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Renewed: 9/1/66 (6 ma. to 3/1/67) cr. #L34 Activated: 7/3/56 Renewed annua].I,y to 9/L/6i Date: August 4-, 1967 Geor•e 0. Ge M.D. Assoc. Prof. :`_3 ameof (mestigotor(s): (includeTUe ond Degrees) PRINCIPLE INVESTIGATOR: 6E g y~ ~ Asst. Prof. Surg. S Phys. Chem.; 2)Mary Reed, Ph.D., Res. Assoc.; 3)Roland Pattillo, M.D., Fellow S 4 C h r Armstron ne at e Emer. Surg. & Dir. Finney-Howell Can, Res. Lab. CO-INVESTIGATORS: 1)Chiun, T. Ling, Dt:D., Scd., i g urg., ) d antibody. Department of Surgery ••5)Darwin-Chee, Grad. Student '' The Johns Hopkins Medical-Institutions .6)Tom Depner, Med. Student eells,maylbe observed to grow and function with the elaboration after challenge of specific circumstances under which immunologically competent cells, such as lymphocytes and plasma (Ling f, Gey). One prime objective is the evaluation of the nutritional requirements and This J - For the 16-montfi period given in item 4 with two additional years required. & Brief Descripton.of Objecluves or5pecificAims: 1) Studies on nutrition and. environmental, factors affecting the growth of cells in culture request to June 30, 1968. 5. Anticipoted Durotion of this Specific Study: C-• OF FELLO{4SHIPS. 4. Propoted5tartinD-Date: March 1, 1967 (Period March 1-Aug. 31 previously committed). cell to virus (Chee f,, Gey). 4) Evaluation of cellular transformation in vitro--Role of tumor DNA (teznikoff & Gey). 5) Evaluation of HeLa cell antigens in a study of genetic exchange of information from host o , c arac erization o c orionic gona r p t ate, Address: Finney-Howe1L Cancer Research Laboratory Reznskoff, Ph•D. cands ., Baltimore, Maryland 21205 yr. IV, Res. Assoc. 3. ShortTideofBrojed: CONTINUATION OF STIIDLES ON CHARACTERISTICS OF NORMAL CELL. GROhTH IN RELATION TO INVASIVE CARCINOMA, EMBRYONAL TO ADULT FORMS. SUPPORT Isolation and studies of normal and malignant Iung cells--cytology, karyology, low temper- ature storage properties, mucous secretion and surfactant production (Reed & Gey). ) Factors contributing to functional growth of malignant trophoblast. Che>aical and biological t o i derived in vitro (Pattillo f Ge ) f h d h 6) Search for immunoglobulinS.in cultured lymphoblasts of the MBILI (deBruyn-Gey) line (Depner & Gey). , on known histogenic cell types. 17 We have already created a number of in vitro cell isolates in attempts to evaluate in vivo cell systems especially in a study of neoplastic processes. Cells "in culture C.i•Dermit fund'amental studies of growth, differentiation and mallignant transformation. tsikich- can also be learned of the functional capacity of normal, and maLignant cells and. may, indeed, provide the best systems for the evaluation. of a vari-ety of specific stresses 7. Give a Brief Statement of your. Working Hypothesis: .r domm `-

A. Physical Facilfies Available (Where Other 1hanAdministering Organization Indicate Geographical Location) ~. Biographical sketches of all principal and professional personnel (append). SEE ATTACHED:SNEETS'. 12. list of publications: (Fi've most recent as pertinent) (append) SEE ATTACHED SHEET. cy- 0 ~WR V~I y~I W =

