Launch the Icebergs!

Who was Max Perutz? There are plenty of good answers. He was an X-ray crystallographer, someone who uses X-rays as a tool to discover the three-dimensional structure of molecules. He was an accomplished skier and climber, with a sideline research interest in glaciology. He was a scientific manager, who founded and presided over Cambridge’s spectacularly successful Laboratory of Molecular Biology. He was a science communicator, who contributed to the pages of the LRB. He was a Nobel laureate, and a recipient of the Order of Merit, among other accolades. All these things were enough for many to call him famous. Perutz, who died in 2002, was convinced enough of his own standing to ask Georgina Ferry to write his biography. But he also realised that few people knew what he was famous for.

In spite of her book’s title, reminiscent of Harry Potter and the Philosopher’s Stone, Ferry never suggests that Perutz was famous for discovering the secret of life. So what was his involvement in the discovery? What, for that matter, is the secret of life? Ferry keeps to the conventional meaning of the phrase, encouraged by Francis Crick’s announcement in the Eagle pub in Cambridge in 1953, and since then widely adopted among popular science writers. To learn the secret of life is not to discover how organisms become adapted to their surroundings, how blood is circulated, or any of nature’s other more minor confidences uncovered by the likes of Darwin or William Harvey. To learn the secret of life is to figure out that DNA has a double-helical structure. And while Perutz did not make that discovery, he did run the Cambridge research unit in which the most notorious episodes of the double-helix story took place – the episodes that involved Crick and James Watson.

Perutz’s role appears rather shady in Ferry’s account. As is fairly well known, Watson and Crick made use of unpublished data, from Rosalind Franklin’s rival group at King’s College London, in coming to their conclusions about the shape of DNA. Perutz was the conduit for some of those data. A member of the Medical Research Council biophysics committee, he had received it as part of an MRC review of Franklin’s laboratory. When Crick asked to see the data, Perutz saw no problem in passing him the file, on the grounds that the papers hadn’t been marked ‘confidential’. Some of Perutz’s peers would later suggest his action was nonetheless a ‘breach of faith’. Perutz also knew that Maurice Wilkins, who worked alongside Franklin at King’s, had shown Watson a new X-ray photograph of DNA that Franklin had taken. Perutz understood how important this photograph had been in Watson’s reasoning about the structure of DNA. When Watson and Crick produced their double-helix model a few weeks later, Perutz wrote to the secretary of the MRC, Harold Himsworth, telling him of the result:

They used … a certain amount of unpublished X-ray data which they had seen or heard about at King’s. All these X-ray data were either poor, or referred to a different form of structure, and while they indicated certain general features of the structure of DNA they did not give a detailed guide to its character. While Watson and Crick were building their structure here, Miss Franklin and Gosling at King’s obtained a new and very detailed picture of DNA. Watson and Crick only heard of this photograph when they sent the first draft of their paper to King’s, but it now appears that this new photograph confirms the important features of their structure.

Perutz’s letter contains claims about Watson and Crick’s access to the King’s group’s work, and about its importance in their reasoning, that he must have known to be false. Thanks to historians of the DNA affair we now understand the significance of Franklin’s work much better.

Ferry’s ‘secret of life’ is sometimes the double-helical structure of DNA, sometimes ‘heredity’. In spite of appearances, these are not the same thing, at least not if we understand by ‘heredity’ the fact that like organisms roughly produce like. Even if one accepts, as Ferry does, the controversial metaphor of DNA as the molecule that ‘encodes the instructions to make a living organism’, it does not follow that in understanding the structure of DNA we thereby understand why offspring develop from egg to adult in such a way that they resemble their parents. If the works of Shakespeare were air-dropped into the Amazonian rainforest, they would give rise to theatrical performances that resemble our own only if local conventions for reading and staging were similar to ours. So even if we accept that the instructions for producing an organism are reliably passed from one generation to the next in the form of a DNA code, offspring will resemble their parents only if the instructions are read in roughly similar ways from one generation to the next. To explain heredity would then require that we explain stability in the biological machinery that reads DNA instructions, in addition to explaining how those instructions are passed on.

Perutz’s own remarks on the ‘secret of life’ cast further doubt on the notion that life has just one big secret. An essay of 1993, originally given the sober title ‘Before the Double Helix’, was later renamed ‘How the Secret of Life Was Discovered’ when it appeared in a popular collection of Perutz’s work. In it, he describes his journey to Cambridge to do graduate work with Desmond Bernal as a kind of pilgrimage: ‘In 1936, I left my hometown of Vienna, Austria, for Cambridge, England, to seek the Great Sage. I asked him: “How can I solve the secret of life?” He replied: “The secret of life lies in the structure of proteins.”’

