Tobacco Documents Online

My name is Rodger L. Bick; I am the medical director of i San Joaquin Hematology & Oncology Medical Group. I am also assistant professor of medicine, specializing in hematology I medical oncology, at the School of Medicine of the UCLA iter for the Health Sciences in Los Angeles. I am on the :nical faculty for hematology and oncology of the Wadsworth a. Hospital in Los Angeles, and hold adjunct teaching positions the Wayne State University Specialized Center for Thrombosis ;earch in Detroit and at the Wesley Medical Center and _versity of Kansas Medical School in Wichita. I received my medical degree from the University of .ifornia at Irvine School of Medicine in 1970. In 1973 and '4, I was the Director of the Hemostasis/Thrombosis Research -oratory, Chief of Hematology/Medical Oncology, and Director of '.ical Education at the Rern County General Hospital in ersfield, California. From 1974 till 1977, i worked for the Area Hematology Oncology Medical Group and Bay Area atology Oncology Clinical and Research Laboratories in Santa .ica. From 1980 to date, I have been an associate professor of ied Health Professions and of Nursing and Health Sciences at ifornia State University in Bakersfield.

294 I am a member of numerous professional societies, s including the International Society on Thrombosis and Haemostasis„~ ;;>£ and the American Society of Hematology, and serve as editor for -- . . several journals in my field. I have written over 100 published " articles on various aspects of the field of hematology. I have long been interested in the subject of blood coagulation and its possible relationship to heart attacks and': cardiopulmonary disease in general. Recent reports have appeared"; in the literature describing alleged isolation and biological'l properties of certain brown pigments from cured tobacco leaf,., cigarette smoke condensates, and saline extracts of smoke. These pigments have been generally referred to as "tobacco glycoprotein" (TGP). Becker and co-workers have reported tha*_, TGP produces allergic skin reactions, induces the formation of , antibodies, and activates early clotting factors. Based upon these rather simple experiments, with respect to early blood clotting factors, Becker and co-workers have drawn far reaching conclusions that TGP therefore must also activate the remainder of the clotting system, clot lysing system, and complement system. However, there is no evidence for this sequence of events in either the Becker articles or in subsequent work. In spite of this lack of evidence, these authors have hypothesized that these possible sequential pathological events represent the ci 295 pathophysiological link betweer cardiopulmonary disease which has be To investigate more carefu al., our group, in collaboration wi by the previous published methods c 7roup found that the final produc nrocedure of Becker contains an contaminant that is