by Matthew Cobb
Although this was the first public suggestion that a gene contained something like a code, in 1892 the scientist Fritz Miescher had come up with something vaguely similar. In a private letter, Miescher had argued that the various forms of organic molecules were sufficient for ‘all the wealth and variety of hereditary transmission [to] find expression just as all the words and concepts of all languages can find expression in twenty-four to thirty alphabetic letters.’49 Miescher’s view can appear far-seeing, especially given that he was also the discoverer of DNA, or, as he called it, nuclein. But Miescher never argued that nuclein was the material making up these letters and his suggestion was not made public for nearly eighty years. Above all, the vague letter and word metaphor was nowhere near as precise as Schrödinger’s code-script concept.
Schrödinger then explored what the gene-molecule might be made of and suggested that it was what he called a one-dimensional aperiodic crystal – a non-repetitive solid, with the lack of repetition being related to the existence of the code-script. The non-repetition provided the variety necessary to specify so many different molecules in an organism. Although Troland, Muller and Koltsov had all suggested two decades earlier that genes might grow like crystals, Schrödinger’s idea was far more precise. His vision of gene structure was focused on the non-repetitive nature of the code-script, rather than on the relatively simple parallel between the copying of chromosomes and the ability of crystals to replicate their structure.50
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Schrödinger’s words would have had little influence had they simply hovered in the Dublin air and briefly resonated in the minds of the more attentive listeners. The sole international report to describe the lectures, which appeared in Time magazine in April, did not refer in detail to anything that Schrödinger said, and there are no indications that any of his ideas escaped to the outside world. The only detailed account appeared in The Irish Press, which managed to condense his main arguments, and included both the code-script and aperiodic crystal ideas.51 Other newspapers found it difficult to give the story the attention it deserved; when Schrödinger gave a version of his lectures in Cork in January 1944, the local newspaper, The Kerryman, gave his talk equal coverage to the Listowel Pig Fair (there was good demand for the 126 pigs on sale, they reported).52
Schrödinger felt that the public would be interested in his views, and as soon as he had finished the lectures he began to turn them into a book, with the addition of a brief and deliberately controversial conclusion. Schrödinger had closed his lectures with a pious nod in the direction of his overwhelmingly Catholic audience, proclaiming that the ‘aperiodic crystal forming the chromosome fibre’ was ‘the finest masterpiece ever achieved along the lines of the Lord’s quantum mechanics’. But in a new Epilogue, written specially for publication and entitled ‘Determinism and free will’, Schrödinger explored his lifelong belief in the mystical Hindu philosophy of Vedanta. He argued that individual human identity was an illusion, and he criticised official Western creeds for their superstitious belief in the existence of individual souls. His point was not that there was no evidence that souls exist but rather that individual consciousness is the illusory expression of a single universal soul. He expressed this in what he admitted were ‘blasphemous and lunatic’ terms for the Christian tradition, but which he apparently considered to be true: ‘I am God Almighty’.
The book was about to be printed by a respected Dublin publishing house when someone in the company got cold feet. In 1940s Ireland the Catholic Church retained a stranglehold over culture, and it was not possible to criticise Christian beliefs in the terms that Schrödinger had used in the final chapter. The publisher pulled out. Undeterred, Schrödinger sent the manuscript to a friend in London, and it was eventually published by Cambridge University Press in December 1944. The combination of Schrödinger’s name, the intriguing title and a prestigious publisher with a global reach, coupled with the imminent end of the war, meant that the book was widely read and has remained in print ever since. Despite the commercial success of What is Life?, that was the end of Schrödinger’s excursion into biology. He never wrote publicly on the topic again, even after the discovery of the existence of the genetic code in 1953.53
The immediate impact of What is Life? can be seen from the enthusiastic reviews it received in both the popular press and in scientific journals. There were over sixty reviews in the four years after publication, although few writers noticed what now seem to be far-seeing ideas – the aperiodic crystal and the code-script – and it was translated into German, French, Russian, Spanish and Japanese.54 There were two extended reviews in the leading scientific weekly Nature, one by the geneticist J. B. S. Haldane, the other by the plant cytologist Irene Manton. Haldane got straight to the heart of the matter, picking up on the aperiodic crystal and the code-script innovations and making a link with the work of Koltsov. Manton also noted Schrödinger’s use of the term code-script, but she took it to mean ‘the sum of hereditary material’ rather than a particular hypothesis about gene structure and function. The New York Times reviewer put his finger on the central point:
The genes and chromosomes contain what Schrödinger calls a ‘code script,’ that gives orders which are carried out. And because we can’t read the script as yet we know virtually nothing of growth, nothing of life.
