Life's Greatest Secret (6 page)

Seven months later, in October 1946, the New York Academy of Sciences held a special meeting on ‘Teleological mechanisms’ at which Wiener spoke, outlining the ideas in the Yellow Peril that had been withheld from public view the year before.
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Wiener explained that underlying all examples of negative feedback control there was a single unifying idea, which he called the message – all control systems involved communication, and could be understood using the same conceptual framework. Inspired by Schrödinger’s
What is Life?,
Wiener made a link between information and entropy, going even further than Szilárd’s discussion of Maxwell’s Demon, in that he defined entropy as ‘the negative of the amount of information contained in the message’. This was ‘not surprising’, Wiener went on, because ‘Information measures order and entropy measures disorder. It is indeed possible to conceive all order in terms of message.’ The laws governing communication, he argued, were ‘really identical’ with the second law of thermodynamics. So, for example, once a message has been created, subsequent operations can degrade it but cannot add information. The arrow of entropy points only one way, and all that life can do is to temporarily halt the process; it cannot truly reverse it. One of the main explanatory frameworks used by postwar science – the role of information in biology – was emerging and was now connected with the fundamental measure of order on a cosmic scale.

A month later, von Neumann took a step towards linking the study of control systems with visions of how life reproduces itself. He was increasingly convinced that Wiener’s focus on modelling human behaviour was a mistake: the human brain was far too complex. At the end of November 1946, von Neumann wrote a long letter to Wiener outlining a startlingly different approach, which dominated science for decades to come.
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He began with a self-criticism, pointing out that through their shared enthusiasm for studying the human central nervous system, ‘we selected … the most complicated object under the sun – literally.’ But the problem was even greater than the mere complexity of the brain, argued von Neumann. He felt they had first to understand the underlying molecular mechanisms before they could hope to understand higher level activity:

nothing that we may know or learn about the functioning of the organism can give, without ‘microscopic’, cytological work any clues regarding the further details of the neural mechanism.

Von Neumann’s solution was radical. He concluded that they should focus on what he termed

the less-than-cellular organisms of the virus or bacteriophage type … They are self-reproductive and they are able to orient themselves in an unorganized milieu, to move towards food, to appropriate it and to use it. Consequently, a ‘true’ understanding of these organisms may be the first relevant step forward and possible the greatest step that may at all be required.

Von Neumann’s grasp of virus biology was flimsy – he told Wiener that a virus was ‘definitely an animal, with something like a head and a tail’ (in fact viruses are not even alive by most definitions). Despite being a poor biologist, von Neumann’s suggestion that simple systems can reveal principles that apply to more complex forms of organisation was absolutely right. He calculated that each virus consisted of around 6,000,000 atoms, and ‘only … a few hundred thousand “mechanical elements”.’ Von Neumann explained to Wiener that it should be possible to understand the interaction of these components, although he recognised that even this proposal was challenging:

Even if the complexity of the organisms of molecular weight 10

–10

is not too much for us, do we not possess such means now, can we at least conceive them, and could they be acquired by developments of which we can already foresee the character, the caliber, and the duration.

Von Neumann suggested to Wiener that they should study the ‘physiology of viruses and bacteriophages, and all that is known about the gene-enzyme relationship’. His explanation for this approach was that viruses could give an insight into genes, which suggests he understood more about viruses than implied by his statement that they were animals:

Genes are probably much like viruses and phages, except that all the evidence concerning them is indirect, and that we can neither isolate them nor multiply them at will.

Von Neumann was becoming interested in genes because one of the essential features of life that fascinated him was its ability to replicate itself. Indeed, from his previous thinking about self-reproducing automata, von Neumann now felt sure that ‘self-reproductive mechanisms’ in living things could be understood in terms of the framework that he and Wiener had been developing:

I can show that they exist in this system of concepts. I think that I understand some of the main principles that are involved. … I hope to learn various things in the course of this literary exercise, in particular the number of components required for self-reproduction. My (rather uninformed) guess is in the high ten thousands or in the hundred thousands, but this is most unsafe.

Von Neumann adopted this approach after attending the Ninth Washington Conference on Theoretical Physics, which had taken place at the end of October 1946. The subject of the small conference, ‘The physics of living matter’, was inspired by Schrödinger’s
What is Life?
and had been chosen by an eccentric physicist and lifelong friend of Max Delbrück’s, George Gamow (pronounced Gam-off).
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The conference dealt with many of the points outlined by von Neumann in his letter to Wiener. As the rather excitable conference press release put it:

During the past three days, a group of theoretical physicists and biologists have been meeting at The Carnegie Institution of Washington and The George Washington University here to discuss problems relating to ‘the physics of living matter.’ Much of the discussion has concerned problems of heredity and the mechanisms by which the almost fantastic gene is able to imprint its characteristics on the cell constituents in a hereditary fashion. … It was clear from the discussions this year that the borderline area between physics and biology will see a great deal of research activity during the next few years.

The excitement may have been heightened by the fact that at the beginning of the meeting, it was announced that one of the thirty-six attendees, Hermann Muller, had been awarded the Nobel Prize in Physiology or Medicine for his work on genetics. Also at the meeting were two representatives of the new wave of geneticists: George Beadle and Max Delbrück. The question of the material basis of heredity – what genes are actually made of – was at the centre of everyone’s attention. This interest was reinforced by a dramatic discovery that had been made more than two years previously in New York by a man who was not a geneticist and who would never have dreamt of going to any of the speculative conferences on the link between physics and biology that took place at this time.

