Tobacco Documents Online

Tjir•. Cou.NCIr. FoR ToB ~ September 14, 1976 H K51 0 1 7 0 0 5 & 0 P GRANT APPLICATION NO. 105kR1 MEMORAPIDM TO: The project committee comprising Drs. Bing, Jacobson and Somrners SIIDJECT: Herbert McKennis, Jr., Ph.D., Medical College of Virginia, Richmond, Va. First renewal application No. 1054R1 "Studies aimed at developnent of immuno-assays for nicotine and nicotine-nietabolites " HISTDRY CTR grants for study of Enzymatic Transformatio.n: bf hicotine and Related Compounds at the Medical College of Virginia began in 195 with an appropriation of $29,080 to Drs. Larson, Haag and ricKennis followed by two renewals in the following years. Then, with MKennis as Principal Investigator, ten more annual grants were made for continuing the work through 1968. During this period, which began in a practically virgin field, a great deal of progress was made in describing the pathways of n I icotine metabolism and in isolating, identif3~i~,g, and characterizing tne intermediates. This grbup became the acknoHleflged world authority on nicotine metabolism. • From 196Z: into 1G72, the enterprise received supplementary, and then full support (unded- several titles) from the American Afe3ical Association's Educational and Research Foundation. C.T.R. grants were suspended. When the Ah'lAERF was terminated, C.T.R. made a grant of $60,000 to McKennis (#868) for study of the Biological Activity of Tobacco Smoke Comuonents and Allied Substances. (October 1, 1a72 By this time, the Board and Staff of C.T.R. felt that further elaboration of the metabolic mrocesses should be deferred in favor of increased efforts to apply the accumulated information to specific problems of practical importa.nce. An application for renewa]l of Grant # 868 was therefore denied, though supplements were made for phase-out and termination. bctensive conversations were held with Dr. McKennis in an effort to interest him and his team in a rather drastic c hange pf direction. A new application Qr970, January 1, 1974) for study of the Pharmacodvnamics of Cotinine came closer to the mark but was denied as still non-co:npetive in terms of C.T.R, needs at the time. Another, ri1029, submitted as of May 1, 1975 met the same fate. Meanwhile, Dr. McKennis had held his experienced staff together by eoxtxemely economical use of residual funds from the A.r1.A.E.R.F. grant that extended to about May 1974, in addition to the CTB grants. THE CURREI;T PROJECT #1054 At this point it becaune quite apparent that Dr. Castro's project for producing a radioiamuno assay for nicotine could benefit oy the assistance

Grant Application No. 1054R1 3. RENEtdAL APPLICATION HKO1017 u06 1 Dr. McKennis hhs submitted such a proposal which is attached. It suggests a twe4ve month budget of $67,870 which is very close to the monthly rate at which he actually spent the $45,000 appropriated for this year. (This budget is subject to scrutiny.) SIGIJ1F'ICAME There has been a feeling among the staff and several Board members, I believe, that h.ighl.specific and sensitive imauno assays for nicotine and its metabolites, irequirirdg oaly sma]l quantities bf blood serisn and speedy as well as simple in a~pl,ication, could open a new era in "biocher.iical pharmacology" of nicotine. Labelled antibodies applicable to locating binding sites in tissues could greatly augment the potentials of such agents. A long list of `practicaA" questions that might be solved by use of such agents has accumulated. If we now have a first-class team available for cooperation on the two ph3ses of the research, a continuation of support for both phases seems justified. , RCH/lp nncls. R.C.H. P.S. The "offici2l"•signed copy of the application wrill be forthcoming momentarily. Dr. I•?cKennis is also suppl.zng cotinine N-oxide and nicotine N-oxide for other projects.