Document wDx6mewZdB4V9GBpNxGznva2d
PLAINTIFF'S EXHIBIT
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I WH-1091
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C13CU0HA 07 TH3 LDI03 13 1SBXST0 YllTZ&f
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unn w. mar. m. d.
Profoosor of Tmtholocy
Nodical Ccllafo of South Cato Hi*
CharlOOtOO
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(.'teniry of proasatation at tho Soroath S^mu Sjapcoiua, Sara&ae, Irv Iorh Soptsafcor 2V, 1952)
Psrhapo tho &*li Justifieatioa for my scoop taaoo of tha laTitatica to dioemss tho ruhjoot of this papor im this eoapaay roots la
Hy iitorost la tho ijuooticaa eeaeoraod aero than 1a uqr ipotlil con
fer it*.Uc* th*t I al$ht Mho oat of * rmthor shotshy tad iporaodle %F
iadilssnco la offorts to soIto than. Z aa n? that othors vto tro
pro a oat hero tro hottor jaliflo4f tad ay pxrpoio Is t* (ala fro*
thoa-rathor thsa to *j?+et thoa to boaaflt frooi $mj efforts* of mino t
Vh* la 19JV 1 had tho opportunity to oraalto hy aocropsj tho
04L30 of cardacaa of tha laa* that vms to hoaoao spparoatly tho
first of not && oonnaeo la a ouo of Mtoitsiii to ho formally
set la to published records^ thoro iaaoditioly troso tho qjiostica of
a posslhlo cansal relationship la tho prior atato of chronic Inn*
disoase* Vo had for i oror si years boss dooply latorostod la asbostc
and this aons *ocnrrsnee produced aa additional question for thought
and lares H*rticA
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At laost op to that tlao chronia laflsaaatory disease, or ohroz
Irritatica, particularly vith fibrous prodootim aad disarrmaeaont ocacornln* tho
of structure, was tho n&la anchor la speculations L \ etiology of
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MLfletr, particularly epithelial types, la adrancad asbastosls an opportunity for the occurrence of .carcinoma of tAo lm< ca that bull umd to he good. Actually nothing.has yet occurred to cast cert that possibility.
la the in to ironing tine, during vtieh *o vere to encounter tro other Ilia cases, thare appeared scattered reports of tho iu* occurrence la othor locations j until, by. ampliation la 19**7 Humthir2iUti that there wn than recorded at lout 31 in stances of eanoer of tho lung la 235 casoa of ashestosli, an autopsy prulaouary cancer incidenco of 13*25 la par sou suffering fro* uboetoils.
for a fully acceptable comparison of this incidence of ocurae one wold ho Hal tod to* tho uso of a catopsy series frcm a (elosolji^ siniliT/^romp^ la age and sz tad at least la 111a ocrlrnrioftt for a slallar period of tine ezeept for ezporars to asho a too inhalation. Xren those rather loosely sat eriteria ceroid hardly ho aat ubere nsaburs eculd ho largo enough to prerido^a ftl.uiaal chance of orror la statlrtlirtdg'-tyye'.aalerdlatlcgi.
Tho Boat that can ho dona at tho proaaat Is to talo uhat Is aral labia as rridocoo for or against an otlo'loticol has la for cancer of tho luag la asbestos!*, at tha suae tlaa recognising that tho ^
largo chaaoo of statistical error door act alloy proof to ho cl si mod bat anroly rttrpltlea to ho supported or not sapper tad.
At pr-aseat rah eridefioe as la arallahla appears to support tha susplclea ted ta Justify farther inreetigetiTo effort of stutt erer aaturo aay ho altlflcally'%VS!S?f,y At least tho aTailable rrldcooo does aot allay tha suspicion.
