The feasibility of extracorporeal fecundation (also called in vitro
fertilization) has experimentally confirmed our basic knowledge of the
fundamentals of human reproduction. Besides this scientific achievement, the
new techniques have opened possibilities which deserve careful
The fundamentals of life
Life has a very, very long history but each individual has a very neat
beginning: the moment of his or her conception. As it has been amply
demonstrated (1) the whole biology of vertebrates teaches us that ancestors are
united to their progeny by a continuous material link, for it is from the
fertilization of the female cell (the ovum) by the male cell (the spermatozoon)
that a new member of the species will emerge.
The material link is the thread-like molecule of DNA. This ribbon,
roughly one metre long, is divided into segments (23 in man), and each segment
is carefully coiled and packaged in the form of a little rod, clearly visible
under the microscope: the chromosome.
As soon as the 23 maternal chromosomes encounter the 23 paternal
chromosomes, the full genetic information, necessary and sufficient to spell
out all the inborn qualities of the new individual, is gathered.
Exactly as the introduction of a minicassette inside a tape recorder
will allow the "re-creation" of the symphony, the information included in the
46 chromosomes (the minicassettes of the symphony of life) will be deciphered
by the machinery of the cytoplasm of the fertilized egg (the tape recorder),
and the new being begins to express himself as soon as he has been
The fact that the baby will develop inside the womb for the next nine
months is irrelevant at this point as in vitro fertilization has amply
The technicalities of fecundation
In natural conditions, the ripe ovum is expelled from the ovary by
rupture of the follicle and is recuperated by the fallopian tube. Inside this
tube it migrates toward the uterus and en route, encounters the sperm which,
alone among millions of others, will fertilize it.
At the end of the journey the fertilized egg, already dividing
feverishly, and organizing itself in a minuscule embryo of 11/2
millimetres in diameter, accommodates itself inside the uterine mucosa
(nidation) around 6 to 7 days after fertilization. There, firmly implanting
itself, it will continue its growth, thanks to its placenta, until birth.
It is because normal fertilization occurs in a tube, with ovum and
sperm floating freely inside the liquid, that test tube babies are possible.
Indeed, in vitro fertilization uses a tube of glass instead of a tube of living
tissue, but the process is, in other respects, identical.
Initially, artificial fertilization outside the maternal body was
suggested to circumvent some cases of feminine sterility. It sometimes happens
that fallopian tubes are blocked, most often as a sequel of sexually
transmissible disease. In such cases, the spermatozoa cannot reach the egg nor
the egg reach the uterus. To circumvent this blockage, the ripe egg is removed
from the ovary by laparoscopy and put into a vessel containing an appropriate
medium. The addition of sperm will lead to fertilization.
The early embryo will be delicately transferred a few days later,
through the cervix of the uterus so that it can continue its development in the
All this explains why Dr. Edwards and Dr. Steptoe could witness in
vitro the very beginning of the exceedingly young Louise Brown, whom they
replaced a few days later in the womb of her mother, Mrs. Brown. Thanks to the
fundamentals of life already known, they were totally assured that this
berry-looking being could not be a tumor nor an animal.
With hundreds of cases already described in various countries of the
world we now have living witnesses for the first time in our own species: the
early human embryo develops by its own virtue and it has incredible
Viability outside the womb
That the early human being is fully viable outside the maternal body
is of no surprise but a confirmation of general principles.
Even in ordinary conditions, with a rather simple culture medium (the
fluid of the fallopian tube), the early human embryo can continue its growth
and development for days, maybe a week, and manage its own organisation; after
one week, implantation is a necessity but the viability of the early human
being is such that even the uterine mucosa is not a pre-requisite.
Up to two months, an embryo implanted inside the fallopian tube is
fully efficient. In these extra-uterine pregnancies the tiny human being,
smaller than a thumb is perfectly developed, the only danger being that its
continuous growth would rupture dramatically the walls of the tube which cannot
extend as a uterus would do. Even in extreme cases of extragenital pregnancies,
when the foetus anchors itself in the abdominal cavity, directly on the
peritoneum, the growth can be astonishingly normal for many months.
