Paper reporting the content of a "meeting of [the] Pharmacologic and Clinical Approaches in Smoking Working Group." Reports group considered various avenues of research on nicotine agonists, antagonists, and other compounds that may be useful in smoking cessation. Discusses behavior of Dr. Gori, reporting when statements were made while Gori was looking at author and speculates whether those statements would have been made in private.
(indexer.indexer_email WAS INVALID IN OLD DATABASE: CPM)
- Nicotine Aerosol
- Nicotine Bioavailability
- Named Person
- Adams (Dr.)
- Brand (Dr.)
- Denson, G. A. (Dr.)
- Domino, E. F. (Dr.)
- Gori, Gio Batta, Ph.D. (Tobacco Consultant, formerly w/ NCI, Industry Expert)
1993 Started career at NCI and then went to work for the industry. Believed a safer cigarette could be made, and that there were safe threshold levels for exposure to the chemicals in cigarette smoke.
- Hill, T. (Dr.)
- Horn, D.
- Jarvik, M. (Dr.)
- Kare (Dr.)
- Kensler, C. (Dr.)
- Koelle, M. (Dr.)
- Kreutzer (Dr.)
- Lenfant, C. (Dr.)
- Long, J. (Dr.)
- Morley (Dr.)
- Nixon, P.
- Owen, T. B. (Dr.)
- Riker, W. K. (Dr.)
- Vanacces, H.
- Vesor (Dr.)
- Jacob, E. J.
- New Hampshire
- Atlantic City
- Named Organization
- A. B. Little & Company
- American Health Foundation (Health Research)
- American Public Health Foundation
- Bell Laboratories
- Food and Drug Administration
- Huntington Laboratories
- National Cancer Advisory Board
- National Cancer Institute
- National Heart and Lung Institute
- University of California at Davis
- University of California at Los Angeles
- University of Iowa
- University of Michigan
- University of Oregon
- University of Pennsylvania
- #18391 (carbon monoxide)
- Content Analysis
- Research Methods
- Tobacco Industry Scientists
Page 1: 00003898
AED CLINICAL APPROACHES
IN SMOKING WORKING GROUP
Atlantic City, April 15, 1973
Dr Kensler opened the meetinl~ by notin~ that it was the
fifth meeting of the ~roup in ~he somewhat more than a year since
it has been foxed.
Dr. Gio Gori of the NCl,.Chairman;
T.B. ~en, Manage~ ~f ~he Tobacco Se~en% in .
the Carcinogenesis Section of the
NCI Executive See~etamy"
D~. E:-F. Domi,..o, Phm~oologist of the Univemsity
Dr. G.A. Dens.u, Pharmacolcgis$ at ~he University
of California at Davis, California
D~. John ~ng, Pha~eologist at the University of
Dr. Claude L'Enfant, of the National Heart and
D~. Charles Kensler of A. D. Little & Co, any; .
D~. Murray. Jarv~, Pharmacologist at U.C.L.A.;
Dr. George Koelle, Pharmacologist at %be University
of Pennsylvania ;
D~. William K. Riker, Pharmacologist at the University
of Oregon; and
~. T. Hill, of Wynder's American Health Foundation
All of.the above were either meters of the co~ft%ee
(p~es~ably in the case of Dr. Hill) representing meters. Also
present by invltation were Drs. Morley K~re and Brand of ~he Monell
Chemlcal Senses Center of the University of Pennsylvania.
Dr. Golf noted that the meetfn~ was, according to law~
open to the p~lfe. He sa!i that their meetings were always open
MINNESOTA TOBACCO LITIGATION TIMN 418881
Page 2: 00003899
and that he was pleased to welcome two visitors, a reporter
from the Blue Sheet (a newsletter on subscription to various
~nstltutions and researchers, etc.), and' myself. Chamlie Kenslem
had intmodueed me to Dr. Gori.before the meetir~ started; .and we
had had a short but pleasant eonversatlon.
The minutes of the last meeting were approved,
the outline of the areas of investiEatlon the ~oup felt worthy
of pursuit. [Apparently, the ~oup proceeds by developing pro-
tocols for research in various fields whleh, ~t ~s planned, well
.~ be open %o publlc bid.]
