The essential characteristic of hereditary qualities is their
stability during successive generations. However, a new character may suddenly
appear and be transmitted indefinitely as such. Such an unforeseeable variation
is extremely rare, but in 1927 Muller (1) proved that the frequency of such an
event could be considerably increased by exposure to X-rays.
Subsequently, this phenomenon has also been observed in the most
varied living organisms, from bacteria to Drosophila and from fungi to mice,
and may be considered as established in man himself.
This change in the genetic heritage of the irradiated cells seems to
amount to a chemical alteration in the gene substance, and the molecular scale
on which this occurs explains the four main laws governing mutagenesis caused
1) The mutations are of a chance nature, i.e. the new character
produced by the disturbance of a few atoms is completely unforeseeable.
2) The mutations are generally unfavourable, by reason of their chance
nature. The random changing of a character selected for generations has, in
fact, very little chance of being immediately favourable to the individual that
The following comparison, illustrating the harmfulness of non-adaptive
changes, has often been made: imagine an amateur with a screw-driver who
decides to make a random change in one of the connexions in a radio-receiver ;
it is extremely improbable that this blind interference will immediately
improve the functioning of the apparatus ; on the contrary, there is every
likelihood that the result will be unfortunate.
3) Once they are produced, mutations are stable and are thereafter
transmitted indefinitely as such ; they can henceforth only be modified by a
new process of mutation.
4) Although the new character cannot be foreseen, it is possible to
predict the mutation rate. This rate is directly proportional to the dose
received by the cells ; for example, 200 r an the gonads will give twice as
many mutations as 100 r.
The extrapolation of this ratio to very small doses (25 r in
Drosophila) (1), and even limiting doses (a few photons of X-radiation on the
lysogenic system, of Escherichia coli) (2) indicates that any dose, no matter
how small, has a certain mutagenic power which persists, although very
Moreover, with the same total dose, the effect of small repeated doses
is identical to that of one massive dose. Thus, an irradiation of 30
milliroentgens per day over 30 years is as dangerous genetically as a sudden
irradiation of 330 r. This absence of a threshold of action, combined with the
additive nature of the effects of repeated doses, shows that no irradiation of
the gonads is negligible, since the genetic effect depends an the sum of the
doses received from birth until reproduction.
As the time interval separating two human generations is about 30
years, it has been agreed to speak of the gonad dose per 30 years, these 30
years being obviously the first 30 years of life.
To evaluate the dangers arising from a given irradiation, the simplest
and most representative method is to compare the affects with those of the
inevitable natural mutations which occur without any human intervention.
Generally a parameter is used, known as the doubling dose, which
corresponds to the gonad dose per 30 years, capable of producing as many
additional mutations as those appearing spontaneously between two
This doubling dose is fairly well established for insects such as
Drosophila, or even for the mouse, the only mammal chose genetics is well
known, and in whose case about 50 r are sufficient to double the mutation rate
Experiments cannot be carried out with human beings, but observed
results agree fairly well with the order of magnitude of the experimental
figure just quoted.
Three major classes of mutagenic effects have been studied and
detected in the progeny of irradiated parents:
1) lethal effects taking the form of an increase in miscarriages and
2) harmful effects leading to an increase in congenital malformations
3) lethal effects restricted to the male sex and taking the form of a
decrease in the relative number of boys after irradiation of the mother.
These various findings are summarized in the table below:
Table I : Remarks on the progeny of irradiated individuals
|Observed effects||Irradiation during the
war||Occupational irradiation (radiologists)||Therapeutic
|Intra-uterine and neonatal mortality||A not
significant increase (5)||A not significant increase (8) (9)||No
effect observed (7) No effect observed (6)
|Malformation at birth||No significant effect observed
(5)||Significant increase of congenital heart malformations
(9)||No significant effect (2) No effect observed (7)
|Decrease in the relative number of males
born||Decrease in the number of boys after irradia-tion of the mother
(5)||A not significant decrease in the number of boys in the progeny of
male radiologists (9)||Decrease in the number of boys after irradiation
of the mother (6) (7)
On the basis of deviations in the proportion of males born after
irradiation of the mother, on the one hand, and in relation to the ageing of
the mother an the other (10), we have attempted to calculate a doubling dose
directly, and found it to be about 30r.
In addition, observation of the somatic mutation rate, which in the
mouse is at least as high for the same dose of X-radiations as the germinal
mutation rate (11), has been attempted by Court Brown and Doll (12) by studying
the increase in tee frequency of leukaemia after therapeutic irradiation.
Here again, 30 r are thought to be sufficient to double the natural
It can, indeed, by no means be excluded that this doubling dose is
less than 30 r, but it may be taken to be at least 3 r per 30 years, since this
dose corresponds to the one we receive as a result of the natural radioactivity
of the earth's crust and of cosmic radiation.
The effect which a doubling of the mutation rate would have on the
physical and mental characteristics of our descendants is not easy to
Broadly speaking, the present frequency of genetic defects is tube
result of an equilibrium between the appearance of new mutations in each
generation and their removal by natural selection.