Perutz’s decision to tell the story of his youth as a fable suggests he didn’t take talk of the ‘secret of life’ too seriously. That said, part of the effect of quoting Bernal is to point out that even the Great Sage could be mistaken about life’s secrets, for DNA is not a protein. Perhaps Perutz is endorsing the view that the double helix is indeed the secret, and that Bernal’s failure to anticipate it only underlines the greater genius of Watson and Crick. But another of Perutz’s essays, first published in 1978 as ‘Haemoglobin Structure and Regulatory Transport’, was retitled ‘The Second Secret of Life’ when it appeared in the same collection: once it is agreed that there is more than one significant secret of life, it’s hard to restrict the number to two. The essay outlined Perutz’s own explanation of a problem quite different from the DNA question: the mechanism (the ‘Perutz Mechanism’) by which the haemoglobin molecule carries oxygen. Perutz exploited the absurdity of talk of the secret of life when he wrote to his children, in partial mockery of newspaper hyperbole, as he set off for Munich to speak about haemoglobin at a conference in 1962. He imagined a journalist, ‘Anthony Scooper … who follows my every step’: ‘MFP settled in a empty carriage, immediately unpacked various coloured files and proceeded to work on manuscript of world-shaking discovery relating to Secret of Life … Ventured a few words by offering to help with his luggage. Declined charmingly. Delightful personality … Look for next report “On the Spot with MFP” or the Secret of Life in tomorrow’s column.’

The letter reminds us once again of Perutz’s concern with his own fame. Its basis as he saw it was neither his involvement with Watson and Crick, nor even the Perutz Mechanism, but an apparently more modest discovery, which he described as ‘the most exciting moment in all my research career’. His interest focused, for most of his working life, on understanding the structure and function of haemoglobin. He first set out on this path as a graduate student. X-ray crystallography makes use of the way X-rays are disturbed as they pass through a crystal to gain information relating to its structure. Anyone who studied physics at school will probably remember demonstrations, using a water-filled ‘ripple tank’, of the way secondary circular waves are produced when a wave hits a set of obstacles. The same phenomenon can be seen when waves in a harbour hit small boats. These circular waves pass across one another on the far side of the obstacles and, in doing so, interfere with one another. As they combine, their peaks and troughs add up to produce what is called a ‘diffraction pattern’. The pattern produced depends on the spacing between the obstacles. X-ray crystallography makes use of the same phenomenon to infer the spacings between atoms in a crystal, using the diffraction pattern produced when X-rays are scattered by those atoms. The diffraction pattern can be captured in a photograph as a series of intense spots.

X-ray crystallography was bedevilled by something called ‘the phase problem’. A diffraction pattern gives you the overall intensity of the X-ray radiation arriving on the plane of the photograph. But this is a product of several component waves as they interact. In order to infer the positions of the atoms creating the diffraction pattern, you also need to know how the peaks and troughs of the component waves are aligned. That is, you need to know their ‘phase’. But this is not something that could be reliably inferred from the diffraction pattern itself, at least not when dealing with comparatively large organic molecules of the sort that Perutz was investigating.

Perutz’s key innovation, which enabled more reliable use of X-ray crystallography for uncovering protein structure, was to compare the diffraction pattern from a protein crystal in its normal state with the pattern from a crystal that had been altered by the addition of a heavy atom. By analysing the change in pattern one could solve the phase problem. This so-called ‘isomorphous replacement technique’ had already been used successfully on smaller molecules, and Perutz’s old teacher Bernal had suggested as early as 1939 that it might also be used on proteins. But many crystallographers believed it wouldn’t work. Perutz showed that it did, and it was this breakthrough, in 1953, that set him on a zigzag path to articulating the structure of haemoglobin. He told Andrew Brown, Bernal’s biographer, that the application of the replacement technique to proteins was ‘my idea and my discovery. If you like, it’s what I am famous for.’ In 1962, Perutz’s work on the structure of haemoglobin won him the Nobel Prize for chemistry, which he shared with his colleague John Kendrew.

