the risk of delinquency is greater for an XYY man
than for a "normal" XY (although not greater than for an "abnormal" XY). But
what about the condition of translocation carriers, not suffering any
detectable genetic damage themselves but able to give birth to children
suffering from an imbalanced karyotype? And what about complex translocations
which, due to aneusomie de recombinaison, can occur in two different although
morphologically identical karyotypes, one entirely balanced, leading to
perfectly normal adults, the other severely imbalanced, and sometimes lethal or
dramatically dysmorphogenic.
Intermingled with all the preceding cases is the cumbersome problem of
mosaicism. Every human being is a mosaic due to some mitotic malsegregation in
some part of the body; the dividing line between normal and pathologic is a
matter of percentage: if 50% of abnormal karyotype is considered as
deleterious, what about 40%, 20%, 5%, and what about topographical
distributions? Obviously here some "technical" judgment has to be made about
the human qualities resulting from a given constitution, and careful analysis
of the burden imposed upon affected individuals, their families, and society
must be made.
The burden to the individual himself is very difficult to assess
because only the affected person can tell us about it. The overwhelming
majority of patients suffering from a genetic disease (and able to express
their feelings) do regret their affliction but do not regret being themselves
and alive. The social burden possibly could be easier to estimate, but the
suffering of the family will stay outside of any "technical" evaluation.
Nevertheless, many precise but very complex questions must be solved. For
example: is the Turnerian way of life to be accepted? is the 21-trisomic way of
life to be protected? ..., and the like. Willy-nilly we come to the conclusion
that such a difficult matter, that of deciding what is desirable and should be
respected and what is undesirable and should be rejected, deals with
considerable "technical" intricacies. In such situations the common practice is
not to leave the decision to unprepared or to directly involved persons, but to
resort to some jurisdiction, or some body of counselors.
Thus the time is ripe to see what kind of facility for research and
applied eugenics should be constituted to manage these problems. Indeed, there
would be no reason whatsoever to limit the competence of this facility merely
to chromosomal aberrations, but its terms of reference should include all
inborn errors, either genie or chromosomal. In order to work out entirely this
"technical" approach, let us read the minimal statutes that such a facility
should have.
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Elements of the Statutes of a New Facility for Research and
Applied Eugenics Haut
Article I
Considering the disputed issue of mankind's betterment, noting the
burden imposed upon society by genie and chromosomal diseases, and recognizing
the limitation of the available solutions, a special Institution for Research
and Applied Eugenics is created: "THE NATIONAL INSTITUTE OF DEATH."
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Article II
Under the scientific scrutiny of a board of specially appointed
advisors, the NATIONAL INSTITUTE OF DEATH will:
A. Decree on undesirable genes or chromosomes.
B. Deliver unhappy parents from unwanted pregnancies.
C. Discard embryos not fitting standard requirements.
D. Dispose of newborns not reaching minimal specifications of
normalcy.
E. And generally, destroy, delete, or decry any human condition
voted against by the above-mentioned board of advisors of the NATIONAL
INSTITUTE OF DEATH.
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Article III
To prevent any possible error, concern, or prejudice, the advisors
shall be chosen from among knowledgeable persons not belonging to any
philosophy, society, or race.
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The individual approach
Leaving the board of advisors of the NATIONAL INSTITUTE OF DEATH to
its intrinsic "technicalities," we have to remember that we have set aside the
core of the problem: when does man begin? To make a short story long (for the
beginning of life is just the brief instant of egg fertilization), we can
investigate at what stage of development the future human being can be
considered as an individual. The available in-formation is spread over many
fields of biology but can be summarized under the two headings defining an
individual, that is, unity and uniqueness. It is actually impossible to state
firmly at what time these two qualities appear, although we know for sure that
it is after fertilization. But it is possible to delineate with the aid of
pathological findings, the time after which these qualities cannot be
appreciably changed.
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Unity and Chimeras
According to the classical rules of human genetics, every individual
is constructed out of one cell, the fertilized egg. This formal statement had
no exception until the discovery of human chimeras in hermaphroditism. For
example, in the constitution XX/XY, careful analysis of blood groups shows that
the red cells are composed of two subpopulations, each of them carrying a
particular array of genes coming from the parents. The primary mechanism of
these chimeras is poorly understood but, broadly speaking, it can be asserted
that two fraternal twin zygotes have collaborated to build together one embryo
instead of two. Speculations about simultaneous fertilization of a reduced egg
and of one of its polar bodies have been made, and diploid/triploid mosaics
seem to owe their origin to a rather similar type of accident. Although other
mechanisms could as well be postulated, the moment at which the process can
occur is very early in development.
