Beside the pure intellectual curiosity, which is admiration of the
marvels of the world, welfare of mankind is the final goal of any science.
So much will be exposed during this Congress about the new
achievements of Genetics, from basic molecular mechanisms to practical
application to human health and wealth, that I want to focuse, not on the
general human welfare, but more precisely on the human mental welfare.
Mental welfare requires absolutely two conditions : the liberty of
using the power of thinking and the very possession of this power.
The history of Genetics can show us how those two conditions can and
must be realised.
As for any science the liberty of using all the powers of our mind,
without any bias or ideological restriction is, so to speak, "consubstantial"
to genetic knowledge.
The blind alley to which LYSSENKOISM was leading genetics, is an
experimental demonstration of such a necessity.
Years ago, when I first came in this country, I had the priviledge of
being an eye-wittness of this phenomenon. It was short after the observation of
the chromosomal aberrations which can afflict human beings, and I remember an
anecdotic but very revelating event.
In front of some pictures of human chromosomes, showing trisomy 21 of
Down's Syndrome, Haplo-X condition of Turner, and soon, a very vivid discussion
arose, in the exhibition, between scientists.
Some of them declared that such things were forgery because Mr
LYSSENKO had prescribed genes and chromosomes were pure fancy, not fitting his
theory. Hence they should not exist at all.
Others were of the opinion that eventually nature knew better than
theoreticians and reckognized that if theories were not fitting the facts, it
was the theories which should be rejected, not the facts.
This disputation came to a real turmoil and if I recall it today it is
for the new generation of scientists who even do not know about what happened
in those years long past !
They have to realize not "in abstracto" but in historical context that
the laws of the creation are our only teacher; not the laws which are,
temporally, accepted or imposed, according a theory.
Developing this subject of the prerequisite liberty of the geneticist,
would nowadays be considered, either as a common place argument, or as a rather
subversive allusion, depending upon what is politically implied by the term of
liberty.
Without trying a difficult navigation between these two pitfalls, let
us look at the other side which is the actual possession of the power of
thinking.
Amongst the deleterious phenotypic effects resulting from genetic
disasters, from point mutation to chromosomal mistakes, one is the most
dramatic, the debility of intelligence. This is the most typically human
disease because only humans can suffer of it and also the most inhumane, for it
prevents the patients of sharing their full part of mankind's patrimony, the
blossoming of the thought.
To try to understand what is hampering the intelligence of genetically
affected people, we can possibly first ask ourselves whether the intellect is
really imprinted in this accretion of matter, we call the human body.
A very typical example of the power of the intellect is the field of
geometry, the purest or at least the most abstract of all sciences.
History again can be of some help here.
It is generally believed that geometry was invented by old Egyptians
and such a statement seems very plausible.
Before the Asswan reservoir was built, there was every year a great
flood of the Nile. After the withdrowal of the waters the land was very leveled
off indeed. Hence what more natural than to sow few pyramids on that flat plane
!
Although I do not object to the ingeniosity of ancient Egyptians as a
geneticist, I do not guess that geometric knowledge really started that
way.
Let me propose you another origin, which is perfectly undemonstrable,
but as remarked a french philosopher: "the most true stories are not always
those which have happened".
As everybody knows lovers spend long hours (too short nevertheless)
looking at each other eyes. This is so true that quite all human languages have
the same definition of the circular opening of the iris, this dark little
window though which we observe the world. In French as in English they call it
"la pupille" "the pupilla", which means in Latin the little girl. Spanish would
say " la nina del ojo". Greeks would call it "chorea" ; Iranians : "Mardomak" ;
Arabians "Insan el Ein" ; Vietnamese : "Ngu oï" and Japanese "Hito me".
The reason of this universality is obvious. When you look very close
to the eye of your beloved you see your own image reflected by the convex
mirror of her cornea and this tiny puppet is the most luminous against the dark
back-ground of the iris opening.
I would be inclined to suppose that women discovered first this
interesting optical property ; hence most of languages using the term of
"little girl" (and not "little boy").
The postulate we have to make now is that one day a would-be geometer
fall in love (such things can happen, even to, mathematically minded people)
and he discovered geometry.
The cornea is a segment of sphere, intersecting another sphere of
greater radius, the ocular globe.
