More Than a Prize Unwon: The Manifold Legacies of Rosalind Franklin (Women in Science 50!)

When Rosalind Franklin (1920-1958) succumbed to cancer at the age of thirty-seven, she left behind monumental contributions to three different fields of science, any one of which would have placed her on the short list of the world’s most significant twentieth century scientists.  And yet, when we talk about Franklin, we don’t tend to say, “She ascertained the structural relation of the protein and genetic content in the tobacco mosaic virus,” or, “She discovered the molecular reason that certain types of coal can’t be graphitized,” but rather, “She wasn’t sufficiently recognized for her part in the discovery of DNA’s double helical structure.”

Unique among scientists, she’s remembered for something that happened to her, at the expense of the magnificent things she actually did.  Nothing would have irritated her more than to have the stupendous scientific output of her final five years doing virus research at Birkbeck systematically ignored in favor of lascivious conspiracy theories about Watson and Crick stealing DNA’s structure from under her nose.  For there is much, much more to Rosalind Franklin than a citation scandal.

She was a scientist from the start.  She showed felicity with mathematics and careful observation even in grammar school, and there seems to never have been a doubt that scientific research was what she wanted to do with her time on Earth.  She came from a wealthy family that was as proud of its Jewishness as of its Britishness.  Her father was frugal and energetic, with a passion for intellectual confrontation and insistence on expressive precision that would become hallmarks of Franklin’s meticulous laboratory procedure.

Co-existing with the perfectionist laboratory Rosalind Franklin, however, was a rough and tumble adventuring Rosalind Franklin, one who loved nothing so much as scrambling across mountains at breakneck speed, sleeping in minimal shelter, and making delicious meals from whatever was at hand.  Meeting foreign people and exploring challenging nooks of the world with them were the delights of her non-scientific life, and would be until the progress of her cancer reduced her to motor touring the areas she had once trekked boldly through.

Attending Newnham College at Cambridge, she finished her coursework as quickly as possible, ignoring the social rounds of dating and dances to concentrate on physics and chemistry, and soon landed a job during the Second World War researching coal for the government.  That might sound a relatively dreary and unromantic first assignment, but it was actually of critical importance, and the work Franklin did in carbon made her name long before she even touched a DNA strand.  The government’s wartime interest in coal came from its ability to resist the incursion of some gases, but not others.  Charcoal in gas masks had saved the lives of thousands because of its ability to filter out poisonous gases.  Knowing that it worked, the British war department wanted to know why it worked, and that was Rosalind Franklin’s very first task.

She performed meticulous analysis of different types of coal, and hypothesized that the existence of miniscule pores explained the varying diffusive properties of different types of coal.  By subjecting coals of differing carbon contents to various physical transformations, she was able to construct relations between porosity, temperature, and pressure.  That work resulted in an invitation in 1947 to do further coal research in Paris in the lab of the great crystallographer Jacques Mering.

These were her halcyon days, working in an intellectually stimulating cosmopolitan center, drinking her afternoon coffee in lab beakers with her fellow researchers while debating Sartre and Stalin, engaging in the boisterous good-natured bickering of Parisian daily life which she loved.  And there was the research, learning crystallographic techniques at the elbow of a charismatic master-hand.  According to the accounts of her closest friends, she fell in love with Mering, the first person she had ever had anything approaching romantic feelings for, though he had a wife and an inevitable mistress already.  Franklin’s work soon uncovered the fact that certain types of coal could not be graphitized.  No matter what you did, how much you heated them, they couldn’t be forced into the layered carbon sheets that are the hallmark of graphite.

She became a master of X-Ray techniques, firing the beams at her carefully prepared samples and then interpreting the pattern of resulting dark and light spots as a physical structure, methods that she would perfect in her work on DNA and viruses back in London.  She was also briskly unconcerned with the health effects of working in such close proximity to the energetic rays without shielding, which no doubt contributed to her early and tragic death.

