E.B. Wilson medalists, 1983

It is often said that a scientist is lucky to make one great discovery in a career; those rare individuals who make more than one are very special indeed. Joseph Gall has made not one but several major discoveries which have both theoretical and practical consequences. His early research on lampbrush chromosomes of amphibians established many facts about chromosome structure. For example, he directly showed that DNA in a chromosome is a double-stranded molecule, something we take for granted now but that had never before been demonstrated. He was a co-discoverer in 1968 of specific gene amplification first shown for the ribosomal RNA genes in Xenopus. Not only is gene amplification an important mechanism for the control of gene expression, but it has come to the attention of cancer researchers recently with the discovery that resistance to some drugs used to treat cancer is due to gene amplification. Joe Gall went on to demonstrate gene amplification in the oocytes of certain insects. These accounted for many cytogenetic observations on nuclear structures that had been noted over the years. In about 1970 Joe Gall and a graduate student, Mary Lou Pardue, developed in situ hybridization technology. This method remains one of the most essential in molecular biology for localizing genes on chromosomes or within cells. He and his colleagues made several important biological findings using this method. For example, the term heterochromatin had been used for many years to describe an especially condensed and genetically inactive form of chromatin. Joe Gall was the first to show that highly repetitive "satellite" DNA is a major constituent of heterochromatin, often located in telomeres and centromeres of chromosomes. With this discovery there was a molecular explanation for the genetic inactivity of heterochromatin-it consists mainly of simple sequence DNA that cannot encode protein. Following up on this, his lab was the first to sequence a simple repeat in satellite DNA. Further, he showed that polytene chromosomes of Drosophila replicated only the euchromatin and not heterochromatin. Differential replication of ribosomal RNA genes, embedded in heterochromatin, was discovered in his lab. Recently he has mapped genes on lampbrush chromosomes by hybridizing DNA probes to nascent RNA. The importance of in situ hybridization methods for molecular biology and biomedical research therefore cannot be overestimated. The location of single genes on mammalian chromosomes is now done regularly and chromosomal abnormalities related to oncogenes associated with chromosome breakage in malignant cells are being probed. One does not have to look far for the medical relevance of this basic researcher's discoveries. Indeed, there is no one working today in the area of molecular cytogenics who does not owe much of their knowledge and ability to make advances in their research to Joe Gall. We have always had the suspicion that Joe Gall was going chapter by chapter through E. B. Wilson's famous book The Cell in Development and Inheritance explaining in molecular terms each puzzling cytological finding described therein. It is, therefore, highly appropriate that we honor Joe Gall with the awarding of the E. B. Wilson Medal. Dr. Gall is currently at the Department o f Embryology, Carnegie Institution of Washington. Dr. Hugh Huxley's career is a superb example of how a focused study of one major cell type, using a variety of techniques, has provided fundamental concepts of widespread importance to the field of cell biology. Dr. Huxley began his career as a physicist interested in biological problems. He developed a new technique for the study of muscle, which he saw was possible because of the structural regularities present in striated muscle, thus pioneering the use of x-ray diffraction in cell biologic research. This led to a wealth of data on muscle organization and influenced later studies on many varieties of striated and smooth muscle. Some of the implications of his findings were followed in his subsequent studies with Jean Hanson in which they showed that in muscle two different proteins were present in two different types of filaments, thus beginning to account for the x-ray diffraction results. They developed improved techniques for electron microscopy and also used interference microscopy to study protein disposition. Dr. Huxley was then able to show that the two types of filaments observed appeared to slide past each other when a muscle ~ontracted. This demonstration, together with the deepening significance of the cross bridges that he discovered, led to a radically new conception of the mechanism of muscle contraction. Dr. Huxley's work then led in the direction of the role of tropomyosin in the regulation of muscle contraction and further studies of the cross bridges. X-ray diffraction of living muscle followed, together with time-resolved studies, which he is now pursuing. In the meantime, Dr. Huxley had discovered the polarity of actin in vitro in thin filaments, and the self-assembly of myosin, both of which illuminated the sliding filament model. To do this, he perfected the method of negative staining which he also used to study ribosome structure. These discoveries and methods have deeply influenced the study of cytoplasmic fibrou.s structures in a variety of cell types. Actin and myosin are widely distributed and it is hard to find an area of the cytoplasm or a cell type to which his ideas and methods have not penetrated. The importance of cross-bridging and subsequent sliding between two different proteins is now as accepted in the area of microtubule-dynein interaction as in actinmyosin interaction. It appears to be relevant even to the rotary cytoplasmic streaming in plant cells. Dr. Huxley's work has been distinguished by its high quality, its penetration, elegance, and thoroughness. The clarity of his ideas is matched by his mastery of different techniques as needed for a given aspect of a given problem. He has contributed deeply to our understanding of how cells move. But he has not been a lonely scientist, for he has encouraged many young investigators, not only in the field of muscle contraction. Because of his innumerable fundamental contributions to the field of cell biology, we honor Dr. Hugh Huxley this evening with the awarding of the E. B. Wilson Medal. Dr. Huxley is currently at the Molecular Biology Department, Medical Research Council.