2nd MEETING OF SCIENTIFIC RESEARCH GROUP
MONTREAL AUGUST 6th-8th 1986'
Present: Dr. R. E. Thornton BAT Co. London
Dr. S. R. Massey T Imperial Tobacco Ltd., Montreal
Dr. M. Bi I imori a
Mr. R. G. Nicholls W.D. & H. 0. Wills, Sydney
Dr. G. Smith BAT UKE, Southampton
Dr. F. Knabjohann BAT Cigaretten Fabriken, Hamburg
Dr. F. Seehofer
Dr. J.G. Esterle Brown & Williamson, Louisville, Kentucky
Dr. G. Gori Consultants
Dr. W. Templeton
Nicotine
Dr. Gori discussed the results of a behavioural study of 799 subjects carried
out in the U.S.A., strongly pointing to nicotine as the basis of the smoking
habit. For example plasma nicotine levels were almost constant, regardless
of measured machine smoked delivery levels, as were the number of cigarettes
smoked per day. Dr. Gori went on to discuss the possibilities for products
in the future including changes in Tar/Nicotine ratios and nicotine aerosols.
Dr. Gori said that further work to demonstrate that some of the effects of
smoking were due to nicotine was still required.
In a broad look at nicotine toxicology, covering carcinogenicity, promoting
activity, mutagenicity and a possible role in cardiovascular disease Dr. Gori
considered the evidence that nicotine had activity to be equivocal at best
and frequently weak or non-existent. Some good studies also existed in which
no activity was seen (e.g. carcinogenicity). However he suggested that a
repetition of a well planned study looking at carcinogenicity might be justified.
Dr. God also commented on the mul ti factori al nature of cardiovascular disease.
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Dr. Gori considered that work in relation to diseases negatively associated
with smoking might be justified, e.g. colon cancer, Alzheimer's disease etc.
Finally in regard to the allegation that nicotine was addictive, Dr. Gori
said that this was a problem in semantics and pointed out that the reinforcing
effects of smoking (and presumably nicotine) were entirely positive.
Dr. Templeton described the distribution of receptors for acetylcholine
and the current status of work using materials such as . I to
probe for binding sites. It was now realized that -< -bungarotoxi did not
necessarily bind at the same sites as nicotine; implying, perhaps, that an
endogenous ligand exists for such sites. However, since there is some binding
of nicotine at "bung arotoxi n" sites the possibility exists that the effects of
nicotine might be enhanced by effects at the adjacent "bungarotoxi n" receptors.
Studies of receptor sites using modern techniques of molecular biology were
described. Brain acetylcholine receptors have been shown to possess 4 cysteine
units at similar places. With regard to the human diseases (Parkinsons and
Alzheimer's disease) it was pointed out that patients presenting were at an
advanced stage of degeneration because the brain functioned even with 70% or
so of neurons out of action.
With regard to the effects of smoking on cognitive performance more work was
needed to clarify the research of Warburton which was rather isolated,
particularly concentrating on nicotine and on whether it caused an intrinsic
increase in performance.
Experiments in non-human primates did not support the view that smoking was
addictive. Training non-human primates to smoke required a reward and water
(a basic necessity of life) had to be used. and after removal of the reward the
% of 'smokers' was as low as 2%. Attempts to classify materials such as
nicotine, amphetamine, caffeine, heroin etc. showed that each material was unique.
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August 7th Present: As on 6th August, but without consultants.
Delegates reviewed the previous day: it was agreed that the presentations
by Dr. Gori and Dr. Templeton were of great value.
Agenda items:
1. No specific comments: a brief summary was given to those not present
in Nice.
2. Terms of Reference agreed as written (with the addition of "interactions
with the non-smoker" thereby including passive smoking).
3. Dr. Seehofer discussed his paper outlining plans for his visit to Japan.
It was noted that the J.T. I. had approached U.S. companies for financial
support towards their programe. Find plans, priorities to be discussed
with RET in Hamburg. Visit should be between September and November
1986, probably of 2 weeks duration.
4. Agreed that passive smoking be included, but that additives, which
relate specifically to products, should be considered separately.
The prime aim of the S. R. G. is to review the literature, identify gaps
in knowledge, commission research and monitor the results. Individual
companies could, of course, carry out their own research as appropriate
but should place any work on the S.R.G. data base.
5. Funding. RET will write a paper for consideration in Sydney and
individual companies would consider the position.
6. Grant Applications. Six applications had been received in the U.K.
and were being considered in BATCo. Members agreed that 2 (Clamp and
Carter) appeared to fall within areas which the S.R.G. had identified
as deserving further work (see item 7). Ideally such applications would
in future be considered by BATUKE, bringing the U.K. into the.practice
of local consideration typical of the rest of the group.
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7. It was agreed that work was desirable in the following areas:
a) Nicotine receptors, to include the CK -bungarotoxi receptor which
might synergize the nicotinic receptor. This could include work
on subjects such as Alzheimer's or Parkinson's disease which
appear to involve degeneration of CNS mechanisms.
b) Novel behavioural work, to complement the studies of Professor
Warburton.
c) Subject to views from consultants, it appears that the fate of
nicotine is not fully accounted for. This may need further work,'
and at least a literature search.
B. This is being compiled.
9. A brief job description was circulated and accepted. As far as possible
members would be kept in touch with progress. Target date for
employment: late 1986.
10. There was an exchange of information on external activities, including
funded research of passive smoking and the 1987 Nicotine conference
to be held in Sydney.
11. Dr. Seehofer described his discussions with distinguished German scientists
in which their views on smoking issues were solicited.
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