introduced by f .noears to be a side product of the ..sed to form the gels for sepa -on*_aminant, polymethylmethacrylat orthopedic and dental surgery and t been implicated in allergic reactio •.:e subjected the contaminant to th clo*_ lysing, complement, and kinin Eound that the contaminant complex early coagulation Factor, Factor XI completely erroneous impression th However, it was found to have no ac currently used by the Bureau activation of the blood clotting sctivation of numerous of the earl :.ikewise, there was no activation c effect on the complement system, -3-

295 pathophysiological link between cigarette smoking and cardiopulmonary disease which has been reported. To investigate more carefully these claims by Becker et al., our group, in collaboration with Dr. Stedman, extracted TGP by the previous published methods of Becker and co-workers. Our group found that the final product obtained by the isolation procedure of Becker contains and consists primarily of a contaminant that is introduced by the methods of separation and appears to be a side product of the photo-polymeri2ation reaction used to form the gels for separation. (Relatives of this contaminant, polymethylmethacrylates, are widely used in orthopedic and dental surgery and traces of these compounds have been implicated in allergic reactions and clot formation.) When we subjected the contaminant to the aforementioned coagulation, clot lysing, complement, and kinin generation assay systems, we found that the contaminant complexed with small amounts of an early coagulation Factor, Factor XII, giving the superficial and completely erroneous impression that activation was occurring. However, it was found to have no activity on thrombogenic assays currently used by the Bureau of Biologics for detecting activation of the blood clotting system. Nor was there any activation of numerous of the early coagulation Factors tested. Likewise, there was no activation of the fibrinolytic system, no effect -on the complement system, and no effect on the kinin

generating system. Further, we found that there was no effect of this contaminant on the normal clot inhibiting proteins found in human blood. Our studies strongly suggest that TGP isolated by the general published procedure of Becker and co-workers consists of a contaminant which is introduced during the separation process and contributes to, or more likely, is entirely responsible for the biological activites noted by Becker and co-workers. The presence or absence of a substance in tobacco smoke and certainly unproven. It is obviously of importance to examine the significance, if any, of tobacco glycoprotein; however, a good deal of controversy does exist and it has been impossible to duplicate previous findings. In this one instance it appears that erroneous and superficial observations have led to far reaching hypotheses which cannot be confirmed by carefully performed studies. This author's plea would be for adherence to confirmed scientific fact, rather than emotion, in attempting to study and delineate the biological effects, if any, of cigarette smoking on the blood coagulation complement or kinin systems. My own research and review of the scientific literature lead me to the conclusion that whether and how smoking might cause heart attacks or cardiopulmonary disease remain open questions. 