Drugs and Genes
Authors: ARNO G. MOTULSKY
Journal: Annals of Internal Medicine (1969)

Editorials1 June 1969Drugs and GenesARNO G. MOTULSKY, M.D., F.A.C.P.ARNO G. MOTULSKY, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-70-6-1269 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptEarly during this century Garrod (1) described various inborn errors of metabolism and as an extension of his studies suggested that unusual reactions to drugs might be caused by genetically determined aberrations in metabolic pathways. Garrod was far ahead of his time, and little attention was paid to his pioneering observations. Some 50 years later the British geneticist Haldane (2) made similar suggestions to explain untoward drug reactions. In the 1950's when several "idiosyncratic" drug reactions, such as primaquine-induced hemolytic anemias and suxamethonium-induced prolonged apnea, were clearly explained on the basis of genetically determined enzyme deficiencies the field of pharmacogenetics...References1. GARROD AE: The incidence of alkaptonuria—a study in chemical individuality. Lancet 2: 1616, 1902. CrossrefGoogle Scholar2. HALDANE JB: The Biochemistry of Genetics, Allen and Unwin, Ltd., London, 1954. Google Scholar3. MOTULSKY AG: Drug reactions, enzymes, and biochemical genetics. JAMA 165: 835, 1957. CrossrefMedlineGoogle Scholar4. VOGEL F: Moderne Probleme der Humangenetik, Ergebn. Inn. Med. Kinderheilk 12: 52, 1959. Google Scholar5. LA DUKALOW BNWR: Pharmacogenetics. Ann. NY Acad. Sci. 151: 691, 1968. Google Scholar6. HARRIS H: Enzyme variation in man—some general aspects, in Proceedings of the 3rd International Congress of Human Genetics, edited by CROW, J., NEEL, J. V., The Johns Hopkins Press, Baltimore, 1967, p. 207. Google Scholar7. EVANS DA: Genetic variation in the acetylation of isoniazid and other drugs. Ann. NY Acad. Sci. 151: 723, 1968. CrossrefMedlineGoogle Scholar8. EVANSDAVISONPRATT DAKRT: The influence of acetylator phenotype on the effects of treating depression with phenelzine. Clin. Pharmacol. Ther. 6: 430, 1965. CrossrefMedlineGoogle Scholar9. PERRYSAKAMOTOTAN HMAEM: Relationship of acetylating enzyme to hydralazine toxicity. J. Lab. Clin. Med. 70: 1020, 1967. Google Scholar10. VESELLPAGE ESJG: Genetic control of dicumarol levels in man. J. Clin. Invest. 47: 2657, 1968. CrossrefMedlineGoogle Scholar11. MOTULSKY AG: Pharmacogenetics, in Progress in Medical Genetics, vol. 3, edited by STEINBERG, A. G., BEARN, A. G., Grune & Stratton, Inc., New York, 1964, p. 49. Google Scholar12. SOLOMON HM: Variation in metabolism of coumarin anticoagulant drugs. Ann. NY Acad. Sci. 151: 932, 1968. CrossrefMedlineGoogle Scholar13. LEWISSPIVAKSPAET RJMTH: Warfarin resistance. Amer. J. Med. 42: 620, 1967. CrossrefMedlineGoogle Scholar14. O'REILLYPOOLAGGELER RAJGPM: Hereditary resistance to coumarin anticoagulant drugs in man and rat. Ann. NY Acad. Sci. 151: 913, 1968. CrossrefMedlineGoogle Scholar15. VESELLPAGE ESJG: Genetic control of drug levels in man: antipyrine. Science 161: 72, 1968. CrossrefMedlineGoogle Scholar16. VESELLPAGE ESJG: Genetic control of drug levels in man: phenylbutazone. Science 159: 1479, 1968. CrossrefMedlineGoogle Scholar17. COHENSACHSWICKERCONRAD RJJRDJME: Methemoglobinemia provoked by malarial chemoprophylaxis in Viet Nam. N. Eng. J. Med. 279, 1127, 1968. CrossrefMedlineGoogle Scholar18. KELLEYGREENEROSENBLOOMHENDERSONSEEGMILLER WNMLFMJFJE: Hypoxanthine-guanine phosphoribosyltransferase deficiency in gout. Ann. Intern. Med. 70: 155, 1969. LinkGoogle Scholar This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Departments of Medicine and Genetics University of Washington Seattle, Wash. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCombined Analysis of Phase I and Phase II Data to Enhance the Power of Pharmacogenetic TestsComparison of Nonlinear Mixed Effects Models and Noncompartmental Approaches in Detecting Pharmacogenetic CovariatesDose-response to pancuronium in identical twinsETHANOL METABOLISM: REGULATION BY GENETIC FACTORS IN NORMAL VOLUNTEERS UNDER A CONTROLLED ENVIRONMENT AND THE EFFECT OF CHRONIC ETHANOL ADMINISTRATIONHalothane Biotransformation in ManPreventable Drug Reactions — Causes and Cures 1 June 1969Volume 70, Issue 6Page: 1269-1272KeywordsApneaDrug metabolismDrugsEnzymesHemolytic anemiaInborn errors of metabolismMetabolic pathwaysPharmacogenetics Issue Published: 1 June 1969 PDF downloadLoading ...