It is no exaggeration to say that What is Life? is one of the most impor- tant scientific books of all time. —Graeme K. Hunter1p252

On professional biologists the book had probably little or no influence. In so far as they bothered at all to read “What is Life?,” they probably consid- ered the title a piece of colossal nerve. At their most charitable, they must have viewed the book with amused tolerance. —Gunther S. Stent2p3

The Austrian scientist Professor Erwin Schrödinger. He shared the 1933 Nobel Prize for his research into atomic theory. 18 /Autumn 2015 © Hulton-DeutschThe Collection/CORBISPharos The remarkable life of Erwin Schrödinger’s What Is Life?

Curtis E. Margo, MD, MPH, and Lynn E. Harman, MD Dr. Margo (AΩA, Emory University, 1974) is Clinical The audience was diverse, ranging from students to dignitaries, Professor of Ophthalmology, and Pathology and Cell including Eamon de Valera, the Irish prime minister. Because Biology at the Morsani College of Medicine, the University so many people had to be turned away, Schrödinger repeated of South Florida. Dr. Harman (AΩA, University of the lecture the following Monday to another packed hall. The South Florida, 1993) is Clinical Assistant Professor of lectures continued weekly into March, with little falloff in at- Ophthalmology at the Morsani College of Medicine, the tendance. Interest in the talks was understandable, given the University of South Florida. novelty of hearing a renowned physicist (who just fifteen years earlier had helped to disassemble the common-sense universe n the evening of February 5, 1943, famed theoretical of Newton) discuss a subject so removed from the physical physicist Erwin Schrödinger delivered the first in a sciences. Even in America, as the nation was transfixed on series of lectures titled “What Is Life?” In the weeks the aerial bombardment of northern Germany and fighting in Oprior to the event, news spread that it would be open to the Guadalcanal, the lectures made news. But coverage in the press public. The lecture was held at Trinity College, Dublin, where was trifling. TIME magazine devoted more space to describing Schrödinger was head of the Institute of Advanced Studies. Schrödinger’s love of the Gaelic language and Irish music than

The Pharos/Autumn 2015 19 The remarkable life of Erwin Schrödinger’s What Is Life?

