The birth of quantum mechanics

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Acknowledgements This research was supported by a grant from the Research Corporation and grants GM 18292 and HL 18679 from the U.S. Public Health Service. I would like to express my sincere appreciation to Aaron Janoff (Stony Brook) and James Travis (University of Georgia) for gifts of the human neutrophil leukocyte elastase used in this research.

References I Mittman, C., ed. (1972) Pulmonary Emphysema andProteolysis, pp. 1-537,AcademicPress,New York 2 Turino, G.M., Rodriguez. J.R., Greenbaum, L.M. and Mandl, I. (1974) Amer. J. Med. 57, 493-503 3 Hance,A.J. and Crystal,R.G. (I 975)Amer. Rev. Resp. DIS. 112,657-711 4 Janoff,A., Blondin,J., Sandhaus, R.A., Mosser, A. and Malemud,C. (1975) in Proteases and Biological Control(Reich, E., Rifkin,D. B.and Shaw, E.,eds),pp. 603-620, ColdSpringHarbor Laboratory, New York 50hlsson, K. (1975) in Proteases and Biological Control (Reich, E., Riflcin, D.B. and Shaw, E., • eds),pp. 591-602, Cold Spring Harbor Laboratory, New York 6 Bough, R.J. and Travis, J. (1976) Biochemistry 15, 836-841 7 Barrett, A.J. (1975) in Proteases and Biological Control (Reich, E., Rifkin, D.B. and Shaw, E., eds), pp. 467-482, Cold Spring Harbor Laboratory, New York 8 Blow,D. M. (1971)in The Enzymes (Boyer,P. D., ed.), 3rd edn, Vol. 3, pp. 185-212, Academic Press, New York 9 Hartley,B.S. and Shotton, D.M (1971) in The Enzymes (Boyer,P. D., ed.), 3rd edn, Voh 3, pp. 323-373, AcademicPress,New York 10 Robertus, J.D., Alden, R.A., Birktoft, J.J., Kraut, J., Powers,J.C. and Wilcox,P.E. (1972) Biochemistry 11, 2439-2446 11 Powers,J. C. and Tuhy,P. M. (I 973)Biochemistry 12, 4767-4774 12 Thomson, A. and Denniss, I.S. (1973) Fur. J. Biochem. 38, I-5 13 Thompson, R.C. and Blout, E.R. (1973) Biochemistry 12, 44--47 14 Shaw,E. (1970) PhystoL Rev. 50, 244-296 15 Tuhy, P.M. and Powers,J.C. (1975) FEBS Lett. 50, 359-361 16 Poulous,T. L., Alden,R.A., Freer,S.T., Birktoff, J. J. and Kraut,J. (1976)J. BioL Chem. 25I, 10971103 17 Segal,D. M., Powers,J. C., Cohen,G. H., Davies, D.R. and Wilcox, P.E. (1971) Biochemistry 10, 3728-3738 18 Rossmann,T., Norris, C. and Troll, W. (1974) J. Biol. Chem. 249, 3412-3417 19 Hess, G.P. (1971) in The Enzymes, 3rd edn (Boyer,P. D.ed.), Vol.3, pp. 213-248, Academic Press,New York 20 Robillard,G.T., Powers,J.C. and Wilcox,P.E. (1972) Biochemistry I 1, 1773-1784 21 Powers,J.C. and Carroll, D.L. (1975) Biochem. Biophys. Res. Commun. 67, 639-644 22 Elmore,D.T. and Smyth, J.J. (1968) Biochem. J. 107, 103-107

IUAGO J'YEARS The birth of quantum mechanics In 1926 Erwin Schrrdinger published several papers in the Annalen tier P h y s i k with the general title 'Quantization as a Characteristic-value Problem' [1]. This work brought to an end a period of great uncertainty and puzzlement in physics and chemistry. It made possible the development of modern chemistry, including biochemistry and molecular biology. Many striking discoveries had been made during the preceding 30 years, beginning with the discovery of the electron in 1896, the discovery of X-rays and of radioactivity, and the discovery of the nucleus of the atom. Quantum theory began in 1900, when Max Planck showed that-the distribution of energy as a function of frequency in the light emitted by a hot body could be explained by the assumption that the light is emitted or absorbed, not continuously, but rather in amounts equal to the frequency of the light multiplied by Planck's constant, h. In 1905 Albert Einstein stated that there was good evidence that the light itself consists of quanta (now called photons), each with this amount of energy. Also, shortly thereafter he suggested that the atoms in crystals can vibrate only with certain amounts of energy, equal to an integral multiple of the vibrational frequency multiplied by h. Einstein developed the theory of photochemical reactions, pointing out that the frequency of the light that causes a certain reaction must be greater than a certain threshold value in order that the energy provided by the photon be enough to cause the reaction to occur. In 1913 Niels Bohr succeeded in applying the quantum theory to the motion of the electron around the proton in the hydrogen atom. He showed that it is possible in this way to account for the values of the frequency of the different kinds of light given out by a hot hydrogen-atom gas. Progress was then rapid in applying the old quantum theory to the problems of the spectra of more complicated atoms and the structure of atoms and molecules. Although rapid progress was made, it became quite clear, in the period between 1915 and 1925, that there was something wrong with the old quantum theory. The