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la Bcuth Carolina tha autopij larriea that has furnishtd tha bsaan notarial for cur studli* la aabastosis 1 la a canara! hospital that through tha pa&rs night ha axpaetad to produea a amts >ctlca of tha ra of sariou# dlnuii of tha conual tj of location*
Tor such Talua an It *47 hart v* tara anal73 ad tha findings la tha 39W3 eatopaias occurring in that aarrlea frcm 1926 to 1950 in tha aga parled of tvantj jaari or orar, tha parpoaa baing to cc-rar a span of tvnnty-fiTa 7tara that ooxraaponda roughly to tha parlod of obaarratloa of aabastosis and an ago {reap that would also ceTar tha oecorranoaa of that eoedition*
In- that total ontopaj sarlas vara found V6 lnataneaa of diagnosis of aabostosia by xicxcsoopie aridcues, including all cases raganilss* of dag7*a, and oneng thaa a V6 vara thraa vlth
othara earolnooa of tha lung ocesrred 53 tines, aa laaldanca of Obricusly inch a ceaparison la of linitad ralna, aa ara all
othc.r-i frea vfcicfa tha question has baan posed, although taJean aa a vhols tha7 aro at laaat in agreement that earclnrai of tha lung haa bacc consistently nor* ocaaca than van to ba expected 1a r a porta on asbesteals* Gas incidence of thgt ordar la laai than in soaa othar r*porta, while cur genera.1 lneldaaea of oarelnona of tha lung la ecnpcrahls to xema CBoabnrjer) bat laaa than othara (Higdon 4 JLlrahoff), Car iaeidaaee in ojbagtools would approach that given la othar ra porta If tha calculation vara and a vithia tha group of nadirs and advanced grades of asba steals, in *&lch araa tha thraa iaataacas of palaoxury caxcincan occurred. In that group va had t3 eases, and tho incidence vithia th* group would b* 10
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Incidentally! ^or TOCix *upPort it a*7 fiT to the eonoa report of frovia* preraleact of careiaoma of tic lun*, vc find that la tic first thirl of the tiac period covered la oar aeries the incidence of careinona of the Inn* vu 0.?5, in tho secoad third 1.15 end la the la.to at third 2.25, apparent ly a atoady increase duria* the treaty-fire year period, rraa though a till not a hlfb a* reported fro* aoac other areas.
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Vi the* t
thia time attempting to kill a thorcngh mamlyds of
th pnbliahad papers mad raeorda, a fav raecnt pertinent raporta trt
noted.
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la cne of the Lateat, Stoll, Baaa and iagriat^repcrt an addition
al oaj* of exnoer of the Imag in mmaoclmtlem rith mabeatcais mad cmjt up the Utermtera aa of 1951* Thoy rafor to Xaxtvothar'a 15^7 ropo?t, 04 prrrioualy noted heroin, aad also ref or to a report by Vyora la 19^9 recording a aerlea of 115 oii of mabeatoaia la vhich thara vara 17 iaatonaaa of aasoolatod pglffcamry carcinoma, am mutopa; arlaa incidence of lV,8, aa compered to Xerevether'a 13*3.
Hcabarjej? reported three addltlomal eaaaa of maaoelmtlcm of pulsonor7 cmrelacme mad mabeatoaia la hia amto pay aerrlee. Ia hlj leriea of oatopaiaa f^oa 1918-1938 there vara V5 eaaaa of pmlmotimry earelaeaa, aa incidence of l.Odjf. Ubestosia m diegnoaed 8 timaa and la \ of tho 8 aasas pmlaomary aaralaoma vaa alio farad.
for amah ecmperiaeu ea any ha ellevmble, Bigdcm mad lirehoff*
reported in 1951 a palao&ary cmnoar Inaldamea of 7*5% (87 la 892)
In && sntoppt aarlas la indiriduala 3 years of 14a tad elder la Tex vculd hast
7h47 raggaat "that fra^uanc7 of center of-the lmmc/be eatebllihed fr
a aerlea of catcpilaf," om meocmat of the marelimbility of demth
cortlfiemteo CssniterbeLlaaelng at lecjt a oat* of the velght of oTldaaea of
r peril of aaaaar of the .lmag memo dmtad vith mi be a to mia It the
vidoapreod incremne of pnlnmaury center la the (curtl pepmlntioa
that has been raeogalaed daring the imm period of time. 1 frv
refomneea vlU aerro to fou that traaeedoui problem.
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Grtte^jia 1951, saji, TBronehocenie cxreincua differs froa
other eaaMri in tvo important respects: (1) it has shoen an
eaoracua iacrease in the last 35 7*1*) (2) there bat been a pr-osreesirely larger incidence in the nale sex."
H* states that idler in 1912 could eollest cn17 37% cases of
cancer of tbt lung froa the vorld'a literature, xhile Indirldual
experiences in this country greatly exceed that total of reported cases froa the uhole vorld, and that cancer of tht Inn* has adTanetd to a position of first plaet in non froa ont of 8th plact in frequency = and this all vlthla the last 35 or ^*0 years*
Dali and EiU? refer to a British joraraaiant report vfcloh ihov*
that for tht 25 year period froa 1922 to 19%7 the incidtnoe of lunr eanotr in autopsies via Ireland sad Vales increased fifteen tines or
vhat it had been preriously, in editorial note in The Lancet in January, 1952, strikes a t:
note in referring to Hill's report that "in at least 17 out of 29
boroughs Cave trope 11 tan), deaths frca neoplasa of the lung and bron<
vers ac7 smeroua than deaths frca tabor coles Is" and in remarking
"This is something quite nsv."