Protected by his life-capsule (the zona pellucida first and, later,
the amniotic sac he constructs around himself) the early human being is just as
viable and autonomous as an astronaut on the moon, refuelling with vital fluids
as required from the mothership.
A purely artificial fluid supplier has not yet been invented. But if
it ever possible, complete development outside the womb would belongs to
himself. If the bottle (or test tube) could argue: "This baby baby is my
property", nobody would believe the bottle.
Time at a standstill
Careful refrigeration of living cells, protecting their precious
molecular edifice, is of common use for long preservation. At very low
temperature (-190c in liquid nitrogen) the vibrations of the atoms are
restricted. Time is suspended, so to speak.
Frozen sperm can thus be kept for years. If thawed carefully they
fully recover their potential as intrepid navigators. Sperm banks are a common
tool of industrial breeding.
The same is true for early embryos. Some mouse embryos, deep frozen
and thawed have managed, after implantation, to develop into perfectly normal
mice. No such experiment has yet been reported in our own species; proposals
are numerous although their ethical and scientific legitimacy is at least
Twins at will
If the zona pellucida is split and the embryo is cleaved in two
halves, each mass can be inserted in a separate zona pellucida.
Identical twins have thus been produced, in cattle and in sheep. Some
have proposed to do the same in man. Their rationale is not "a production line"
but the possibility of checking the genetic makeup of one of the twins. The
scenario goes as follows: one twin is deep frozen, until further transfer, at
the proper time, into a recipient uterus. The other twin is allowed to grow for
a time and then examined for chromosomal constitution, normality of growth, and
its various chemical properties. If this twin,the sacrificed twin, is declared
O.K., the spared twin will then be transferred. If not, the spared would give
full insurance for successful childbearing even for an at risk mother (for
chromosomal or genetic disease).
Simple arithmetic (see annexe I) is not so promising or hopeful. A
success rate of little more than a few per cent can hardly be expected. On
average the egg donor would need to be tapped some twenty times :for each
successful pregnancy: an extremely heavy burden, not to mention the 20 to 40
embryos who would not survive the whole experiment.
Wombs for hire
If properly kept in "suspended animation" (there is no synchronisation
of ovarian cycles in the population), an early embryo could be transferred at
any suitable time into a recipient uterus. Many possible cases have been
For example, a widow could accommodate an embryo fathered long before
by her deceased partner. A candidate, affected by an inheritable disease could
receive an egg from a healthy donor. Or, a uterine foster-mother could be hired
if the true mother could not carry the pregnancy for medical reasons. The
possibility of surrogate mothers could enable some women even to avoid the
inconvenience of pregnancy.
Surrogate pregnancy is a difficult issue. Should the foster mother be
forced to give back the baby nine months later? Would she be denied the right
to refuse termination of pregnancy if abortion were legal in her country? These
questions are for lawyers. For the biologist, no matter what the alleged
pretext, such practices would break the only assured link between generations.
Up to now whatever the uncertainties of paternity, motherhood was an absolute
certainty at delivery.
To be sure the technique works in cattle. But what is good for calves
may not be good enough for children and mothers.
The full viability of the early being and its tenacity for life allow
The cells of two different embryos can be mixed together; they thus
result in a "compound" animal (called a chimera). Such experiments have been
carried out with mice. To the best of our knowledge, no compound mouse has yet
been obtained from more than three cell lines mixed together (2). This fact
recalls that during the first cleavages of the fertilized egg (occurring within
minutes of conception), there is an odd stage of three primordial cells. It
maybe that this threecell stage has something to do with the individuation
It must be remembered that normally the zona pellucida prevents these
admixtures: in a sense this bag ensures our early private life. It is an open
possibility that normally the human embryo emerges from its zona pellucida only
when its biological individuality is so strongly established that a chimeric
accident is no longer to be feared.
But even if mixing must be restricted to two or three cell-lines, what
about an "artistic" embryo, an "athletic" embryo and a "scientific" one, fused
Would not that create a kind of superman?
Or, if DNA manipulation comes in: what about embryos receiving special
sequences, producing exceptional endowments?
These fictional experiments are not worthy of discussion. These
nursery tales for grown-ups should be totally rejected: to devise a man wiser
than we are, we should be already wiser, than we can be.