to the content of the presentation.3 Schrödinger, however, missed Austria. In 1936, he ac- Following the lecture series, Schrödinger prepared the cepted a professorship at the Karl Franzen University of Graz, material for publication, adding an epilogue on determinism along with an honorary position at the University of Vienna. and free will that had not been presented originally. The book Ostensibly unconcerned about the threat of Nazism, he found What Is Life? was released in December 1944. At $1.85 a copy, himself in considerable danger when Adolf Hitler annexed it sold briskly despite wartime austerity. As the upheaval of Austria in 1938. Schrödinger was viewed by the government as World War II ended, the book remained surprisingly popular. untrustworthy, and ordered by the Nazi rector of the university A second edition without substantive editorial revision was to write a public apology (or confession) to the Führer. The published in 1948. It was eventually translated into seven lan- letter was published in German and Austrian papers, leaving guages and sold over 100,000 copies.4p403 Schrödinger humiliated and his British colleagues bewildered. As the sophistication of biochemical and genetic research Soon thereafter, he was summarily dismissed from the profes- soared in the 1950s and 1960s, opinions concerning What Is sorship at his alma mater. With the help of friends in England Life? among elite scientists became oddly polarized. Some and Ireland, he managed to escape Austria with his family claimed the book was an influential document that ushered before war descended on the continent. in the new epoch of molecular biology, while others viewed Schrödinger was unable to return to Oxford as an émigré of it as factually misleading and unoriginal. Biochemist Graeme a combatant nation once the war began, but he obtained a posi- Hunter proclaimed it “one of the most important scientific tion as head of the newly created Dublin Institute of Advanced books of all time,” 1p252 while bacteriophage biologist Gunther Studies. He remained in Ireland for seventeen years. Stent thought any admiration as unwarranted.2 Few twentieth- century science books have received more divergent appraisals. The book Though no single explanation may adequately address this What Is Life? is a concise manuscript of roughly 27,000 anomaly, exploring the contradictory verdicts may shed light words, slightly shorter than George Orwell’s Animal Farm.5 on the factors that have shaped modern biology. It conveys an excitement about deciphering genetics that conventional textbooks never approach. Schrödinger may Erwin Schrödinger not have expected the intended audience to understand the Erwin Schrödinger (1887–1961) was born and raised in mathematics or physics behind the arguments he proposes, Vienna, Austria. The only child of a wealthy bourgeoisie fam- but he did want readers to sense the power of human intellect ily, he enjoyed a comfortable life insulated from the social to comprehend nature. He covers subjects as different and strife that marked the waning years of the Hapsburg Empire. complex as statistical mechanics, the laws of thermodynamics, His aunt Minnie taught him English at an early age. A brilliant and Mendelian genetics through the liberal use of analogies student, he excelled in mathematics and the humanities at and nearly a dozen line drawings. The book contains scattered Akademisches Gymnasium and the University of Vienna, from footnotes, a rare reference, and no bibliography. In the first which he was awarded a Doctor of Philosophy in physics in three chapters, Schrödinger summarizes the modern physicist’s 1910. Schrödinger rose steadily through the ranks of academia approach to investigating atoms and molecules, the biological to become Professor of Theoretical Physics in Zürich in 1922. mechanism of inheritance, and recent animal experiments His greatest intellectual achievement occurred four years with X-ray induced mutations. Although these reviews are later, with the publication of six papers on wave mechanics in superficial and prone to oversimplification, Schrödinger fuels Annalen der Physik. These works culminated in the wave equa- expectations that some magnificent insight is always lurking tion, which describes the behavior of particles in the atomic on the next page. and subatomic world. A computational cornerstone of quan- Schrödinger accommodates the nonscientist by assuming tum mechanics, the wave equation (which now bears his name) the role of a supportive teacher. This was a particularly exciting catapulted Schrödinger to the most prestigious academic posi- time in biology. The chromosome that biologists were just be- tion in Germany: Professor of Theoretical Physics in Berlin and ginning to explore is what he calls an aperiodic crystal, “a mas- successor to Max Planck.4 terpiece of embroidery” equivalent to a “Raphael tapestry.” 5p5 After Schrödinger arrived in Berlin in 1927 he found the While praising the organic chemist for contributing knowledge political and social atmosphere increasingly disturbing. In 1933, about this tapestry, he laments the physicist for having done he abruptly left Berlin to become a Fellow of Magdalen College, next to nothing to further understanding of the molecule. He Oxford, a decision many friends believed was in protest of is both perplexed and awed by this genetic substance, undoubt- Nazi malevolence. After arriving in Oxford, Schrödinger was edly a polymer, because it reproduces itself with remarkable awarded the Nobel Prize in Physics for his wave equation. This fidelity for generations. To emphasize this key point with a international recognition not only highlighted his awkward tangible example, he selects the infamous Hapsburg lip, faith- departure from Berlin, it insured that the Nazi officials would fully preserved throughout the long dynasty. remember the move as an insult. In the second chapter, Schrödinger introduces the term