Such intersection is thus a circle. On this circle is anchored the
radial muscle of the iris (the dilator pupillae) and its fibers are stretched
by the constriction of the orbicular muscle which delineate the pupilla
itself.
Hence, under the sun of Egypt, the cholinergic orbicular muscle was
quite closing the pupilla so that the inventor of geometry, observed
experimentally the only perfect plane existing in this world, a surface
anchored on a circle and defining the shortest possible distance between any
two points of its fibers.
Euclide in a glimpse of love, how it would be comforting for school
bays to learn that! (A friend of mine recently told me that modern geometers do
define the plane from the tensorial calculus !).
We can go deeper, but it took few millenaries before DESCARTES
achieved it. If you gently press your closed lids in a rather dark room, you
will suddenly see a kind of chessboard made of tiny cells alternatingly dark
purple and shiny golded, defining exactly the so-called cartesian coodinates,
imprinted in the network of the retina long before any man was there to notice
them.
DESCARTES discovered it because he was doubting and doubt prompt you
to rub your lids to see if you have well seen. Hence the analytical geometry
that everybody uses intuitively and only algebrists are talking about.
We know still mare nowaday. Neurology has lead us farther on the
visual pathways. From the little window through which light is entering, to the
obscure center which sees (in the calcarine region of the posterior part of the
brain), we can follow all the development of modern mathematics.
Projections, bijections, rings and ideals, fibrous spaces, matrices
and lattices, all the progeny of the ensemble theories were genetically there,
only awaiting topologists took notice of them.
And this mirror of the soul, as the eye is generally called, reveals
immediately to a human geneticist if the child he examines is intellectually
unfitted or mentally gifted.
The look of a child affected by trisomy 21, is typically atonic and
does not have this sparkling light that a normal child would show.
Here we can take advantage of the fact that the radial muscle of the
iris is adrenergic and the orbicular muscle, cholinergic. By installating in
the eye various drugs which can either stimulate or paralyse the adrenergic or
the cholinergic mechanism, the answer of the muscles can be observed by the
opening or the closing of the pupilla.
This very simple clinical investigation showed us that trisomic 21
children are hypocholinergic and, eventually, this minute symptom will reveal
itself as very important for understanding the chemical basis of the disorder.
But, before discussing this particular subject we should better
consider more generally the substratum of intelligence and figure out what
difficulties could impair its functioning.
Two ways are open here, one is to enumerate the impressive array of
genetic diseases known to produce mental deficiency; but how to give some
sensible order to such a lengthy and frightening listing?
The other way, is to look for an equivalent of the human mind or, more
modestly, to analyse the functioning of the machines which can simulates some
of the intellectual fonctions. The calculating machines are an obvious model.
Although they vary greatly in their particular construction all of them respond
to some general characteristics, imposed by the performance they must
achieve.
From the "machine arithmétique" of Pascal using only the geometric
invariance of gears and barrs, to the giant electronic computers, (without
forgetting Jet deflexion systems, laser driven informatic devices, or purely
magnetic bubles running in a proper circuity), all of these engines satisfy to
three constraints.
a) a logical network entirely preprinted.
b) a clean transmission of signals from place to place, with no
diffusion and no short-circuits.
c) a two-way choice at each intersection of the network. (As Alfred de
Musset said " il faut qu'une porte soit ouverte ou fermée" "A door must be
open or shut". This is the very root of the binary logic, represented by the
"gates" of electronic devices).
These three conditions are stringent because logic is anti-randomness
it sole function is to forget about the fortuitous to keep only the
deducible.
Hence the path followed must be meaningful in itself, and all the
turns made inside it, must be "yes or no" and never "may be".
A calculating machine is not allowed any variance in its running, in
accordance with the fundamental law of informatics : the amount of information
carried is the inverse of the variance : I = 1/?
But eve comparison with the biggest machine actually bundled, the
brain of an average human geneticist is at a reassuring advantage.
First its complexity is overhelming.
With some eleven thousand of millions of neurons it outnumbers largely
any forseable computer. Every neuron itself is already a mini-computer, far
each junction it makes with other cells is the equivalent of one transistor. As
each neurone can make and recieve some thousands to ten thousands of these
junctions, the number of synapses, the basic components of our machine, must
amount to some 10 to the power 14; an astronomical chiffre!
