The Mysterious World of the Human Genome. Frank Ryan
Читать онлайн книгу.
import into the scientific pool of the laboratory. And while Bragg and Perutz saw proteins as the great unsolved puzzle, Crick was more interested in the mystery of the gene.
As 1949 elided into 1950, Crick would subsequently confess that he still did not realise that the genetic material was DNA. But he knew that genes had been plotted out in linear arrays along the chromosomes by people like Barbara McClintock, and that proteins, which had to be the expression of the genes, were also being plotted out as linear arrays, however lengthy and complicated. There had to be some logical way in which one translated into the other. By 1951, two years after his arrival into the Cavendish Laboratory, Crick perceived that these were two different, if necessarily related, puzzles – the mystery of how genes appeared able to copy themselves, and the mystery of how the linear structures of genes translated into the linear structures of proteins.
The wide-reading, voraciously inquisitive Crick needed what Judson termed a catalyst. This arrived in the form of the gangly, equally inquisitive Watson that same year, 1951. From their first meeting, it would appear that here was one of those rare working conjunctions of two odd-ball personalities that, when they come together, make an extraordinary creative whole that is more than the sum of the individual ingenuities. And yet it very nearly didn’t happen.
*
We should recall that Watson was extremely junior within the department. A recent PhD graduate, he had arrived into Kalckar’s laboratory on a Merck Fellowship funded by the US National Research Council. The terms and conditions were laid down and signed for back home, but now here he was abandoning those carefully laid intentions to gallivant from the work in Denmark to follow some giddy new inspiration in England, a place he had never visited in his life and where he knew absolutely nobody. Impulsive and single-minded, Watson would subsequently confess that his head was filled with curiosity about that single DNA photograph. He had tried to engage with Wilkins in Naples after the lecture, at a bus stop during an excursion to the Greek temples at Paestum. He had even tried to take advantage of a visit from his sister, Elizabeth, who had arrived to join him as a tourist from the States. Now here were Maurice Wilkins and Watson’s sister, Elizabeth, finding a common table to take lunch together. Watson sensed an opportunity and barged in, with the intention of ingratiating himself with Wilkins. But the self-effacing Wilkins excused himself, to allow brother and sister the privacy of the table.
His plans foiled, Watson refused to let go of this exciting new avenue of interest. ‘I proceeded to forget Maurice, but not his DNA photograph.’
He stopped over in Geneva for a few days to talk to a Swiss phage researcher, Jean Weigle, who provoked yet more excitement by informing Watson that the eminent American chemist, Linus Pauling, had partly solved the mystery of protein structure. Weigle had attended a lecture by Pauling, who like Bragg in Cambridge had been working with X-ray analysis of protein molecules. Pauling had just made the announcement that the protein model followed a uniquely beautiful three-dimensional form – he had called it an ‘alpha-helix’. By the time Watson arrived back in Copenhagen, Pauling had published his discovery in a scientific paper. Watson read it. Then he re-read it. He was confounded by his lack of understanding of X-ray crystallography. The terminology, in physics and chemistry, was so far beyond him that he could only grasp the most general impression of its content. His reaction was so childishly naïve as to be touching: in his head he devised the opening lines of his own imagined paper in which he would write about his discovery of DNA, if and whenever he discovered something of similar portent.
But what to do to get on board the DNA gravy train?
He needed to learn more about X-ray diffraction studies. Ruling out Caltech, where Pauling would react with disdain to some ‘mathematically deficient biologist’, and now ruling out London, where Wilkins would be equally uninterested, Watson wondered about Cambridge University, where he knew that somebody called Max Perutz was following the same X-ray lines of investigation of the blood protein molecule, haemoglobin.
‘I thus wrote to Luria about my newly found passion …’
The world of science was smaller in 1951 than it is today. Even so, it would appear a hopelessly optimistic ambition for this impulsive young graduate to merely ask his mentor to fix his arrival into a leading laboratory in England to engage in a line of research that he knew absolutely nothing about.
The amazing outcome was that Luria was able to do so. By happenstance, he met Perutz’s co-worker, John Kendrew, at a small meeting at Ann Arbor, in Michigan, where, by a second and equal happenstance, there was a meeting of minds – both scientific and social. And by a third happenstance, Kendrew was looking for a junior to help him study the structure of the muscle-based protein myoglobin, which contained iron at its core and held on to oxygen, just like the haemoglobin in the blood.
Twice in his short career the young American scientist had leapt into the unknown and landed on his feet. First it had been through Luria’s patronage in Bloomington, and by extension also Delbrück’s, two of the co-founders of the phage group; and now the gift of happenstance extended further, again through Luria’s patronage, to Kendrew, and by proxy to the Cambridge laboratory and Max Perutz. Watson’s arrival into the laboratory would bring him under the ultimate tutelage of Sir Lawrence Bragg, a founder of X-ray crystallography. It would connect him directly to his future partner in DNA research, Francis Crick, and further afield – through the connection between the Cambridge laboratory and the X-ray laboratory at King’s College London – with Maurice Wilkins and a young female scientist, Rosalind Franklin, who were working on the X-ray crystallography of DNA.
I think there was a general impression in the scientific community at that time that [Crick and Watson] were like butterflies flicking around with lots of brilliance but not much solidity. Obviously, in retrospect, this was a ghastly misjudgement.
MAURICE WILKINS
In the opening pages of his brief, witty and brutally candid autobiography, James Watson recounts a chance meeting in 1955 with a scientific colleague, Willy Seeds, at the bottom of a Swiss glacier. It was two years after the publication of the discovery of DNA. Watson and Seeds were acquainted, Seeds having worked with Maurice Wilkins in probing the optical properties of DNA fibres. Where Watson had anticipated the courtesy of a chat, Seeds merely remarked, ‘How’s Honest Jim?’, before striding away. The sarcasm must have bitten deep for Watson to not merely remember it distinctly, but even to consider the term ‘Honest Jim’ as the initial title of his life story, before being persuaded to adopt the more descriptive alternative, ‘The Double Helix’. It was as if the former colleague was questioning Watson’s right to be recognised as the co-discoverer of the secret of life.
He had been taken aback, reflecting on meetings with the same colleague in London a few years earlier, at a time when, in Watson’s words, ‘DNA was still a mystery, up for grabs … As one of the winners, I knew the tale was not simple, and certainly not as the newspapers reported.’ It was a more curious story, one in which his fellow-discoverer, Francis Crick, would freely admit that neither he nor Watson was even supposed to working on DNA at the time. Equally curious was the fact that up to the day of the discovery, neither Watson nor Crick had contributed anything much to the many different scientific threads and themes that, when finally put together, like the pieces of a remarkable three-dimensional jigsaw puzzle, laid the molecular nature of DNA bare for the first time in history.
Watson’s welcome into the Cambridge laboratory was quintessentially English in its lack of formality. He arrived in Perutz’s office straight from the railway station. Perutz put him at his ease about his prevailing ignorance of X-ray diffraction. Both Perutz and Kendrew had come to the science from graduation in chemistry. All Watson needed to do was to read a text or two to become acquainted with the basics. The following day Watson was introduced to the white-moustached Sir Lawrence, to be given formal permission to work under his direction. Watson then