20 The Pharos/Autumn 2015 code-script to describe the key function of the chromosome. He among scientists,” yet cautioned that this “meaty exposition” soon apologizes for the inadequacy of even this term, stating was not light reading.7p283 that the material of life is more than just a blueprint. Consider More thorough reviews appeared in professional journals. it instead both an “architect’s plan and builder’s craft—in Distinguished geneticist J. B. S. Haldane, writing in Nature, re- one.” 5p22 His translation of science to the vernacular is artful spectfully disagreed with many of Schrödinger’s “details” and and absolutely necessary to offset the rapid pace at which he “fundamental principles,” but admitted that the work was fas- introduces complicated ideas. Technical words and theorems cinating to read.8 Herman Muller, perhaps the most eminent are seemingly plucked from nowhere. Schrödinger eases the geneticist of the World War II era (and who performed much tension of scientific jargon with the implicit assurance that of the original work on radiation-induced genetic mutations), everything will eventually make sense. complimented Schrödinger for emphasizing the need for From the third to sixth chapters, Schrödinger discusses strengthening the liaison between the physical and biological the quantum nature of genetic mutations and the application sciences. But he, too, warned readers not to take the genetics of the second law of thermodynamics to living matter. Gaps in and chemistry too seriously, because they were incomplete development of concepts are inevitable without mathematics and flawed.9 or sufficient space. The crux of his thesis is found in the fourth After the molecular revolution that followed the discovery chapter: “In the light of present knowledge, the mechanism of of DNA structure in 1953, What Is Life? began to be viewed in heredity is closely related to, nay, founded on, the very basis a different light. It was no longer just a quaint or misguided of quantum theory.” 5p47 Schrödinger, the consummate theo- work about genetics. To some it was inspirational, and to oth- retician, is searching for a universal truth. Intuition tells him ers prophetic. genetic inheritance has a quantum mechanics solution. The reward for readers who are unable to follow the scientific argu- Nostalgic reflections ment will be the final answer. As Schrödinger continues his dis- The mystique surrounding What Is Life? may have come cussion in the sixth chapter, he confronts the effect that body to a head in 1966, with the publication of The Double Helix temperature has on the motion of atoms. The molecular chaos by James Watson. In the second chapter of this best-selling predicted by thermodynamic theory appears to undermine the memoir, Watson paid tribute to Schrödinger’s work by main- order demanded by his quantum-theory model. taining it was a major factor in why Francis Crick left physics The seventh and final chapter is reckoning time. How will for biology. He went on to give Schrödinger credit for elegantly Schrödinger reconcile the contradiction he has created? It expressing “the belief that genes were the key components of turns out he cannot. Abruptly, as if reading a murder mystery, living cells and that, to understand what life is, we must know the author turns the plot on its ear, admitting that the order how genes act.” 10p18 Francis Crick would confirm the conse- demanded by life is inexplicable. The current laws of physics quential role that this little book played in changing his career, cannot explain the behavior of living organisms.5p80 He ends but admitted that when he read What Is Life? he knew little the book with a four-page epilogue on unrelated subjects—de- chemistry or biology. As he realized later in his career, neither terminism and free will. did Schrödinger.11 Even without mathematical derivations the book is chal- One biographer of Watson recounted that What Is Life? lenging to read, with layers of abstract concepts mixed with an also played a pivotal role in directing Watson into molecular incomplete picture of genetics. The Encyclopedia Britannica biology, but added that he read the book while a teenager at describes What Is Life? as “an application of quantum me- the University of Chicago.12p22 Watson had planned to apply chanics to genetics,” 6p973 but it is something other than that. to graduate school in ornithology, but changed his mind, ap- The biochemist Graeme Hunter appreciated the work as an parently convinced that Schrödinger was correct in seeing the exploration of “the workings of the hereditary mechanism future of biology in genetics. There was never anything scien- at a philosophical level.” 1p250 Given the shortcomings of this tifically explicit behind Watson’s admiration for What Is Life?, quirky little text, it should have faded into obscurity. There but the same could be said of the reasons other prominent were few clues that could have predicted its long and contro- scientists were drawn to the work. versial future. Maurice Wilkins, co-recipient of the 1962 Nobel Prize with Watson and Crick, also found inspiration in What Is Life? In Early reviews his Nobel lecture, Wilkins attributed his impetus to leave solid What Is Life? received favorable reviews following its pub- state physics for biology to this short book.13p328 He read it at a lication, although some were critical of the epilogue that was time of moral confusion after having worked on the Manhattan not part of the initial lecture series. These reviews, however, project.13,14 Although details surrounding his epiphany remain were either cursory or measured their praise carefully. A book vague, it must have been reassuring for Wilkins to have a review in Scientific American claimed Schrödinger’s “brilliant physicist of Schrödinger’s stature portray research in biology hypothesis has aroused lively and mainly favorable discussion as exciting.

The Pharos/Autumn 2015 21 The remarkable life of Erwin Schrödinger’s What Is Life?