The wiring , relating these components between theme is not known in
details, but its total length can be roughly estimated. Possibly something
like, from here to the moan and back!
And the most bewildering of all is that the precise instructions
necessary and sufficient to build this fantastic machine, is properly imprinted
in the some eleven thousand millions of bits of information of the DNA enclosed
in the first human cell, the fertilized zygote! Let him live, he will think:
that the human destiny.
Here were touch the fundamental difference between computers and mind
Sure enough computers have been produced by the intelligent thought of their
maker: machines are truly speaking disenchanted intelligence; it's why their
power is sometimes frightening.
Men in the contrary are incarnation of intelligence. It's why they are
so precious.
Another difference is an the way matter and energy are mastered by the
synapses of the brain. These tiny bodies, apply the greatest paradox of
quantified physics, they separate the particule of matter exactly as the
ingenious devil of Maxwell was supposed to it.
Starting with a mixture of particules running at different speeds, the
Maxwellian devil was opening or shutting his minuscule gate, letting bight
velocity ones go one way, and closing the door to the slow ones. So he could
separate in two vessels, one hot, one cold, what was at the beginning a
statistical mixture. He was ordering the disorder and running against the
entropy.
Synapses just do that. When a molecule of mediator, say acetylcholine
or adrenaline is released from the vesicules situated at the end of a neurone,
the axonal button, they change suddenly the properties of the receptor, of the
next cell. Abruptly this membrane can engulf, one by one, ions of a given type,
and thus work against entropy. And there is no wonder to find this equivalent
of the Maxwell devil at the very heart of the brain machinery. If really logic
is founded on the exclusion of randomnes its substratum must use the only
physical paradox which allow to do so.
Possibly, the failures we can observe in the calculating machine,
could lead us to analyse the genetic conditions which impair human thought.
All these failures can be put under thee headings: destruction or
mistakes of the network itself, abnormalities of the insulating material and
disfunctioning of the components.
Genetical errors leading to malfabrication of our precious network
are, alas, too frequent, ranging from total anencephaly preventing the
development of the whole brain, to partial misplacement of tissue, through
specific aplasia like arrhinencephaly of trisomy 13 or agenesia of corpus
callosum of trisomy 18.
Also the hydraulic pressure of cephalo-rachidian fluid can laminate
the brain in hydrocephalia.
Abnormalities of the insulating substances also occur. In most of them
the cell can manufacture the substances (because a complete lack of them would
be incompatible with the building of the brain), but cannot dispose of the
surpluses and accumulate them to the point of being killed by this excess.
In Tay-Sachs disease for example, the lack of ß-hexoseaminidase lead
to an accumulation of cerebroside substance and progressively the neurones die.
Hence the tragic and progressive destruction of the brain of children born
apparently healtly, although genetically and microscopically abready
affected.
Nieman Pick disease, Gaucher's disease are terrible example of these
disorders.
Even if the network is correct and the insulating system properly deve
lopped, genetic mistakes can prevent the function. Generally speaking, one get
the feeling that the machine is running but cannot develop its full power.
Exactly like a motor to which the fuel is not provided in correct amount.
And the speed with which information can move inside our brain matters
greatly. As every body can experience by himself we have to think at a proper
path: try to speed up a reasoning and all the arguments will stumble on each
other. More disappointingly we cannot brake either.
If we slow down too much the path of our reasoning, another idea will
cross over our consciousness and we will loose the thread of our thought.
Temperature also is critical, below 30 degree, it's a comalike state
above 40 degree, delirium appears.
In feeble mindness with no gross brain lesion, it is probably the
speed which is the limiting factor. Being unable to handle every duty at the
same time, feeble minded people, apparently shut same network and close some
circuitries. They let their mouth open and their tongue prodruding because they
cannot control every thing at once. Even a normal person would do so if all his
attention is directed to a very demanding task or if he is admiring some object
of beauty.
Also in feeble mindness the slowness of the elocution and the
viscosity of the ideation are typical symptomes.
One would believe that either the brain does not dispose of enough
energy or that some toxic is impairing its ignition process.
Among the most common toxic and among the most dateable indeed, Vodka
is a perfect example. After the euphoric period, related to the shut down of
some self-control circuitries, comes a progressive diminution of the brain
activity.