R: REDACTED MATERIAL A. Sa(aries (Penonnel by names) Professional '7,George 0. Gey, M.D., Assoc. Prof. Emer'. Surg. i::',`,thiun T. Ling, M.D., Sc.D., Nut_i. Biochem. F, Asst. t.:"Surg. (also Asst. Prof. Physiol•. Chem.) I•; Mary V. Reed, Ph.D., Research Associate : ;;: _ . . . . . , - •niml " • I,;.Hedda Linden, Ti~ssue Culture Tech. `.hfary Jo Koryto, Secretary " "'Charles Lane, Laboratory Assastant Ph A t l Pf if L b F Mi h oratory. . ae e er, a otog. ss ~ c r _ Franklyn Greene, Laboratory Asst. E. Consumablo Supplies Qist bycotegories). ': j `'sGlassware "Chemicals (including photographic) .Biologicals (serum, extracts and procurement) •Cost of animals and care. . 'Photographic film, plates and prints SubJotot" -- C. Other Expenses (itemize) Prof. 100%' 50% 100 : 100 :' Sub1QoQa9 (6k): Welfare Benefits 2,b12.T8 $764.00 600.00 600.00 300.00 40000 . Sub Tota! $7i2;615.12 .S2 0,( 6.10, Contingency Cephone Rental avel D.,Permanent Equipment (t.mize) ~ This amount to cover part of $3,332.00 purchase of Technicon.Sequential Amino Acid Analyzer ($12,340.00). Balance from American. Cancer Society and other sources E. Orerhead (l5'/0 of A+B+C) Estimated Future Requirementf: Salaries Consumable Suppl. Other Expenses Totall Permanent Equip. 7,182.'f8 $58,L00.00 i wu kcat-' 19 G}I ~~ /', - ,_Overhea Total d Year2 _We hope to.stress pathogenesis of early tumors such as choriocarcinoma (3 mo.(?) Year3 ;,induction period) in comparative normal versus carcinoma cell siudies. More travel expe ses needed to retrieve specimens. Total cost pre~t basis. It is undentood that the applicant and institutional offiten In apphling for a grant have reod and found acceptable the Councif's "Statement of,Policy Containing Conditions and Terms Under Which Project Grants Are Made: " similar to "1~..~. Signature ~ r / r' ~ Sig:iatu.e_ .rue... arr... et t,. ie,rsw .n h T l ep one e Telephone

Ust f•mancial support for r.s.arch from all sourea, Ineludinp own Institution, for this and/or r.lated research aroiects. I -------- --- - "Evaluating Factors Contributinr; to Nornal and Malignant Cell Growth" •F-273-1 t, ! Personnel support in collaborative studies with Dr. Milton Edgertonts group on systemotio wave leng-th dependent laser studies Sourc. Ameriean Cancer Society ,, Amount I Duration 7/1/67 - 6/3o/Eg ' 4 years , .

I'ACI LI'f ICS AVaI LIIBLE Tiie F_innev-(-fht:ell Cancer Research Laboratory of the•Department of Surgery has its fa:cilities established in the Johns 1,Ibp3cins 1?bspital. Its facilities include: -. (a) An integrated and cor~plete tissue culture laboratory including, cubicles ' accommodating our regular group and pre and post-doctu2a,l cancer trainees; also, diusti.lled water autoclave, refrigerator centrifuges, low-temperature refri.€erai:ors, speci:ad incubators and speciall ob:,crtiation booths for tissue cu].ture studf•. (b) A Cryo',ii.ology storage faci Pity includina nit.rogern refrigerators and pxogr.am!;tinb eCl;uipIlent. (c) A biochemical laboratory for cell nutriltion studies and other cheriical studies on che~:iicali1y-clefined media, serum proteins, and tissie-c culture products. (d) A motion picture laboratory including: 1) A shock-prcof time lapse motion pi.cturey asscn:blj• and a special ti.me lapse data• recording microscope ('Rei,mcr and Gcy) fone cell pc,•nula~tion stud7.es. .. _. ~ 2) A 35 mm. antomatic fil:m: processor. - 3) Dark 'rocm f-aci.].ities. (e) Electr•on microscope laboratory (Siemens-1bl•a].si.e unit) con~pl.etc with dark rooms and thin sectioning equipment. - (f) Adequate animal housing quarters. (g) Adequate animal cperating rooms.• - Some of our hrojects ane carriedi out in collaboration r:ith others as ~ indicated iii the statement regarding interdepartmental, collFboration. Of W -. particular importance are the- opportunities for collaboration with the Department of PalWobiology (Dr. F. B. Bang) on viruses, the Department of f~ Gynecology and Obstetrics in cooperati~on with Dr. 1-lug5 Davis and: others on ~ studies on the developmentt of invasive carcinoma o.f the ccr.•ix. Of speciall ~ importance is our access to operative specimens from tlaiis. and reany other ~ hospitals and, the excellent esprit de corps here:and in many. remote places• i•n• the i•:orUd allor:ing, rare specimens to be obtained by our f oa•:'.rer fel lows or other frienchs.. The frec{:u^nt nccd for choriocarcinoma and' other raire specir-men-, requires that the facilities of others be availahle ar.d in aKldition. to the T=issuc; i'rocuTei^ent D'ivisions'of the \.C..I. which are aTso: bei,ig u_.ed. Ourr personnel and speciai facilities have aJ.vayss bcen at-a:ilable. to othe-s in thiss and other institutic-.is for conferences and especially for their benefit in allor:'ing pPOCUremerat of coatinuous culltures of nuuny different cell types.