their responses because so much “pro- fessional malaise” existed at the time.2p3 Stent, a molecular biologist with first- hand knowledge of the advances made in biology before and after World War II, picked apart Schrödinger’s major thesis that genetics would prove incomprehen- sible within the framework of conven- tional physical knowledge.2p4 But what rankled Stent the most was the failure of Schrödinger to recognize the contribu- tions of bacteriophage research to genet- ics, including the work of Alfred Hershey, Salvador Luria, and Max Delbrück. Stent viewed bacteriophages as living molecules ideally suited to explain the physical ba- sis of biological self-reproduction. But Schrödinger never mentioned bacterio- phage research in his discussion.2p5 To overlook the contributions of this en- 1962 Nobel Prize winners display their diplomas after formal ceremonies in Stockholm's Concert Hall. They are (L to R): Professor Maurice H. Wilkins (Medicine); tire field of research was not how nar- Dr. Max Perutz (Chemistry); Dr. Francis Crick (Medicine); author John Steinbeck ratives of science should be presented. (Literature); Prof. James D. Watson (Medicine); and Dr. John Kendrew (Chemistry). Stent was not the only biologist to chide Bettman/CORBIS. Schrödinger for this oversight, but he may have been the least forgiving.1,4,13 When Linus Pauling eventually Schrödinger’s foray into biology had similar influences on weighed in on the controversy, he was characteristically blunt: the lives of other notable researchers of this era. Seymour “When I first read this book, over 40 years ago, I was disap- Benzer, who was trained in solid state physics but spent the pointed. It was, and still is, my opinion that Schrödinger made bulk of his life studying bacteriophages, said the small volume no contribution to our understanding of life.” 16p229 English altered the course of his career.14p272 Hermann Staudinger, the biochemist and Nobel laureate Max Perutz was less charitable: 1953 Nobel laureate in Chemistry for his work in macromol- “Sadly, however, a close study of his book and of the related ecules, professed a personal affection for What Is Life?13p19 literature has shown me that what was true in his book was not Tributes for What Is Life? seemed unreasonable for a treatise original, and most of what was original was known not to be filled with tenuous arguments and an imperfect grasp of genet- true even when the book was written.” 17p243 ics. Such accolades were bound to provoke closer scrutiny. Subconscious influences Critiques When Schrödinger was preparing his lectures in 1943, With thirty-five-year hindsight, science historian E. J. Yoxen the prevailing belief was that genes were large proteins. In observed that “the archaic style, the abstruse argument, and the February of the next year, a team of bacteriologists led by elaborate, dated message of Schrödinger’s book seem a curi- Oswald Avery published their classic study using strains ous sort of inspiration for the thrust and power of molecular of pneumococci to show that nucleic acid was the genetic biology, as we perceive it today.” 15p17 Indeed, from a modern substance.13p181 Some find Schrödinger’s insights into genet- perspective, much of the book reads more like a Jules Verne ics as all the more remarkable because he had no knowledge novel than a scientific treatise. Critical examination of the of the macromolecule responsible for reproduction.1,15,18–19 short volume in the years after its polite reception began to Indeed, he appeared to anticipate DNA structure and function highlight its imperfections. rather well through his choice of metaphors, the most quoted Perhaps the earliest rebuke came from Gunther Stent in the of which were the aperiodic crystal (or polymer) and the code- introduction to a Festschrift to Max Delbrück in 1966, in which script.6 Yet crediting Schrödinger with foresight based on the he recognized that the book had great “propagandist impact choice of metaphors is risky, since metaphors are prone to on physical scientists” but went on to compare it to “a kind of vastly different interpretations. ‘Uncle Tom’s Cabin.’ ” 2p3 Conceding that the book may have Metaphors facilitate the understanding of new ideas stirred passions among scientists, he nevertheless downplayed through other more familiar ideas. Modern English has a

