The Code Breaker Read online

  James Watson

  As a middle-class Chicago boy breezing through public school, James Watson was wickedly smart and cheeky. This ingrained in him a tendency to be intellectually provocative, which would later serve him well as a scientist but less so as a public figure. Throughout his life, his rapid-fire mumbling of unfinished sentences would convey his impatience and inability to filter his impulsive notions. He later said that one of the most important lessons his parents taught him was “Hypocrisy in search of social acceptance erodes your self-respect.” He learned it too well. From his childhood into his nineties, he was brutally outspoken in his assertions, both right and wrong, which made him sometimes socially unacceptable but never lacking in self-respect.1

  His passion growing up was bird-watching, and when he won three war bonds on the radio show Quiz Kids he used them to buy a pair of Bausch and Lomb binoculars. He would rise before dawn to go with his father to Jackson Park, spend two hours seeking rare warblers, and then take the trolley to the Lab School, a cauldron of whiz kids.

  At the University of Chicago, which he entered at fifteen, he planned to indulge his love of birds, and his aversion to chemistry, by becoming an ornithologist. But in his senior year he read a review of What Is Life?, in which the quantum physicist Erwin Schrödinger turned his attention to biology to argue that discovering the molecular structures of a gene would show how it hands down hereditary information through generations. Watson checked the book out of the library the next morning and was thenceforth obsessed with understanding the gene.

  With modest grades, he was rejected when he applied to study for a doctorate at Caltech and was not offered a stipend by Harvard.2 So he went to Indiana University, which had built, partly by recruiting Jews who were having trouble getting tenure on the East Coast, one of the nation’s best genetic departments, starring the future Nobel Prize winner Hermann Muller and the Italian émigré Salvador Luria.

  * * *

  With Luria as his PhD advisor, Watson studied viruses. These tiny packets of genetic material are essentially lifeless on their own, but when they invade a living cell, they hijack its machinery and multiply themselves. The easiest of these viruses to study are the ones that attack bacteria, and they were dubbed (remember the term, for it will reappear when we discuss the discovery of CRISPR) “phages,” which was short for “bacteriophages,” meaning bacteria-eaters.

  Watson joined Luria’s international circle of biologists known as the Phage Group. “Luria positively abhorred most chemists, especially the competitive variety out of the jungles of New York City,” said Watson. But Luria soon realized that figuring out phages would require chemistry. So he helped Watson get a postdoctoral fellowship to study the subject in Copenhagen.

  Bored and unable to understand the mumbling chemist who was supervising his studies, Watson took a break from Copenhagen in the spring of 1951 to attend a meeting in Naples on the molecules found in living cells. Most of the presentations went over his head, but he found himself fascinated by a lecture by Maurice Wilkins, a biochemist at King’s College London.

  Wilkins specialized in crystallography and X-ray diffraction. In other words, he took a liquid that was saturated with molecules, allowed it to cool, and purified the crystals that formed. Then he tried to figure out the structure of those crystals. If you shine a light on an object from different angles, you can figure out its structure by studying the shadows it casts. X-ray crystallographers do something similar: they shine an X-ray on a crystal from many different angles and record the shadows and diffraction patterns. In the slide that Wilkins showed at the end of his Naples speech, that technique had been used on DNA.

  “Suddenly I was excited about chemistry,” Watson recalled. “I knew that genes could crystallize; hence they must have a regular structure that could be solved in a straightforward fashion.” For the next couple of days, Watson stalked Wilkins with the hope of cadging an invitation to join his lab, but to no avail.

  Francis Crick

  Instead, Watson was able, in the fall of 1951, to become a postdoctoral student at Cambridge University’s Cavendish Laboratory, which was directed by the pioneering crystallographer Sir Lawrence Bragg, who more than thirty years earlier had become, and still is, the youngest person to win a Nobel Prize in science.3 He and his father, with whom he shared the prize, discovered the basic mathematical law of how crystals diffract X-rays.