'4 In substance, the laPeas for eonslderation and
~.~.~ ~:p~ p~otoools were as follows:
~., ?:'~; ,.:;:.~"~ ~.~, I. Clinical eval'uat~on of agents for ellnieal
~-, ~'- ."-..:~ use in disoou~aging smoking.
r~:~.....:.Y".~ :~ [In general, apparently %his a~a was ~o eove~ ~hose
~ ~:=~ ~.:~ .~.~ s~stances which had already been s~ficiently screened
~ ~J ~! ,-~ so that they could be used in tests on h~ns.]
~ ~, ~ ~. Bfoassay and evaluation of the above in lab0ra~o~
~ ~ ~ antis.
.~.~, ~ B. Nicotine agonists to be evaluated in laboratory
~ an~Is ~elf~naPy sePeenfn~ to dete~ine whether the
s~s%anee is suit~le fop eo~idePa%ion fo~
testln~ in h~ns).
MINNESOTA TOBACCO LITIGATION
Page 3: 00003900
W. Nicotine antagonists to be evaluated in
5. Modification of organoleptic responses.
6. I~munologie approach.
Dr. Gorl mentioned that Dr. Hill's p~o~eet
had been revised after review by statisltieians at the NCI. He
mentioned that the p~eet dealt with antaEon~s of nleot~e.
At this poi~,-D~. Kensle~ began to take ove~ and or~nize
the d~seussion. He seemed fo~ the ~est of the day the de facto
ehai~a~ of the ~oup. [At one point, someone referred to h~ as
having been p~evlously elected as charon and he jowlly stated
that he had not yet accepted.]
The~e was a discussion of eo~o~ds to be included as
antagonists of nicotine This began with a p~otocol Pelating to
the effects of s~kln~ on the pmoteln bind~g of nieotlne. The
~eport of a Boston ~oup that propoxylane is less effective
smokers was discussed, with the question being raised as to how
it couldbe less effective there than an~here else (since,
appa~ntly, everyone thought it to be generally ineffective)
.D~. Go~i ~epo~ted tha~, ~der contract to Brandeis, the
NCI has developed a ~adioi~unoassay of nicotine. The sensitivity
was at the pieo~am level and the ~eseareh was Helen Vanacees --
The pmepamem of the proto~l ~. Rike~) mentioned that
the Barkos couple were locking for something which might be a mo~e
sensitive area than what everyone had previously been led to ~der-
MI SOV TOS CCO UTm TmN -- - TIMN 418883
Page 4: 00003901
stand had been developed st Brandeis. It was, after discussion,
suEgested that Riker should review what has been done at Brandeis
%o see whether the Barko~ should use a different method or whethem
the Brandeis technique should be incorporated into the protocol.
Apparently everyone considered that the news of the
Brandeis results was potentially of Ereat value in dete~mininE
nicotine levels in the blood and was a eonside~ble advance ove~
what had been previously reported.
~ R~kem stated that, after assay, he wanted to consider
~-' ,- both passive and active immunization. He wanted to have nicotine
~ ~~ "soaked up" so that it did hot do what it otherwise would in such
•- _ a~eas as pressor response, free fatty aclds,.cateeholam~nes,
•.,~ tachycardia, etc. Apparently this work was to be done in rabbits.
~. Jarv~.k mentioned that Dr. Kreuzer of Bell Laboratories
<.., ~:~ ~ had developed an infrared speettoE~eaphy technique that could detect
~i!~ '.i~ ~- parts per billion of nicotine in exhaled air.
~g~:=,:: }i Other techniques of mass spectrometry could find
~o~ ~.:~ 200 molecules of nicotine, but it was felt that they were neither
>. t~ sensitive not specific enouEh.
~ ~ Dr. Gori said that someone should collect the information,
% ~£~ pPobe it and mev~ew ~t to see what should be done in this a~ea.
¢ Dr. Kensle~ was selected to do so.
Kensler noted that Riker's ~munization approach appea~ed
Eood and should be followed through.
MINNESOTA TOBACCO LITIGATION
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Riker observed that the trouble with examining why
hepatitis patients were reluctant to smoke was that it was
difficult to get controls. Koelle pointed out that the recovery
of the desire to smoke by sueh patients came very soon.
