Drug and fikohol Dependence, 23 (1989) 183 - 218 183 Elseiver Scientific Publishers Ireland Ltd. The Committee on Problems of Drug Dependence: A legacy of the National Academy of Sciences. A historical account Everette L. Maya and Arthur E. Jacobsonb “Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, VA 23298-0613 and bLaboratory of Medicinal Chemistry, National Institute of Diabetes, DigQShVQ and Kidney D~SQ~ZSQS, National Institutes of Health, Bethesdo, MD 20892 Il7.S.A.) (Received March 20th, 1989) The history of The Committee on Problems of Drug Dependence is traced from its beginning (1929) as The Committee on Drug Addiction to 1989, its sixtieth anniversary. A brief account of the etiology of The Committee from The Bureau of Social Hygiene, established in New York City by John D. Rockefeller, Jr. in 1913 is also given. Key words: physical dependence potential; abuse liability: narcotic analgesics and antagonists; agonist/antagonists; stimulants and depressants; animal and human testing; drug addiction and evaluation. Introduction tive Committee. It is hoped that the achieve- ments of the CPDD since its inception (1929) The purpose of this article is to review the will be well focused and that this history will history of the Committee on Problems of Drug give insights into contributions of CPDD to Dependence (CPDD). This history was solutions of drug-dependence problems. undertaken on the recommendation of CPDD, Although the principal source of material for acting on the suggestion of its Chairman, Dr. the period ending in 1971 was that of reference Mary Jeanne Kreek, in order to summarize and 1, CPDD minutes, reports and proceedings then update the detailed history presented in were consulted frequently, especially after the volume ‘The National Research Council 1971. Involvement in the Opiate Problem (1928- 1971) by Nathan B. Eddy, published by The Beginnings - The Committee on Drug National Academy of Sciences [l]. Of particular Addiction concern and interest are the years that fol- lowed the termination of sponsorship by The The origin of the Committee on Problems of National Research Council in 1976 and the tran- Drug Dependence is traceable to the Bureau of sition years that culminated in the structuring Social Hygiene established m New York City in of an incorporated committee affiliated with 1913 by John D. Rockefeller, Jr., to promote several highly regarded scientific societies. The research in the general field of social hygiene authors have been closely associated with with especial emphasis on criminology. How- Committee activities since 1960 (E.L.M.) and ever, because of the increasing problem of 1974 (A.E.J.), principally as coordinators of the abuse of drugs*, particularly narcotics, and testing program for evaluating the physical dependence potential and abuse liability of *A special committee of investigation in 1919 arrived at a analgesics and other compounds, and as figure of 100 000 addicts (including cocaine abusers) in the members of the Board of Directors and Execu- United States. 0376-8716/89/)03.50 0 1989 Elsevier Scientific Publishers Ireland Ltd. Printed and Published in Ireland 184 pressure from the public and the medical pro- time to address the latter problem, perhaps fession, the Bureau was urged to get involved because the abuse of cocaine had waned consid- in the area of drug abuse. Consequently, the erably following the introduction of the Bureau of Social Hygiene established a ‘Com- (synthetic1 substitute, procaine. mittee on Drug Addiction’, whose notable The DMS under the Chairmanship of Dr. accomplishments have been previously set Ludwig Hektoen (pathologist), who succeeded forth in a scholarly treatise, ‘The National Dr. White as chairman of DMS on June 30, Research Council Involvement in the Opiate 1929, expanded the membership of the ‘Tempo- Problem’, authored by Nathan B. Eddy and rary Advisory Committee on Drug Addiction’, published by the National Academy of Sciences to include the following: Chairman, William [ll. Charles White, Consultant Pathologist, In 1928, the newly appointed Director of the National Institute of Health and Chairman, Bureau of Social Hygiene, Lawrence B. Dun- Committee on Medical Research, National ham, reassessed the Bureau’s involvement in Tuberculosis Association; Charles W. Edwards, the drug-addiction problem and proposed to the Professor of Materia Medica and Therapeutics, National Research Council, National Academy Chairman, Department of Pharmacology, the of Sciences (NRC, NAS) that this body accept University of Michigan; Ludwig Hektoen, Path- funds from the Bureau for the support of a ologist, Director, John McCormick Institute of scientific investigation of narcotic drugs to be Infectious