Had all things been equal, she probably would have stayed in Paris, living a thrifty and exciting life of varied intellectual and physical challenge, but the fact was that her family was in England, and they wanted her to come back home.  The chance came with an offer to work at King’s College on the crystallography of DNA under JT Randall.  She in no way wanted to trade the rich and expressive cosmopolitanism of Paris for the stodgy and silent English Way, but came anyway, intrigued at the prospect of applying her techniques to complicated biological molecules.

DNA at the time was not the genetic superstar it is now.  When DNA was first isolated in the nucleus along with a small flotilla of various and exciting proteins, it was thought to be a minor player in cell development.  Chemically, it was just not interesting enough to be the source of life’s incredible variety.  Common scientific wisdom held that the far more likely source of nuclear inheritance were the nuclear proteins, with the DNA playing some unknown subservient or organizational role.  It wasn’t until 1943 that Oswald Avery did his critical experiment demonstrating DNA’s role in heredity, and even then with no explanation for how such a bland molecule accomplished what it did.

Rosalind arrived in England and set glumly to work, not realizing that circumstances were against her before she began.  Randall had told Franklin that she was to work alone on DNA while he told two other researchers, Maurice Wilkins and Alec Stokes, that they would also be on the project.  The result was that Franklin was outraged and defensive every time Wilkins tried to interpret her data, and Wilkins was flabbergasted at what the big deal was, since as far as he knew she had been informed all about his part in the project.  Wilkins felt bullied, Franklin felt betrayed, and in that uncongenial atmosphere she labored away with her assistant, Raymond Gosling, to map the geometry of DNA through crystallography.

She quickly came upon a significant result, namely that DNA existed in two forms, and that the images taken thus far were an unclear combination of the two.  By hydrating the DNA, it stretched out into a pure “wet” or “B” form, while unhydrated DNA took what was called the “A” form.  The difference between the two structures suggested to her right away that, if DNA possesses a helical structure, the phosphate groups must be on the outside in order to allow them to interact with the water.  When Watson and Crick and, an ocean away, Linus Pauling, built their original DNA models, they featured inward-facing phosphorous atoms, and it was Rosalind Franklin who set them straight on their error, allowing them to move forward.

Utilizing hydration techniques she’d learned in France, and a new multiple angle camera system, she was able to take what are generally considered the most beautiful crystallographic images of the mid Twentieth Century, images which clearly showed, to those capable of interpreting them, DNA’s helical structure as well as some hints about how it packed itself.

Watson and Crick were model builders, who worked from the known information about base ratios (the A and T bases were always found in equal amounts, as were the C and G bases), molecular lengths, and crystalline structures to build likely models that filled in the unknowns.  It was an approach that relied on leaps of intuition and a willingness to jump into untested territory.  Franklin, by contrast, took the data from her crystallography and set down to the hard work of mathematically interpreting it using Patterson analysis to slowly build up a three dimensional model from a mass of accumulated data.  For her, Watson and Crick’s methods were slapdash because they couldn’t prove what they had dreamt.

Sometimes slow and steady doesn’t win the race, particularly when the hare is shown a shortcut.  Franklin’s best photograph of DNA, the famous Photograph 51, was given by her assistant, Gosling, to his thesis supervisor, Maurice Wilkins.  Wilkins in turn showed it, without Franklin’s knowledge, to Watson, who saw at a glance what it meant.  Discussing the image with Crick, they realized at once that it implied a two strand, anti-parallel structure which, when coupled with their previous insights about base pairing, resulted in both the modern model of DNA structure and the solution to the mystery of how DNA replicates itself.

Franklin would, doubtlessly, have gotten there via her own more systematic route, but she didn’t see the anti-parallel strand implications of her own picture, as Crick did, and hadn’t been messing around with different base pair configurations to discover that, in a certain state, the A-T and C-G structures were the same length, as Watson had, and that turned out to make all the difference.  When Watson and Crick published the full article announcing their results in 1953, Franklin’s crystallography work was included in a separate article, but was outshone in the public perception by the elegance and implications of the Watson-Crick model.

