A stimulating and informative course on the concepts and methods that are current in investigations concerning the chemistry of heredity was offered by the Third Annual Advanced Study Xnetitute of Molecular Biology. Spetsai, Greece, July 4 through July 16, 1966. Dr. Marianne Grunberg-Mansgo (Paris) and Dr. A, Evdingelopoulos (Athens) were responaible for arranging the Institute, which was sponsored by NATO with some financial assistance from the U. S. Office of Naval Research. The cooperation and generosity of the Greek government also contributed to the success of the Institute. The decision to hold this course in Greece stemmed from the growing interest and activity in molecular biology in that country, and a desire to stimulate that research by personal contact between Greek investigators and their foreign colleaguerl. The Institute was held MI the ieland of The five hours of lectures each day were held in the morning and evening. were used, Sane 25 lecturers from Greece, Great Britain, France, Germany, Israel and the United States, each delivered between two and four one-hour lectures, These were followed by lively discus- sion periods, and the discussions continued through the afternoons and late evenings. Reading lists and brief abstracts for each lecture were distributed. The pleasant physical surroundings, the The facilities of a small college on Spetsai -2- absence of mechanized transportation, and the availability of dormitory and hotel space in close proximity fostered the niaximum contact between students, and students and lecturers. The reoulting atmosphere was similar to that found at a Gordon Conference. The 130 students (chosen from over 1000 applicante) reprcscnted lli countries with the large majority fron i\estern Europe, and Grecce (twenty came from North America). They ranged from graduate students and recent graduates working in molecular biology, to established investigators working in related fields. The lectures assumed a basic knowledge of modern biochemistry and genetics and started with a general review of the experiniental findings on which che I.ntest concepts are based. Each speaker then presented the most recent findings from his mrn laboratory and since some of thie work is among e'he most exciting and elegant being carried out in the field, a high level of scientific exuberance was maintained. An initial talic by I. Photaki (Athens) on modern methods for the chemical cynthesis of peptides was followed by a group of lectures on various aspects of the structure of nucleic acids. The electronic structure of mononucleotides and polynucleotides was discussed by B. Pullman (Paris). H, Boedtker (IIarvard) and P. Doty (Wrvard) spoke on the physical propertics of €Ut\ and DNA, recpectively and gave particular emphasis to the problem inherent in the methods that &re available for studying these molecules in solution. Methods €or obtaining and analyzing x-ray diffraction data for nucleic acida, thus yielding infoxmation on the overall three-dimensional configuration of these molecules, was discussed by R. Laneridge (Cancer Research Foundation, Boston). summarized the information on polynucleotide secondary structure that has been derived from studies with synthetic polymers. stressed the fact that the physical properties characteristic of high molecular weight polynucleotldea begin to develop even with dinucleotides. within the structure is, in large part, responsible for their stability and their optical properties, while hydrogen bonds control the specificity of base pairing. hydrogen bonding between purines and pyrimidines was further elucidated by A. Rich (M.1.T.) who described recent studies on crystalline complexes between derivatives of guanine and cytosine, and, similarly, adenine and uracil, M. Cohn (U. of Penn.) discussed the use of nuclear magnetic resonance in elucidating the nature of the interaction between an enzyme, divalent metal ion, and nucleotide. A. M. Michelaon (Paris) He Michelson also concluded that the stacking of baaes The specificity of the J. Su'atson (Harvard) introduced the next group of lectures with a lucid description of current views on the mechanism of protein biosynthesis and in particular the variety of roles played by RNA in that process. He took special care to point out those areas -4- which are in need of concentrated work. mentioned agarin in the talks that followed. lectured on what is known and what io not known about the structure of the rtbooane and its components, ribooaplirl RNA and protein. HQ also undertook the difficult job of suosnsrizing and avalurring the litaratura relevant to the biosyntheeie of riboeaues. recent work on the primary structure of two serine transfer RNAs Eraa yeast as an example, W, Zachau (Kb) spoke QR the primary and secondary structure of transfer RNA, emphasizing the relation of structure and function. Particularly useful for the artudents was his detailed dcecription of the methodology used in work of this kind, Many of there areas were Thus, R. Monier (broeille) Using his own The biosynthesis of polyribonucleotides was the rrubject of several detailed lecturee. 3. Richardson (Paris) eunmarized the evidence that the DNA-dependent RNA polymerase is responsible for the synthesitii of RNB within bacterial cells. laboratoxies, he described the detaile of the mechanism of thts reaction which have been elucidated during the pact year. Grunberg-Manago emphasieed the cmaensua that polynucleotide phos- phorylase la probably a degrddative enxyme in vivo, and want on to describe recent 8tudie8 with the highly purified enzyme from 2. coli. U. Z. Littauer (Rehwoth) and A. Peterkofsky (N.I.H.) discussed enzymatically catalyzed structural modifications of polynucleotides. The former talked on the methylation of RNA and DNA while the latter Mentioning work from many M. - 5- brought everyone up to date on the occurrence and synthesis of the thionucleotidss in E. coli transfer RNA. Theories and experiments on the repllcation of viral RNA in VIVO and in vitro, a subject which is under intensive study in several laboratories, was reviewd by H. Boedtker. determination of the structure of naturally occurring and synthetic polynucleotides waa covered in a lecture that I gave. cussed, in detail, the nucleases of E. coli and speculated on their respective physiological roles, The use of nucleases ae analytical tools for the I also dis- The next series of lectures concerned the mechanism of translation of messenger RNA. work that led to the chemical description of the genetic code. "wobble theory" of codon-anticodon recognition was presented by F.H.C. Crick (Cambridge, England) who also described experiments with so-called phase shift mutanEs of T4 bacteriophage. These latter genetic experiments complement in vitro studies on the reading of the genetec code. Recent experiments on the initlation of polypeptide chain synthesis, which have led to the elucidation of specific initiator codons on messenger RNA and related transfer RNAs were deecribed by B.F.C. Clark (Cambridge, England). This topic was discussed further by M. S. Bretscher (Cambridge, England), with particular reference to the binding of transfer RNA to riboeanes. Bretscher introduced the question of the mechanism of termination of M. Grunberg-Planago gave a resume of Tho polypeptide chafns, whieh was discussed in more detail by A. Garan (Yale). data on becrerial euppresslon which have indicated a genetic control of the epecificlty of codon translation. factors involved in thier control are ipecific transfer me, was presented by J. D. Watson In ai talk which deacribed in vitro protein synthesis in systems utilizing RNA fran RM-containing bacteriophage as mcabsengere. orgslniams other than 1. of the role of palyribosanes In in vitro systems derived from reticulocytes as well a8 E. coli. Garen's excellent lectures reviewed the genetfc and biochemical Biochemical evidence that A. Rich then reminded us that protein is made by and Its phage and presented a review The regulation of protein biosynthesis was presented from B. Ames (N.I.H.), uefxq5 his own work on the several viewpoints, histidine operon of Salmonella 8s an example, lectured on the general nature of the opczron and theories of repression. gave a review of the evante that follow the infection of E. & with virulent and temperate bacteriophage. in the reguliatfon of catabolic metabolism -8 given by I. C. Gunealua (U. of flllnols) who S~SO discuased the regulation of tryptophan biosynthesis in detail. E. FPlgner (M.I.Ts) A more general visw of problems In rccognithn of the growing interest of many molecular biologists in the nervous oystem, E.S. Caneflakis (Yale) concluded the Znstitute with a general review of the phyeiology and metabolism of the nerve cell. Maxine F. Singer National Inotftute of Arthritis and Metabolic Dioeaseo mtiOlaa1 XIkStitUteE Of Health