A short history of nearly everything (56 page)

Unfortunately, Avery was opposed by one of his own colleagues at the institute, a strong-willed and disagreeable protein enthusiast named Alfred Mirsky, who did everything in his power to discredit Avery’s work—including, it has been said, lobbying the authorities at the Karolinska Institute in Stockholm not to give Avery a Nobel Prize. Avery by this time was sixty-six years old and tired. Unable to deal with the stress and controversy, he resigned his position and never went near a lab again. But other experiments elsewhere overwhelmingly supported his conclusions, and soon the race was on to find the structure of DNA.

Had you been a betting person in the early 1950s, your money would almost certainly have been on Linus Pauling of Caltech, America’s leading chemist, to crack the structure of DNA. Pauling was unrivaled in determining the architecture of molecules and had been a pioneer in the field of X-ray crystallography, a technique that would prove crucial to peering into the heart of DNA. In an exceedingly distinguished career, he would win two Nobel Prizes (for chemistry in 1954 and peace in 1962), but with DNA he became convinced that the structure was a triple helix, not a double one, and never quite got on the right track. Instead, victory fell to an unlikely quartet of scientists in England who didn’t work as a team, often weren’t on speaking terms, and were for the most part novices in the field.

Of the four, the nearest to a conventional boffin was Maurice Wilkins, who had spent much of the Second World War helping to design the atomic bomb. Two of the others, Rosalind Franklin and Francis Crick, had passed their war years working on mines for the British government—Crick of the type that blow up, Franklin of the type that produce coal.

The most unconventional of the foursome was James Watson, an American prodigy who had distinguished himself as a boy as a member of a highly popular radio program calledThe Quiz Kids (and thus could claim to be at least part of the inspiration for some of the members of the Glass family inFranny and Zooey and other works by J. D. Salinger) and who had entered the University of Chicago aged just fifteen. He had earned his Ph.D. by the age of twenty-two and was now attached to the famous Cavendish Laboratory in Cambridge. In 1951, he was a gawky twenty-three-year-old with a strikingly lively head of hair that appears in photographs to be straining to attach itself to some powerful magnet just out of frame.

Crick, twelve years older and still without a doctorate, was less memorably hirsute and slightly more tweedy. In Watson’s account he is presented as blustery, nosy, cheerfully argumentative, impatient with anyone slow to share a notion, and constantly in danger of being asked to go elsewhere. Neither was formally trained in biochemistry.

Their assumption was that if you could determine the shape of a DNA molecule you would be able to see—correctly, as it turned out—how it did what it did. They hoped to achieve this, it would appear, by doing as little work as possible beyond thinking, and no more of that than was absolutely necessary. As Watson cheerfully (if a touch disingenuously) remarked in his autobiographical bookThe Double Helix , “It was my hope that the gene might be solved without my learning any chemistry.” They weren’t actually assigned to work on DNA, and at one point were ordered to stop it. Watson was ostensibly mastering the art of crystallography; Crick was supposed to be completing a thesis on the X-ray diffraction of large molecules.

Although Crick and Watson enjoy nearly all the credit in popular accounts for solving the mystery of DNA, their breakthrough was crucially dependent on experimental work done by their competitors, the results of which were obtained “fortuitously,” in the tactful words of the historian Lisa Jardine. Far ahead of them, at least at the beginning, were two academics at King’s College in London, Wilkins and Franklin.

The New Zealand–born Wilkins was a retiring figure, almost to the point of invisibility. A 1998 PBS documentary on the discovery of the structure of DNA—a feat for which he shared the 1962 Nobel Prize with Crick and Watson—managed to overlook him entirely.

The most enigmatic character of all was Franklin. In a severely unflattering portrait, Watson inThe Double Helix depicted Franklin as a woman who was unreasonable, secretive, chronically uncooperative, and—this seemed especially to irritate him—almost willfully unsexy. He allowed that she “was not unattractive and might have been quite stunning had she taken even a mild interest in clothes,” but in this she disappointed all expectations. She didn’t even use lipstick, he noted in wonder, while her dress sense “showed all the imagination of English blue-stocking adolescents.”[44]

However, she did have the best images in existence of the possible structure of DNA, achieved by means of X-ray crystallography, the technique perfected by Linus Pauling. Crystallography had been used successfully to map atoms in crystals (hence “crystallography”), but DNA molecules were a much more finicky proposition. Only Franklin was managing to get good results from the process, but to Wilkins’s perennial exasperation she refused to share her findings.