R: REDACTED MATERIAL Present Address: Finney-Howell Cancer Research Laboratory., 13th Floorj RU #1 -'. ' SCIENTIr"IC ArJI} xC1iDE`tIC POSITIONS : 1921 - Carnegie Research Assistant, Cold Springs Harbor,, L.I., N.Y.. 1921-22 - Instructor in Zoology, University of Pittsburgh. 1922-23: - Guest Research Student, Dept. of E,-nbryoloey, Carnegie Inst., - Baltir.,ore j }id.. 1923-29 - Cancer Research Fellorr, Colunbia--.Hospital, !1ilrraukee, ~ffisc.. 1929-33 - Director, Tissue Culture Laboratorg, Dept, ol" Suro ery, and Student Assistant in Sur;ertr, Johns Hopkins ',-edical School. 1929-39'-- Guest Research Associate, Dept. of Embryology, Carnegie Inst, of Washington, Balt:Lmore, "d.. 1933-38 - Assistant in Surgery.. Johns Hopkins ?-tedical School. 1933-36 - Surgeon (R), U.S.P,H~.S., National Cancer Institute. Director, Cancer Research - CorOperative.Studies, i7.S.P.N•.S, and Johns Hopkins Medical School, Baltimore, ?1d.. 1940-41 - Finney-Hov+ell Cancer Research FeTlow, 1941-45 - Comr.iander, Emergency ;ledical Services, Office of Civilian• Defense, Eastern. District, Baltimore, Md.. 193$-46 - Instructor in Surgery, Johns Hopkins Medical School. 1940-Ct6 - Assistant. Director, Division of Ce11.Physiol:ogy j Dept. of Surgery, Johns Hopkins Medical Schbol. y- 194•7- - - Assistant Professor of Surgery, Johns Hopkins -tedical School. 190- - - Director, vinney-Ho•rr.ell Cancer Rescarch Laboratory, DepartrLent of Sur~ery, The Johns• Hopkins 'redieGl School and Hospital. -195h, - Lectr. Pathobiolo p~/-, School of xiygiene and Public Health, The Johns I3opkins "edical School. 100354656'7 ~ 1958 - Associate Prof. Surg. The Johns Hopkins Medical School , . 1966 - Associate Prof. Surg. (Emeritus): Active Duty, The Johns Hopkins bledical School.

George 0. (with Lewis, IT.H. ): Clasnoatocytes and Tumor Cells in Cultures of ;; 0 Mouse Sarcoma, Bull. Johns Hoj~lcins Hosp, p L:369, 1923. . and Thalhimer, W. 1924, Observations on the Effects of Insulin Introduced into the Medium of Tissue Cultures, . J.A,?1,A. ~, 82':1609. with Cron, R.S. 1927. The Viability of t'ne Cast.-Off Menstrual Endometrium: Am, J, Obs, & Gyn. 13:61i5. Studies on the Cultivation of Human Tissue Outside.ttie Body. 1929'. - bifZsconsln J. J, 28:11. An Improved Technic for Massive Tissue Cultures, 1933. Am. J. Cancer 17:752. with Stone, H.E.,~and O:vingsy J.C.__ 1933. LLiving Grafts of Endo- crine Glands, CaZifornia and'%Jestern t:tedicine~ 38: No, 6; 39: Nos. 1 and 2, June, July and AuJust, 1933. r ~ Glands, Am. Jour. Surgery, rTejv Series, 21 :1934. wtith. Stone., H.R., and O:vings:, J.C., Living Grafts of Eiadocrine with, Stone, H,B..* and 0•ringsj J.C. -1931x. Transplantation of Living, Grafts of Thyroid and:Parathyroid Glands. Annals of Surg. 262, with, Stone, H.B., and Owings, J,C. Feb. 1M, Living Grafts of Thyroid and Parathyroid!Glands~. Surg. Gyn. Obs.. ar.d,M,K, Gey. The Haintenance of Human Normal Cells and Human Tumor Cells in Continuous Culture. .1. Preliminary Report. Cultivation of i,iesoblastic Tumors and Normal Tissue and; Notes on Methods. 'of Cult1vation,. Am. J. Cancer 27:45. May 1936. ° with Seegar., G.E., and Hellman, L.ri, The Production of a ~ Gonadotrophic Substance (Prolan,) by Placental Cells im Tissue Culture. Sci. 88:306 1938. ; 'Assembly, Memphis, Tenn. Feb, 16, 1938, with Stone, H.B'., and Gtivirigs, J.C, 1938. Further Reports on Grafting of Endocrine. Glands, AFiis-South. Post.-Graduate Medical and• Bana,, F.B,. Eacperimental Studies on the Culttvcal Behavior and the Infectiv'ity, of Lymphopathia. Venerea. Virus 11taintained i,n Tissue Culture, Bull. Johns Hopkins Hosp., 45: No.s$ Nov. 1939, with Gemmill, C.L., and' Austrian, a. The ;.:etabolism of Tissue Cultures of Walker Rat Sarcoma! 319~ Bull, Johns Hopkins Hosp., 66: 167-18l1., 191'10. - - _ ~ 1003546668