22 The Pharos/Autumn 2015 surplus of metaphors to explain how DNA looks and what 5. Schrödinger E. What is Life? The Physical Aspects of the Liv- it does: twisted ladder, immortal spiral, blueprint, template, ing Cell with Mind and Matter & Autobiographical Sketches. Com- fingerprint, database, book, and text, to name a few. Each to bined reprint. Cambridge (UK): Cambridge University Press; 1967. some degree simplifies understanding of structure or function. 6. Schrödinger, Ernest. In: The New Encyclopedia Britannica in Schrödinger’s metaphors, however, were created before any 3 Volumes, Micropaedia Volume VIII. Chicago: Encyclopedia Britan- knowledge of DNA existed. Was he simply lucky in the figures nica Inc.; 1978: 973. of speech he chose, or do these metaphors indicate astonishing 7. A.G.I. What Is Life? By Erwin Schrödinger. Scientific Am insight into how genetic data are stored and transmitted? In June 1946; 174: 283. 2011, Michael Hendrickson, a surgical pathologist with a keen 8. Haldane JBS. A physicist looks at genetics. Nature 1945; 155: interest in this subject, observed that “the powerful metaphors 375–76. that have become indispensible [sic] to our understanding of 9. Muller HJ. A physicist stands amazed at genetics. J Heredity genetic material can be traced back to Schrödinger’s What Is 1946; 37: 90–92. Life?” 20p47 10. Watson JD. The Double Helix: A Personal Account of the Whether Schrödinger’s aperiodic crystal and code-script Discovery of the Structure of DNA. New York: Mentor Book; 1968. were explicit ideas that subconsciously led researchers towards 11. Crick F. What Mad Pursuit: A Personal View of Scientific our current understanding of DNA is a matter of conjecture.1,20 Discovery. New York: Basic Books; 1988. The merits and limitation of DNA analogies like aperiodic 12. Baldwin J. DNA Pioneer: James Watson and the Double He- crystal have been subject to debate, but code-script is a univer- lix. New York: Walker & Co.; 1994. sally embraced metaphor of DNA function. Whether its origins 13. Olby R. The Path to the Double Helix: The Discovery of DNA. in the context of genetic inheritance have been correctly traced New York: Dover Publications; 1974. to What Is Life? is beyond the purview of this discussion, but 14. Judson HF. The Eighth Day of Creation: Makers of the Revo- the claim has withstood general inquiry.1 lution in Biology. New York: Simon and Schuster; 1979. 15. Yoxen EJ. Where does Schroedinger’s “What Is Life?” belong Summary in the history of molecular biology? Hist Sci 1979; 17: 17–52. In the seven decades since Schrödinger’s book was pub- 16. Pauling L. Schrödinger’s Contribution to Chemistry and Biol- lished, it has gone through stages of differing appraisal, starting ogy. In: Kilmister CW, editor. Schrödinger: Centenary Celebration with guarded approbation in the 1940s. When several lumi- of a Polymath. Cambridge (UK): Cambridge University Press; 1987: naries in molecular biology described the work as influencing 225–33. their careers, the book’s renown increased. In What Is Life?, 17. Perutz M. Erwin Schrödringer’s What is Life? and Molecular Schrödinger examined genetics from the perspective of a theo- Biology. In: Kilmister CW, editor. Schrödinger: Centenary Celebra- retical physicist, and conjured up ideas that dilettantes admired tion of a Polymath. Cambridge (UK): Cambridge University Press; and experts slighted. Schrödinger sowed his most important 1987: 234–51. ideas in terms of metaphors, allowing readers considerable 18. Olby R. Schrödinger’s problem: What Is Life? J Hist Biol 1971; latitude for interpretation. Some found nothing worthwhile in 4: 119–48. the book, only chemical naivete and ignorance of work that had 19. Symonds N. What Is Life? Schrödinger’s influence on biology. already been done. Others found deep inspiration and a desire Quart Rev Biol 1986; 61: 221–26. to understand biological reproduction, even if it required new 20. Hendrickson MR. Exorcizing Schrödinger’s Ghost: Reflec- paradigms of physical science. What Is Life?—like the ancient tions on ‘What Is Life?’ and Its Surprising Relevance to Cancer Biol- parable of the blind men and an elephant—is an example of the ogy. In: Gumbrecht HU, Harrison RP, Hendrickson MR, Laughlin ineffable nature of truth, pitting subjective experience against RB, editors. What Is Life? The Intellectual Pertinence of Erwin the totality of the reality. The legacy of What Is Life? may ulti- Schrödinger. Stanford (CA): Stanford University Press; 2011: 45–104. mately be respect for different opinions. The author’s addresses are: References Curtis E. Margo, MD, MPH 1. Hunter GK. Vital Forces: The Discovery of the Molecular Department of Ophthalmology, Basis of Life. San Diego (CA): Academic Press; 2000. 12901 Bruce B. Downs Boulevard 2. Stent GS. Introduction: Waiting for the Paradox. In: Cairns J, MDC Box 21, Tampa, Florida 33612 Stent GA, Watson JD, editors. Phage and the Origins of Molecular E-mail: [email protected] Biology. Cold Spring Harbor (NY): Cold Spring Harbor Laboratory of Quantitative Biology; 1966. Lynn E. Harman, MD 3. Schrödinger. TIME 1943 Apr 5; 41 (14): 42. Department of Ophthalmology, 4. Moore W. Schrödinger: Life and Thought. Cambridge (UK): 12901 Bruce B. Downs Boulevard Cambridge University Press; 1989. MDC Box 21, Tampa, Florida 33612

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