297 can Fra-:cisco, r•a;if-rr.-'s rit.a] S'a s: arried ._....er x'-_a Ca:if , ' S a_ata: ~ni.=rsi,y of : 3''0 - a et .. _-:r: . cs. "'c.•-ia 't .. n. eg c, a n. .'~!'y':911 -'' .]'2,,~= p: Cai:`ornia a-.d iil 'C; p_ t9t6 - Sa, C `307 - - =:d ;' .'.d icg r '.aic` r.e, i367. • -°,rt•!i r ar~i: -o -.2AiCai .-'.,i ...: -:5 -... 7a1 r ._<e_rch __ ~ %-1iy 1973 - ',;y :9.'4. :'or of ',, a] d at:cn: Ker~ Cc er; 1973 -'day 1974. %I

297 San Fra-:ci.sco, r_a;if_rr'_s .:rri?d S!21/;2 :;N : "r. -_ry: . -cra .._,..rec .. ul, fa;if-•.._`a °'7h cC` ;1, .ra, ,..._ .:-is :.<i:y,?f i: et _.. - . . _ .. ._-_~. i;v 'r~ 2 9'l n - .r-:1 = y: ~,_ly i9 1' e^:?;2, .__._.:.:.p: ol CLa _-cer .or ... - a 9_..:.: , Cali__rnia __ .'_.i1 ife7c ..;,by -'li.: ...p: 7g'6 - Sa'~?c-.lr ;?'•6. d1' _._. 91. `I " _, 1 .i a L?St -vt .-.._._ _ ~ .. rs r :.{ b7. i', -1 Jf adi: ne , _ .. ay _d `or ... . ..._:ng ._ _e.ch, _ 4z 1 cz <dici.e, 'sS. ?o _-.._or :i----'-- .. .-1 . . .zr.•, ....r -.y --.:=a1 7S• ° - ... e, -..S '-.t __._r,e. _ -:_t ee c•r :.; a zl - < ital, ?z'< d, Caii.cri;a, C~iefr -e~_tclc e?:cal C^ :y, }'=:n _ ty ._ : .. , a1, .. c d. =slSfor.^ia, .'•uiy 1973 - `ay :9.'4. D::•r tor of . dical Ed:;cati.m: Ke:1 C: z%ty Ca:iEornia, Ju1y 1?'3 - 51ay io-4. trA T

298 r 29 CL'3RI~_~l!".d VITAE: -G:3 L, °'CK, 'd,D. - Ts (cO7t.): !f_^l,cr: Cancer St. 7clin's 1`Er: i.~<__cclt C__':i?tee, S S.:_3 _3 tl, .-.a _'..i•a, l.~___ 2:.Jr ?:,il•d, `;a.^3 .cnica "`tr: .._.cC'r C;:_•ittee, Fa:.ta M".'1'_ COrjl.`ltr-lt: . "b?rZa F.'-,_J1Cy-y Ca: er, =a. Fc_ id`ng D1:Ectar: C-c~1C5y Unit, 32.n.t3 ... '3 ,:. _ _.31, " .-_:3, '._A Director: ional ?le-:stas.s . .-. .:sis Sc .rs ; " - _ -r oa CcRrin... .n.g ;-t.'.dic31 Fd'.:C3t2^n, nE_-._-1 $cC .ty Of 1.171_a1`- -'S4-`s 'e" cal Staff: BCL> "e. ar for the Fes ::7 _,s =a . r c a l Staff: Sa :ta `;c ca . ital -.- _ caI C~-c r . . . ...._ ._4 '.al Stsff: St. sri-l -9 att!, er, zta :A .s?s..,rth ,..,_--_ _ cal St rf: Gr- ter 3a.ersfield . ar`s1 He_ a1. . -'.:•.al ^ff: _s:t _.3•:, iZ C:;-~_- :y -._ al, _°.aff: ascy ~csi:i:al, -_,~_-__~?•i, C31if.-.rr;3 Ch C=.,,_er Cc-7pit. ~;a -;_-;n s•_.=a: "W.-or ".:ard, Inc. Jo e ia F: Ca::io:ria f IiI P•-o;e..t, I_:_sa cf Co-I cr: AT C... . -+t: . ?rri 1 `.~r • _lacco . arch "-, cS and Rnt aa_r Re. _•w l.i.-.. .51 K5.1 Group Clir-ca1 in•-._ -atcr: 'zericxn DADE .:•iic.31 ._. s. .. C-'_ter ~le•:tr.::;ics 2c3,d or rs, 'tericls .ris: r;' C . ~oclety of C1:-~ica1 ~:~.._'_ogists. E`C'iLTY ;??. c• ,t r_o~`_sor f ic1:e {e-, o'.' y,'` .'ic31 1, t_-f ..ed'•.ie, S ol of lr„ic:-:e, ;iCL4 .,r e -.