Wolf Prize Laureate in Medicine 1988
Affiliation at the time of the award:
Catholic University of Louvain, Belgium
“for the biochemical elucidation of lysosomal storage diseases and the resulting contributions to biology, pathology, prenatal diagnosis, and therapeutics.”
The whole field of genetic storage diseases (thesaurismoses) except for a few glycogen storage conditions (nonlysosomal) was a complete mystery. The diseases were known mostly by the names of the clinicians who first described them: Hunter, Hurler, Tay-Sachs, Niemann-Pick, Gaucher, Pompe, Fabry, etc. Morphological studies had shown the presence of abundant abnormal deposits in the tissues of the patients, hence the term “storage disease”, and in some cases the chemical composition of the deposits had been identified, at least roughly. The underlying enzymic deficiencies were unknown, but were generally believed to affect some biosynthetic pathway.
Thanks to the work of Professors Hers and Neufeld and to the investigations they have sparked, more than 30 genetic storage diseases are now known to be deficiencies of lysosomal digestion and a common pathological pattern with unique features has been recognized. These discoveries have led to major advances in cell biology, including the identification of a number of new lysosomal enzymes, the recognition of the importance of lysosomal autophagy, and the elucidation of the remarkable mechanism whereby lysosomal enzymes are targeted to their destination. From the medical point of view it has now become possible, in this group of rare but diverse and tragically crippling diseases, against which no prevention or therapy was available, to provide genetic counselling through the detection of heterozygotes, to effect prenatal diagnosis in time for therapeutic abortion, and even to seriously consider and investigate the possibility of replacement therapy.
Professor Henri-Géry Hers discovered the first such disease and fathered the concept that allowed an extensive elucidation of one of the most mysterious chapters of pathology in a span of less than ten years. This important achievement is not an isolated chance event. It arose as an offshoot of a life-long commitment to the study of carbohydrate metabolism, which started in the early 1950s with the description of the “Hers pathway” of fructose metabolism and ends, provisionally, with the discovery of a new intracellular messenger of major significance: fructose 2, 6-bisphosphate. In between are a long series of papers devoted to the control of glycogen metabolism in the liver, a number of contributions to genetic pathology (in addition to lysosomal storage diseases), and studies on purine metabolism.