In contrast, some scientists later recalled that they had been unimpressed by the book. In the 1980s the Nobel Prize-winning chemist Linus Pauling claimed that he was ‘disappointed’ on reading What Is Life? and stated: ‘It was, and still is, my opinion that Schrödinger made no contribution to our understanding of life.’55 Also in the 1980s, another Nobel laureate, biochemist Max Perutz, wrote of Schrödinger: ‘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’, while in 1969 the geneticist C. H. Waddington criticised Schrödinger’s aperiodic crystal concept as an ‘exceedingly paradoxical phrase’.56 As well as these restrospective criticisms, some dissenting views were voiced at the time. In a review, Max Delbrück was critical, even though he had received a publicity boost from Schrödinger’s espousal of his work in the Three-Man Paper. He claimed Schrödinger’s term aperiodic crystal hid more than it revealed:
genes are given this startling name rather than the current name ‘complicated molecule’ … There is nothing new in this exposition, to which the larger part of the book is devoted, and biological readers will be inclined to skip it.
This was distinctly ungenerous, as Schrödinger’s hypothesis was in fact quite precise and did not simply involve coining a new name. Delbrück concluded by grudgingly accepting that the book ‘will have an inspiring influence by acting as a focus of attention for both physicists and biologists.’ In another review, Muller said that he, too, expected that the book would act as a catalyst for ‘an increasingly useful rapprochement between physics, chemistry and the genetic basis of biology’. Muller clearly felt aggrieved that Schrödinger had not cited his work, and pointed out that he had suggested the parallel between gene duplication and crystal growth in 1921 (Muller did not mention that he had taken this concept from Leonard Troland). He also dismissed the idea that there was anything novel in Schrödinger’s discussion of order and negative entropy, as these were both ‘quite familiar to general biologists’. Neither Delbrück nor Muller made any comment about the code-script idea.
Despite their overall scepticism, Delbrück and Muller were absolutely right: Schrödinger’s book did indeed inspire a generation of young scientists. The three men who won the Nobel Prize for their work on the structure of DNA – James Watson, Francis Crick and Maurice Wilkins – all claimed that What is Life? played an important part in their personal journeys towards the double helix. In 1945 Wilkins was handed a copy of What is Life? by a friend when he was working on the atomic bomb in California. Shaken by the horror of Hiroshima and Nagasaki, Wilkins was seduced by Schrödinger’s writing and decided to abandon physics and become a ‘biop
hysicist’. Crick recalled that his 1946 reading of Schrödinger ‘made it seem as if great things were just around the corner’; Watson was an undergraduate when he read What is Life? and as a result he shifted his attention from bird biology to genetics.57
Even though some of the ideas developed in What is Life? were visionary and the book undoubtedly inspired some individuals who played a central role in twentieth-century science, there are no direct links between Schrödinger’s lectures and the experiments and theories that were part of the decades-long attempt to crack the genetic code, and historians and participants differ about the significance of Schrödinger’s contribution.58 The view of mutation put forward in the Three-Man Paper, which Schrödinger espoused so vigorously, had no effect on subsequent events, and his suggestion that new laws of physics would be discovered through the study of the material basis of heredity was completely mistaken. Even the code-script idea, which looks so prescient today, had no direct effect on how biologists looked at what was in a gene. None of the articles that later formed part of the discovery of the genetic code cited What is Life?, even though the scientists involved had read the book.