In a way, it was just as well, because Franklin was simply done with working at King’s College.  She was starved for intellectual companionship, frustrated with Randall’s handling of her work, tired of the cloistered mundanity of the school, and exhausted from the constant condescension.  When a chance came to work with the brilliant JD Bernal at Birkbeck College, she grabbed it, leaving Gosling to wrap up their joint work of the previous three years.  It was good bye and good riddance to DNA and a position that had only ever annoyed her, and hello to the most scientifically fruitful years she would ever know.

Bernal was a polymath genius who could converse about anything, and who had a knack for gathering together brilliant people and then leaving them alone to do what they did best.  He paired Franklin with Aaron Klug to investigate the structure of the tobacco mosaic virus through crystallography, and a more perfect scientific duo has there rarely been.  Franklin was all rigor and method, while Klug was speculative and imaginative, and together they published a flurry of papers that unlocked the secrets of plant virus structure, including the relative positioning of the protein and nucleic acid content.  At her height, she was publishing six and seven papers a year in the most prestigious scientific journals of the day, while American universities fell over themselves to provide her with raw virus material.

The Rosalind Franklin of a year after the discovery of DNA was not a wounded and bitter woman unable to forget slights of the past.  She was a successful and universally respected scientist at the very top of her game, doing precisely what she wanted to do.  Unlike the vast majority of other researchers, she was not a university lecturer or attached to a private research institute – neither of those career paths interested her because she saw both as taking away from the purity of her work.  Leaving King’s, life was suddenly and fully as good as it had been back in Paris, and scientifically even better.  Franklin was poised to become the world expert on viral structures.

A pair of cysts growing on her ovaries ensured that would not be the case.  She began feeling abdominal pains while on tour in America and, upon her return, she had to have all of one and part of the other ovary removed, to be followed by a later full hysterectomy.  That gave her time, but the cancer returned and Franklin underwent experimental chemotherapy treatment to try and fight the disease long enough to finish her work.  Some days she was so weak that she had to physically crawl up the steps from her basement laboratory to her office, refusing all offers of assistance.  She kept her illness to herself for as long as she could, continuing to carry out her experiments so long as she had the energy to stand, gearing her lab up for a study of polio virus structure that she would not live to see completed, spending her spare time with the Crick family (she, Watson, and Crick had long since buried the hatchet on whatever animosity there might once have been) or with her brothers, who were sensible enough not to keep asking about her health.

She died in a hospital bed in 1958, her body wasted away from the disease, the treatment, and the heroin she’d been given to cope with the pain, and her mind in a fog of hallucinations about Klug, the lab, and the work that had shaped her brief, brilliant life.

FURTHER READING: Brenda Maddox’s Rosalind Franklin: The Dark Lady of DNA is my favorite book about Franklin, and is perhaps my favorite non-Feynman scientific biography ever.  It eschews raking up drama and outrage where Franklin felt none, and focuses on how much happiness and first-caliber work she was able to do once she left the poisonous atmosphere of King’s College.

FURTHER THANKS: Well, that’s 50 episodes right there I reckon.  This series would never have happened without the instigation and encouragement of Amy Davis Roth, or the support of the people at MadArtLab (Anne, Donna, Emily, Beth, Brian, Ashley, Lauren, and Elizabeth, each of whom has at one point or another done something amazingly kind to help the column).  Lauren Uhde, Anne Bean, Jaideep Singh, Xaquri Rzetelny, and the people at LabOutLoud and WomenYouShouldKnow have been so wonderful in helping get the word out about the series that I don’t suppose I’ll ever stop thanking them.  The scientists who took time out of crazy schedules to chat with me about their work likewise, including Toni Morelli, Tania Singer, Carolynn Smith, and Sandrine Hazan.  And, of course and primarily, for all of you who come back every other week to read about these remarkable human beings and their magnificent work.  Thank you, and thank you.