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p.m. Tuesday 11th a.m,/p.m. ( ,~'I AGENDA Plenary Session : Joint R&D/Marketin@ (i) Marketing overview of worldwide scene (A.M. Heath & P.M. Bingham) (ii) Talk by R.P. Ferris : "The functional significance cf smoking in everyday life". (F. Seehofer will present additional material). (iii) Main thrust of relevant parts of Group R&D Programme (L.C,F, Blackman) and GR~DC Product Application Group (A.L. Heard) Research only : Presentations by CAC Companies (a) Brief review of present business situation (b) T~sh~j~l pr_ior]tJes (short- and long-term) (c) Interf¢c~ with GR&DC/Group R&D Programme (d) Any other topics felt to be important/relevant Presentations in the order Amatii BATCF B&W ITL Souza Cruz ~-~ General discussions of some m ajo~ th[eats~gpportunities for BAT Grou~ - with formal brief (approx 10 minute) ~=~ ~b in~od~ions, as indicated : G~ Smoking behaviour research Consumer testing and response Nicotine Compensation/elasticity Sidestream/ambient smoke Smoking & health Process innovations Leaf Processlng/Primary {Brazil) Tobacco Diotechnology P.J, Dunn E.E. Kohnhorst C.l. Ayres/F. Seehofer A.L. Heard L.D.F. glackman/P.J. Dunn L.C.P. Blackman/F. Seehnfer E, Rittershaus/P,M. Denton C.J,P. de Siqueira F. Seehofer/A,L. Heard

Wednesday 12th 5 p.m. Joint meeting with Marketing. The theme will be that, in marketing terms, product innovation is only relevant if it contributes to a real or perceived consumer benefit. #he aim will be to identify clear consumer needs and preferences in the major markets, and then to agree jointly a l~umbe~ of major_~y~.dgct~ese]~pmen~ oRportunities that should be Rursued with urgency within the Group. A con%e~uence of the conference should be the ca%iogalisation of.p[oj#c~s (whether stemming from Marketimg or R&Di, ensuring that the allocation of R&D time and resources to product development is in line with agreed priorities relevant to consumer needs. Social Evening L Thursd~ 13th a.m. p,~l. Joint Marketing/R&D continued - Agreement ojZ~Jl]~tes of Joint Meeting Research~ Brief summary of GR&DC organisation and current expenditure followed by consideration of the proposed revision of Group R&D Programme in the light of previous discussions. (M.J. Hardwick) p.m. General discussions, but to include : + ÷ past and future specialist meetings techno_l_ogy_excha~ge staff exchange pub~icaPions poLi~ final agreement of R&D Conference minutes Depart ~b C~

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( SUMMARIES OF RECENT TECHNICAL EXCHAKGE MEETINGS - BIOLOGICAL - NICOTINE - SMOKING BEHAVIOU~ MARKETING - FLAVOURIST - STRUCTURED CREATIVITY - NEAR INFRA-RED C Note : The remorts on each of these meetlngs wil~ De available al the Conference. Gm

• BIOL0GICAL CONFERENCE~ SOUTHAMPTON~ 9th-11th APRIL~ 1984 The 1984 Biological Conference covered three themes: a) Project RIO b) Biological activity of nicotine c) BAT needs in the future This note sum~arises the main conclusions and actions required, I. The Ames test is the main screening assay and from the results to date it is clear that: (i) Cigarette brands can be readily distinguished. This is in contrast with the earlier mouse skin painting results. An unfortunate side-effect is that the sensitivity increases the probability of an Ames League Table appearing. A further unfortunate examination is that, to date, it is not uncommon for BAT brands to have a higher result than those from the opposition. (ii) Important fractionation work in Montreal indicates that the Ames ac%~yJty is associated with the~basjc-materials]n cigarett___ e_cp~densate, Again, this is in contrast to the mouse skin painting results, where the bulk of the activity resides in the neutral fraction. Any response to this observation must wait until the initial work in Montreal has been completed. (iii) Initial results indicate that reduction in circumference reduces act j_v_i~ y,, (iv) Early results from Hamburg indicate that the addition of casings and f]#yours can increase the Ames activity. Obs'egvations from Montreal~uggest that--c~rtain other casimgs bring about a reduction in Ames activity. (v) Ventilation brings about an increase in mutagenicity which with Canadian cigarettes was not significant. German cigarette} however s_howed a significant increase, It could ~e ~portant to evaluate changes in desig~fe~tures with a number of cigarette types as the interaction with the tobacco blend could well be important, (vi) Montreal is to produce a review examining variations in design parameters and mutagenicity. Contd/,.. :) Om