Riker observed that more than n.~cot£ne is involved, so
it is misleading to talk of nicotine. ~here are at least 55 drugs
shown m~lecularly in the mass spectvttm, and he wondered whether
investigation of ~he other 55 should be taken. Kensler observed
that some 1500 or so co~onents of smoke ~ad been
Several ~f those present see~d to be ~aware of this and expressed
sunrise that the~e were mo~e than a fe~. I~ was decided that a
lls*.of eo~onents and of their levels should be co~iled fo~
Gor~ refer~ed to the effort ~o years ago to ~dentify
eo~onents. Ke~lee ~efe~ed favorably to it, and pointed out
that it had been published in the 1971 edition of "Health.Consequences
of Smoking." He suggested that the others could ~efe~ to it there.
Gorl pointed out that ofthe components identified, perhaps
were p~esent £n parts per billion.
Kensle~ observed.that the objective of this ~oup was .to deal
with nicotine, and that the Tobacco Wo~ing Group had responsibility
fo~ othe~ components. .Go~ said that everyone should ~ what else
was involved. Kensler agreed, but pointed out that
p~am to dete~ine co~os/Tion of smoke and that vePy few of the
CONFIDENTIAL: TIMN 418885
MINNESOTA TOBACCO LITIGATION
Page 6: 00003903
components were related to nicotine.
Jarvik asked whether any of the other components had
the pha~macologlc activity of nicotine. In one voice, Gorl and
Kensler said "carbon monoxide." Kensler went on to say cyanide
Domino said that it would be useful to show that the
levels of nicotine present in the lowest n~eotine clgaPettes that
were eo~emcial successes were pha~colog~cally active.
Gori observed that it depended on the method of smoking
aS to whether ~iven levels of nicotine were pha~cologically active.
Also, s~ce how the nicotine was presented is ~ortant, data in
~n is needed.
Japv~k suggested that the pba~colo~ie effects of smoke
PefePable ~o nicotine alone be listed. KensleP Pefe£,Ped
pul~nary f~ction and blood flow. Gori again mentioned carbon
monoxide. JaPv~k observed that i% was possible %hat the
effects wePe potentiated by other smoke co~onents. KensleP
indicated that this was a co~lex d~g ~te.raction problem. Jarvlk
observed %hat if all 1500 components were active, it would be a tough
pPobl~. It was a~eed that the focus should be on nicotine as ~he
point of. departure.
Go~i suggested that Rikem should s~dy what other com-
ponents weme involved so that They could be meas~ed in ~n. They
sa~d That they weme st~ll %~ing %o get the tools as they do not
MINNESOTA TOBACCO LITIGATION
Page 7: 00003904
have methodoloKy for this purpose.
Denau said that they should eonslder not only hepatitis
patients, but also pregnant women who also lose The desire to smoke.
Cori observed that psyehologlc effects were involved. Kensler
observed that many of these women were told not to smoke. Denau
said that nevertheless such women should be studied, since the
ones ~nvolved are Those that get morning s~ckness. Jarvik referred
to the s~k~g ~nkeys and wondered whether, they could be given
hepatit~s. Gorl said ~t ~s not ~own whether the-b~n v~rus
could be-glven to ani~Is [a newspape~ ~epo~t that ve~ day indicated
Gomi observed that t.he loss of ~esi~e to smoke ~ p~e~nant
~aetieal to ~ke people nauseate~ so Chat they would not s~ke.
He also questioned, not jocularly, how to get a
Jamvlk again suggested that p~lot work could be done with
monkeys ~o see ~f they could get hepatitis. Kensle~ obsePved that
the hepatitis phenomenon could involve othe~ s~ke eo~onen%s than
n~eotine, om taste factors •
Dr. B~and said ~hat they were wo~kin~ on %be pemeeption
of b~tter taste factors. He said ~% was pmobably ~e complicated
than nicotine alone when wo~kln~ ~n the ~aste aspect of smokinK,
particularly when refer~Jn~ to some of the co~o~ds mentioned to
CONFIDENTIAL: TIMN 418887
MINNESOTA TOBACCO LITIGATION
Page 8: 00003905
h~m, which were taste antagonists to smoke.
Reference was made to .dentists' f~ndings that silver
nitrate administration also lessened the desire to smoke.
In considering the use of either a lozenge or a drug
to give smoking a bad taste, it should be. remembered that the use
of taste antagonists is not unusual. Fbr example, MSG,: and
nucleltides, are strong kelators. A glycoprotein.
