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e+-Rr'~r~r~r~r~°'e~~~~a,r~- ....~-. T}Il. CC)Y'-NCIL FoR ThBR- H KW 2 '':D:)1) 3 2 GRANT APPLICATION NO. 1054R1 rfEh:oRAr'DtJM September 14, 1976 ` r . /~ ~~ ' ~ 51~1~`s ~fTO iL• Y 3® T0: The project comrnittee comprising Drs. Bing, Jacobson and Sommers SU3JEECT: Herbert McKennis, Jr., Ph.D., Medical College of Virginia, Richmond, Va. First renewal application Na. 1054R1 "Studies aimed at development of immuno-assays for nicotine and nicotine-ttetabolites" qISTORY C7R grants for study of Enwr,~atic Transformations of Nicotine and Related Cecroounds at the NedicalT C~ ollege of Virginia began in 1956 with an appropriatior, of $29,080 to Drs. Larsorr, naag and h:ci:ennis followed by tYro renewals in the following years. Then, with I•:cKer.nis as Principal Investigator, ten more annual grants were made for continuing the work t:.rough 1r,-h6. During this period, vhicn began in a practically virgin field, a great deal of progress was made in describing the pattnmrays of nicotine metabolisn and in isolating, ide: tif;,ling, and characterizing the intermediates. This gronp became the acknokledgeu world authority on nico tine metabolisr:. Fra;. 1964- into 1972, the enterprise received supplementary, and then full support (under several titles) froa the American Medical Association's Educational and Research Foundation. C.T.R. grants were suspPnded. t3hen the Al1%;r."2F was terminated, C.T.R. made a grant of $60,000 to Afc3tennis (#'?68) for study of the BioloFical Activ.ity of Tobacco Smoke Co::ponents and Al.:ied S.ubstances. (October l, 1972 By this time, the Board and Stc.ff of C.T.R. felt that further elaboration of the netabolic orocesses should be deferred in favor of increased efforts to apply the accinulated information to specific problems of practical importance. An application for renekal of Grant T4r' 868 was therefore denied, though supplements were made for phase-out and terr.iination. Fbctensive conversations were held with Dr. McKennis in an effort to interest him and his teau: in a rather drastic change of directior.. A new application (r970, January 1, 1974) for study of the Pharmacodvnamics of Cotinine came closer to the mark but was denied as still non-comnetive in terms of C.T.R. needs at the time. Another, #1029, submitted as of 2r,ay 1, 1975 met the same fate. Meanwhile, Dr. AfcKennis had held his experienced staff together by extremely economical use of residual funds frau the A.bi.A.E.R.F. grant that extended to about b,ay 1974, in addition to the CTR grants. THE CU'n.RE?':T F^i,OJECT ;:1054 At this point it beca.+fte oaite apparent that Dr. Castro's project for producinr a raflioir-muno assay for nicotine could benefit by the assistance

•. ~~ C7 V C V al a V V Grar.t Application No. ,1054R1 3. REMOUAL i,PPi.ICATIOW Dr. t.cKe:Lnis has submitted such a proposal which is attached. It suggests a twelve month oudget of $67,870,which is very close to the n:or.t:Lly rate at which he actually spent the $45,000 appropriated for this year. (This budget is subject to scrutiny.) ~ IG'.ZT IC.1h"E There has been a feeling anong the staff and se-,reral Board members, I believe, that high;,snecific and sensitive i.=uno assays for nicotine and its met2boli tes, requiring only small quantities of blood serum and speedy as vell as sic~ele in application, could open a new era in "biochemical pharmacoldGy" mf nicotine. Labelled antibodies applicable to loca`„inr binding sites in tissues could greatly aug^aent the potentials of such agents. A long list of "practical" questions that might be solved by use of such agents has accunulate3. If we noi; have a first-class tea:m available for cooberation on the two paases of the rese2xcn, a co:,tinuation of support for ooth pzases seems justified. P.S. The "^r`_~:iciai" sig'7ed copy of the aDDlicatlon wll'Je fo'_"thcC•.'.i:]"Ca mo-aen ta;i1; `r. !:c"r.e~.ris is also su_-ppj;.zng coti nin? .:-oxifie and nicotine _;-okide for other nrojects.