PUBLTC~;r:TIONS (CONTtD) Gey, George 0.s Cytological and Cultural Observatioras'on Transplantable Rat Sarco- -tained in Continuous Culture: Cancer Research, 1:737, 1941. mata Produced by the Innoculation of Altered Normal Cells 1'.'ain- Hopl:ins Hosp. 72:26. by Placental Cells 1-4aintained in Continuous C1z7.ture: Bull. Johns."; with Seager Jones t G.E~, and Gey, M.K. 1943. Hormone Production. and F3.ror,. i~~:: ~. 191t5. Observations on the Conversion of Nbrmal Into Malignant Cells. 'Annals of Sur.= 121. Yiith Gey., M.K., Inui, F. and Ved•der, H. 1944. Penicillin Action, on Strains of Normal and Cancer Cells. A,A.A.S'. Res. Conf. on Cancer, 321. _ Gey,. M.?C., Inuii, -=F.,, and Vedder, H. The: Effects of Crude and Purified Penicillin on Continuous Cultures of Normal and ?11alignant cells. Bull. Johns Hopkins Hosp. 77:116-131•, 19450 with Firor, Phase Contrast ?ficroscop,y of Living Cells. Annals - •of Sur., 125:604. _ Hanks, J.H., and Barrett, Rachel. 1948. Retardation of Growth ~ and Ttetabolism of Normal and Malignant Cells During Continuous Cultivation. . Gcowth 12:69D with Bang, F.B. 1948. A Fibrillar Structure in Rat Fibroblasts as seen by Electron iTicroscopy. Proc. Soc. Exptl. Biol. '!ed;. .• 69:86. with Bang, F.B. 1949. Electron 1licroscopy of Tissue Cultures Infected tirith t~ze Virus of Eastern Equine Encephalomyelitis. Proc. Soc. Expt1.. Biol. ,'•fed. 71:78. Gey., ?a.K., Firor, and~ Selif, V%0. 1949. Cultural and Cytologic Studies on Autologous Normal and Malignant Cells of Specific in vitro•Origin. A,cta. Un. Int. Con. •Cancrum. 6:706. and;Bang, F.B. 19,5•1. Viruses and Cells. A Study in Tissue :._ C!Lilture Applications. I. Cells Involved-Availability and Sus- ceptibility. Trans. N.Y. Acad. Sci. 14:15. with Bang, F.B. 1951. Viruses and Cells. A Study in Tissue Culture Applications. II. Effect of Several Viruses on Cell TSrpes and the 1'.mount of Virus Produced. Trans. N.Y. Acad. Sci. 13 :324. • with Bang., F.B, and Levy, E. 1951. Some Observations on Host- ' Cell Virus Relationships in: Forl Pox. I. Gr~ o:vth~ in Tissue Culture, IT. The Inclusion Produced by•the Virius on the Chick Chorio- P;llantoic 1•2embrane. J. Im.•mzm. 66; 329. 10U3S46r69

