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. 0 4 2 9 0 71 A Deoemb+r 29, 14T1 ME+owuDcK sUJECr: Chrooic B.oke Inbalation rsperistsata In respeet to 1aeK t.rm esperissata ia.olvLg si9srrtt- or other astoke inbalati.on, for y.ars ssioe, rsts sad latar, bs.stars baYe been esployed. These soa].1 .ni.ali w a.silLable in large smbals ax .odartte oost, their o.lateaaace sad eapoaura s~n tadLaiaalu feasible, and tney have the aCvaatav of relative s.natia Da.ogsnsit,T is rep strains, A11 these ani.al axparia.ats sattar ft.aia the aafaat of trtiej to iniduce Qiseaaes a.turally oaaurring in old bsaaa beings ia relativslw 7oung aaSaals. Lif.lar4 s.oice syostiras orarao.. !ai• It aeala b. D.ZDfnl to employ larger aniastiis~ sveh as deis, priast.s, Pi6s, aattla, ata, 8.olca exposu" sboule as alosa3y as possibLa resmble that of hua.rss, Buab t.cbaiaal sbartants as lbe4lng nosa ts ' imder presRU'a, .tr.c.beotaq, tmunal saaka asposure aroles sM plug" aosa vitb wc to itsree aoptb br.athias vitista the biologiosl s of the axparissats, and reduce thes larplp to lsbaratory trielu. ho& wcposure.* bsrt also mt heretofore peodno.d aepr ritelp saept,ad psitiva endpoints in respect to chronic lung disaasas, iaaledl.eK e.aow. 0s this ba.is lLrtber sveo.ssl41 eapsriasats along tba abwra 11"s aaamt be anticipated w prediated, To wA.rtaka ehronia satota sYposw-as of awimls smb as priaatas and 6ess, suitasbla llata .aska bsve ser be.o dsvelop.d, masa sppaaa to be prasentlj the mst saitabla mrtboQ of r.oto aspoaara, ma a.laaL sbonld be sufficiently mseroas to s11ov ststLtiasl .a.pariaani, m.ac• posed aad sbea s.oiciai aostsols ara desirabl., beascu.e the latter aro ao+r kao+ws to sbar ssaaar6bla stress re.etiaw, aenrtisallp pare •traias of pristas sad iota w sot svalLbla, asd tbeir virolep is art wll attidied, ToM...r, at lwt karla"ing of l.dcoaItes and tibroblasts, sed praser.atioa of tlresaa s.rs lhm at istarraL !w latst virelegismi o.alrsis ora dsirobh. w.stais osibw ot sisitiea.l r.gair.rts !be aav.ria.atal ..sia .w pev+ri,e.t by Dt. ArOw lotot at Sa atliaberg .adtsr...s aa r..piratoer .areiaep...is. !s. .~r6sip dwLt trltrl, ae.. ~esai !I~ • eoepotet. 5is arsalt aet 1. !n fts, basrms. tfaro w as 8aba 3af3rRlM sDsa sar iro vi11 Nwre 1 t ww. AalMala dwl,l 1U lbl3rwM M 1Mir A. .q.ei...t Ae.iam.t Is bope d• s.ree ..ftadaA dii a.t •e saitoble also M datanir beeaiitis~s-fo4001, Me'arey Mit. 3w ra~ !s 1W NON *.rse !a wt TO ppPMENT. su91ECt tA CONfIDENt1AU1Y AORAAtE": .. ~...~,. ...:,._.: . 4.,... . * CTR HN 014953

•G• Deceaber 29, 1971 Camns:ra:Ie in ns.v !nslancee by groes and sLicz~osc~pic pst.hologic stndies al.ooc. Reca:: t?,e 14o5e: Prize given PibiErer for indueing lua; c&ncer isi rat e vith a parasite, vbicb evantual.l,y proved to be only aquamoas se•.aplaria secoaCa.-y to vitanin A deficiency. Tac:lities to undertate trsnsplanta:ion, tissue culture, bio- cbericel ana2~rses an3 electron aicroecogv are needed if nalignant neaplata<s a: e kidel,jr >letastatic cancers in part oa.ke some speci.al stuC:e_ le;s c-ucia]., but there is no present intormation that setastasis• i.cc cancers rria be found in prisates and dogs, for exaar,~le. It seall, or aicroseopie, or borderline lung lesions oocur, since th2re is a notorious variation in the diagnoses of various pa•.bolo`:cls, sae- torm of peer review, or panel, or eonsultation is necessa.ry. Probt31;.• at lA.aat 50 oaapetent diagnostic pathologists are svaila.:l! il t."! V. .^., ar.e Ca,rtiar~_a *.o e,re in active practice, interested tn canc,!r d-::' cr*i'.d be aaked t.o review the saterial. Pathologists from other cou.^.:r:es would be belp_1.1. It ia desirable not to include eseritus psthologir:-, no satter bow vell known, because the diagnostic eye needa da:`v practice and uae on the organ in question. 7be type~ of sec:ions me.ie to seara`h for all but the aost videspreaG cancerz di:'tar ^•r. the approved vt.ale lurK sectio:u now videly asoplo.veA to er.alyze for aar_.hwsa-s. Excellent sec=ior.r for possible oancer &n" fo- po:.sib:e a-,~ not porcible trac •.h^ aer.^ lung or aataal. To try bo :~- is to ach;eve nai!`:cr Coal. Wl:ole lwg sections praperly ~ preparer of co•.:rsr. .rtll re•: ear obviour cance.-s, and if only one me4fiod is to be used, tL:s is the better. In erph,;•!mn, since there are so sany ditferencea of expert opinion, peer review or a panel to axazire the sa!erial is neoessary, Probsbl,v 20 aueh experts eould be found in the U. 3, and Canada. Various physiologic testa of lung function, blood 6a.es, etc., aaterially laprove the e+ccuracy of the final we?uatioa. Controls ssust of oourse be handled with equal care in oas:parably large msbers. The e=sination of the various t?pes of dateriala should be earried out by persons tilto do not Imov the exposure Qotp or history. After the various aRramsos.l, asroloQio, patboLoQic and bioobesiosl studies hane beesl roearded, els.elud nitb the r.rievers or alesrsd by the paAel, then all eonoerAed aaW afterrards be told the es;periseatat p involved. Sis is soareelr woidable wAer other aireaatane.s, ssud eontroia tend to be Qegleotedc finaLly, the resalts should be reported before a r.gatar soientitiC sseting iselndiess persoos eXperieneed is tbe lmt field, trita fora.l and inlbraal disonsliomf subsequent y&lioatioa La a Journal taat requires refereeing of amwesiyta !s dNis7ble* mis .arT eapeasive and l+ong ters study of ea!'lioieat aaiaals, if esrefol]y asigmed, sqerria.d, sad tbe aateriai oorsitill,y oollaated, S'F11S pOCUMENT SUBJECT T0 CONfIDENTiAIITY AGREEMENT. CTR- MN 0 1 49EA

` . -3- D.ceaber 29, 1g71 prxeseerr, revieved by ccapetent oonaultants an st.atistics, exper!&mr.a1 design, pethologic d:aZftosis, tissue culture, electron iicro.oapy, traasplan•„ntior, and pa:hapkrsiology sbovld advsace our 1mo+rledge cerainb the possible relation of moke inhalation either to rmptLyseaa or to lur.,; caac-2r. /larvers coaceraiag bo•.h reQuire• two sepa.rate eacperiae.n:s. S. C. Sasers ~g DQqlMQIT SUBJECT TO MNRDEKTLkJTy A6REEMENT. ~.~ ~~ C `(° R 11MIN 0 14 9-