In fact, the meaning of Schrödinger’s ‘code-script’ did not have the same richness as our ‘genetic code’. Schrödinger did not think that there was a correspondence between each part of the gene and precise biochemical processes, which is what a code implies, nor did he address the issue of what exactly the code-script contained, beyond the vague suggestion of a plan. Ask any biologist today what the genetic code contains, and they will give you a one-word answer: information. Schrödinger did not use that powerful metaphor. It was completely absent from his vocabulary and his thinking, for the simple reason that it had not yet acquired the abstract wide-ranging meaning we now give it. ‘Information’ was about to enter science, but had not done so when Schrödinger gave his lectures. Without that conception of the content of the code, Schrödinger’s insight was merely part of the zeitgeist, a hint of what was to come rather than a breakthrough that shaped all subsequent thinking.
–TWO–
INFORMATION IS EVERYWHERE
While Schrödinger was in neutral Ireland, away from the horrors of the Second World War, other scientists all over the world joined in the war effort, keen to use their skills to develop new ways of killing people on the other side, or at least to find ways of stopping people on their side from being killed. This was particularly true in the US, where in June 1940, eighteen months before the US eventually entered the war, President Roosevelt instructed the vice-president of the Massachusetts Institute of Technology (MIT), Vannevar Bush, to set up a National Research Defense Committee (NRDC) in order to develop new weapons. The NRDC went on to mobilise more than 6,000 American scientists, including those working on the ultra-secret Manhattan Project, which eventually produced the atomic bomb.1 The scale of spending was immense: by 1944, the federal research budget was $700m per year – more than ten times the amount spent in 1938.*
One of the scientists involved in this work was a brilliant and mercurial mathematician from MIT named Norbert Wiener (pronounced Wee-ner). In September 1940, 46-year-old Wiener – a portly, cigar-smoking vegetarian, who was short-sighted and wore a rakish van Dyke beard – wrote to Vannevar Bush offering his services: ‘I hope you may find some corner of the activity in which I may be of use during the emergency.’ Wiener had been a child prodigy; he later studied logic with Bertrand Russell and made important contributions to mathematics in the 1920s and 1930s.
Wiener’s involvement in the preparations for war was motivated by a mixture of patriotism and deep hostility towards the Nazis – his father was a Russian Jew. However, Wiener’s wife was profoundly anti-semitic and an avid supporter of Hitler, while members of her close family in Germany were Nazis. During the war, Wiener’s daughter, Barbara, was punished at school for reciting passages from her mother’s copy of Mein Kampf. All this made for an interesting home life.2
Vannevar Bush felt that the US was insufficiently prepared for an air attack, and that the country needed to develop ‘the precise and rapid control of guns’ in order to shoot down enemy planes.3 This was the area that Wiener began working on. In autumn 1940 he showed that it was theoretically possible to develop an automatic anti-aircraft system that could destroy enemy planes with minimal human intervention. In December 1940, Wiener’s proposal to turn his theoretical idea into reality was given a paltry $2,325 budget and stamped ‘secret’ by the newly formed section D-2 of the NRDC. Section D-2, which funded eighty projects to the value of around $10m during the course of the war, organised research on ‘fire control’ – systems for controlling artillery fire. The section was run by the director of the Rockefeller Institute, Warren Weaver, who two years earlier had coined the term ‘molecular biology’.4
Existing anti-aircraft systems could involve up to fourteen men: some spotted the plane, some identified its trajectory, others rapidly calculated where the aircraft was predicted to be, while a final group cranked the gun to the appropriate orientation and elevation and then fired. But if the pilot took evasive action after the shell was fired, it would miss its target – the calculations assumed the plane was flying in a straight line. Wiener’s bold idea was to find a mathematical formula for predicting where the plane would be, whatever the pilot did.
