'What is Life?' Fiction, Not Science

What is Life? The Physical Aspect of the Living Cell. Erwin Schrödinger. Cambridge University Press, New York, 1967. 96 pp. (Originally published in 1944.) Schrödinger's book is written is an engaging, lively, almost poetic style ("The probable lifetime of a radioactive atom is less predictable than that of a healthy sparrow.") Up to 1948 it drew 65 reviews and it has probably by now sold about 100,000 copies. It has become a classic that has provided a nourishing habitat for historians, sociologists and philosophers of science who have commented on it, on the comments on it, or on the comments on the comments on it. A Ph.D. thesis published on the subject in 1979 contains over 120 references, excluding the 65 reviews. Schrödinger's book begins with a chapter on "The Classical Physicist's Approach to the Subject." Schrödinger asks how events in space and time taking place in a living organism can be accounted for by physics and chemistry: "Enough is known about the material structure of life to tell exactly why present-day physics cannot account for life. That difference lies in the statistical point of view. It is well-nigh unthinkable that the laws and regulations thus discovered (i.e. by physics) should apply immediately to the behavior of systems which do not exhibit the structure on which these laws and regularities are based." Schrödinger jumps to that conclusion after reading that genes are specific molecules of which each cell generally contains no more than two copies. He had entered Vienna University in 1906, the year that Boltzmann died and had been taught physics by Boltzmann's pupils. He remained deeply influenced by Boltzmann's thoughts throughout his life. According to Boltzmann's statistical thermodynamics, the behavior of single molecules is unpredictable; predictable is only the behavior of large numbers. In genetics, therefore, Schrödinger concludes, "we are faced with a mechanism entirely different from the probabilistic ones of physics." This difference forms the guiding theme of his book. The next two chapters are called "The Quantum-Mechanical Evidence" and "Delbrück's Model Discussed and Tested." They are largely paraphrased versions of a 1935 paper by N.W. Timofeeff -Ressovsky, K.G. Zimmer and Max Delbrück on "The Nature of Genetic Mutations and the Structure of the Gene." In the final section of this paper, Delbrtick concludes that it is premature to make the description of the gene any more concrete than the following "We leave open the question whether the single gene is a polymeric entity that arises by the repetition of identical atomic structures or whether such periodicity is absent; and whether individual genes are separate atomic assemblies or largely autonomous parts of a large structure, i.e. whether a chromosome contains a row of separate genes like a string of pearls, or a physico-chemical continuum." Schrödinger reformulated Delbrück's hypothesis by postulating that the gene is a linear onedimensional crystal, but lacking a periodic repeat: an aperiodic crystal. I wonder why Schrödinger did not adhere to Delbrück's much better description. One could argue over the distinction between aperiodic and identical, but Delbrück could not have meant structures that are completely identical, since these could contain no information. Schrödinger states that the nature of the gene allows only one general conclusion: "Living matter, while not eluding the laws of physics as established to date, is likely to involve other laws of physics hitherto unknown which, however, once they have been revealed, will form as integral a part of this science as the former." He describes the organism as a clockwork and the hereditary substance is "the single cog … that is not of coarse human make, but is the finest piece ever achieved along the lines of the Lord's quantum mechanics." He must have been unaware that the true chemical nature of that "finest piece" was actually published while he was writing his book. In January 1944 there appeared in the Journal of Experimental Medicine the classic paper by O.T. Avery, C.M. McLeod and M. McCarty which reported conclusive evidence that genes are made not of protein, but of DNA. In the fullness of time, that discovery has led the majority of scientists to the recognition that life can be explained on the basis of the existing laws of physics. Schrödinger's last two chapters do contain his own thoughts on the nature of life. In "Order, Disorder and Entropy" he argues that "the living organism seems to be a macroscopic system which in part of its behaviour approaches to that purely mechanical (as contrasted with thermodynamical) conduct to which all systems tend, as the temperature approaches the absolute zero and the molecular disorder is removed." He comes to this strange