As for the proposals of manipulating embryos in order to produce spare
parts for repairing children or adults, they are so far-fetched that no
critical analysis can be made. Conceivably grafts of stem cells could be of
theoretical interest; but they are already catered for from voluntary donors
(bone marrow graft for example). In any case which tissues are going to develop
into particular organs are not yet detectable in the pre-implanted embryo.
A sex choice
As BRUNGS Stated succinctly about the advent of generalised
contraception and, later, of efficient in vitro fertilization: we have gone
"from sex without babies, to babies without sex".
But the sex of the baby still matters.
The preference for a "King" means a son for a first child and often
for the second. The same applies to the man in the street; and even for
suffragettes and, now, the feminists. All opinion polls show the same results:
if free choice were given, a formidable excess of males would result!
Thank God no sieve is available to select preferentially the male
sperm (carriers of the Y chromosome). Thus pre-determining the sex of the
embryo is at present completely out of reach.
If an acceptable technique were someday to be available, the State
could not remain indifferent before such a predictable disaster: woman-deprived
population! In order not to infringe upon free choice and not to favour anyone,
enormous computers would process the demands, producing optimal decisions. As
demonstrated by GROUCHY (2) the best algorithm is not too cumbersome to
calculate: toss a coin as before!
The real question
But do we ask the real question? If our only goal is to help women who
cannot conceive because of tubal difficulties, have we chosen the right
Let us return to technicalities. If the early embryo is really not
experimental material to be split, mixed, manipulated or anything else, what is
so interesting about this excursion of a few days into the outside world?
Dr. CRAFT and his colleagues (4) have already shown that the
fertilized ovum can be implanted right away in the womb. Could we not get even
closer to the actual physiological process? Possibly the egg could be placed in
the uterus during the actual laparoscopy, the sperm being already supplied by
Why not study more closely the fluid of the fallopian tube? Would it
not be the best medium for early development?
Research workers would be wise to explore such new avenues instead of
following automatically the long detour of in vitro fertilization.
The future of medicine
Arguments have been put forward repeatedly that in vitro fertilization
would help in discovering the cure of a whole array of disease, even breast
cancer! But all available evidence points towards other directions of research
as shown-by three recent examples:
Among the genetic scourges afflicting humanity, mental retardation is
the most inhuman. It deprives the afflicted of one of the most precious aspects
of our heritage: the full power of thought.
Some ten per cent of the mentally retarded show a peculiar fragility
of the X chromosome. Numerous examinations have shown that this fragility can
be healed if the cells are cultivated in a medium containing various chemicals
(5); a simple vitamin, folic acid and its derivatives, is especially efficient.
If it is added to the regimen of these patients their X chromosome gap seems to
disappear as well. Moreover, preliminary clinical trials show that their mental
status can be partially ameliorated (6).
Actual cure of the disease has not yet been discovered, but it is the
first time that a chromosomal disease and its deleterious consequences have
been successfully attacked - and, this, without resorting at all to "science
Another terrible disease resulting from imperfect closure of the
neural tube in embryonic life, seems also to be amenable to vitamin therapy. As
demonstrated by SMITHELLS et al (7) and confirmed by LAURENCE et al (8) vitamin
therapy, including folic acid, given at the appropriate time to the mother at
risk, diminishes drastically the frequency of spina bifida. Here again no
experiment on the embryo was required.
A third advance has been made in genetically transmitted anaemias.
During life in utero and after, haemoglobin is produced by an array of
different genes working in succession: the first during the embryonic stage;
the second in the foetus; and the third in the whole adult life. If this last
gene is mutated, an abnormal haemoglobin is made (as in thalassemias or in
It has been discovered that the silent genes can be reactivated by a
special chemical (azacytidine). LEY et al (9) took advantage of this property
with the result that patients suffering from abnormal adulttype haemoglobin
started to produce again their normal foetal-type. This type of rejuvenation
could be of great significance for further therapy, without involving any
manipulation of embryos or the foetus.
