The Double Helix

1. The Allure of the Gene: DNA's Central Role

If true, this meant to Francis that proteins would not be the Rosetta Stone for unravelling the true secret of life.

Early biological interest. James Watson's journey into DNA began with a fundamental question: what is the gene? Initially, he hoped to solve this without delving into complex chemistry, a sentiment shared by his mentor, Salvador Luria, who distrusted most chemists. However, the groundbreaking experiments by O. T. Avery, demonstrating that hereditary traits could be transmitted by purified DNA, shifted the focus from proteins to nucleic acids as the likely carriers of genetic information.

DNA's growing importance. Francis Crick, initially focused on protein structures, was also drawn to DNA after reading Erwin Schrödinger's "What Is Life?". Schrödinger's elegant proposition that genes were the key components of living cells, combined with Avery's findings, convinced Crick that DNA, not protein, held the "true secret of life." This realization set the stage for a pivotal shift in scientific inquiry, moving away from the long-held belief that proteins were the sole genetic material.

The chemical challenge. Despite DNA's perceived importance, its chemical structure remained largely unknown, with few chemists actively working on it. Watson's initial postdoctoral work in Copenhagen on nucleic acid biochemistry proved uninspiring, as he couldn't see its immediate relevance to genetics. This frustration, coupled with a chance encounter with Maurice Wilkins's DNA X-ray diffraction picture, ignited Watson's passion for structural chemistry, convincing him that the gene's secret lay in its three-dimensional arrangement.

2. Clash of Personalities and Methods: King's College Dynamics

Not that he was at all in love with Rosy, as we called her from a distance. Just the opposite—almost from the moment she arrived in Maurice's lab, they began to upset each other.

Strained collaboration. At King's College London, Maurice Wilkins held the de facto "personal property" of DNA research in England, using X-ray diffraction. His collaboration with Rosalind Franklin, a skilled crystallographer, was fraught with tension from the start. Franklin viewed DNA as her independent project, not as assisting Wilkins, leading to constant friction and a lack of open communication that significantly hampered their progress.

Franklin's meticulous approach. Rosalind Franklin was a highly disciplined and rigorous crystallographer, committed to deriving the DNA structure purely through detailed X-ray analysis. She distrusted speculative model-building, viewing it as a "last resort" and believing that "hard facts would come only when further data had been collected." This methodical approach, while scientifically sound, contributed to her reluctance to share preliminary findings or engage in the more intuitive, rapid model-building favored by others.

Wilkins's frustration. Maurice Wilkins found Franklin's unyielding nature and insistence on autonomy deeply frustrating. He struggled to maintain a dominant position in the lab, which he felt was necessary to think unhindered about DNA. The personal animosity, combined with Franklin's refusal to share her latest results or even allow him to take new X-ray photographs of the crystalline DNA she controlled, created an unproductive environment, leaving the crucial data locked away.

3. Pauling's Shadow and Crucial Error: A Missed Opportunity

Our first principles told us that Pauling could not be the greatest of all chemists without realizing that DNA was the most golden of all molecules.

Pauling's towering influence. Linus Pauling, a Nobel laureate and arguably the world's greatest chemist, cast a long shadow over the field of structural biology. His dramatic discovery of the alpha-helix in proteins, achieved through intuitive model-building and fundamental chemical principles, inspired Watson and Crick. They recognized that Pauling was keenly interested in DNA, viewing it as "the most golden of all molecules," and knew he was a formidable competitor.

The race intensifies. Pauling's request for Wilkins's DNA X-ray photographs signaled his active pursuit of the structure, creating immense pressure on the King's College group. Watson and Crick, aware of Pauling's genius and speed, felt an urgent need to "imitate Linus Pauling and beat him at his own game." This competitive drive fueled their early, albeit flawed, attempts at model building, emphasizing the high stakes involved in the discovery.

