VISIT TO
P-OF. HANS SELYE, UNIVERSITE DE MONTREAL
WEDNESDAY, 4TIT NOVEMBER 1970
Present: Prof. H. Selye
Sir Charles Ellis
Mr. L. C. Laporte
Dr. M.A. Nisbett
Dr. D. G. Felton
Introduction
Prof. Selye is in receipt of an annual grant of $100,000
for three years, jointly donated by CTR (US) and the Canadian
industry to investigate Stress and Relief from Stress. The
project is now well into the second year and a report on the
first year was submitted in mid-June 1970.
Selye is a. gnomish man who surrounds himself with memorabilia
and photographs of great medical scientists. His office resembles
a library in a large country house. He is, by contrast, very
informal in his dress and manner, but clearly likes to be the
centre of attention. Selye had come forward voluntarily to give
evidence in 1969 before the Canadian Standing Committee on
Cigarette Smoking Hazards and had stated, quite unequivocally,
that he believed smoking has many beneficial aspects and that
people would continue to smoke.
Theory of Stress
Selye explained that since animals don't like to smoke, it
is difficult to use animal experiments to extrapolate to human
beings. On the other hand, nicotine and tar are toxic to a range
of species and detoxication mechanisms seem to be common to all
species. However, he illustrated the dangers in his own approach
by referring to work with a fish which did not have glomeruli in
the kidney and Which had obviously developed by evolution an
alternative type of excretion process,
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lie believes that the act of smoking is a deviation from
stress (avoidance mechanism or an emotional discharee) and tha
the lesser stress of nicotine is a means of deviating the greater
stress it combats.
CDE raised the hypothesis of action of nicotine on the
hypothalamus and the way in which thi might enable the body to
mobilise the defences to stress. Selye suggested that this may
not be a phenomenon uniquely dependent on nicotine.
All stressors have counter-stressors and Selye elaborated
on this theme, mentioning cross-resistance in which one stressor
can confer resistance to another stressor. This brought the dis-
cussion around to catatoxic steroids, Selye I current major
too,," interest. (cata- = against).
Catatoxic Steroids
These are substances which affect liver microsomes, producing
from the ribosomes specific enzymes for metabolic degradation
of foreign substances, e.g. drug-metabolising enzymes. Catatoxic
steroids can include cortico-steroids, male and female sex
hormones and other types of steroid substances, including syn-
thetic steroids. A large number of these have been tested and
seven appear to have no other action than a catatoxic effect.
The most potent are 16-carbonitrile steroids which, when admini-
stered orally at a microgram level, have no other effect than to
stimulate the detoxifying enzymes of the liver. They require
to be administered at doses several thousand-fold greater before
they manifest any toxic effect themselves. The administration
of a catatoxic steroid in microgram quantities to rats completely
prevents death following a subsequent injection of a normally
lethal dose of nicotine. Only a few hours are necessary for the
stimulation of the detoxifying enzymes, but the effect is short-
lived and repeated doses are.necessary to maintain the protective
action.
Se I ye has in mind that the continual oral administration of
a catatoxic steroid of this nature could be used for the detoxi-
NJ
fication of nicotine in cases of cardiovascular disease, blood %@C
_Ct@-
pressure disorders and the like. In his view, this would still
co
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leave the act of smoking for the deviation of stress.
It seen;'i a curiously naive view for a man of his intelligence
in that the same effect could be achieved by smoking nicotine-
free cigarettes. Selye did not apparently know that this type of
product could be produced. He did not know whether there would
be any residual nicotine activity in the brain or whether the
catatoxic steroid would reinforce detoxification processes in
other tissues.
He went on to refer to a test devised by Huggins in which
the adrenal glands are used as a screening tevt for certain car-
cinogens. He showed photographs of a swollen adrenal following
treatment with DMBA and a normal-looking gland from an animal
protected by administration of a catatoxic steroid. There was
less opportunity for discussing this stage of his work as he was
called awav at this point. He mentioned that 16 pharmaceutical
companie@ are collaborating with him in testing various series of
catatoxic steroids.
Conclusions
In discussion afterwards, it was agreed that Se lye was
unlikely to be diverted from his current programme and that his
approach, while interesting, was not really pertinent to the task
of proving the benefits of smoking in overcoming stress.
Selye I idea of using catatoxic steroids to speed up nicotine
metabolism appeared to neglect the fact that nicotine is apparently
essential for the psychopharmacological action of smoking on the
activity of the brain and also that the body is rapidly detoxified
of nicotine in any case. However, the application of catatoxic
steroids in some of the neuropharmacological experiments at
Huntingdon and Harrogate may be a useful tool in unravelling the
various pharmacological effects of nicotine and the sites of
action.
C:)
DGF/SEW/5.4 NJ
%lo
16 th November, 1970
BATCo document for Province of British Columbia 19 April 1999