--..- -e . , .5 '-.nsa•~s, Cal:f-rnia C1i-ical -"zvity V.A. •- .z', . _ .: Ca' -nia =te essar of ._-_ d 9~a_ih r .sfie_i, California v C1=n.._:1 k<_sociate .^- .fesscr of -_ , '. . ..-;a ' _. :ersity, SaT:ersfield, C4 :,61-52 ct soc:ate rofessor cf `-_ '*%s`z"s~, r ~ _ ^~ • e \---' ~S: g;n (rrs .ge :o ., ,~e+o =: .:>flc'3 _'d I .-._. . =.el . _ . . . . : : i l • ~l'-:,LV: _ _ . ' C c l ~ _ . cr a-] .._ -- `~ • - - a~.~_;1 cc ^ol, itiictlta, i:`^., as -s = = ' -~`r L. in 3ab:e.sfield,C,1._~ ia for .._-...-as__ _ - ?4:CATE ."-=TCTICE: Say Area ?e-atolc;y ^ncology ;ted_ ,1 . .:p _-d ay _.=a . _ • ~' :3Y Clinical and Sesea:ch '_aboratcrizs, S:::ta '.:rica, ''_l_`-:-ia,~_3 1- i377. '•?edical Director: California C3ag'iiaticn ..a,..-Ic., __ :=__.•id, CA. -'- :S -~ t.•,)1 c.'~ .._- in c,~JEr 1477 'O ~ P_ E:tt. ~T"TS ?=pC'_n2D: A. A:•Ethod for t.`.e ._ ~e Scalz <. c. ai of 3. A Yot~:d f~r the Sczle Fract_c:.at: Sh Fa,~tor VIII C,ce,t t? C. 4:•'et: ~d for t':e 1=rge Scale 'r;ctic-at' :... -. , LF. ==f ={~Ti;1j• . . _`or Fe- --.ars -k, 3r, ;4C, rear --n, ~.C, ct'_?it, R: 2ts of r _ v _:..a ..v~ c_r±al 9 t' e t _zl y ~.t e. = e L•: ° ,.. g-.. _ -_69. ?.C, E• -i.c -_- , :k 3L, ..::~=.t, J: S. iss --- - -ng --"- ~--2C a----~-• =i ;r -.'.ar,`_ron, E: ZC c-,ach to the d:.- is of b';e `.1• _- •.._ r i,, 1:23, iy72 ' ~L, 31s. _ PC, and S!•ar.1-ca, E: L tic =ctisity ;n ar t_ aez_di-1 i.:f, . J. CI`n. :sth. 57:3:9, 1972. G7 :_. etr; `_, ,.iosy 39:213, 19-2. .alt, J, Scara:.`3rst, R: A CJ ;' _>:n Jf a..., t ~~1 _S for }ie,-3tltls. ='.^Se, :972. rr .~_ i^-_r ~C ,'_s-- t, N: cl ? r3 f_ st`°. tctaI ca-'_ - J. - :569, 1973. ~ _ick, RL: eriiSr'_:ol sis in eirr.`.osis -~. J. Gast_:,e-.,aro_osy 50:_50, i9-3. 95-077 0-82-20

299 CG ;11',.?f 6IT.- ?RICA?E P;..CTICE CQon*.): San ,'_a-.ain ia \,~:e-ber 1977 to -ire_ent. FATE.`:TS P=OC_wD: A. B. A *Set~ od `or t:`.e ; -e Scsle A :.et':od for the L-ge y- aie igh Pot -=y FactorV[II ' .- C. A:'e*_`.-~d for .' e rge ccale --sctic;:'t--n .. : . .t___=`_:z _ :3 . .. . . , LF. r;'31--.>7P;\S: Co-S'i':r for Sea -'.zrs _a 2ick, :lt, Giolli, ;iC, R: . . e f r e c t s o f _ - - Y - . . a . . . - - ~ -d tie .l sl of = ..:eLr.:.s- ..^s .ats. 3i,.•k, RL = .-P, RC, •.,.eh_}n E: 1 -'. . t5 C i _.ltia ~ . 1970. 'ick, RL, J: c!, RT ron, E: A ., .:c to t`e d'._, :-s .,t 9:23,1972 :'ed:~CO~'tteTJ r Ezc~; BL, 3`sti•,p, aC, and i. Fi'?r: oI}tic acti•:ity ;n ac:t: .r. J. CI`1. ~..th. 57:3E9, 1972. -_ck, :ZL, '',=-;scn, C,_ etrics-G;-.c- 3y 39:213, 19=2. ?ick, PL, :. .alt, J, S,hza: orst, -a: - atralia ..,r._sei: A coz.;sri_:n ot =._. at high r:sk •`^.r he-=-titis. 1.,. J. C L'n. .^_be, :9-2. . :tc, iL, l^.r, i[ _,_t -<r, N: J.'Csr___ as. ?--,rg. _ :SE9, 1973. Pises, P, ?ick, RL: HyparfiSrirol>sis in cirr.`,asis am. J• Gaetr:,e:.tsro'_o;y 50:=00, :y 3. 95-077 0-82-20