Pauling's critical blunder. In early 1953, Pauling published his proposed DNA structure: a three-chain helix with the sugar-phosphate backbone in the center. To Watson and Crick's astonishment and relief, they quickly identified a fundamental chemical error: Pauling's model assumed un-ionized phosphate groups, which contradicted all known nucleic acid chemistry. This "blooper," as Watson called it, was an unbelievable misstep for such an astute chemist and bought Watson and Crick crucial time.

4. The Power of Collaboration and Intuition: Cambridge's Advantage

Finding someone in Max's lab who knew that DNA was more important than proteins was real luck.

A synergistic partnership. Watson's arrival at the Cavendish Laboratory and his immediate connection with Francis Crick proved serendipitous. Crick, though initially focused on proteins, shared Watson's conviction about DNA's paramount importance. Their dynamic, often boisterous, collaboration contrasted sharply with the strained atmosphere at King's, allowing for rapid exchange of ideas and a relentless pursuit of the DNA structure.

Model building as a strategy. Inspired by Pauling's success with the alpha-helix, Watson and Crick adopted a model-building approach, relying on simple chemical laws and molecular models. They believed that "the key to Linus' success was his reliance on the simple Laws of structural chemistry." This intuitive, hands-on method allowed them to quickly test hypotheses and discard unworkable configurations, prioritizing simplicity over initial complexity.

Overcoming early setbacks. Their first attempt at a three-chain helix with a central sugar-phosphate backbone, based on Watson's recollection of Franklin's data, proved stereochemically unsound. This failure, coupled with Bragg's directive to cease DNA work, was a significant setback. However, their underlying belief in a helical structure and the importance of DNA remained, leading them to continue thinking about the problem, albeit discreetly.

5. Franklin's Unsung Contributions: Indispensable X-ray Data

The instant I saw the picture my mouth fell open and my pulse began to race.

The "B" form revelation. A pivotal moment occurred when Maurice Wilkins, in a rare moment of openness, showed Watson Rosalind Franklin's X-ray diffraction photograph of the "B" form of DNA. This image, taken when DNA was surrounded by a large amount of water, was "unbelievably simpler" than previous patterns and, crucially, displayed a "black cross of reflections which dominated the picture [that] could arise only from a helical structure."

Unlocking helical parameters. The B-form photograph provided several vital helical parameters directly, including the 34 Å repeat along the helical axis and a diameter of about 20 Å. This clear evidence for a helix, which Franklin herself had been reluctant to fully embrace due to her rigorous standards, was a game-changer. It allowed Watson and Crick to refine their model-building efforts with concrete experimental constraints, moving beyond mere speculation.

Backbone on the outside. Franklin's data also strongly indicated that the sugar-phosphate backbone must be on the outside of the molecule, with the bases facing inwards. This was a crucial piece of information that contradicted Watson and Crick's earlier, failed models. Her "past uncompromising statements on this matter thus reflected first-rate science, not the outpourings of a misguided feminist," a realization that came to Francis Crick later.

6. The Chemical Insight: Tautomers and Base Pairing

The tautomeric forms I had copied out of Davidson's book were, in Jerry's opinion, incorrectly assigned.

Chargaff's enigmatic rules. Erwin Chargaff's biochemical analyses of DNA revealed a curious regularity: the amount of adenine (A) always equaled thymine (T), and guanine (G) always equaled cytosine (C). Initially, Watson and Crick did not fully appreciate the significance of these "Chargaff's rules," dismissing them as potentially irrelevant or chemically complex. Francis even attempted to prove attractive forces between like bases, but his experiments yielded nothing.

Jerry Donohue's critical correction. The breakthrough came from an unexpected source: Jerry Donohue, an American crystallographer sharing their office. When Watson proposed a "like-with-like" base pairing scheme, Donohue immediately pointed out that the tautomeric forms of guanine and thymine depicted in textbooks were incorrect. His chemical intuition, based on crystal structures like diketopiperazine, strongly favored the keto forms, a correction that proved absolutely essential.

The complementary pairing. With the correct tautomeric forms, Watson began arranging the bases on his desk. He "suddenly 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." This complementary pairing, A with T and G with C, not only explained Chargaff's rules but also provided a mechanism for gene replication, where one strand could serve as a template for its partner.