If Franklin was not warmly forthcoming with her findings, she cannot be altogether blamed. Female academics at King’s in the 1950s were treated with a formalized disdain that dazzles modern sensibilities (actually any sensibilities). However senior or accomplished, they were not allowed into the college’s senior common room but instead had to take their meals in a more utilitarian chamber that even Watson conceded was “dingily pokey.” On top of this she was being constantly pressed—at times actively harassed—to share her results with a trio of men whose desperation to get a peek at them was seldom matched by more engaging qualities, like respect. “I’m afraid we always used to adopt—let’s say a patronizing attitude toward her,” Crick later recalled. Two of these men were from a competing institution and the third was more or less openly siding with them. It should hardly come as a surprise that she kept her results locked away.

That Wilkins and Franklin did not get along was a fact that Watson and Crick seem to have exploited to their benefit. Although Crick and Watson were trespassing rather unashamedly on Wilkins’s territory, it was with them that he increasingly sided—not altogether surprisingly since Franklin herself was beginning to act in a decidedly queer way. Although her results showed that DNA definitely was helical in shape, she insisted to all that it was not. To Wilkins’s presumed dismay and embarrassment, in the summer of 1952 she posted a mock notice around the King’s physics department that said: “It is with great regret that we have to announce the death, on Friday 18th July 1952 of D.N.A. helix. . . . It is hoped that Dr. M.H.F. Wilkins will speak in memory of the late helix.”

The outcome of all this was that in January 1953, Wilkins showed Watson Franklin’s images, “apparently without her knowledge or consent.” It would be an understatement to call it a significant help. Years later Watson conceded that it “was the key event . . . it mobilized us.” Armed with the knowledge of the DNA molecule’s basic shape and some important elements of its dimensions, Watson and Crick redoubled their efforts. Everything now seemed to go their way. At one point Pauling was en route to a conference in England at which he would in all likelihood have met with Wilkins and learned enough to correct the misconceptions that had put him on the wrong line of inquiry, but this was the McCarthy era and Pauling found himself detained at Idlewild Airport in New York, his passport confiscated, on the grounds that he was too liberal of temperament to be allowed to travel abroad. Crick and Watson also had the no less convenient good fortune that Pauling’s son was working at the Cavendish and innocently kept them abreast of any news of developments and setbacks at home.

Still facing the possibility of being trumped at any moment, Watson and Crick applied themselves feverishly to the problem. It was known that DNA had four chemical components—called adenine, guanine, cytosine, and thiamine—and that these paired up in particular ways. By playing with pieces of cardboard cut into the shapes of molecules, Watson and Crick were able to work out how the pieces fit together. From this they made a Meccano-like model—perhaps the most famous in modern science—consisting of metal plates bolted together in a spiral, and invited Wilkins, Franklin, and the rest of the world to have a look. Any informed person could see at once that they had solved the problem. It was without question a brilliant piece of detective work, with or without the boost of Franklin’s picture.

The April 25, 1953, edition ofNature carried a 900-word article by Watson and Crick titled “A Structure for Deoxyribose Nucleic Acid.” Accompanying it were separate articles by Wilkins and Franklin. It was an eventful time in the world—Edmund Hillary was just about to clamber to the top of Everest while Elizabeth II was imminently to be crowned queen of England—so the discovery of the secret of life was mostly overlooked. It received a small mention in theNews Chronicle and was ignored elsewhere.

Rosalind Franklin did not share in the Nobel Prize. She died of ovarian cancer at the age of just thirty-seven in 1958, four years before the award was granted. Nobel Prizes are not awarded posthumously. The cancer almost certainly arose as a result of chronic overexposure to X-rays through her work and needn’t have happened. In her much-praised 2002 biography of Franklin, Brenda Maddox noted that Franklin rarely wore a lead apron and often stepped carelessly in front of a beam. Oswald Avery never won a Nobel Prize either and was also largely overlooked by posterity, though he did at least have the satisfaction of living just long enough to see his findings vindicated. He died in 1955.