conclusion on the ground that living systems do not come to thermodynamic equilibrium, defined as the state of maximum entropy. They avoid doing so, according to Schrödinger, by feeding on negative entropy. The Oxford physicist Sir Francis Simon pointed out to Schrödinger that we do not live on entropy, but on free energy, and that the entropic contributions to the reactions in the living body are small compared to the enthalpic ones. In fact, it was known when Schrödinger wrote his book that the primary currency of chemical energy in the cells is ATP, and that the free energy stored in ATP is predominantly enthalpic. The final chapter restates Schrödinger's central theme. The nature of the gene allows only one general conclusion: "Living matter, while not eluding the laws of physics as established to date, is likely to involve other laws of physics hither to unknown which, however, once they have been revealed, will form as integral a part of this science as the former." The apparent contradictions between life and the statistical laws of physics can be resolved by invoking a science largely ignored by Schrödinger. That science is chemistry. When Schrödinger wrote "The regular course of events, governed by the laws of physics, is never the consequence of one well-ordered configuration of atoms, not unless that configuration repeats itself many times," he failed to realize that this is exactly how chemical catalysts work. Given a source of free energy, a well-ordered configuration of atoms in a single molecule of an enzyme catalyst can direct the formation of an ordered stereospecific compound at a rate of 103-105 molecules a second, thus creating order from disorder at the ultimate expense of solar energy. Enzymes are sufficiently large to form unique, well-ordered, stable structures, capable of immobilizing DNA in their active sites while they catalyze the replication of the genetic message. They even provide proofreading mechanisms that keep the error rate of replication as low as 10 -10. I was asked by the organizers of the Schrödinger Centenary Symposium to review the influence of his book on molecular biology. I accepted with the intention of doing honor to Schrödinger's memory, but to my disappointment, a close study of his book and of the related literature has shown me that what was true in his book was not original, and most of what was original was known not to be true even when the book was written. The book also ignores some crucial discoveries that were published before it went into print. It is more fiction than science, which may account for its huge sales. Perutz works at the Medical Research Council's Laboratory of Molecular Biology, Cambridge CB2 2QHQ, UK, with support from the U.S. National Institutes of Health and the U.S. National Science Foundation. Editor's Note: This year marks the centenary of the birth of Erwin Schrödinger, the Austrian physicist who was instrumental in developing the mathematical equations of quantum mechanics. Leading scientists from around the world gathered last week at Imperial College, London to commemorate the event and look back on Schrödinger's contributions and their impact on modern science. Schrödinger's quest to understand the quantum world led him to devise his famous cat "thought experiment." Used to demonstrate flaws in the strict interpretation of quantum physics, this experiment envisions a box containing radioactive material, a radioactivity detector, a bottle of poison and a cat. It is set up so that there is a 50-50 chance that a radioactive atom will decay in a certain time and emit a particle, causing the poison bottle to break and the cat to die. According to quantum theory, the outcome of the experiment is not known until an observer opens the box and looks inside; until then, the cat is in limbo, both dead and alive, neither alive nor dead. Obviously, Schradinger sought to point out, the cat cannot be both dead and alive at the same time. Schrödinger's impact was not limited to the physical sciences. His book What is Life?, published in 1944, put forth the notion that life could be understood in terms of the laws of physics. Molecular biologists were influenced by the ideas expounded in this book and although errors have been cited over the years, it remains a classic. In the following review, M.F. Perutz, who shared the 1962 Nobel Prize in chemistry for determining the structures of hemoglobin and myoglobin, takes a fresh look at What is Lzfe?with emphasis on the book's influence on molecular biology. It is an abbreviated version of his contribution to a book of the proceedings of the London conference, Schrödinger, Centenary Celebrations of a Polymath, to be published by Cambridge University Press.

'What is Life?' Fiction, Not Science

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