  At the Cavendish Lab, Watson met Francis Crick, forming one of history’s most powerful bonds between two scientists. A biochemical theorist who had served in World War II, Crick had reached the ripe age of thirty-six without having secured his PhD. Nevertheless, he was sure enough of his instincts, and careless enough about Cambridge manners, that he was unable to refrain from correcting his colleagues’ sloppy thinking and then crowing about it. As Watson memorably put it in the opening sentence of The Double Helix, “I have never seen Francis Crick in a modest mood.” It was a line that could likewise have been written of Watson, and they admired each other’s immodesty more than their colleagues did. “A youthful arrogance, a ruthlessness, and an impatience with sloppy thinking came naturally to both of us,” Crick recalled.

  Crick shared Watson’s belief that discovering the structure of DNA would provide the key to the mysteries of heredity. Soon they were lunching together on shepherd’s pie and talking volubly at the Eagle, a well-worn pub near the labs. Crick had a boisterous laugh and booming voice, which drove Sir Lawrence to distraction. So Watson and Crick were assigned to a pale brick room of their own.

  “They were complementary strands, interlocked by irreverence, zaniness, and fiery brilliance,” the writer-physician Siddhartha Mukherjee noted. “They despised authority but craved its affirmation. They found the scientific establishment ridiculous and plodding, yet they knew how to insinuate themselves into it. They imagined themselves quintessential outsiders, yet felt most comfortable sitting in the inner quadrangles of Cambridge colleges. They were self-appointed jesters in a court of fools.”4

  The Caltech biochemist Linus Pauling had just rocked the scientific world, and paved the way for his first Nobel Prize, by figuring out the structure of proteins using a combination of X-ray crystallography, his understanding of the quantum mechanics of chemical bonds, and Tinkertoy model building. Over their lunches at the Eagle, Watson and Crick plotted how to use the same tricks to beat Pauling in the race to discover the structure of DNA. They even had the tool shop of the Cavendish Lab cut tin plates and copper wires to represent the atoms and other components for the desktop model they planned to tinker with until they got all the elements and bonds correct.

  * * *

  One obstacle was that they would be treading on the territory of Maurice Wilkins, the King’s College London biochemist whose X-ray photograph of a DNA crystal had piqued Watson’s interest in Naples. “The English sense of fair play would not allow Francis to move in on Maurice’s problem,” Watson wrote. “In France, where fair play obviously did not exist, these problems would not have arisen. The States also would not have permitted such a situation to develop.”

  Wilkins, for his part, seemed in no rush to beat Pauling. He was in an awkward internal struggle, both dramatized and trivialized in Watson’s book, with a brilliant new colleague who in 1951 had come to work at King’s College London: Rosalind Franklin, a thirty-one-year-old English biochemist who had learned X-ray diffraction techniques while studying in Paris.

  She had been lured to King’s College with the understanding that she would lead a team studying DNA. Wilkins, who was four years older and already studying DNA, was under the impression that she was coming as a junior colleague who would help him with X-ray diffraction. This resulted in a combustible situation. Within months they were barely speaking to each other. The sexist structure at King’s helped keep them apart: there were two faculty lounges, one for men and the other for women, the latter unbearably dingy and the former a venue for elegant lunches.

  Franklin was a focused scie
ntist, sensibly dressed. As a result she ran afoul of English academia’s fondness for eccentrics and its tendency to look at women through a sexual lens, attitudes apparent in Watson’s descriptions of her. “Though her features were strong, she was not unattractive and might have been quite stunning had she taken even a mild interest in clothes,” he wrote. “This she did not. There was never lipstick to contrast with her straight black hair, while at the age of thirty-one her dresses showed all the imagination of English bluestocking adolescents.”