It can therefore be predicted that if the number of mutations is
doubled, the frequency of genetic defects will finally be doubled also, but
only after a more or less extended period, depending on the hereditary nature
of the defect. Recessive defects, such as albinism or phenyl-pyruvic idiocy,
for example, would in, crease in frequency only very slightly, and centuries,
if not millennia, would pass before a new equilibrium is reached and the number
of sufferers doubled. On the other hand, serious dominant defects, such as
achondroplasia, aniridia or retinoblastoma, would become twice as frequent in
less than a century. In addition to these serious abnormalities, an increase in
minor hereditary defects and predispositions to diseases would also have to be
feared anal would perhaps represent a much heavier burden for society than the
few catastrophic defects of which we have just spoken.
It should be remembered also that these speculations ignore the
influence of medicine, which, by enabling severely handicapped individuals to
survive and reproduce, works, so to speak, against selection ? consequently,
there are strong reasons for thinking that a doubling of the mutation rate
would be much mare dangerous for modern man than for a wild species.
However, even a dose of 30 r per 30 years would probable not endanger
the survival of our species (13).
The general conclusions to be drawn from this brief review of data at
present available, are that any dose of ionizing radiation reaching the human
gonads is genetically harmful and that all artificial irradiation should be
restricted to the lowest level technically possible.
Irradiation, of the gonads during radiological examinations may result
either from direct exposure to the incident flux (examinations of the pelvis
for example) or from scattered radiation (all other types of examination).
Such irradiation of the gonads depends not only on the region examined
and the number of examinations, but also on the type of apparatus used and the
manner in which the image is received, i.e. radiography, radiophotography or
It is consequently very difficult to establish a mean value for a
population as a whole. However, surveys carried out in three different
countries have resulted in very comparable estimates of the gonad dose per 30
years received on the average by men and women today as a result of
radiological diagnosis clone. The figures obtained are 1-3 r for England (14),
4-5 for the United States (15) and rather more than 4 for France (16) ; there
is every reason to believe that these values also apply in greater or lesser
degree to Italy.
These figures show that the normal practice of medicine results in an
artificial irradiation of the gonads equal to or perhaps greater than natural
irradiation in the technically advanced countries.
The genetic consequences of this irradiation are in proportion to the
doubling dose, which we have discussed above, and it may be said that present
day medical radiology probably adds a number of additional mutations amounting
to one-tenth of the spontaneous mutations.
Such a genetic effect is by no means negligible in man, bearing in
mind that a mutation exercises its harmful effect by inflicting on the person
carrying it a morphological or biochemical defect, which finally causes
suffering or disability in the individual.
Although there can be no question of indicting medical radio loge and
the immense benefits which we owe to it, it may well be asked whether the
present gonad dose is the inevitable concomitant of technical progress.
Happily, this is by no means so and it can be affirmed that, without
limiting the effectiveness of radiological examinations, it would be possible
to reduce the exposure to one-hundredth of what it is at present.
Without discussing here the special techniques which make it possible
to considerably reduce the irradiation associated with a radiological picture
(use of high kilovoltage and filtration of radiation, special screens and image
amplifiers, use of radiography instead of fluoroscopy), it may usefully be
pointed out that a few simple precautions lave already given very good
Recently (17) we have systematically studied the gonad dose received
in radiophotographic examinations for case-finding of pulmonary
As can be seen from Fig. 1, the spin dose, i.e., the dose measured at
the centre of the dorsal field, increases in proportion, to the age of the
subject, corresponding to the greater thickness to be traversed by the rays. On
the other hand, the lover curve in the same figure shows that the gonad dose is
distinctly higher in very young children than in adults.
Still more eloquent is the curve in Fig. 2, showing the change in
ratio of gonad dose to spin dose with the age of the subject. It can be seen
that there is au exponential decrease in relation to age.
This fall is due to the simple fact that the gonads of adults are
farther from the edge of the beam than those of small children, for obvious
reasons of site, since the screen and the diaphragm, are permanently fixed in
such equipment. Although the gonads are outside the beam in all cases a
diaphragm, adapted to the site of the subject would make a considerable
decrease possible in the scattered radiation affecting the gonads of children.
In conclusion, it is urgently necessary for radiologists to become
conscious of the dangers of even very small amounts of radiation reaching the
gonads of young subjects. The employment of all the technical means available
should lead to the reduction of this useless irradiation almost to zero.
In addition to the simple technical problem, the use of ionizing
radiation results also in a moral problem. In applying this new energy, our
generation involuntarily bears an immense responsibility, that of safeguarding
the physical and mental make-up of our descendants.
Even if the dangers involved in the present use of medical apparatus
are probably still very small, it is urgently necessary to warn every physician
and radiologist about them, since the basic principle of medicine, primum non
nocere, applies not only to the patient himself but to all his future
Fig. 1. - Skin dose and gonad dose in relation to
the age of the subject.
Fig. 2. - Variation of the ratio of gonad dose to skin dose with the age
of the subject
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