Rosalind Franklin Saw DNA First

It’s a standard science trivia question: Who discovered the structure of DNA? With the basic concepts of molecular biology now taught at a fairly detailed level in grade school, and with DNA being so easy to isolate that it makes a good demonstration project for school or home, everyone knows the names of Watson and Crick. But not many people know the story behind one of the greatest scientific achievements of the 20th century, or the name of the scientist without whose data Watson and Crick were working blind: Rosalind Franklin.

Born in London in 1920, Rosalind Elsie Franklin was the second child and first girl of a prominent and wealthy banking family. According to her aunt, even at the age of six she showed “alarmingly clever” tendencies, excelling at memory games and performing arithmetic for fun. She was impeccably educated and encouraged in her academic pursuits by her family, her father being a sort of amateur scientist who taught electricity and magnetism at a men’s college. He even bought a woodworking bench and tools, so that his children might learn a useful trade. Rosalind was the primary user of the tools, learning skills that would eventually serve her well in science.

Starting at Newnham College, the women’s college at the University of Cambridge, just as the world was falling apart in 1938, Rosalind excelled at chemistry. Determined to do her part for the war effort, Rosalind signed on to the British Coal Utilisation Research Association (BCURA) in 1942. She would make valuable discoveries about the microscopic structure of coal which would lead to improvements in gas mask designs, important to both the military and civilians, with memories of the horrors of chemical warfare still fresh from the Great War.

Rosalind in Paris. Source: Royal Society of Chemistry

After the war, Rosalind spent several years in Paris, studying X-ray crystallography under Jacques Mering. The fact that crystalline substances diffract X-rays into patterns characteristic of their structure was long known, and by this time all the low-hanging fruit of naturally crystalline materials like metals, or easily crystallized organic substances, had pretty much been played out.

The interesting problems in X-ray crystallography were turning to biologically important molecules, like penicillin, hemoglobin, and insulin. These would prove to be much tougher nuts to crack because they were vastly more complex than a lump of carbon and therefore much harder to crystallize. It was such amorphous substances that Mering worked on with Franklin, and as her skills as a crystallographer grew under his guidance, so did her reputation.

Rosalind left her beloved Paris in 1950 when she was offered a fellowship at King’s College in London. Originally assigned to use X-ray diffraction to study proteins, the director of her unit, John Randall, quickly switched her to work on nucleic acids. Both proteins and nucleic acids, like DNA and RNA, had proven difficult to analyze with X-ray diffraction, and Rosalind’s skills were sought to bolster the unit’s existing crystallography group.

Rosalind would quickly learn how badly things can go when communications break down. Rosalind arrived to find less than adequate facilities at King’s. The college had suffered greatly during the Blitz, with a bomb crater in the courtyard that still needed to be navigated around. Maurice Wilkins, who had already started work on DNA crystallography at King’s, was somehow under the impression that Franklin would be his assistant. He had been on sabbatical when Franklin arrived and was distressed to learn that she had taken over his lab, having not only rebuilt the X-ray camera but also started advising his former doctoral student, Raymond Gosling. This was what the director wanted, but Randall had never communicated that to Wilkins. Understandably upset and obviously upstaged by the far more skilled Franklin, this set the stage for the academic intrigue that was to come.

If Randall’s poor management style was like gasoline poured on a pile of brush, the spark that lit it off was James Watson. Arriving at the Cavendish in 1952, the brash American wunderkind was intent on figuring out the structure of DNA. He was certain that physical model building was the way to accomplish this; after all, it had worked for Linus Pauling in working out the structure of alpha helices in proteins.  Along with Francis Crick, Watson had accurate scale models of all the components of DNA — the sugar deoxyribose, the phosphate groups, and the bases adenine, guanine, cytosine, and thymidine — built out of wire and sheet metal by the Cavendish machine shop.

Try as they might, Watson and Crick couldn’t come up with a structure for DNA that made sense. At one point they even invited Franklin and Gosling over from King’s to look that their model; Rosalind, who by this point had determined crystallographically that there were two forms of DNA, the A-form and the B-form, knew in an instant that their model was wrong, and told them so in no uncertain terms. The Cavendish director, Lawrence Bragg, was humiliated and told Crick and Watson not to build any more models of DNA.

Photograph 51, an X-ray crystallogram of the B-form of DNA, by Gosling and Franklin, 1952. Source: Wikipedia

Without official support, Watson and Crick struggled in their work on the structure of DNA. It was during this time that they became aware of the existence of the now famous Photograph 51. Photo 51 was the best X-ray image yet produced by Franklin and Gosling of the B-form of DNA, which is the most biologically relevant form and the hardest to crystallize. How the photo got into the hands of Maurice Wilkins isn’t clear — Gosling himself says it could have been him or it could have been Rosalind. However it got to him, Wilkins took Photo 51 to the Cavendish and showed it to Watson and Crick.

A glance at the excellent image, with the characteristic X shape of a helix, was all that the model builders needed to see where their model had gone wrong. The spacing of the spots on the photo gave them the critical parameters they needed to complete their model. The structure of the molecule of life had been solved.

Whether Rosalind ever knew about the subterfuge or if she would have cared isn’t known. Watson and Crick didn’t directly acknowledge Franklin’s data in their 1953 paper, instead referring to their “stimulating discussions.” Rosalind, unhappy with the less than collegial environment at King’s, accepted a senior research position at Birkbeck College just before their paper was published. She continued X-ray diffraction work on nucleic acids; she and Gosling published the structure of the A-form of DNA later that year, and she made major contributions toward understanding the structure of RNA. She also set about using X-ray diffraction to study the structure of even more complicated structures — viruses — and managed to elucidate the structure of tobacco mosaic virus and many other plant viruses.

Sadly, Rosalind would never get to see the fruits of her work. She died of ovarian cancer in 1958, a few months shy of her 38th birthday. She was engaged and remarkably productive right up until the end, publishing papers and continuing work on the structure of poliovirus. She didn’t live to see Watson, Crick, and Wilkins win the Nobel Prize in 1962, but her closest friends — including Crick and his wife — agree that her only regret was leaving so much work unfinished.

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