  Franklin refused to share her X-ray diffraction pictures with Wilkins, or anyone else, but in November 1951 she scheduled a lecture to summarize her latest findings. Wilkins invited Watson to take the train down from Cambridge. “She spoke to an audience of about fifteen in a quick, nervous style,” he recalled. “There was not a trace of warmth or frivolity in her words. And yet I could not regard her as totally uninteresting. Momentarily I wondered how she would look if she took off her glasses and did something novel with her hair. Then, however, my main concern was her description of the crystalline X-ray diffraction pattern.”

  Watson briefed Crick the next morning. He had not taken notes, which annoyed Crick, and thus was vague about many key points, particularly the water content that Franklin had found in her DNA samples. Nevertheless, Crick started scribbling diagrams, declaring that Franklin’s data indicated a structure of two, three, or four strands twisted in a helix. He thought that, by playing with different models, they might soon discover the answer. Within a week they had what they thought was a solution, even though it meant that some of the atoms were crushed together a little too close: three strands swirled in the middle, and the four bases jutted outward from this backbone.

  In a fit of hubris, they invited Wilkins and Franklin to come up to Cambridge and take a look. The two arrived the next morning and, with little small talk, Crick began to display the triple-helix structure. Franklin immediately saw that it was flawed. “You’re wrong for the following reasons,” she said, her words ripping like those of an exasperated teacher.

  She insisted that her pictures of DNA did not show that the molecule was helical. On that point she would turn out to be wrong. But her other two objections were correct: the twisting backbones had to be on the outside, not inside, and the proposed model did not contain enough water. “At this stage the embarrassing fact came out that my recollection of the water content of Rosy’s DNA samples could not be right,” Watson drily noted. Wilkins, momentarily bonding with Franklin, told her that if they left for the station right away, they could make the 3:40 train back to London, which they did.

  Not only were Watson and Crick embarrassed; they were put in a penalty box. Word came down from Sir Lawrence that they were to stop working on DNA. Their model-building components were packed up and sent to Wilkins and Franklin in London.

  * * *

  Adding to Watson’s dismay was the news that Linus Pauling was coming over from Caltech to lecture in England, which would likely catalyze his own attempt to solve the structure of DNA. Fortunately, the U.S. State Department came to the rescue. In the weirdness engendered by red-baiting and McCarthyism, Pauling was stopped at the airport in New York and had his passport confiscated because he had been spouting enough pacifist opinions that the FBI thought he might be a threat to the country if allowed to travel. So he never got the chance to discuss the crystallography work done in England, thus helping the U.S. lose the race to figure out DNA.

  Watson and Crick were able to monitor some of Pauling’s progress through his son Peter, who was a young student in their Cambridge lab. Watson found him amiable and fun. “The conversation could dwell on the comparative virtues of girls from England, the Continent, and California,” he recalled. But one day in December 1952, young Pauling wandered into the lab, put his feet up on a desk, and dropped the news that Watson had been dreading. In his hand was a letter from his father in which he mentioned that he had come up with a structure for DNA and was about to publish it.

  Linus Pauling’s paper arrived in Cambridge in early February. Peter got a copy first and sauntered into the lab to tell Watson and Crick that his father’s solution was similar to the one they had tried: a three-chain helix with a backbone in the center. Watson grabbed the paper from Peter’s coat pocket and began to read. “At once I felt something was not right,” he recalled. “I could not pinpoint the mistake, however, until I looked at the illustrations for several minutes.”

  Watson realized that some of the atomic connections in Pauling’s proposed model would not be stable. As he discussed it with Crick and others in the lab, they became convinced that Pauling had made a big “blooper.” They got so excited they quit work early that afternoon to dash off to the Eagle. “The moment its doors opened for the evening, we were there to drink a toast to the Pauling failure,” Watson said. “Instead of sherry, I let Francis buy me a whiskey.”

  “The secret of life”

  They knew they could no longer waste time or continue to honor the edict that they defer to Wilkins and Franklin. So Watson took the train down to London one afternoon to see them, carrying his early copy of Pauling’s paper. Wilkins was out when he arrived, so he ambled uninvited into the lab of Franklin, who was bending over a light box measuring the latest of her ever-sharper X-ray images of DNA. She gave him an angry look, but he launched into a summary of Pauling’s paper.

