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Race to the double helix took many twists, turns

About noon on Feb. 28, 1953, two men burst into their favorite pub, a scruffy spot called The Eagle near their Cambridge University laboratory. As people sipped their beers and forked down shepherd's pie, one of the men gleefully announced: "We have discovered the secret of life."

The scene - which played out 50 years ago this week - is one of the most famous of 20th- century science. It marked the conclusion to an intellectual footrace to find the structure of deoxyribonucleic acid, better known as DNA.

Playing with a crude cardboard model of the DNA molecule, Francis Crick, a 36-year- old Englishman, and his 24- year-old American partner, James Watson, had puzzled out DNA's now-familiar double helix early that day.

Their discovery solved the fundamental mystery of heredity, how everything from eye color to crippling disease can be passed through generations.

A half-century later, historians are still filling in the details of the story behind the discovery and resurrecting old questions about who should get credit. In a tale that turns out to be as twisted as the strands of the double helix itself, the role played by a little-known chemist, Rosalind Franklin, is getting new attention.

In a biography published in October, author Brenda Maddox shows how Franklin's photographs and measurements of the molecule, which Watson and Crick acquired secretly, led them to a Nobel Prize. The book raises anew questions about whether the pair went too far and if Franklin's contributions were adequately recognized.

"Rosalind seemed doomed to remain the invisible woman in many minds, the faceless nurse who hands the surgeon the scalpel," Maddox wrote.

'Intellectual crush'

James Dewey Watson and Francis Harry Compton Crick met in October 1951 - and it was love at first sight.

"They apparently fell into a kind of intellectual crush on each other," wrote science historian Horace Freeland Judson in The Eighth Day of Creation: Makers of the Revolution in Biology.

Born in Northampton, England, Crick was known for his nonstop talking and stiletto-sharp intellect. He had little to show for it - only the mines he designed for the British Admiralty during World War II. But his Cambridge colleagues soon learned that he had an annoying way of swooping in and attempting to solve their scientific problems.

Watson, meanwhile, was an eccentric skirt-chaser from Chicago who loped across the manicured Cambridge lawns in untied tennis shoes and shorts - even in the winter. He mumbled and had a bad habit of staring. But he was no intellectual slouch, graduating from the University of Chicago with a degree in zoology at 19.

Both altered their careers after stumbling upon physicist Erwin Schrodinger's book What is Life?, which argued that genes were the essential stuff of life. Nobody really knew what genes were made of, though DNA was one possibility.

The book inspired Crick, at the relatively late age of 33, to abandon physics for biology and pursue a doctorate at Cambridge. Watson, too, had become obsessed with DNA after reading Schrodinger and went to Cambridge with hopes of unlocking the molecule's secrets.

Although the two were officially assigned to other things, unofficially they spent most of their time talking about DNA over tea in Room 103 of the Cavendish Laboratory or over lunch at The Eagle.

"I daydreamed about discovering the secret of the gene," Watson later wrote.

Early developments

Discovered in 1869, DNA was considered only a bit player in genetics. Scientists thought proteins, which perform most essential tasks in the body, were most likely to be responsible for passing on hereditary traits. DNA appeared to be too simple a molecule to do that.

Among the handful of scientists interested in DNA was Linus Pauling at the California Institute of Technology, a chemist who went on to win two Nobel Prizes. He had an unorthodox approach to solving problems: he liked to build Tinkertoy-like models of molecules, rearranging the pieces until they fit.

Just before Watson arrived at Cambridge, the 50-year-old Pauling had used his toys to pull off a scientific coup, discovering that certain proteins had a corkscrew - or helix - shape.

Some scientists were speculating that DNA also might be helix-shaped. Watson, who saw DNA as the "most golden of all molecules," worried that Pauling might try to find out.

"They saw Pauling as a definite threat," said Robert Olby, a historian of science at the University of Pittsburgh.

In fact, in the fall of 1951, Watson and Crick knew that Pauling was sniffing around for good photographs of DNA.

"We knew what to do: imitate Linus Pauling and beat him at his own game," Watson wrote in his 1968 bestseller, The Double Helix.

The place to which Pauling - and soon Watson and Crick - would turn for photos was King's College in London, where Maurice Wilkins and Rosalind Franklin were taking the world's finest portraits of DNA.

Their technique was to shine X-rays on the molecule and, as the beams ricocheted off the atoms, capture the result on film. Called X-ray crystallography, it was the best tool scientists had to deduce the structure of complex molecules like DNA.

The photos, however, were extraordinarily hard to interpret. DNA showed up as a fuzzy, cross-shaped blob.

'Dark lady' in lab

Although Wilkins and Franklin were only two hours by train from Watson and Crick, in temperament and experience they were worlds apart. Wilkins, a 36-year-old New Zealander, was a veteran of the Manhattan Project and had spent several years working on DNA. Franklin, a Briton four years his junior, was an expert on the molecular structure of coal, with a stack of scientific publications to her name.

The pair repulsed one another as strongly as Watson and Crick connected. To his good friend Crick, Wilkins constantly complained about the "dark lady" in his laboratory who glared at and routinely ignored him.

Franklin felt she had good reason. Before she went to King's College in January 1951, she had been promised that she would have DNA to herself. When she found she would be collaborating with Wilkins, she fumed and refused to share her experimental results.

The rift would ultimately work in Watson and Crick's favor.

In November 1951, Wilkins invited Watson to London to hear Franklin speak at a seminar. Hoping she would show her DNA photos, Watson eagerly accepted.