C Contd/... -2- 2. 35 Clearly we need tests in addit1"on to_the ~es test and Southampton is obtaining encouraging results with an enzyme induction assaz. There was general agreement that the wor~h~l~ b'e activ-e]~ pursued. Similarly it was agreed that the "yeast system" showed promise as a useful assay and should be followed up. The eventual need for a long-term bioassay, preferably based on inhalation, was considered. The significance of such a test to the tobacco industry was discused, particularly if the animals used were pre-treated with a known initiator such as radon. No firm conclusions were reached but it was agreed that Southampton should explore the feasibility of a long-term assay. I. 2. 3. i 5, Nicotine At normal dose levels, there is no problem with nicotine with regard to mutagenicity. A possible gap concerns chromosome aberrations and Southampton will prepare a protocol for circulation to Hamburg and Montreal. Although the cocarcinogenic effect of nicotine is still unresolved, no further ac~-i~fs prop~.dT--- The role of nicotine and cardiovascular disease was outlined, in particular the role of smoke in decreasing prostaeyclin and increasing thromboxane levels. Hamburg will prepare a review paper for discussion at the 1985 Biological conference. There is a need for a 'teratology type' study examining nicotine. A review of smoking and teratogenicity is to be prepared by Southampton. A review of the role of nicotine and effect on the foetus will be prepared by Southampton, D' Opb~lr~ >," ;i Future Needs l. It was pointed out that there were advantages in publishing some of our toxicity work. It was agreed that this complex question should be raised at the Research Conference. C.9 2. It was thought prudent to ensure that the Company could show no ~.a adverse effects op_sjdestream toxicity for a product de_~gned~o h~lower visible sidestream. P-~ 3. It was agreed that where possible all work on additives should be carried out in BAT laboratories. ~l 4m~ 4. Work should be initiated, albeit within existing resources, on the evaluation of smoke/condensate generated by human smoking conditions. Contd/...

C Contd/... - 3 - 5. Southampton should review the work on chronic obstructive lung disease (COLD). 6. The pryotJngeffect of tobacco smoke isgaining momentum and Southampton shDuId prepare a review for the 1985 Biological conference. 7. Southampton should similarly review the ~os_ition on clearance mechanisms. GO C~

NICOTINE CONFERENCE: SOUTHAMPTON~ 6th-Sth JUNE, 1984 The main conclusions reached were;- a) Plasma nicotine/cotinine measurements can give reliable estimates of the nicotine uptake by groups of smokers, and with suitable precautions, by an individual smoker. Many smokers appear to obtain 12-14 mg. of nicotine per day from their cigarettes. b) Cigarettes which have a delivery of less than 0.7 mg. of nicotine per cigarette as measured on a smoking machine, do not achieve large volume sales. Providing smoke is inhaled - even shallow inhalation - 95% of the nicotine is retained. d) Intuitively it is felt that "satisfaction" must be related to nicotine. Many people believe it a "whole body response" and involves the action of nicotine in the brain. e) Although many smokers appear to approach a plateau or constant level of nicotine in the blood, it is not known: (i) whether a smoker feels the need for another cigarette when his blood level falls significantly below this plateau level Ol or (ii) whether the smoker is seeking the more transient peak levels super-imposed upon the general plateau level. ~.w f) If level in the brain is the key feature, we have little idea ~t J-~ present on the relationship between blood levels/pattern and those 0"~ in the brain. g) An immediate sensory affect associated with nicotine is the "impact" ~ on inhaling. Is this sensation a genuine part of the reward a smoker is seeking, or is it a "cue", i.e. a smoker has learnt by experience, that if he perceives a particular level of impact, he will receive an acceptable degree of satisfaction~ b) If we are to make better use in product terms of the levels of nicotine in smoke currently available - and even more so if we are forced to market cigarettes with reduced levels of nicotine - then i% is important to significantly increase our understanding of impact/satisfaction, There is an urgent need for experimental cigarettes in which the levels of nicotine in smoke (and smoke pH) are carefully controlled.

OBJECTIVE: C ( SMOK[I{G BEH~VIOUR/~AEYETE~CG CQIIFERENCE. MONTREAL 9th-12th July, 1984 To promote a discussion among the delegates on the most appropF1ate future dlrectlons and feasible mean~ of ¢o~unication within/between divisions and Companies. The following five general topics were used to guide the discussion and to Tevlew/rev~slt points raised ear, Ear in the conference. 1. KNOWLEDGE OF CONSUMER RELATING ID SMOKING BEBAVIDDR II. KNOWLEDGE OF PRODUCT Ill. HLIMAN SMOKING BEHAVIOUR RESOURCES IV. COMMUNICATION V. FUTURE CONFERENCES These notes are ±o be used as a guide for the key discussion points raised. mnd are presented in no specific order of priority. K~O~LEDGE OF THE CONSUMER RELATING TO SMOKING BEHAVIOUR ~ TheTe was general dls~usslon regarding ~onsumer s~Itohlng tniormablo~. how this information is gathered, on what basis and whether it is used O~ to full advantage. clJ |t was suggested that m~rket~g switch~ng models should be ~nvestlgated to see if they provide direction to smoking behavioural Fesearch and Facilltate its link wlth the marketplace/consumer. It was pointed out that particular care should be taken to ensure that the needs