<> ~ is more exotic. It is of high chendcal weight and acts at the
.... :? ~ cell surface, Zu~n~ng the sou~ taste of acids to sweet.. The
~ . ~ ~. ~;~ ~ntensit9 of ~he sweeZness ~s eo~mela%ed w~Zh the
~ , ~.~,:~-~-~ Acids extracted f~om %he leaves o£ a t~opiual plant p~oduce
~ ~ .... ::'~ taste antagonism by ~on~e washi~, whereby ~he abil~Ty to taste
:. ~ " ~:" sweetness ~s lost.
.... ., .~.~ ~ Thus, one could ~nwsti~a~e the
c: :.:.:: ~ wlth othe~ e~ga~ette smoke antagonlsts ~om the point of v~ew of
~ ~.~ ...... taste b5oehe~stmy. One could look fo~ any d~ect 5nte~aetion
~, ":~ w~th nicotine oD othem s~ke v01atiles. Then one could investigate
the p~operties with recently developed isolated cell p~epamations
from the ~aste buds, using cow tongue. The problem here is not
~usual and fluorescence changes can be used. Any pmomlsing smoke
antagonist or s~stanees on the G~S PDA l~st can be clinically
tested ~ediately slnee the Monell Center has available psycholo-
gists who can evaluate clinically the taste and smell approsches.
CONFIDENTIAL: TIMN 418888
I INNESOTA TOBACCO LITIGATION
Page 9: 00003906
So Brand hopes that someone has a class of antagonists available
for smoke taste investigation. He also ~bserved that hepatic
patients were available at the VA hospital where Dr. Vesor (the
psyehologlst) is located.
Kessler observed that a lot of work on flavor had been
done by the industry. He sa~d ~ha~ it was clear %ha~ nleo%~ne was
not per se dete~native~ s~ce the Same a~unt can be in c~ga~ettes
w~%h both zood and awful ¢astes. Brand pointed out ~t one needn't
taste n~eotine for n~eot~ne antason~sm to work. R~ker asked about
selee¢iv~, poin¢~g out that the s~stanee ~¢ abolish other
tastes as well and that he didn't know of any which were s~f~eien¢ly
selective Go~i observed that the proposal related ¢o a research
approach for basics and that the question for the group was one of
priorities. Kensler observed that a cl~cal psychol-og~st could be
b~uEht ~n early and without a basic ~esea~eh p~Eram. Ja~vlk observed
that the mole of n~eotine ~n taste must be eonse~ential, since it
is a bitte~ alkaloid, and he ~estioned whethem people s~ke fo~ o~
in sp~Te of taste. He said he thins they smoke ~n spite of taste
as do opi~ smokems.
Go~ said he ¢hou~ht the area was womth explo~in~ and
asked ~f Dr. Brand would ~ke a specific proposal which could be
sent to ¢he meters of the ~oup before %he next mee%in~ so it
could be acted upon at the next meeting.
Kate obse~ed ¢hat you can't skip f~om species ¢o species
MINNESOTA TOBACCO LITIGATION
- TIMN 418889
Page 10: 00003907
with respect to taste, and That the~e were no freely available
animal models for humans, since natume ha, s p~ovided that all
species do not compete for the same food material. Kensler observed
that the need is for data referable to man. Jarv~k and Gori then
asked about tobacco plant parasites, which must be able. TO counter-
act nicotine, and about parasites whichI resist nicotine preparations
used as pesticides.
Dm. Hill's pPoposal was then c~roulated and, when the
Blue Shee~ ~epom~e~ souEh~ to take a copy, Kensle~ ~efused to let
h~, say~nE that i~ was not p~lie i~o~aZion since
a potential ~ant. [Since it Pelated to a p~toool fore a p~lio
bid, I did not thi~ Kenslem's pos~t~on well take. Indeed, I
have question whether even ~ant applications which a~e circulated
at open meetings can be kept eonfidentlal.]
The Hill proposal is said to be designed to help people
who want to st~ smoking but can't. They w~sh to follow physic-
logical ehanEes ~n people copmelated w~th ehan~es ~n smok~nE ~ the
context of co, fete smok~ and medical ~sto~ies. They wish to
put people on various d~uEs for periods of t~ and see ~f the~e age
eha~es in vamious pamameters. This. is to be done do~le
as suggested by the NCI.
One.test ~eferred to was tunnel yislon acuity, said to
affected by smokinE. Some expressed surprise that smok~E would
affee~ t~nel vision, but Hill said tha~ "his om~anlzat~on had data