* Most of that federal money was poured into the private sector. Before the war, 70 per cent of government-sponsored research was undertaken by federal organisations, 30 per cent by companies and universities. By 1944, those figures had been reversed. There was plenty of cash to go round: both universities and the private sector were drowning in money from government contracts focused on military problems (Noble, 1986).

–   THREE   –

In December 1943, the Australian virologist Macfarlane Burnet disembarked in San Francisco after a three-week crossing of the Pacific. He was on his way to Harvard, where he had been invited to give a lecture – despite the war, academic life continued, for some. In his mid-forties, handsome and with wavy hair, Burnet had made his reputation working on influenza and other viral diseases; in 1960 he received the Nobel Prize in Physiology or Medicine for his work on the immune response to infection. After the Harvard lectures were over, Burnet travelled to Chicago and then New York, where he had an astonishing discussion with Oswald Avery – a small, bald microbiologist in his mid-sixties, whose quiet manner impressed those who met him. Salvador Luria, a pioneer of virus genetics, recalled:

Talking with Avery was a marvellous experience. He was a wonderful, short man. Very unpompous … He had the dignity of the nondignified people, very simple; and as he was talking he would close his eyes and rub his bald head. And always very precise.

Avery had spent the whole of his academic life studying pneumococci – the bacteria that cause pneumonia – and had gained an international reputation for his work using immunological responses to characterise different pneumococcal strains. But the story that Avery told Burnet had nothing to do with immunology. As Burnet explained to his fiancée, Avery ‘has just made an extremely exciting discovery which, put rather crudely, is nothing less than the isolation of a pure gene in the form of desoxyribonucleic acid’ or DNA.
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Avery’s claim was amazing for several reasons. First, it was not accepted that bacteria actually had genes; second, most scientists thought that genes were probably made of proteins, not DNA; finally, Avery was not a geneticist and had no experience in the field. He was nearing retirement, and seemed an unlikely revolutionary. But revolutions can arise in many ways.

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Oswald T. Avery – generally known as ‘Fess’ (short for ‘Professor’, although he never actually held the title) – had worked at the Rockefeller Institute Hospital in New York since 1913, apart from a brief period as a soldier during the First World War. His laboratory was on the fifth floor of the hospital; the lab had once been a hospital ward and the original partitions were still in place. The lab desks were covered with microbiological paraphernalia – Petri dishes, Bunsen burners, wooden-handled wire loops and needles, microscopes, incubators – while sinks and a fume hood were placed around the edge of the room. The whole place had the distinctive smell of a lab working on pneumonia – the microbes are bred in a blood-based broth. Avery’s private lab had once been the ward kitchen; behind the swing door there was a roll-top desk that was generally crammed full of unanswered letters – Avery hated his routine to be disturbed, and even important invitations to travel to conferences would be left for weeks without reply. When he did respond, he almost always declined.

Before antibiotics became widely available in the 1940s, pneumonia was a major killer – in the US more than 50,000 people died each year of the disease. Physicians were powerless: treatment had little or no effect on survival rates. Some strains of the pneumonia microbe caused disease – they were ‘virulent’ – while others did not; Avery’s approach to finding a cure was to understand why there were these differences between strains. Much of Avery’s early work was carried out with his colleague, friend and flatmate, the opera-loving Alphonse Dochez. As a colleague recalled,

not infrequently he [Dochez] returned from the Metropolitan Opera, discovered Dr. Avery, with whom he shared an apartment, reading quietly in bed, and then would sit down in full evening dress and with vast animation describe to his old friend some of the illuminating thoughts on the subject of microbiology which had occurred to him during the second act of

Together with Dochez, Avery showed that it was possible to detect differences between types of pneumococci by injecting bacteria into a mouse and then observing the presence of specific antibodies in the animal’s blood serum. Avery’s technique was soon widely adopted as a way of identifying pneumococci and other infectious bacteria.

Insight into the origins of differences in virulence between strains of bacteria came in 1921, when the British microbiologist Joseph Arkwright noticed that colonies of virulent dysentery bacteria had a smooth surface, whereas non-virulent bacteria formed small colonies that appeared rough when inspected under a microscope. Rather obviously, the virulent strains were called S (smooth) and the non-virulent were called R (rough). Two years later, Fred Griffith, a medical officer with the Ministry of Health in London, showed that in pneumococci, too, virulent strains were smooth, whereas avirulent strains were rough. Avery studied the differences between the S and R strains and discovered that when pneumococci became virulent and smooth they produced a capsule that was up to four times the size of the bacterium itself. Avery showed that the capsule consisted of a layer of complex sugars or polysaccharides, which protects the bacterial cell from the body’s defence mechanisms and gives the virulent colonies their smooth appearance.

Back in London, Griffith was exploring the mysterious fact that rough bacterial colonies could change into smooth colonies if they were mixed with smooth bacteria, a phenomenon that had first been described by Arkwright. Arkwright thought that this process was the outcome of competition between the two kinds of microbe; Griffith began to suspect that the avirulent R bacteria had actually changed into virulent S bacteria in a process he called transformation. Astoundingly, Griffith discovered that transformation could occur even if dead S bacteria were mixed with R colonies. Griffith injected mice with live, avirulent R bacteria together with killed S pneumococci. Some of the mice died; they were found to be full of S bacteria, even though the only living bacteria that had been injected were of the R strain. Griffith reported these and many other findings in a dense 45-page article that was published in the
Journal of Hygiene
in 1928.
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