300 YIT1.c: r':3LIC.TiC':S ^t.): B' ct RL 3is`op ?C Tse, D, -. _..broa, E: F:ctor V: A sspiifiel o:je staae --say :.si-g ;_. -.__-_c -:,1, 3.itr. 2. Path. 15?:511, I:'3 Sick, RL, =.da^s, T, Goi.";:ert, LS: A PreV1oUS L.-Y. Cr0't:-d C'33U1atiCn "liyies-StcCen s~T.droire. . . Ci-.n. 7,es. 21:264, 1973 Si.k, RL, Sc..-alhorst, WA: az zbo:ytic *_.`:erapy :ai.h = _.a _.. t_ .-..,_, t Va=c. Surg. 8:152, 1974'. 4L: Sick , -:d t_ca..ernt .7ad. C^'.~;:te_po_nt 6::8, 19+4. 3i ck, T: 3i. ?cc4 ±L, . . _~, T, a-.i , __tk, K: S.::gi.-1 _ 'ostasis . th a J.A.?L A. 2:9:153, 1974. Bi •k n s T LS: :e : ..shcs-Sto': ea i-itr. ._t4. 3d. 153:.:0, :9'4 Blck, ;L: Fi' ri^oiytic ~=-tia1 in ._ra :'~. ...th. 3d. lii:-07, 1974 Sick, RLN, '.4, C:.:°ord, ?late_rt f:-,.ti.n _ iitSes in `s. Circ'ji.,.__n =3. •,k 17 t c., ,.st 77 in -.r:rx ~.+c_r.-..te: use in s of c.`. ic :;;er '.ise=_se. Am. J. D:;?s. Z0:'=1, 1975 .-_t RL, C-:w..:d, L. : .-.-_n, , _.-s, T, Sick, RL, 5:` __? rst, h'R, L: 3L:_.a a=sri-s:ad r.tr -ascui:r c_ _on T.saf' si_•n, 16:561,- 19'6 301 C_aRICU'_:^a VITAE: ^;;9LIC:TICYS (cont.)• Bick, RL, Adams, T, Schmalhorst, WR: Bleeding times, platelet adhesion, and aspirin Am. J. Clin. Pathol. 65:69, 1976. Bick, RL: Alterations of hemostasis associated with card Thronb. Res. 8:285, 1976. Bick, RL: - Adriamycin and fibrinolysis. Thromb. Res. 8:467, 1976. ~' Bick, RL, Fekete, L. Murano, G, Wilson, NL: Duano"tycin and fibrinolysis. Throc.b. Res. 9:201, 1976. , - Bick, RL, Fekete, L,.Kot'acs, I: A new two-stage functional assay for antithroml clinical and laboratory evaluation. Thromb. Res. 8:745, 1976. Wilson, WL, Andrews, NC, Frelick. RW, Nealon, 1 Preli^inary re_ort on the use of CC?.U (\SC-790: Hexamethvlmelamine. (,tiGf.-]~R75) in careino^;a_of Cancer Treat. Rept. 60:269, 1976. Fe;ete, LF, Bick, RL: Laboratory modalities for assessing hemostasis Semi&ars in Thromb. and Hemostasis 3:83, 1976. Bick, RL, Dukes, ML, Wilson, WL, and Fekete, LF Antithrombin III as a diagnostic aid in dissemi Thromb. Res. 10:721, 1977. Bick, RL: Complement levels in disseminated intravascular Am. J. Clin. Path. 68:93, 1977. Bick, RL: Alterations of hemostasis associated with malig diagnosis and management. Sem. Thronib. and Hemostasis, 5:1, 1978. -5- -4-

301 C,?.HICu'!J!( 'dIT.;E: L. 3'.CK, `d, D. PtiBLIUTIC`S (ccnt.): Bick, RL, Adams, T, Schmalhorst, WR: Bleeding times, platelet adhesion, and aspirin. Am. J. Clin. Pathol. 65:69, 1976. Bick, RL: Alterations of hemostasis associated with cardiopulmonary by"2ass. Thromb. Res. 8:285, 1976. Bick, RL: Adriamycin and fibrinolysis. Thremb. Res. 8:467, 1976. Bick, RL, Fekete, L. Murano, G, Wilson, WL: Duanomycin and fibrinolysis. T.:romb. Res. 9:201, 1976. Bick, RL, Fekete, L,.Kovacs, I: A new two-stage functional assay for antithrombin III (heparin-cofazter) clinical and laboratory evaluation. Thromb. Res. 6:745, 1976. Wilson, WL, Andrews, NC, Frelick: RW, Nealon, TF, Bick, RL, :dams, T: PreliTinary -eport on the use of CCAU (NSC-79037), Adrianycin (NSC-123127), and