First, these events happen at the same ovulation period, for embryos
a month apart could not fuse into one. Second, to realize the almost-perfect
mixture of the two kinds of cells found in every tissue, the symbiosis must
establish itself well ahead of the first general organization of the future
embryo. This leaves us with a period of uncertainty not exceeding weeks and,
quite likely, as short as a few days or hours if the polar body is involved.
This problem of the unity of an individual of chimeric origin is intriguing.
Compound animals can be artificially produced, like the mouse manufactured from
blastocysts of different embryos, thus having many mothers and many fathers.
Such a monstrosity fortunately is not be be feared too much in our species, at
least, as long as the good old manners of reproduction will be in use!
Nevertheless, it seems likely that natural chimeras in our species are about
twice as frequent as XX/XY hermaphrodites. The reason is that if two fraternal
zygotes, both XX or both XY, fuse, the individual will be perfectly healthy and
never examined. It is entirely possible that some here are not the pure clone
they believe themselves to be, but are harmonious chimeras resulting from the
full integration of two cellular races. Is it entirely chimerical to think that
such a fruitful and peaceful coexistence between populations of cells, carrying
different tables of the law of life, hopefully could be a model for human
societies?
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Uniqueness and Twins
The uniqueness of each man is also an old rule of genetics. Without
developing any statistical demonstration, it can safely be assessed that the
precise genetic constitution of every fertilized egg is unique, has never been
realized before, and will never occur again. But at what moment is this
uniqueness definitely established? Monozygous twins show that two or sometimes
more individuals can emerge from the same primordial genetic information.
Nobody, I venture, would seriously argue that identical twins are not
individual persons although they share the very same nature. The splitting in
two embryos surely can occur at the first cleavage of the egg, but what about
the latest stage possible? The observation of double monsters demonstrates that
complete separation cannot take place after the finalization of the neural
crest. Hence, we are left again with an indeterminate period of assuredly less
than one month and probably of two or three weeks at most.
Incidentally, again to break one of the old rules, twins coming from
the same egg are not necessarily alike. If a chromosomal error intervenes
during or just after cleavage, identical twins can be different. If a
chromosome 21, for example, is present in triplicate in one twin and normally
diploid in the other, the twin set will be composed of a typical 21-trisomic
individual and of his normal co-twin, identical but for the 21 trisomy
condition. If the accident prevents the transmission of the Y chromosome to one
of the twins there will be one normal male (XY) and a female identical twin
with Turners syndrome (XO). In a case of this type, the XO girl apparently
suffered from a very strange psychological disturbance which greatly intrigued
the psychiatrists: she pretended she was seeing her brother when she looked at
herself in a mirror. For the geneticist, such an intuitive knowledge of a
complex situation was not at all troublesome, but a mere affirmation of the
facts. But, coming back to our timing problem, in what way can all these
remarks help us in answering our basic question: "when does a human being
begin?"
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The molecular approach
During the transmission of life, the link between parents and infants
is continuous. Without reviewing the complex machinery of coded molecules, from
DNA and RNA-to ribosomes and proteins, we can safely assume that at every
moment this link between generations is material. Nevertheless, with exactly
the same degree of certainty, we know that no one molecule, no one individual
atom actually present in the fertilized egg, will have the slightest chance of
being transmitted to the next generation. Obviously what is "transmitted" is a
form, an accident of the matter, and not matter itself as such. This apparent
paradox is the very basis of any reproductive process. For example a statue
cannot be built out of void; it needs a material substrate such as marble or
clay. During reproduction by molding, the link between the statue and its
replicate is at every instant a material one; but what is reproduced is
definitely not the marble or the plaster but the form, or, more precisely, the
information imprinted on matter by the genius of the sculptor.
Applied to biology, this principle of information transfer is
perfectly relevant because we know that, if not disturbed and if not deprived
of nutrient supply, the fertilized egg on its own will produce a full-blown
individual by an extremely complex but entirely deterministic mechanism. In
utero relations between the mother and the fetus do not affect at all this
fundamental determinism, as is clearly demonstrated by the egg of the hen. By
such reasoning, the information specialist reaches the conclusion that the more
deterministic and materialistic his conception of life, the earlier a human
constitution is entirely spelled out. If man is considered as an accretion of
matter such that his very nature is entirely dictated by the information
imprinted in these materials, then a new man begins at the precise point the
necessary and sufficient information is gathered, that is, at the very
beginning.