^
Saith^ in-1952, states that long cancer has shcua an increase
oear and abore shat oculd be expectod aa a result of increases in
saahers of elderly persons. St states also that high lung nor tali
has been recorded for beth sen and venaa patients vith sebestosls
in ltaglsnd^
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Perhaps -si-personal sots is peraissible to illustrats the ap
parently uniTeraai'axperienoe in ssatop*7 serrices during the last
forty years that earci^oaa ef ths lung has changed frca a rarity t
a ocwacaplaes. Is a resident in ths fhiladolphia General Hospital
^Ss,
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I hnd dene an autopsy on vhat I took to be a eui of tuberculosis,
and had discarded ellxr*anji end tissues exespt the small piece* fr vhich I prepared mie'rosVopie sections. When I shoved the resulting
glide* of core inone of the Inn* to my ehlef and had to acknowledge
that I had thrown the lnno away, he aro*e sternly from hi* mic
roscope end literally hootedsne dovn the atalrs.
Perhaps I nay also note that the *carclt7 of resident* in p&th
\ their ofj nowaday* ha* gfrq brought abqut a difference ln/treataent, al
though possibly not so such difference in their deserts*
BCPSaiKSmi STUDIM Because of the question raised by autopsy etaes-ratiom of
% associated asbestosis and caneer of th* lung, and among the many
apparently experimental studies that/ha re been done and '.or: are now joing on by subjection ot experimental anlaal* to respiratory exposure to a rariety of suspected substances, 1 hare undertaken to see whether rrldoact of enreinogenit aeties on the part of asbestos or of tho ecaditica: of asbestosis sight be gott in this way, low in tho third yaer, we haTe such a project under way, supported .in pert by. `a national Caneer Institute grant.
In drrising such an experiment, cat is, of course, faced with scary questions, saong which are tho choice of experimental animals, the awthdr of exposure, the mechanical questions iatc174 in aotheds-, tho practical matters of time and help, etc,, e
3cerase, *0 far as I mm aware, bo aainal except man Ijas shovr bronchogenic earcincaa of the lssg naturally (or experimentally
for that matter)
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cbc to vsrJc'irlth a itrala or ales Icovn to drrslop tdsnca-
atcud tutors of ti lunf la roffular pr*-alculabli occorrenc*.
La till*
y* bars on*
lift spaa, of fcaovn lunf
fr=r producti-rsas** that night to susetpiibls to lafluaaea la that aatara2 occurronco, and at tha sons tiaa as good as tnj othir proipaet for broachcsaaio earciscua so far as is kaovn. Tha strain, chosoa is tho AC^ hybrid (A sals and C fan ala) first janaratloa froa braadluj stock obtained froa tha Rcacoa B. facicsoa Manorial Laboratory. Appro rlnataly aqual nsabara of mica ara
bain* axpoaad and ktpt as controls. Xxporora ehaubars ara of our
an darlslng. Regular dust jousts ara sad#, with ecaciaitratioas
obtainad
.
of dust as hith as asj bvithout risk of killing th* anlxals.
As near as faasibla, tha aeao as baa to 3 as our buasn css a a ax-
pariaaeod is balng trad as dust.
is tha anlaals axa aanriflead thsj ara antopsiad and tha
nuabar, alsa, aad distribution of lung ta&ora rteerdad. in attamp
to grads tha a a nil also b* aada, It would ba praaatura to giTa
an/ sasirsia of this data as jut. govrrar, ac apldaracld cur ti
neas hhs yit baa obsurrad,
^T****?
Boosas0 w rlshsd to alMTugh sooths? tad larftr ajoiasl, a aretar of dott^sr* aiaa fcaiW^psbiaatsd, to start la? dusting la
span ally jMiftatgCrt^d shsfi^jra,. 3 hr, of ecursa, a m< longar ta c=ptria*At, sajfiso report ossa ha aoda upea it at this tlaa.
