Molecular Biology

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MOLECULAR BIOLOGY Proteins and Nucleic Acids. Eighth Weizmann Memorial Lecture Series, April, 1961. By M. F. Perutz. (Pp. 211+x; illustrated. £2 1Os.) Amsterdam, London, and New York: Elsevier Publishing Company. 1962. In this series of lectures Max Perutz-who soon after they were delivered received the Nobel prize for his outstanding contributions-describes the spectacular progress made in the field of molecular biology. Though the lectures were given in 1961 the book has been brought up to date, and there could be no more welcome introduction to this subject. It is one so new that few of the present generation of doctors were students when it had its beginnings, and unless their own interests have been directly touched upon many will have failed to make themselves systematically familiar with this important expansion of scientific knowledge. Yet we will all have to become fully conversant with D.N.A., R.N.A. (whether transfer, ribosomal, or messenger), with the one-gene-one-polypeptide hypothesis, with the genetic code, and with structural and regulator genes. Rarely can there have been such a swift transition from highly theoretical speculation to immediate practical interest. In this book with less than 200 pages of text, 57 figures, 8 tables, and a detailed subject index the reader is gradually introduced, easy step by easy step, into this new realm, and after what may be no more than a week-end's concentrated reading will emerge with the feeling that he is a partner in mankind's latest effort in probing Nature. Historically, the synthesis of protein has been explored from two aspects: by a study of the protein molecules themselves, and by an investigation of the synthesizing molecules, the nucleoproteins, and in particular the nucleic acids. The combination of the two leads to the observation of the actual synthesizing process in which ribonucleic acid assembles amino-acids and combines them into the polypeptide chains which then associate to form the finished protein. The author himself has been mostly concerned with haemoglobin, but there have been important studies of insulin and myoglobin-all of them proteins which can be purified easily and prepared in quantity. Their primary structure arises from the polypeptide chains they contain, and from the amino-acid sequence in these chains. Their secondary structure is the outcome of the configuration of these chains-which, according to Linus Pauling's prediction, are not straight threads but right-handed spirals or helices. The tertiary structure indicates how these chains fit together to form the complete molecule. This can be ascertained only by x-ray analysis, and has up to now been achieved only for myoglobin and haemoglobin-after Perutz's discovery in 1953 that an answer could be found by comparing the x-ray diffraction pattern arising from an isomorphic pair of crystals, one containing the protein alone and one the protein complex with a heavy atom such as mercury. The other approach was the recognition of the structure of the synthesizing nucleoproteins with their nucleic acids, D.N.A. and R.N.A. These are long-chain polymers containing pentose and phosphate, and adenine, guanine, thymine, and cytosine. Their arrangement has been elucidated by the famous model of Crick and Watson. In the double-stranded D.N.A. an adenine is always opposite a thymine, and a guanine opposite a cytosine. Thus when a single strand duplicates itself to form the double-stranded D.N.A. the sequence of the bases in the second strand is predetermined by that of the first. Furthermore, the sequence of these nitrogenous bases determines that of the amino-acid residues in the polypeptide chains which eventually arise from the nucleic acids. Thus certain base sequences in the D.N.A. of the nucleus form a code which predetermines a corresponding amino-acid in the finished product. The complicated system of the double-stranded D.N.A., the single-stranded R.N.A., the transmission of the genetic message from the nucleus by messenger R.N.A. to the ribosome, where the sessile ribosomic R.N.A. takes over and, according to its coding, forms a given polypeptide -the actual biosynthesis of protein-all this is described in simple terms. The D.N.A. which is part of the original chromosome can be considered a genetic unit, and there must be regulating genes which trigger off a given structural gene. Here, one feels, is a possible point of attack at which the medicine of the future might be able to develop aetiological rather than palliative measures in the treatment of inherited disorders. As far as man is concerned most of the known facts in this field are concerned with haemoglobin, but it is already clear that this fascinating compound is a model, and that the syntheses of other proteins and their genetic variants are much the same. This is a most valuable book written with masterly simplicity. Rather than making concessions to easy understanding by avoiding complicated issues the author has succeeded in clarifying them so that they become as transparent as the rest. H. LEHMANN.