theory sometimes led to conclusions that were almost right, but not exactly right. For example, it was found that the equations for the rotational e.nergy levels of a molecule given by the old quantum theory did not fit the experimental values, but could be made to fit if the rotational quantum number were given half-integral values (l/z, 3/,, s/2 . . . . ) rather than integral values (0, 1, 2 . . . . ). Other proerties, such as the dielectric constant of hydrogen chloride gas and the heat capacity of hydrogen gas, could not be brought into agreement with experiment by any amount of fiddling with the quantum numbers. Of special significance for chemistry is the fact that nobody was able to develop a quantum theory of the chemical bond, even in the simplest molecules, the hydrogen molecule-ion, with one bonding electron, and the hydrogen molecule, with two bonding electrons. After 1916, when Gilbert Newton Lewis of the University of California published his paper on the shared-electron-pair chemical bond, chemists have recognized the chemical bond (called the covalent bond by Irving Langmuir in 1919) as consisting of tw~ electrons held jointly by two atoms. The most able theoretical physicists, including Wolfgang Pauli and Werner Heisenberg, had, around 1922 and 1923, tried to apply the old quantum theory to these problems, but without success. Then in 1924 Louis de Broglie attributed wave character to the electron, and gave as its wavelength the value of Planck's constant divided by the momentum (product of mass and velocity) [2]. A year later Heisenberg, then only 25 years old, published the first paper about quantum mechanics [3]. By a remarkable feat of reason he developed some general equations that, when applied to the harmonic oscillator, gave the correct values of the energy levels, corresponding to the old quantum theory with half-integral values of the quantum numbers. Shortly thereafter, Max Born and P. Jordan showed that Heisenberg's strange mathematics had in fact been developed during the last century by mathematicians, and had been given the name 'matrix algebra' [4,5]. After Schrrdinger had formulated his wave equation, it was shown by him [6] and by a young American, Carl Eckart [7], that Schr6dinger's wave mechanics and Heisenberg's quantum mechanics are in fact mathematically identical. Within a few years it was found that quantum mechanics apparently provides a completely satisfactory theoretical basis for all problems of molecular structure and intermolecular interactions. I set out for Europe, on a fellowship from the John Simon Guggenheim Memorial Foundation, just when Schr6d-

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TIBS - Septentber 1976 inger began publishing his papers. My proposal to the Guggenheim Foundation was to work on atomic and molecular structure and the nature of the chemical bond; it was described by the secretary of the Foundation, Henry Allen Moe, as the effort to study 'the topology of the interior of the atom'. When I arrived in the Institute of Theoretical Physics of the University of Munich (Professor Arnold Sommerfeld), I found Walter Heitler and Fritz London there as students. Later, on the day when Walter Heitler passed his doctoral examination, he, London, my wife, and I went to a restaurant to celebrate the occasion. By 1927 Heitler and London had developed the quantum mechanical theory of the hydrogen molecule, and had lain the basis for future developments. Modern chemistry, including biochemistry and molecular biology, is based on quantum mechanics. A number of the ideas that have been introduced into chemical structure theory were suggested by the quantum mechanical equations. The theoretical insight was, of course, greatly aided by experimental techniques, such as spectroscopy and the determination of the structure of crystals by X-ray