Caa of ths msgis tha deg vu salaotsd -is that obscrratlca of tha
oaauTT^aea of^'as ho stasis bed!os la. th* lung of a doc axposad ia an
asbo a to* faett77 is morli(4
'
So far as I a var, thvra 4l calf cats published rsport of
an lnhalutica caparlaont exposing ales to asbostos dust as a tast
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cf eaactrijsnic aetion. !Mj rtport, by lordaann tad Sorjt^ by the author*
va* claa*d/a4 pojitir* a-ridenc* of such a relationship tad ha* g
boea eitad to that effect by other*. Smith, hov*T*r, analyse*
it to the conclusion that it not only produce* so proof of a
eansal relationship of aibesto* in cancer of the luaj but actually
to tii enatrar7,\la that report ill-defined epithelial change*
v2.?n thought to haT resulted in the lungs of 9 aaiaals cut of aa
original ICO nice, aqpiaacuj metaplasia vas found ia 6, adenocar
cinoma ia on* aad squaacua call carcinoma la ona, / Smith ^uastiona
vhethar tda interpretation vu eorraet U to the demonstration of
actual squamous call carcinoma aad calla attention to the common
occurrence of agunaous call metaplasia in old rata vith chrcnie
pulaonary iafactloaa aad ia aalaala deficient la rltamia 1, '
The only other 5rperiaat of ubieh I as avara share
under arpo.Turo to Inhalation of asbestos dust developed tumor* (
of the lta$ ia a vay suggestive of a ralatloaah.jp occurred ia an
uncompleted experiment of the la* i, TJ* Gardner that came ta my
i
attention through a courtesy from the Saranac laboratory*
j
' la atm of Oardnar'a experiment* la aaba*tc*li ha found a
high lacidanco of the typo of lsn< caaear, to ublch mica are dlipmn
Slnc-a the itraia hm *ms naiad tu uakaoma aa to tmor suieoptiblllt
*ad tiaao tha axaerinaat vaa uncontrolled from that ataadpoint, hi
. 1 ____
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j atopyad 11, apparently intending to aot up a proper experiment to |
jf alley up.t&a samitlca la to*
(. ^ It leaht it dead aot appecr that say reported experiment can
/ be accaptad~aj ccaclaaira* aad I aa laollaod to the
Tier aa
oxprofqed by Smith. that aa to
ao experimental, sracf
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tlut the lnhjLlatlcm of aabaato* or -any other iutarial Vill cause
spiifciio
broachcsai carcinoma haa teen ^resected.
la the natter noY stands, it appears that while idd.lxi.ornl
eYldeaee of tht tu< sort h-13 been collected la the aesntlae, tht
' goeetloa **** yyj railed with our first Tgg U 191? es to whether a a btoels eaa get e * producer of caacer of tht loas la teajls
beings regains as opoa ts It was hea raised.
3o far &s we or* concerned , "CTs*"ccadltloaa la the indrutrj
ore so anch La-prowed that renn the problem of asbestoals fcsa be
come greatly laesaned. Tht ffrxde of experore to the dnst has been
30 reduced la oar territory of axperieace that we nc loader ez-
pt to see the extream of the disease that tcllir naecatrclled
conditions aeoaed.
Bedims to Jna sc | aad although oar easts were those cf/adwaaced
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asbestosls, If the exposure naj be oaaeerigeaie It ecold act ooy
be eertalaly sold that lesser grades of the primary dlseesa would
be ineraae to the tardeaey.
In ell rsspc*^ therefore, the problem remains vlth us tad
ehcrild be subjeetod to ecatisaed iarestigatiea cm its wa aerlts,
esldo frea esty (iTuU^f that would eocrne to the IsTestijatloa of
sell is ant aoeylastie disease os a whole if such u etiologie
feetor were naeowered*
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ROTflfJTCZS
1 Lmeh I K. and Smith, V. A.i Pulmonary Aobestoali III: Car
* claoA of
m lobeoto-Silicoaii. Am. J, Cancer, Tol. XXJ7,
ffo. 1. H*7, 1$3 5*
2. Horovethor, I. R. A.i Annual Report of the Chief tnopector of Factorieo, London, Eli Kaje*ty'* Stationery Office, 1.9^7.
3. 3 to LI. Rotori Baaa, Richard} and An*ri*t, Alfred A.: Asbettcsla
Associated with Bronchogenic Carciacma. ireh. Lat. Ned.. 38. 8^1
(Doe.) 1951.
* ' ''
4, Honbnrjor, F. i The Coincidonco of Primary Carcinoma of tho Lung* mad Pulmonary Asbeatceii. Aa. J. Path., 19il9^3 797-305.
5 HI;don, R. 2. end Eirchcff, Holeai Pregnancy of Cancer of tho Lost In All Kmlitnaneit* Stndied at Antopey. Son. Nod. J. 44>t506, June 1951.
6. Or than, X. l.t Pulmonary Caneer of the Lan* vith Special Confidoritioa of lta Itiolcty, Ball. V. I. Acad. Nod.. 27*261,
Kay 1951.
7. DoLl, Richard and E&l, A. Bradford: ffaokint and Carcinoota of
tho Long. Brit. Med.
#4482, 739-A8, Sept. 30, 1950,
3. Smith. V. 3.] Loa* Cmcor With Special Roforoneo to Experimental
Aapooii. Arch. Lad. Eyf. 4 Oceup, Med., Tol. 5 To. 3, 209,
. Khrca"1952.
.
9. Jcrdaaaa, K., and Scrje, A.: Lzznxonkrobi duxch Aabeititrab la Tierrerruch, Ztaehx, Eroboforsch. 511168-182, 1941.
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