7. The Double Helix: A Structure of Elegant Simplicity

Everything thus looked very good when we went back to have supper with Odile.

A perfect fit. The discovery of the complementary A-T and G-C base pairs, identical in shape and held together by hydrogen bonds, was the final piece of the puzzle. This elegant solution allowed for two irregular sequences of bases to be regularly packed in the center of a helix, with the sugar-phosphate backbone on the outside. The structure was a right-handed double helix, with the two chains running in opposite directions, satisfying all known chemical and X-ray data.

Immediate biological implications. The double helix immediately suggested a profound mechanism for gene replication. "Always pairing adenine with thymine and guanine with cytosine meant that the base sequences of the two intertwined chains were complementary to each other." This conceptual simplicity allowed for a single chain to serve as a template for synthesizing a new, complementary chain, explaining how genetic information could be accurately copied during cell division.

Aesthetically pleasing and scientifically sound. The structure was not only stereochemically sound but also aesthetically beautiful, a quality that Watson and Crick instinctively felt indicated its correctness. Francis, initially skeptical, quickly recognized the power of the A-T and G-C pairs. The model's ability to explain Chargaff's rules and suggest a replication mechanism made it "too pretty not to be true," a testament to the elegance often found in fundamental biological truths.

8. The Race to Publication: Urgency and Recognition

Maurice was back in London only two days before he rang up to say that both he and Rosy found that their X-ray data strongly supported the double helix.

Confirming the model. After constructing a complete model, Watson and Crick immediately sought to confirm its validity against the experimental X-ray data. Maurice Wilkins, upon seeing the model, quickly recognized its merits. His subsequent measurements, along with Rosalind Franklin's, "strongly supported the double helix," validating their theoretical construction with empirical evidence.

Simultaneous publication. The urgency to publish was paramount, especially with Pauling's recent, albeit flawed, attempt. To ensure proper credit and impact, it was arranged for three papers to be published simultaneously in Nature: Watson and Crick's describing the double helix, and two separate papers from King's College (Wilkins and his collaborators, and Franklin and Gosling) presenting their supporting X-ray data. This coordinated release underscored the collaborative, yet competitive, nature of the discovery.

Franklin's acceptance and recognition. Rosalind Franklin's initial skepticism dissolved as she saw the elegance of the base pairs and how the double helix reconciled her own X-ray evidence, particularly the backbone-on-the-outside configuration. Her "fierce annoyance with Francis and me collapsed," and she began to exchange "unconcealed hostility for conversation between equals." This shift marked a crucial moment of scientific acceptance and a belated recognition of her first-rate crystallographic contributions.

9. Science as a Human Endeavor: Ambition, Luck, and Discovery

As I hope this book will show, science seldom proceeds in the straightforward logical manner imagined by outsiders.

The messy reality of science. Watson's account vividly portrays science not as a linear, logical progression, but as a deeply human endeavor driven by personalities, ambition, rivalry, and serendipity. "Its steps forward (and sometimes backward) are often very human events in which personalities and cultural traditions play major roles." The narrative is filled with personal anecdotes, frustrations, and moments of both arrogance and insight.

Role of intuition and luck. The discovery was a blend of rigorous scientific thought, intuitive leaps, and fortunate circumstances. Key moments included:

• Watson's initial excitement from Wilkins's X-ray picture.
• Crick's theoretical prowess in helical diffraction.
• Jerry Donohue's timely correction of chemical tautomers.
• The accidental sharing of Franklin's B-form data.
  These elements highlight how breakthroughs often emerge from unexpected interactions and insights.

Competition and collaboration. The story is a testament to the intense competition in science, particularly the race against Linus Pauling, but also the essential role of collaboration. Despite the rivalries and personality clashes, the ultimate solution emerged from a complex interplay of data, ideas, and discussions across different labs. The Nobel Prize, awarded to Watson, Crick, and Wilkins, recognized the collective effort, even if the path was far from harmonious.

Last updated: January 2, 2026