DRUG METABOLISM REVIEWS, 5(2), i-ii (1976)
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Preface
Drug Metabolism as a Mutation Drug Metabolism in Mutation
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Evolution of living organisms has granted unfailing attention to xenobiotic-metabolizing activity, yesterday’s latest mutation being conjugation with glutamic acid, an ability acquired by anthropoid apes and Homo sapiens, their youngest cousin. Evolution acting through man exerts a formidable pressure on science, one of its creation. Medicinal chemistry, which I teach, was once limited to synthesis, extraction, and analysis of drugs. Gradually, it has mutated to study drug molecules in all their chemical, physicochemical, and biochemical aspects. As aptly described by Alfred Burger [l], medicinal chemistry has become the acknowledged meeting ground of modern organic chemistry and physical chemistry, and of biochemistry. . . In the fertile, interdisciplinary soil of medicinal chemistry has developed the young science of drug metabolism which is the object of your temporary or permanent interest, Research in drug metabolism did and does involve biotransformation of substrates in various biological environments. The resulting accumulation of information gave a reputable status to drug metabolism and established it a s a new scientific topic. But the flood of data threatens to drown workers; they must feel the need to walk uphill in search of original approaches, generalizing models, broad concepts, and far-reaching theories. Truly, drug metabolism must mutate, and is mutating, toward adulthood, toward the status of a full science. The factors controlling the biotransformation of xenobiotics must be unraveled. These needs point to experimental and theoretical work in directions such as physicochemical, electronic, and structural properties of substrates; properties and nature of drug-metabolizing enzymes; and control by the higher levels of bioorganization. New vistas are yours to unveil and then to follow by first critically integrating a large body of scientific results, a process incidentally leading to the production of review articles. This
“. . . .”
i
PREFACE
Drug Metabolism Reviews Downloaded from informahealthcare.com by Monash University on 10/28/14 For personal use only.
ii
is how DRUG METABOLISM REVIEWS can play an indispensable role in helping crystallization of ideas and mapping the routes to progress. Mutations in chemistry, biochemistry, and medicinal chemistry have generated drug metabolism as a scientific topic. Where a r e we led by the evolution now apparent in this mutating science? Which new science will sprout from it? A l l answers to questioning scientists are proffered by science fiction: the choice is yours to make. Open The Dispossessed, by U r s u l a Le Guin [2]: “You do not We cannot come to you. We can believe in change, in evolution. only wait for you to come to us.”
. ..
Bernard Testa University of Lausanne
[ 11 A. Burger, in Medicinal Chemistry, Vol. 1 (A. Burger, ed.), Wdey-Interscience, New York, 1970, pp. ix-x. [ 21 U. La G i n . The Disposewed, Avon, New York, 1975.
Drug Metabolism Reviews Downloaded from informahealthcare.com by Monash University on 10/28/14 For personal use only.
Preface
Drug Metabolism as a Mutation Drug Metabolism in Mutation
-
Evolution of living organisms has granted unfailing attention to xenobiotic-metabolizing activity, yesterday’s latest mutation being conjugation with glutamic acid, an ability acquired by anthropoid apes and Homo sapiens, their youngest cousin. Evolution acting through man exerts a formidable pressure on science, one of its creation. Medicinal chemistry, which I teach, was once limited to synthesis, extraction, and analysis of drugs. Gradually, it has mutated to study drug molecules in all their chemical, physicochemical, and biochemical aspects. As aptly described by Alfred Burger [l], medicinal chemistry has become the acknowledged meeting ground of modern organic chemistry and physical chemistry, and of biochemistry. . . In the fertile, interdisciplinary soil of medicinal chemistry has developed the young science of drug metabolism which is the object of your temporary or permanent interest, Research in drug metabolism did and does involve biotransformation of substrates in various biological environments. The resulting accumulation of information gave a reputable status to drug metabolism and established it a s a new scientific topic. But the flood of data threatens to drown workers; they must feel the need to walk uphill in search of original approaches, generalizing models, broad concepts, and far-reaching theories. Truly, drug metabolism must mutate, and is mutating, toward adulthood, toward the status of a full science. The factors controlling the biotransformation of xenobiotics must be unraveled. These needs point to experimental and theoretical work in directions such as physicochemical, electronic, and structural properties of substrates; properties and nature of drug-metabolizing enzymes; and control by the higher levels of bioorganization. New vistas are yours to unveil and then to follow by first critically integrating a large body of scientific results, a process incidentally leading to the production of review articles. This
“. . . .”
i
PREFACE
Drug Metabolism Reviews Downloaded from informahealthcare.com by Monash University on 10/28/14 For personal use only.
ii
is how DRUG METABOLISM REVIEWS can play an indispensable role in helping crystallization of ideas and mapping the routes to progress. Mutations in chemistry, biochemistry, and medicinal chemistry have generated drug metabolism as a scientific topic. Where a r e we led by the evolution now apparent in this mutating science? Which new science will sprout from it? A l l answers to questioning scientists are proffered by science fiction: the choice is yours to make. Open The Dispossessed, by U r s u l a Le Guin [2]: “You do not We cannot come to you. We can believe in change, in evolution. only wait for you to come to us.”
. ..
Bernard Testa University of Lausanne
[ 11 A. Burger, in Medicinal Chemistry, Vol. 1 (A. Burger, ed.), Wdey-Interscience, New York, 1970, pp. ix-x. [ 21 U. La G i n . The Disposewed, Avon, New York, 1975.