Hexamethylmelamine (NAC-13R75) in r,arrinoma of the lung. Cancer Treat. Rept. 60:269, 1976. Fekete, LF, Bick, RL: Laboratory modalities for assessing hemostasis during cardiopul^cnary bypass. Semiaars in Thromb. and Hemostasis 3:83, 1976. Bick, RL, Dukes, ML, Wilson, WL, and Fekete, LF: Antithrombin III as a diagnostic aid in disseminated intravascular coagulation. Thromb. Res. 10:721, 1977. Bick, RL: Complement levels in disseminated intravascular coagulation. Am. J. Clin. Path. 68:93, 1977. Bick, RL: Alterations of hemostasis associated with malignancy: etiology, pathophysiology, diagnosis and management. Sem. Thromb. and Hemostasis, 5:1, 1978. -5-

302 CURRICULUM VITAE: RODGER L. BICF:, ?I.D. PUBLICATIONS (cont.): Bick, RL: Antithrombin III: diagnostic and therapeutic implications. Presented at the Annual Blood Coagulation Symposium (•lanual), J. Penner, (Ed.) Ann Arbor, Michigan, 1978. Bick, RL: Disseminated intravascular coagulation and related s,,ndroaes: etiology, patho- physiology, diagnosis and management. Am. J. Hematol. Vol. 5, 03, 265, 1978. Bick, RL:' Vascular disorders associated with thrombohemorrhagic phenomena. Sem. in Thrombosis and Hemostasis, Vol. V, No. 3, 167, 1979. Nalbandian, RM, Henry, RL, and Bick, RL: Thrombotic thrombocytopenic purpura: An extended editorial. Sem. in Thrombosis and Hemostasis, Vol. V. \o. 4, 216, 1979. Bick, RL, Fekete, LF: Cardiopulmonary bypass hemorrhage: aggrevation by pre-op ingestion of anti- platelet agents. Vascular Surgery, Vol. 13, No. 4, p. 277, July-August, 1979. Bick, RL: Monitoring heparin therapy. Diagnostic Dialog, Vol. I, \o. 4, August, 1979. Bick, RL, Marcum, JD: vo., Yalebrand's disease. Diagnostic Dialog, Vol. 1, No. 5, November 1979. Bick, RL: Monitoring heparin therapy. Kern County Medical Societ,v, The Bulletin, Vol. XXVI, No. 12, 1979. Bick, RL: In vivo platelet inhibition by piracetam. Lancet, Vol. II, p. 752, 1979. Bick, RL, Bick, MD, and Fekete, LF: Antithrombin III (AT-III) patterns in disseminated intravascular coagulation. Am. J. Clin. Path. 73:577, 1980. -6- 3( PUBL?CATIC]S (cont.) Bick, RL: Malignancy's Effect on Hemostasis: Complex Diag. Dialog, July 21, 1980, Vol. 2, No. S. Bick, RL: Malignancy's Effect on Hemostasis: Part II Diag. Dialog. September 8, 198A, Vol. 2, No Bick, RL: Dissemir.ated Intravascular Coagulation: A C: Annals of the New York Academy of Sciences, Henostasis. Bick, RL: Hereditary Hemorrhagic Telangiectasia and D: A `:e» Clinical Syndrome Annals of the New York Academy of Sciences, 4emostasis. Bick, RL: Disseminated Intravascular Coagulation (DIC; Diagnosis Practical Cardiolugy, 7:145, 1981. Bick, RL: Disse^:inated Intravascular Coagulation (DIC' stanifestations of Related Syndromes. Practical Cardiology, 7:152, 1981. Bick, RL: Clinical Significance of Fibrino(geno)lytic Lab-Lore, 9:683, 1981. Bick, R.L. Hereditary Hemorrhagic Telarigiectasia and Di A New Clinical Syndrome. Vasc. Surg. 15:394, 1981.