By the winter of 1941, Wiener had used his mathematical skills to predict near-random movement by a target, and then to calculate an intercept course to the most probable destination points. Julian Bigelow, a talented young ex-IBM engineer with a taste for messing about with old cars who also happened to be an amateur pilot, was assigned to work with Wiener. The pair constructed a device that simulated the movement of a target aeroplane and the response of an anti-aircraft gun crew, by projecting beams of light onto the ceiling of Room 2–244 on the MIT campus by the Charles River Basin.5 Wiener and Bigelow also went into the field and studied how real-life gunners behaved. Here Wiener made his breakthrough, as he noticed that the soldiers would take actions designed to respond to a pattern of movement by the aircraft. The gunner used knowledge about where he expected the plane to be and attempted to compensate for that predicted movement when calculating where to fire his gun. Wiener set about trying to describe this effect in mathematical terms. The stress began to tell as Wiener gobbled amphetamines – quite legal at the time – in an attempt to meet deadlines. He became irritable and even more garrulous than usual – hardly advisable for someone working on a top-secret project – and eventually had to kick his speed habit. As he later explained: ‘I had to give it up and look for a more rational way of strengthening myself to bear the burdens of war work.’6
Wiener realised that the way the gunner responded to the movement of the aircraft meant that he was acting as part of a feedback system – a phenomenon that was well known from acoustics and engineering. Wiener discussed this insight with a friend from his student days, a Harvard physiologist called Arturo Rosenblueth. They realised that feedback was a common feature of many systems, both technological and natural, and could be seen in the behaviour and physiology of animals. Excited by their theoretical breakthrough, the two men announced their vision at a small scientific meeting held in New York in 1942. The two-dozen strong audience was composed of an eclectic mixture of neurophysiologists and psychologists, along with the husband and wife anthropologists Gregory Bateson and Margaret Mead. Rosenblueth’s speech, which described what he called ‘circular causality’ or feedback loops, was written up as a paper with Wiener and Bigelow and published under the title ‘Behaviour, purpose and teleology’ in the journal Philosophy of Science.7 The use of the word teleology was deliberately provocative, as this concept explains phenomena in terms of their purpose, and purpose had been banished from polite scientific discourse for centuries. According to Aristotle, the ultimate explanation of natural phenomena was their purpose or final cause. For example, a dropped apple will fall to the ground because its final cause is to go downwards. From the seventeenth
century onwards, it was increasingly realised that this approach did not explain anything, and more powerful mechanistic explanations were sought. Wiener wanted to reinstate the idea of purpose by explaining it in mathematical terms.
Wiener and Rosenblueth showed that purposeful, goal-directed behaviour can be seen in organisms and machines, and that it operates through what is known as negative feedback. Normal feedback leads to the uncontrolled amplification of the signal – this is the howl that is produced if a microphone is placed too close to a loudspeaker. Negative feedback means that a given activity ceases when a particular pre-defined state is achieved. In this way a signal can drive a machine or an organism to an end; if the goal is not attained, then continued signals will direct the behaviour towards the goal. For example, a torpedo that homes in on acoustic signals emitted by a battleship uses negative feedback to guide itself to its target – it stops altering its direction when the signal is strongest, as that indicates that the target is dead ahead.8
After the war, Warren Weaver finally got round to reading the Wiener, Rosenblueth and Bigelow paper. He was not impressed: ‘I want to read this article but so far I have not succeeded in getting beyond the first four paragraphs’, he told Wiener.9 If Weaver had ploughed on, he might have found the rest of the document more rewarding, for it marked a shift in scientific thinking. It put all systems on the same level, be they mechanical, organic or hybrid human–machine (as in the case of the anti-aircraft guns), and suggested that behaviour could be interpreted using the same principles and analysed in terms of the same negative feedback loops. When the paper was read to the small New York audience, the effect was electric. Neurophysiologist Warren McCulloch was particularly excited, as it coincided with the models of brain function that he was developing with Walter Pitts, an odd but brilliant 20-year-old maths prodigy.10 Even the anthropologist Margaret Mead was rapt: ‘I did not notice that I had broken one of my teeth until the Conference was over’, she later wrote.11
