Chapters 1–10
The first third of The Double Helix introduces the main players in the research and discovery of DNA’s structure. Watson blends descriptions of personalities with an account of how he arrives at the Cavendish laboratory in Cambridge, England, and begins his relationships with other scientists, both friend and foe. As a young Midwestern man on his first big adventure, Watson decides that ‘‘a scientist’s life might be interesting socially as well as intellectually,’’ and he pursues that philosophy through jaunts to the Alps as well as ‘‘midnight trips to waterfront bars.’’

Watson’s initial purpose in going to the Cavendish lab is to study the molecular structure of proteins by building three-dimensional models of them. Upon meeting Crick, whom he claims never to have seen ‘‘in a modest mood,’’ he is excited at finding a fellow scientist who shares his interest in studying DNA. Because the DNA molecule is too small to be looked at through a microscope, it can be ‘‘seen’’ only in crystallized form through an X-ray. But neither Watson nor Crick is highly skilled in crystallography, and they must turn to the experts at rival King’s College in London for help in getting pictures of the molecule. This act introduces Maurice Wilkins and Rosalind Franklin into the tale. Though these two ‘‘colleagues’’ behave more like enemies, both are involved in researching DNA through crystallography in the King’s College lab.

The three male scientists become friends, but Franklin is portrayed as a woman who has ‘‘belligerent moods’’ and who does ‘‘not emphasize her feminine qualities.’’ Rather than kick Franklin out of his lab, however, Wilkins understands that he needs her expertise to help him compete with Linus Pauling, who is also working on the DNA mystery at his lab in California. Watson and Crick understand the dilemma, too, and decide they should glean as much information from Franklin—one way or another—in order to beat Pauling to the answer. The last line of Chapter 2, ‘‘The thought could not be avoided that the best home for a feminist was in another person’s lab,’’ sums up the tense feelings that permeate the environment at the King’s College lab

In Chapter 10, Watson attends a lecture given by Franklin in which she describes the DNA molecule as a helix shape with a sugar-phosphate backbone on the outside. Watson, however, neglects to take notes on the lecture, believing he can recall Franklin’s theory strictly from memory. This error will prove costly in his and Crick’s progress toward building a model of DNA.

Chapters 11–21
The middle third of the book describes the experiment that costs Watson and Crick about a year of DNA research work. Because Watson cannot remember Franklin’s actual words during her lecture, he gives Crick misinformation about her proposal. The major mistake in the model they build is that the backbone is on the inside, the opposite of what Franklin had said. Proud of their ‘‘discovery,’’ however, Watson and Crick show off their model to Wilkins and Franklin. It does not take long for Franklin and others to shoot down the idea and prove that it is not only wrong but ridiculous. When Lawrence Bragg, the Nobel-Prize-winning director of the Cavendish lab, learns of the failure, he orders Watson and Crick to give up their research on DNA and leave it to the scientists at King’s College.

For the next year, Crick spends most of his time working on his doctorate, while Watson studies the tobacco mosaic virus (TMV). As Watson notes, ‘‘A vital component of TMV was nucleic acid, and so it was the perfect front to mask my continued interest in DNA.’’ Also during this time, Watson invites his sister for extended visits to England, and they both have their share of social revelry and English highlife. On the down side, Watson also struggles with the possibility of losing his research fellowship and must write letters of appeal back to the United States, feigning interest in various fields in order to retain support.

Chapters 22–Epilogue
By now Peter Pauling, son of the famous Cal Tech chemist, Linus Pauling, has arrived at the Cavendish lab, where he shares office space with Watson and Crick. The three become friends and in late 1952 Pauling shows his officemates a preliminary report from his father that he plans to publish as a proposal for the structure of DNA. Watson wastes no time scrutinizing the older Pauling’s work and is delighted to find a major flaw. It is apparent to Watson that ‘‘Pauling’s nucleic acid . . . was not an acid at all. . . . Without the hydrogen atoms, the chains would immediately fly apart and the structure vanish.’’ Confirming the blunder with several colleagues—one of whom ‘‘predictably expressed pleasure that a giant had forgotten elementary college chemistry’’—Watson and Crick sit back and wait for Pauling to present his impossible theory to the scientific world, never once considering warning him of the humiliating mistake that he was about to make. When the Cal Tech chemist’s paper is published in January, 1953, the negative reaction is quick in coming. And with their competitor licking the wounds of embarrassment, Watson and Crick become more determined than ever to resume their position in the race for DNA.

The final chapters of the book describe the various experiments they attempt before arriving at a model with the correct sequencing of the four nitrogen bases in each DNA strand. In order to reach their goal, Watson returns to Wilkins at King’s College for a better look at the X rays from which he and Crick will pattern their model. Watson is happy to learn that Wilkins has secretly been copying Franklin’s notes, and when he sees an X-ray photo confirming that the molecule is a helix, he cannot wait to return to the Cavendish lab to share the news with Crick. On the train back to Cambridge, Watson sketches helix-shaped molecules on the margin of a newspaper and concludes that the molecules are most likely made up of two strands of DNA—a double helix.

Once Watson and Crick publish their findings in 1953, the scientific community concedes that they have indeed revealed the secret of how genes replicate themselves. Even Linus Pauling travels from America to share in a celebration dinner. Only in the book’s epilogue does Watson offer any regrets for his portrayal of Rosalind Franklin throughout his account. In the final paragraph, he admits that both he and Crick:

came to appreciate greatly her personal honesty and generosity, realizing years too late the struggles that the intelligent woman faces to be accepted by a scientific world which often regards women as mere diversions from serious thinking.

Watson ends the book by noting Franklin’s struggle with cancer and commends her for ‘‘working on a high level until a few weeks before her death.’’