' PIMLIGATIoM (coNrM) C2yt George 0,., with Bangs F,B, ~'1952. Comparative Susceptibility of Cultured Cell Strains to the Virus of Eastern Equine Encephalomye]:itis, Bull. Johns Honkins Hosp, 91:427. Cancer Inst, 13:1099. 1952. Proceedings of the Research:Sessi,on on Endocrinologic Aspects of Aging, Edited by V, Korenchevsky. J. Gerontology°, 7, 1953.' Discussion in "Problems of Lging" edited by Nathan'•V•. Siiocks from 15th ?facy Conference, with Ehrmann, R.L. 1953. The Use of Coll Colonies on Glass for Evaluating Nutrition and Growth in Roller-Tube Cultures. J. Natl, with Shooter~ R.A. 1952. Studies on the ,iineral Requirements of Mammalian Cells, Brit, J. aptl. Path,. 33;:98. with Glinosj Andre D.* 1952. HiLmoral Factors. Involved in the Induction of Liver Regeneration in'the Rat. Proc. Soc, Exptl. Biol, Med. 80:421. with Scherer, '7.F., and Syvflrton? J.T. 1953. Studies on the Propagation in vitro of Poliomyelitis Viruses. IV. Viral 'Mu1ti- plication-in a Stable Strain of Human Malignant Epithelial Cells (strain hela):derived from an Epidermoid;Carcinoma of the Cervix. J. E~cptl. Ked. 9'T: 695 « 1954-55, Some Aspects of the Constitution and,Behavior of Normal and ~ialignar,t Cells Maintained in Continuous Culture, The Harvey Lectures, Series L. Academic Press Inc,) N.Y. 154. . ngitated:, Fluid t4ediumy Ann,, N.Y. Acad. Sci. s58:1039-1055. Bangs F'.B., and Gey, 19.K. 1954. Responses of a Variety of Normal and Malignant Cells to Continuous Cultivat:.cn and Some Practical -. -Applications of these Responses to Problems in the Biology Disease. Ann. N.Y. l.cad. Sci. 58:976, with 0rzens., O.v.H.s and Geys M.K. 1954. Growth of Cells in Shaprass. P.,,,. and Boryskos E, 1954, Activities and Responses of Living Cells and their Components as Recorded by Cinephase f'licro- scopy and Electron Microscopy. Ann. N,Y. Acad, Sci:. 58s1089s M.K, 1954, An, Evaluation of'Some Compara- &3nga F.B., and Geys I tive Studies on, Cultured Strains of Normal and rfalignant Cells of Animals and ?.ian4 Texas Reports:. Biol, 'I'[ed. 12:805, 1003546670

PITBLICATIONS (CONTID) Gey, George 0., vaith I:o, 1%H:.Y., Bang, F.B: 'and Shapras a P. 1955. • Rous Sarcoma Z`issue Cultures. "Bul.l. Johns Hopkins I•Iosp. 97:227. genic Effect of the Rous Sarcoma Virus ontChickeniFibroblasts in, Virus Infections in the Chick Enbryo I and II and The Cytiopatho-» .: ti .,... Shapras, P.3 Bang, F.B. and Gey, .1955, Some Relations of Inclusion. Drc-olets (tiinocvtosis-»Levis) and Hitochondrial Behavior :in, Normal and malignant Cel1s. Symposium on Fine Structure of ::_.~gf6j9;;. Ce11s E P Noordhoff Ltd Gron inger~ 38 with- R. L. Ehrmann, 1956. The Grotixth of Cells on a Transparen:t Gel of Reconstituted Rat Taih Collagen, J. IJatl. Cancer Inst. 16:1375. .. Discussion, tissue Culture in the Study of Animal and Human Ttimors. 1957. 19:78lt--785y d. Nat. Cancer Inst. •. Factors Influencing Proliferation of Viruses in Normal and Malignant Cells. 1957. Texas Reports. No. 3• 534r-539. C Nith F. B. Bang, 14. Ford and D. ?r.iranegan, 195•7. Chronic Infections Pr•oduced in Cultured Cell Strains by the Virus•of Eastern Equine Encephalomyelitis. Icad. Press Inc., Virolog,y, 4, No. 3. with H. N. Kent, 1960. Selective Uptake of Serum Globulins and Glycoproteins by'Cells Growing,in Vi,tro. Science, 131:666-68. with M. V. Reed, 1962. Cultivation of Normal and Malignant Human Lung Tissue. Lab. Investigations, 11:8, pp.. 638-52. Paper presented at the Tissue Culture Association Meeting, Washington, _ D.C., May. 31, 1962. ~ trated Corodice for Continuous Cell Culture (7 C's Solution). with J. K. Frost, 1962. Symposium: Cell Modulations, Maturation, and bleoplastic-Transformation,. Acta Cytologica., 6:399-402. : with,C. T. Ling and V. Richters. Chemically Characteri_zed•Concen- with• R. A. I4filcli and M. A. Naughton, 1965, Snbmit Patterns of Rapidly Proliferating Connective Tissues. Biochem. Biophys. Acta 1001:623-26. - C with D'f.. K. Gey, M. Svotelis, and H. Linden. A Motion Picture Sequence Illustrating the Production of Giant Cells from Hypo- diploid Rat Strains NSAT-14pH and -14pL. Presented at the 16th Annual Meeting of the Tissue Culture Association., May 31-June 3, 1965. 1oo3s4ss'~1 with C. T. Ling: The Role and Interaction of Trace Elements in Cell Nutrition. Presented at the 17th Annual Meeting of the Tissue Culture Association, May 31-June 3, 1966. with C. T. Ling. Further Studies on the Role and Interaction of TYace E1emeats in Cell Nutrition. Presented at the 18th Annual Meeting-of :.,ze'Tissue Culture Association, June 4-7, 1967.