Even the most alert molecular geneticist could not decipher a simple
code after some glasses of it; The amount depending partly aPon personnel of
genetical endowment, and partly upon proper training. Hopefully the recovery is
plainly possible, at variance with genetic impairment.
Rather intriguing relationships are obvious between feeble-mindness
and psychotic disturbance. As wisely stated by Chesterton "a fool is a man who
has lost everything but the reason". Contrarily a feeble minded has lost
nothing, but abstractive power. Although the field of psychiatry is in complete
remolding, it seems already sure that many psychiatric disorders depends just
as well, upon genetic factors.
But what about the motor ? the engine which deliver the energy to make
the chimical mediators immediately avaible in the right place, in the right
time, so that synapses can transmit an recieve the signals?
Here again the complexity is bewildering and to get an impression of
it I tried to figure out a "pascalian machine" which could roughly simulate the
intricacies of the chemical pathways.
In this artistic view (if I can say so), only the pathways well
established enough to be found in current text books have been drawn; most of
them uncompletely.
This is to say that the true machinery is much more sophisticated than
this primitive over-simplification.
Nevertheless the analogy can be of some heuristic use. As BERGSON once
stated "we can really comprehend a thing only if we can propose a mechanical
model of it".
Just to fix the ideas, the energy is entering at button left bar
glucose, galactose and fructose and is either stored in glycogen or used via
the glycolytic pathway toward :
1) the krebs cycle, the A.T.P. producing dynamo,
2) the lipid production
3) the insulating substances
4) the purine synthesis via the hexane monophosphate shunt
5) the production of chemical mediators
6) the regulation process of their fabrication
To give an impression of the precision of the regulating process
cystathionine, situated dust in the middle, is a curious molecule, known to
have a taxonomic al significance.
Its amount in the brain is related to the place of the organism on the
ladder of evolution.
A dog has much more than a frog, a monkey more than a dog and a man
much more than any animal.
Over such a scheme, we can superimpose the genetic blockages known to
provoke mental deficiency.
As expected by the analogy with computers, we discover that failures
do happens in parts of the machinery which are normally achieving the three
perequisites we stated at the beginning.
These dots do cluster in specific regions. On. left are the
abnormality of insulating substances and on right the loss by
mucopoly-saccharidose of stuffs used also by the regulatory process. On top
left are mistakes close to the pro-duction of chemical mediators and in the
middle various disturbancies impairing the regulator.
Now medicine has to handle the challenge; how can we improve this
terrible situation, how can we alleviate this heavy burden of mental
retardation affecting some 2 to 5 percent of the children at birth?
Here two ways are open already.
One is the social help and the admirable parental dedication which
achieve every day repeated miracles.
Special teaching, unlimited love and full respect can help immensely
de sinherited children, the poorest of the poorest: for millenary humanity has
more or less striven in this higher direction.
Recently the progress of genetic technology has shifted in another
direction.
Some biochemical errors can be detected early, eventually in utero.
Also chromosomal catastrophies can be observed by analysis of the
foetal cells floating in the amniotic fluid.
A generalized tendency has been to propose systematic screening and
early elimination of the suffering babies. Selective abortion is actually
advertised as a "therapy" or a "management" of these diseases.
Selective destruction is a despair reaction. It is a kind of
sophisticated racism, based on molecular or chromosomal discrimination.
But the dilemma, keep them or kill them, does not sum up the real
situation.
Medicine is the third way. It is the way of the future of mental
welfare.
In very limited cases, the victory has already been won, not against
the patient, but against the disease.
Phenylketonuria, galactosemia, vitamine B6 dependant homocystinuria,
to take few examples, can be properly handled and the children protected
against:.mental deficiency.
Who could believe that during the coming years no new progress will be
achieved?
If the scientific community was realizing the enormity of the task,
the path of the advances could accelerate tremendously.
I do not believe personally about building a superhumanity someday by
some genetic engineering trick. To devise a man, wiser than we are, we should
be already wiser than we can be. Medicine is more modest but much more
efficient.
Not only the severe retardation will be fighted effectively in the
years to come but also a host of actually undefined conditions which impair
mildly mental efficiency.
In this way genetics will play an eminent role at service of mental
welfare of mankind. Suppression or repression of unfit or unconform ameliorates
the statistics but not the heart of societies. Only an intimate union of heart
and of reason will salvage someday human intelligence.
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