There is a surprisingly frank description of Perutz’s secondary research interest in his official Nobel biography for that year: ‘Perutz has pursued one sideline concerned with glaciers, studying their crystal texture and mechanism of flow, but this was mainly an excuse for working in the mountains.’ Perutz’s work on this sideline was weighty enough for an Antarctic glacier to be named after him, but there seems no doubt that glaciology was primarily a means to an end. Ferry’s biography repeatedly brings out the pleasure he found in the mountains, and the delight he took in his alpine skills. Ferry can’t resist an occasional reference to the summits of scientific achievement, but she makes it clear that for Perutz, mountains were not a metaphor for science but were loved for their own sake. Perutz, refreshingly, was no scientific monomaniac: in 1946, just after securing a position as a research fellow at the Cavendish Laboratory, he took two months off to indulge himself with a holiday in the Swiss Alps.

Perutz’s understanding of glaciers led to his involvement in a bizarre piece of secret wartime research. In December 1942, he was recruited to Project Habbakuk, the brainchild of Geoffrey Pyke, a man whom some regarded as a wild eccentric, but whom Bernal described in an obituary as ‘one of the greatest and certainly the most unrecognised geniuses of the time’. The gist of the project is well described in the heading of Pyke’s original proposal to Mountbatten in 1942: ‘Mammoth Unsinkable Vessel with Functions of a Floating Airfield’. To build a gigantic, unsinkable aircraft-carrier, one would ideally make it from a material that was also unsinkable, in plentiful supply and easy to work with. What could be better for the job than ice? Pyke’s proposal was to build a fleet of giant ‘bergships’.

One of the many problems that would need to be overcome before the bergships could be built was that ice was so brittle. A bergship made of unadulterated ice would be prone to snap, spilling aircraft into the sea. Perutz was invited to do his bit by investigating how ice might be modified into a construction material. He spent his time working in a cold store deep under Smithfield meat market on the properties of ‘Pykrete’, the codename given to a frozen mixture of water and wood pulp. Bernal, Mountbatten and even Churchill were all enthusiastic about Pyke’s idea, and considerable momentum gathered behind the project. By July 1943, detailed plans had been drawn up for a Pykrete monster 2000 feet long and 200 feet deep. But as the year drew on, US Navy reports cast doubts on Habbakuk’s viability, and the problems associated with building and then steering the bergship became clear. The final meeting of the Habbakuk board took place in December 1943: ‘The large Habbakuk II made of Pykrete has been found to be impractical because of the enormous production resources required and technical difficulties involved.’

It is perhaps surprising that Perutz was so keen to help with the war effort given his mistreatment by the British government a couple of years earlier. In May 1940, just after Germany attacked the Netherlands, Belgium and Luxembourg, Perutz was taken from Cambridge to Bury St Edmunds under Churchill’s policy of internment. A little later he was moved to Huyton, near Liverpool, and then moved again in mid-June to the Isle of Man. Although no one could have thought Perutz a threat to national security, at the beginning of July he was put on a ship and transported to Canada, a form of treatment reserved for those internees thought to be ‘the most dangerous characters of all’. The transport was shared with German prisoners of war, who, in contrast to internees like Perutz, were entitled to the rights afforded by the Geneva Convention. Perutz was reclassified as a POW on arrival in Canada, where his long and miserable stay was made worse by his concerns about his father’s internment back in Britain. To his sister he wrote that he was ‘sick of waiting and fed up to the brim. I just can’t understand how a man with a ten-year imprisonment term does not commit suicide … I am so tired of it all and so homesick that I nearly cry when I think of it.’ He did not arrive back in Britain until January 1941.

In the year that Perutz and Kendrew won their Nobel Prizes, Watson (who by that time had moved to the US) and Crick shared the prize for physiology or medicine. 1962 was also the year Perutz, Kendrew, Crick and Fred Sanger (a Nobel Prize-winner in 1958, who had previously worked in the biochemistry department) all moved out of central Cambridge, into the brand new building that would house the Medical Research Council’s Laboratory of Molecular Biology. So, within months of the LMB setting up on its new site, it had four Nobel laureates on its senior staff. Perutz’s managerial style – or rather his anti-managerial style – was judged to be a way of dealing with such an embarrassment of self-aware talent. The lab’s governing board comprised the four Nobel laureates, with Perutz wisely named as chairman, not director. Kendrew, Sanger and Crick each headed one of the lab’s three divisions. Himsworth of the MRC had earlier proposed this type of structure as ‘a kind of Soviet of directors’, but Perutz’s approach was far more laissez-faire than the centralised planning model advocated by the Marxist Bernal. Rather than attempting to direct what research should be done, he hired bright people, then made sure that they had the resources to do what they wanted, whatever that might be. It is perhaps the greatest testament to Perutz’s achievement that, to date, eight more Nobel prizes have been won by LMB staff.