Diseases; Claude S. Hudson, Chief, carried out under the auspices of the Division of Division of Chemistry, National Institute of Medical Sciences (DMS). Health; Reid Hunt, Professor of Pharmacology, Accordingly, Dr. Charles White, then Chair- Harvard Medical School; Frederick B. LaForge, man of DMS, with the aid and advice of four Senior Chemist, Bureau of Entomology and eminent members of the NRC, Drs. Claude Plant Quarantine, U.S. Department of Agricul- Hudson and F.B. Laforge (chemistry) and Drs. ture; Torald Sollman, Dean, School of Medicine Reid Hunt and Carl Voegtlin (pharmacology) and Professor of Pharmacology, Western laid the groundwork for the formation of a new Reserve University; Walter L. Treadway, ‘Committee on Drug Addiction’ which first met Assistant Surgeon General, Division of Mental on January 12,1929 as a ‘Temporary Advisory Hygiene, U.S. Public Health Service; Carl Committee on Drug Addiction’. Dr. White was Voegtlin, Pharmacologist, Director, National Chairman ex officio. The discussions of this Cancer Institute, National Institute of Health; group centered on elaboration of a program Harry J. Anslinger, Commissioner, Bureau of which would include: (1) the analysis of the Narcotics, U.S. Treasury Department and chemical and biological literature of the addic- Lawrence Kolb, Assistant Surgeon General, tion alkaloids; (2) the formulation of rules and Division of Mental Hygiene, U.S. Public Health regulations for the legitimate use of alkaloids Service. having addiction properties and the education This committee served without change until of physicians and the public on the knowledge 1939. Its first meeting was held on November 3, of these rules by means of medical schools, 1929 with secretarial assistance from Mrs. Dor- scientific societies and drug-manufacturing othy Nicolson and Mrs. Mary Goodwyn, daugh- firms and (3) the replacement of all present use ters of Chairman White. of addicting alkaloids by substitutes having no addiction properties. The discussions brought Early Scientific Program (1929-1939) forth two subjects for research: (1) the relationship between morphine and codeine (in- Ultimately, the Committee decided upon a cluding possible dissociation of adverse and research plan that involved three components beneficial effects) and (2) the cocaine addiction - chemical, pharmacological, and clinical. The problem. Little, if anything, was done at that chemical effort, under the direction of Dr. Lyn- 185 don Small, a young, talented, Harvard-trained Pharmacology, Womens Medical College of alkaloid chemist (who had also studied in Ger- Philadelphia, joined the staff later while Drs. many for 2 years) was begun at the University Erwin E. Nelson and Ralph Smith of Dr. of Virginia in the autumn of 1929. Small, with Edmund’s departmental staff complemented his modest staff of pre- and post-doctoral stu- the efforts of Eddy’s group. Assistance was dents, was concerned principally with chemical also provided by several pre-doctoral and medi- modifications of the phenanthrene-type alkal- cal students. oids (morphine, codeine, thebaine and neopinel The clinical arm of The Committee’s pro- occurring in opium. A complementary program gram began to develop about 1934 under the on total synthesis of structures vaguely resem- direction of Clifton K. Himmelsbach, M.D., a bling morphine and congeners was directed by young commissioned officer of the Public Erich Mosettig, Ph.D., a young organic chemist Health Service from The University of Virginia ‘drafted’ by Small from Professor Ernst Medical School. Himmelsbach, who was Spaeth’s laboratory, University of Vienna, recruited by the aforementioned Dr. Treadway, Austria. Mosettig also had a small group of pre- had received research training on tolerance and and post-doctoral students, of which one of the physical dependence to morphine in rats at authors (E.L.M.) was privileged to be a small Western Reserve University under Dr. Tarold part from 1935 - 1939. Sollmann and later, at Michigan, with Eddy. Dr. Nearly a year later (June, 19301, when the Himmelsbach began his studies with prisoner need for pharmacological examination became addicts at the Penitentiary Annex of the Fort pressing, Nathan B. Eddy, M.D., Cornell Uni- Leavenworth, Kansas, Prison. This unit was versity, who had practiced medicine briefly but shortly thereafter transferred to Lexington, who, at the time, was teaching physiology and Kentucky. Members of the Himmelsbach pharmacology at the University of Alberta, research team included Drs. Edwin G. Wil- Edmonton, Canada was appointed to direct the liams, Howard L. Andrews (later to spend pharmacology program at the University of many productive years at NIHl, Fred W. Michigan in the laboratory of Dr. Charles