Aldous Huxley, Wolfgang Goethe and the
A last question remains: why is in vitro fertilization such a
fascinating issue? Although the Brave New World is often quoted in this
context, it is probably not the industrial production line of identical twins
which is the key point. At least Aldous Huxley himself stressed another
phenomenon: in his technological society, liberated of every tabco, all obscene
words were in the current language. Nevertheless, editors were obliged to
reprint all literature in order to expurgate it of the only incongruity which
could not be pronounced, and should not even be read and was to be replaced by
suspension points: the word "mother".
Motherhood, a total obscenity: such an inversion of values is a
supreme danger, Aldous Huxley warned us.
But another writer, one of the greatest poets, had already seen much
further, more than a century and a half ago. In Faust (Part I), Goethe told of
the tragic abandonment of the beloved, seduced and pregnant. But in Faust (Part
II) the vision goes even deeper. After his pact with Mephistopheles, Faust
returns to his old laboratory with his diabolic companion. They watch the
successor of Faust producing an homonculus inside an alchemic vessel! The tiny
creature escapes and floats in the air around the head of Doctor Faust who
loses his mind but not his imagination guided as he is by this strange in vitro
After an impossible love affair with the ghost of Helen of Troy, Faust
fially accomplishes his goal. He builds an empire, a fully technical society,
with the magical help of Mephisto. At the very end he gives his last orders: to
silence the little church bell, the only one still ringingin his whole empire,
and to destroy the cabin in which Philemon and Baucis remain, the parragons of
And, when silence comes, when Mephisto returns after having burned the
elderly lovers in their cabin, then, implacably, sorrow invades the heart of
Poets are above science; they see further and feel far more than
technicians could ever grasp. In such important matters it could be profitable
for scientists and legislators to re-read some of the great masters.
But maybe they could rely just as well on other writers, far more
accessible to them - indeed, living among them. I mean newspapermen.
They also do not practise science but witness it from outside, and
their judgment is not to be taken lightly. They know that in vitro
fertilization fascinates their readers and one journalist understood why.
Trying to convey all the significance of what was going on he coined the term:
"test tube baby". Sure enough scientists objected (they preferred to overlook
it) but the journalist knew better.
Indeed, if there is a growing repugnance against any exploitation of
the early human embryo, if people are beginning to feel that experimenters must
have total respect for these marvelous young human beings, it is for a
scientific reason: a newsman discovered in a stroke of intuitive genius - test
tube babies are babies.
(1) LEJEUNE J. On the beginning of life. Testimony before the Senate of
the United States of America. Subcommittee on Separation of Powers. April 13,
(2) GROUCHY J. de. Jumeaux, mosaiques, Chimeres et autres aleas de la
fecondation humaine. MEDSI Edit. Paris 1980.
(3) GROUCHY J. de. Lesnouveaux Pygmalions. Gauthier Villars Edit. Paris
(4) CRAFT, McLEOD F., GREEN S., DJAHANBALHCH O., BERNARD A., TWIGG H.,
et SMITH W., 1982 - Birth following oocyte and sperm transfer to the uterus,
Lancet ii, 1982, 773.
(5) SUTHERLAND, G.R. 1979. Heritable fragile sites on Human chromosomes
I. Factors affecting expression in lymphocyte culture. Am. J. Hum. Genet. 31,
(6) LEJEUNE J. Le metabolisme des monocarbones et le syndrome de l'X
fragile. Bull. Acad. Nat. Med. 1981, 165.
(7) SMITHELLS R.W., SHEPPARD S., SCHORAH C.J., SELLE M.J., NEVIN N.C.,
HARRIS R., READ A.P. et FIELDINK D.W. Possible Prevention of neural tube
defects by periconceptional vitamin supplementation. Lancet i, 339-340, 1980.
(8) LAURENCE K.M., JAMES N., MILLER R.H., TENNANT G.B. et CAMPBELL H.
1981. Double-blind randomised controlled trial on folate treatment before
conception to prevent recurrence of neural-tube defects. Brit. Med. J. 282,
(9) LEY T.J., DESIMONE J., ANAGNOV N.P., KELLER G.H., HUMPHRIES R.K.,
TURNER P.H., YOUNG N.S., HELLER P., NIENHUIS A.W. 1982. 5-Azacytindine
selectively increases 8-globulin synthesis in a patient with B + thalassemia.
New Engl. J. Medicine 307, 1475-1469.