Observations on a decade of alcohol and drug dependence research

Abstract

True landmark discoveries in scientific research are relatively rare. Formulation of the theory of relativity, discovery of the first antibiotics, elucidation of the structure of DNA and the introduction of isotopic tracers into biochemical research, are modem examples of outstanding discoveries that truly inaugurated new eras of rapid progress in their respective disciplines. But the vast bulk of scientific discovery consists of small step-by-step advances, building carefully and logically on preceding knowledge and advancing our understanding in fairly predictable directions and degrees. Given the rarity of genuine ‘breakthroughs’, it is not surprising that the years since the appearance of the first issue of Drug and Alcohol Dependence have not seen any epoch-making discovery in this field, or any fundamentally new concept that has revolutionized our approach to the subject. Nevertheless, in a number of important areas of drug dependence research there has been very significant progress, the cumulative effect of which is a substantial clarification of some major issues. A few examples, drawn from different fields of addiction research, will suffice to illustrate the range and importance of these advances. In the early 197Os, the pathogenesis of severe alcoholic liver disease was known only in a vague descriptive way. Thanks to the excellent metabolic studies by various groups during the 1960s [l-4], the production of alcoholic fatty liver had already been explained on the basis of altered hepatic secretion of lipoproteins, combined with an altered hepatic redox state resulting from the metabolism of ethanol in the liver. However, it was not clear what relation, if any, existed between the easily produced and rapidly reversible phenomenon of fatty liver and the long-lasting and eventually fatal processes of alcoholic hepatitis and portal cirrhosis. The past ten years have seen very promising efforts to explain the causal mechanisms of hepatic cell death and of scar formation. These have included investigations of alcohol effects on mitochondrial membrane and cell membrane transport functions [ 5,6], hepatic oxygen consumption [ 71, sinusoid compression by alcohol-induced hypertrophy of hepatocytes [8] and perisinusoidal fibrosis as a response to (rather than solely a cause of) portal hypertension [9,10]. It cannot be claimed that the hypotheses generated by this