BOOKS Comprehensive enzyme tome Enzyme Kinetics iby Irwin H. Segel, published by Wiley and Sons, New York, £17.05 ($34.10) ( xxii + 95 7 pages). The overall character of this book can best be described as encyclopedic. It is a nearly complete compilation of mechanisms, equations, plots and patterns that might be encountered in kinetic studies. However, its weakness also stems from its encyclopedic nature; namely, major kinetic theory is combined with kinetic trivia, and many of the cases treated have no counterparts in nature at all. Thus, one has the serious problem of seeing the forest through all of the trees. This book is not recommended for the novice who is either attempting to run a few kinetic experiments, or is trying to learn the subject. He would find this book confusing, perhaps misleading, and would get the impression that enzyme kinetics

diffraction and of gas molecules by electron diffraction. I shall content myself with one example. In 1929, stimulated by the new insight provided by quantum mechanics, I formulated a set of principles determining the structure of substances such as silicates and phosphates [8]. It is a consequence of these principles that, although the bonds between two silicon atoms and the oxygen atom joining them in a complex silicate are stable, the corresponding bonds for phosphorus are not; that is, a diphosphate or triphosphate is necessarily a high-energy molecule. This fact was called to the attention of Herman Kalckar by my associate Charles Coryell when Kalckar was visiting the California Institute of Technology in 1939. The important role of high-energy phosphates in energy .transformation in living organisms was emphasized by Fritz Lipmann and Kalckar in 1941. It constitutes one of the important aspects of modern biochemistry. It is hard to imagine what the state of science would be today if Heisenberg and Schr6dinger had not done their work 50 years ago. We might well believe that

quantum mechanics would have been discovered by someone else if Heisenberg and Schr6dinger had not lived, but in fact this discovery might have been delayed by several years, and the development of modern chemistry and molecular biology might have been correspondingly delayed.

is much more complex than is actually the case. On the other hand, the experienced and practising kineticist probably does not need this book, although he will find certain portions useful. The references at the end of each chapter appear complete and up to date as of the time of publication. In addition, sufficient comments are added to enable one to identify which articles to read, and the references are even grouped according to mechanism in several cases. This book contains an immense amount of analytical geometry, and the expression for each slope, intercept, replot, etc. is clearly identified. Thus, this material is a useful reference for graphical analysis of kinetic data, although the reader is generally not told how to interpret the data in terms of mechanism, or how to plan his kinetic studies to deduce an enzymic mechanism. Before attempting to carry out or interpret kinetic studies, one should thus learn some of the basic principles by reading 'The Enzymes', 3rd edn, Vol. II, Chapter 1, and then consult the equations in this book to carry out the graphical analysis of one's data. One should also read Advances in Enzymology 29, 1 (1967) which describes the statistical analysis of enzyme kinetic data because the graphical analysis of data, while an important step in data processing, does not give reliable values and standard errors for the kinetic para-

meters, regardless of what graphical procedure is used. In summary, this book belongs on the reference shelf of libraries, and in laboratories where kinetic studies are done, but is not suitable for use as a text in courses on enzymology, w.w. CLELAND

References I Schr6dinger, E. (1926) Annu. d. Physik. 79, 361, 489: 80. 437; 81,109

2 de Broglie, L. (1924) Thesis, University of Paris 3 Heisenberg, W. (1925) Z. f. Physik. 33, 879 4 Born, M. and Jordan, P. (1925) Z . f Physik. 34, 858 5 Born, M., Heisenberg, W. and Jordan, P. (1926) Z.f. Ph.vsik. 35, 557 6 Schrfdinger, E. (1926) Annu. d. Physik. 79, 734 7 Eckart, C. (1926) Physik. Rev. 28, 711 8 Pauling, L. (1929)J. Am. Chem. Soc. 51, 1010 L1NUS PAULING

L.P. is Fellow o f the Linus Pauling Institute o f

Science and Medicine, and Chairman of the Board of Trustees of the Institute.

DEXTER B. NORTHROP IV. IF. Cleland is a Professor in the Department of Biochemistry and Dexter B. Northrop is an Assistant Professor in the School of Pharmacy at the University of Wisconsin, Madison, Wisconsin, U.S.A.

Not for browsing The Sea U r c h i n E m b r y o edited by G. Czikah,published by SpringerVerlag, Berlin DM139.($57.-) (xvii+ 700 pages). Sea urchin eggs and embryos provide splendid material for the study of a variety of problems in cell biology and early development. The eggs can be obtained in quite large numbers, are easy to handle, and the eggs and embryos may be sufficiently transparent to follow in detail the behaviour not only of individual cells, but in the fertilized egg the formation of structures such as asters and spindles. Historically, studies on them have contributed greatly to our knowledge of cell and developmental biology. The disadvantage of the material is that genetic studies are not available because of the difficulty in raising animals to maturity.