Elizabeth F. Neufeld
Wolf Prize Laureate in Medicine 1988
Elizabeth F. Neufeld
Affiliation at the time of the award:
UCLA School of Medicine, USA
“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.
The work of Professor Elizabeth F. Neufeld is characterized by its perfectly systematic and logical progression: Starting with the chance observation that two cell lines from patients suffering from different genetic storage disease “correct” each other’s defect when cultured together, she has moved unerringly to the recognition of the “correcting factors” as being lysosomal hydrolases,and hence to the elucidation of the precise enzymatic defect responsible for several mucopoly saccharidoses. In addition, by studying the selective uptake of the factors she has discovered that, during their biosynthesis, lysosomal enzymes receive a specific “recognition marker” that serves to target them selectively to lysosomes, and she has identified I-cell disease as a genetic deficiency of this targeting process.