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BIO-AESEAACH CON, SULTA\TTS, I~c. F. MOMtVtGEE. M. D. D4.e+O. F. 5 EtNF tID, Ph. O, D:r.e+...i F....M ~ cowsuLT.rioN n~-- EtSEAECN OtvELDtMEH7 9 COMMEtCIAt wEt+UE CAMEtiD6t, MASSACrUSETTS 01141 (617) 86s-0735 Febr::a_y 7, 1y'r3 Mr. Edwin J. Jacob Lauterstein dc Lauterstein One Rocketeller Plaza New York, New York 10020 Dear Ed: I have today been informed that CTR has decided not to decide ca the conti=uation of our smoke inhalation studies in Syrian har:sters until all ou: histological data will be available. You may recaLl that our preliminary findings of pre-invasive carcinoma in the la:y-nx of some smoke-exposed animals plos two malignant tumors of the nasop.--arynx in s-noldng ani.-:-xals were interpreted by us to sigaify Ciat we R•er e confir:ning Dontenw-ill's recent studies with inhalation of smo:ce f:orn riec:ucicy refe: ence cigarettes. L- is true that we still have to secto_ t'_ss•:es from more than 200 animals and to do this a:~' reSuir t:: ree rncnt:s worR. It is ray personal conviction, however, that, take= together with Dontenari:l's data, our pr esently available resu'.:s :ust:fy to proceed im=.ediately with inhalation studies on various types of ciga: ettes as well as on automobile exhaust gases, a:r from h_g_way tu~els and chemical mi.xtures simulating environ--r.ertal concitioas to show that agents other than eigar ette sToke caa indeed cause zeopiast-c lesions in a test aai.-aal. To me the iidecisiveness of CTR is beyond belief a=d .:rderstLCing. Their slowness in getting us started on our first b.arnster i:`.a;ation study over two years ago caused us to fall be:ind Dontenwill whom we could easily have beaten with our superior technology, earlier developed with CTR sponsorshio. Once more we are being st}^nied rather thar. helped by post?onement after postponement when we could be doing the things that need to be done. It cannot be dissimulated any longer that methods are now available which in hasnsters cause neoplastic lesions wit.4h cigarette smoke, as Dontenwill claims. This was published in Germany and will be confirmed by me in .darch at the Toxccoiogy CTR COHTRACTS 0057112 11225453 CTR HN O4'404

Nir. £dcc-in J. Jacob -2- February 7, 1S73 meetings in New York. Now the cigarette industry ought to utilize this new me`::odoiogy in the most productive way to demonstrate product safety as well as to show the environmeatal respiratory non-tobacco hazards which undoubtedly exist. We could do this irnsnediately and on a scale that would exceed what CTR is a-illing to consider. At best the- y will begin consideration in about three months when our histology will have been read and may come to a conclusion at their Septeaioer rneeting. Our work could not start until about six months later since it takes t:at long to breed appropriate animals. We have at our d:sposal fully ecuipped facilities where work cozic start irr-ne_:a:ely and would be under way as soon as aai..--ials in suLicient number swould be available or about six months a^:er the decision to proceec would have been made. We have also 10, 000 square feet of av¢.ilab:e space that could be used for s-ioke and other exposures Lc ani-.a: rooms with mini-aal alterations that co;ad be doae quickly ze econo:: C=R has been ccnsidering our e=c:osed prcposal of October 10 ic 1•-mi:e_ to seven groups of e::=osed ar.i-:a1s acith smoke of reference ciga- re:tes '--e:.az the prime subject for sr.:dy Nit:: only one group also be_g expose= to a cce=,icai carciceger. ;his project without al:era-:o:.s c° was budge:ecd at $=96, 000 per year for a to:a_ of :_ ee yea_ s. To ai= maxi::al usef:ar.ess fro:rn tLe iahala::on method, at leas: arc::.er seven groups ought to be subjected to izaala: o= of enviro=_-enta: cec:arc.:aants o~_her than sanoke snd to repr esentative cczte-porar;: c va- r e-es R:.ich would br i--g the total cost to about 5600, 000 per year :or. ..: ee years and requi-i_e a.n ia::ial r.oarecurrir.3 expenditu e for altera- tioms a=.d a~par at7.:.s of about $3C0,000. (-his a:nour.: could be sp r eac cve- t:-,e t'=ree years. ) i do no: believe t.ha: CTrZ will aC. expeditiously in the near future a:c anticipate more delay before we can get going on even a limited project. I also whether CTR could even consider a project of this mag==T.:de because c: bud;et limitations. = or these reasons, I now turn to you to seek gu:dar.ce as to how rr;ost e:iectively to approach the individual coW~an ies who could profit froW these studies. I appreciate your help and advice. e ii:d: encl. Your cerely, •Freddy F;ombger, M. D. Presidest anA Director CTR CCiHTRRCTS 0Q571 ~ 11225454 - c-I R HI I 042/ •r.. 5