Watson and Crick’s discovery wasn’t actually confirmed until the 1980s. As Crick said in one of his books: “It took over twenty-five years for our model of DNA to go from being only rather plausible, to being very plausible . . . and from there to being virtually certainly correct.”

Even so, with the structure of DNA understood progress in genetics was swift, and by 1968 the journalScience could run an article titled “That Was the Molecular Biology That Was,” suggesting—it hardly seems possible, but it is so—that the work of genetics was nearly at an end.

In fact, of course, it was only just beginning. Even now there is a great deal about DNA that we scarcely understand, not least why so much of it doesn’t actually seem todo anything. Ninety-seven percent of your DNA consists of nothing but long stretches of meaningless garble—“junk,” or “non-coding DNA,” as biochemists prefer to put it. Only here and there along each strand do you find sections that control and organize vital functions. These are the curious and long-elusive genes.

Genes are nothing more (nor less) than instructions to make proteins. This they do with a certain dull fidelity. In this sense, they are rather like the keys of a piano, each playing a single note and nothing else, which is obviously a trifle monotonous. But combine the genes, as you would combine piano keys, and you can create chords and melodies of infinite variety. Put all these genes together, and you have (to continue the metaphor) the great symphony of existence known as the human genome.

An alternative and more common way to regard the genome is as a kind of instruction manual for the body. Viewed this way, the chromosomes can be imagined as the book’s chapters and the genes as individual instructions for making proteins. The words in which the instructions are written are called codons, and the letters are known as bases. The bases—the letters of the genetic alphabet—consist of the four nucleotides mentioned a page or two back: adenine, thiamine, guanine, and cytosine. Despite the importance of what they do, these substances are not made of anything exotic. Guanine, for instance, is the same stuff that abounds in, and gives its name to, guano.

The shape of a DNA molecule, as everyone knows, is rather like a spiral staircase or twisted rope ladder: the famous double helix. The uprights of this structure are made of a type of sugar called deoxyribose, and the whole of the helix is a nucleic acid—hence the name “deoxyribonucleic acid.” The rungs (or steps) are formed by two bases joining across the space between, and they can combine in only two ways: guanine is always paired with cytosine and thiamine always with adenine. The order in which these letters appear as you move up or down the ladder constitutes the DNA code; logging it has been the job of the Human Genome Project.

Now the particular brilliance of DNA lies in its manner of replication. When it is time to produce a new DNA molecule, the two strands part down the middle, like the zipper on a jacket, and each half goes off to form a new partnership. Because each nucleotide along a strand pairs up with a specific other nucleotide, each strand serves as a template for the creation of a new matching strand. If you possessed just one strand of your own DNA, you could easily enough reconstruct the matching side by working out the necessary partnerships: if the topmost rung on one strand was made of guanine, then you would know that the topmost rung on the matching strand must be cytosine. Work your way down the ladder through all the nucleotide pairings, and eventually you would have the code for a new molecule. That is just what happens in nature, except that nature does it really quickly—in only a matter of seconds, which is quite a feat.

Most of the time our DNA replicates with dutiful accuracy, but just occasionally—about one time in a million—a letter gets into the wrong place. This is known as a single nucleotide polymorphism, or SNP, familiarly known to biochemists as a “Snip.” Generally these Snips are buried in stretches of noncoding DNA and have no detectable consequence for the body. But occasionally they make a difference. They might leave you predisposed to some disease, but equally they might confer some slight advantage—more protective pigmentation, for instance, or increased production of red blood cells for someone living at altitude. Over time, these slight modifications accumulate in both individuals and in populations, contributing to the distinctiveness of both.

The balance between accuracy and errors in replication is a fine one. Too many errors and the organism can’t function, but too few and it sacrifices adaptability. A similar balance must exist between stability in an organism and innovation. An increase in red blood cells can help a person or group living at high elevations to move and breathe more easily because more red cells can carry more oxygen. But additional red cells also thicken the blood. Add too many, and “it’s like pumping oil,” in the words of Temple University anthropologist Charles Weitz. That’s hard on the heart. Thus those designed to live at high altitude get increased breathing efficiency, but pay for it with higher-risk hearts. By such means does Darwinian natural selection look after us. It also helps to explain why we are all so similar. Evolution simply won’t let you become too different—not without becoming a new species anyway.