  For a few moments they argued about whether DNA was likely to be a helix, with Franklin still dubious. “Interrupting her harangue, I asserted that the simplest form for any regular polymeric molecule was a helix,” Watson recalled. “Rosy by then was hardly able to control her temper, and her voice rose as she told me that the stupidity of my remarks would be obvious if I would stop blubbering and look at her X-ray evidence.”

  The conversation spiraled downward, with Watson pointing out, correctly but impolitely, that as a good experimentalist Franklin would be more successful if she knew how to collaborate with theorists. “Suddenly Rosy came from behind the lab bench that separated us and began moving toward me. Fearing that in her hot anger she might strike me, I grabbed up the Pauling manuscript and hastily retreated.”

  Rosalind Franklin

  “Photograph 51”

  Just as the confrontation climaxed, Wilkins walked by and whisked Watson off to have some tea and calm down. He confided that Franklin had taken some pictures of a wet form of DNA that provided new evidence of its structure. He then went into an adjacent room and retrieved a print of what became known as “photograph 51.” Wilkins had gotten hold of the picture validly: he was the PhD advisor of the student who had worked with Franklin to take it. Less proper was showing it to Watson, who recorded some of the key parameters and took them back to Cambridge to share with Crick. The photograph indicated that Franklin had been correct in arguing that the backbone strands of the structure were on the outside, like the strands of a spiral staircase, rather than inside of the molecule, but she was wrong in resisting the possibility that DNA was a helix. “The black cross of reflections which dominated the picture could arise only from a helical structure,” Watson immediately saw. A study of Franklin’s notes shows that even after Watson’s visit she was still many steps away from discerning the DNA structure.5

  * * *

  In the unheated train car back to Cambridge, Watson sketched ideas in the margins of his copy of The Times. He had to climb over the back gate into his residential college, which had locked up for the night. The next morning, when he went into the Cavendish lab, he encountered Sir Lawrence Bragg, who had demanded that he and Crick steer clear of DNA. But confronted with Watson’s excited summary of what he had learned, and hearing of his desire to get back to model-building, Sir Lawrence gave his assent. Watson rushed down the stairs to the machine shop to set them to work on making a new set of components.

  Watson and Crick soon got more of Franklin’s data. She had submitted to Britain’s Medical Research Council a report on her work, and a member of the council share
d it with them. Although Watson and Crick had not exactly stolen Franklin’s findings, they had appropriated her work without her permission.

  By then Watson and Crick had a pretty good idea of DNA’s structure. It had two sugar-phosphate strands that twisted and spiraled to form a double-stranded helix. Protruding from these were the four bases in DNA: adenine, thymine, guanine, and cytosine, now commonly known by the letters A, T, G, and C. They came to agree with Franklin that the backbones were on the outside and the bases pointed inward, like a twisted ladder or spiral staircase. As Watson later admitted in a feeble attempt at graciousness, “Her past uncompromising statements on this matter thus reflected first-rate science, not the outpourings of a misguided feminist.”

  They originally assumed that the bases would each be paired with themselves, for example, a rung that was made up of an adenine bonded to another adenine. But one day Watson, using some cardboard models of bases that he cut out himself, began playing with different pairings. “Suddenly I became aware that an adenine-thymine pair held together by two hydrogen bonds was identical in shape to a guanine-cytosine pair held together by at least two hydrogen bonds.” He was lucky to work in a lab of scientists with different specialties; one of them, a quantum chemist, confirmed that adenine would attract thymine and guanine would attract cytosine.

  There was an exciting consequence of this structure: when the two strands split apart, they could perfectly replicate, because any half-rung would attract its natural partner. In other words, such a structure would permit the molecule to replicate itself and pass along the information encoded in its sequences.