Even interpretation of his theory in philosophical terms will not lead
the information specialist any further. Indeed, it could be argued that all
nuclear and cytoplasmic information included in the fertilized egg is only
describing the "essence" of the future man, not his "existence." But this
reserve vanishes immediately if we accept the fact that existence is essence in
action. Hence since any transmission of information is the action of its
essence, the future man effectively exists either at the first RNA synthesis
or, if we need a more ostensible starting point, at the first cell cleavage.
Whether or not we find that reducing man to the genetic and organistic
information of his primordial cell is intuitively satisfactory, no clear
direction seems open to pursue the argument.
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The practical approach
Many would consider that we have spent enough time on pure and
unproductive speculations and would stop here, saying, "Wait, let us be
practical and see the mere facts."
At the early stages of embryonic development there are only
conglomerated cells, rapidly dividing. This little mass even does not look at
all like a man; it is just a piece of flesh, a very precious flesh because a
human being could sprout out of it - a fact impossible from an ordinary tissue
culture or from any somatic part of the body. But there is no "humanity" there,
just human cells. In this approach, different land-marks can be used in
deciding that "humanity" has been acquired by the "thing." Some will hold that
organs must have differentiated; others will require some development of the
brain; and others will wait until certain reactions to stimuli occur in the
fetus or until any other specified step is attained. It follows that the time
factor we are interested in varies largely with this approach, for example from
fertilization to viability, or, when the disputation is entirely worked out, to
the time at which the "growing thing" will finally be able to pretend that he
is a man. Generally the process of birth is accepted as a convenient term for
the discussion, but this separation from the mother is not relevant whatsoever
to the logic of the argument.
When viewed scientifically, this difficulty in spelling out
"practically" at what precise time a mass of cells becomes a man is not
surprising at all and definitely is not to be ridiculed. If we dissect the
intellectual pathway followed here, it is clear that regardless of the
circumlocutions used, what the "practical" view is looking for is in plain
words: is there some kind of human "soul" or not? Ensoulment theory has been
vividly discussed by theologians but, to the best of my knowledge, never
solved. Thus, it is no wonder that "practical" discussants cannot beat
specialists on their own ground. Curiously enough, we have seen the "molecular
theoretician" coming out with a pure information theory, very akin to physical
representation of the "incarnation of the logos" and the "pragmatist"
discussing the first symptoms of the existence of the "human soul." It could
very well be that such an apparent confusion of disciplines stems from the fact
that we all tried to solve an incomplete problem.
For the sake of simplification, we have devoted ourselves to the
particular query: "When does man begin?" It appeared to be quite a clear-cut
question. But should we not have been better inspired to start with the
necessary question: "What is a man?" No dictionary and even no legislation of
any country or civilization has ever fully answered this question. Depending
upon what different specialists look for in man - his quality, his
individuality, his molecules, or his internal or external life - the
"technician," the "personalist," the "information specialist," and the
"pragmatist" have given their own answers not to the question we asked them,
"When does man begin?" but to the unspelled challenge, "What is a man?"
Certainly this is the crux of the matter, but such a crux is possibly too heavy
to be carried by a human mind.
Here are we left, exactly at the same point we started two thousand
years ago. The Diogenes-geneticist returns to his barrel after turning off his
microscopic lantern. He has not discovered when and where man could be found!
Conclusions from such a circular trip are not straightforward! Nevertheless we
human geneticists have to face everyday reality: disabled children and
distressed parents exist. No formal demonstration being at hand, each of us has
to face the challenge, and I believe our response must be guided by two
sentiments only - humility and compassion. Hu-mility because we must recognize
we have no ready-made answers, because geneticists have not broken the secret
of the human condition, and because scientific arguments are of little help in
ethical issues; compassion because even the most disinherited belongs to our
kin, because these victims are poorer than the poorest, and because the sorrow
of the parents cannot be consoled by science. But should we capitulate in the
face of our own ignorance and propose to eliminate those we cannot help?
For millennia, medicine has striven to fight for life and health and
against disease and death. Any reversal of the order of these terms of
reference would entirely change medicine itself. It happens that nature does
condemn. Our duty has always been not to inflict the sentence but to try to
commute the pain. In any foreseeable genetical trial I do not know enough to
judge, but I feel enough to advocate.
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