Today even schoolchildren know the answers that Watson and Crick were groping for then. DNA looks like a spiral staircase: a twisted double strand of sugar and phosphate molecules forms of the outer rails, while a series of four molecular "bases" - adenine, cytosine, thymine, and guanine - serve as stairs.

But none of this was clear from the few ghost-like X-ray images available then.

Did DNA consist of two, three or even four molecular strands? Were the bases connected between them like stairs or did they face outward like thorns on a twisted vine? Was the molecule even a helix? Nobody knew.

A lazy note taker, Watson tried to memorize most of Franklin's lecture. That was a mistake.

When he returned to Cambridge, he and Crick started to build a model based on his sketchy recollection of Franklin's talk. Finished a week later, it consisted of a three-stranded helix with the bases poking outward.

The pair invited Wilkins and Franklin to see the model. It was all wrong, Franklin said, pointing out several errors of basic chemistry, a subject which the Cambridge scientists acknowledged was not their best. She also argued that there was no evidence that DNA was a helix.

Soon after, Sir Lawrence Bragg, who ran the Cavendish Laboratory, learned what Watson and Crick had been doing and ordered them to forget DNA. It wouldn't be fair, he said, to compete with King's College, whose scientists had started working on the molecule first.

Crick went back to writing his dissertation on hemoglobin, while Watson returned to his official assignment - studying a virus that attacks tobacco plants.

Franklin, meanwhile, kept at her X-ray photos of DNA. In May 1952, she snapped one she labeled Photograph 51. To the untrained eye it looks only slightly less blurry than her other shots. But it would turn out to be key to Watson and Crick's success.

'My mouth fell open'

Watson's fears about Pauling came true around Christmas 1952, when he heard that the Cal Tech scientist had figured out DNA's structure and would soon publish his solution. Watson and Crick were devastated - until they got hold of an early draft.

Pauling's model of DNA was built of three strands. Wrong, just like theirs. An even bigger shock came when they saw that the world's greatest chemist - Pauling literally wrote the textbook on the subject - made a chemistry mistake so elementary that even Watson could spot it.

"We were still in the game," Watson later wrote.

On Jan. 28, 1953, Watson again traveled to London to hear Franklin give a seminar on her latest DNA X-ray results. Wilkins, barely on speaking terms with Franklin by that time, quietly pulled Watson aside and showed him Photo 51.

"The instant I saw the picture my mouth fell open and my heart began to race," Watson later recalled.

Franklin had discovered DNA was a thirsty molecule that soaks up water like a sponge - and looks very different in photos after it does.

Most of the photos that Watson - or anybody else outside Franklin's lab - had seen were of dry DNA, which didn't clearly reveal the molecule's structure. When Watson saw the crisp shot of wet DNA, he immediately recognized it as helix.

Later that evening, Watson pumped Wilkins for measurements from the photos - the distance between each corkscrew-turn of the helix and how densely the atoms were packed. Preoccupied with his troubles with Franklin, Wilkins divulged details.

On the train back to Cambridge, Watson started to sketch in the corner of his newspaper. The molecule he drew had two corkscrew-like helical strands - a guess. A few days later, Watson and Crick secretly started building a new model.

Hoping for more information, Crick invited Wilkins to lunch. He urged his friend to start building models of DNA, and got Wilkins' blessing for the Cambridge pair to construct their own.

During the meal, Wilkins let slip that Franklin had prepared a report on her latest measurements of the DNA molecule for the government's Medical Research Council. Although not confidential, the report wasn't in wide circulation either. Crick later asked a colleague on the council for a copy.

As soon as he saw Franklin's numbers, Crick had a revelation. He concluded that the molecule indeed was made of two strands - a double helix - and that they ran in opposite directions.

The report, writes Brenda Maddox in Rosalind Franklin: The Dark Lady of DNA, "was all Watson and Crick could have hoped for - as valuable as an enemy's code book."

By Feb. 28, the pair had roughed out the arrangement on a tabletop with cardboard cutouts. A few days later, they wired together a rickety metal model that wound toward the ceiling. Eventually, Time magazine dispatched a photographer to shoot the men gazing up at it.

Watson and Crick won a Nobel Prize in 1962, sharing it with Wilkins, who was honored for his X-ray crystallography work on DNA.

But the scientist who took the photograph that led to Watson and Crick's breakthrough would not share the glory. Franklin died of ovarian cancer in April 1958. The Nobel committee does not award the prize posthumously.

'She was close'

In the half-century since Watson and Crick's discovery, historians have debated whether the scientists reached the finish line fairly.

As subsequent examinations of her scientific notebooks showed, Franklin had all the clues she needed to solve the puzzle. As Watson and Crick were working out the last details of their model, Franklin wrote in her journal: "evidence for a 2-chain (or 1-chain) helix?"

"She was close to getting it, no question," said Judson, the science historian. "But the simple fact is she didn't."

After flipping a coin to see whose name would go first, Watson and Crick submitted the paper describing the double helix to the British journal Nature. At the end of the paper appearing on April 25, 1953, the pair acknowledged that their discovery had been "stimulated" by the unpublished X-ray experiments of Wilkins and Franklin.

Watson and Crick never told Franklin that they had acquired her experimental results surreptitiously. But some historians think Franklin must have known.

If the "dark lady" ever harbored bitterness over her fate, she never showed it. She even became friends with the men in her final years, choosing, for example, to stay with Crick and his wife rather than her family while recuperating from cancer treatments.

"Rosalind Franklin did not have her eyes on the prize," Maddox wrote. "Nor did she worry about having been outrun in a race that no one but Watson and Crick knew was a race."

Copyright © 2015, The Baltimore Sun
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