From The Editor | March 12, 2024

Did Science Really Do Rosalind Franklin Dirty?

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By John Oncea, Editor

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Watson and Crick get the credit, but their determination of the structure of DNA would not have happened in 1953 if not for the work of Rosalind Franklin. Was she ignored because she was a woman? Or is the controversy overblown?

“Science and everyday life cannot and should not be separated. Science, for me, gives a partial explanation of life. In so far as it goes, it is based on fact, experience, and experiment.”

— Rosalind Franklin

The Discovery Of DNA: From Miescher To Levine To Chargaff To Watson And Crick

Forgive me for reducing 80 years of research and discovery to 339 words but the story I’m about to tell isn’t the discovery of DNA. Rather, it’s about the allegedly overlooked contributions of British scientist Rosalind Franklin. With that understanding, let’s get busy summarizing.

Swiss physiological chemist Friedrich Miescher first identified nuclein – a term later changed to nucleic acid then changed again to deoxyribonucleic acid, or DNA – in 1869, a discovery that kicked off genetic research.

Numerous scientists conducted research in the decades that followed providing additional details about the DNA molecule, including its primary chemical components and how they joined with one another. Two scientists in particular – Russian biochemist Phoebus Levene and Erwin Chargaff, an Austrian biochemist – conducted research revealing details about the DNA molecule's chemical components and bonding.

Levene discovered the order of the three major components of a single nucleotide, the carbohydrate component of RNA, and the carbohydrate component of DNA, as well as receiving credit as the first person to correctly identify the way RNA and DNA molecules are put together.

Chargaff expanded on Levene’s work by uncovering additional details of the structure of DNA, noting that the nucleotide composition of DNA varies among species. He also discovered that almost all DNA, no matter what organism or tissue type it comes from, maintains certain properties, even as its composition varies.

In 1953, with these foundations in place, American biologist James Watson and English physicist Francis Crick reached their groundbreaking conclusion: the DNA molecule exists in the form of a three-dimensional double helix.

“Watson and Crick were not the discoverers of DNA, but rather the first scientists to formulate an accurate description of this molecule's complex, double-helical structure,” writes Nature. “Moreover, Watson and Crick’s work was directly dependent on the research of numerous scientists before them, including Miescher, Levene, and Chargaff.”

Watson and Crick’s derivation of the three-dimensional, double-helical model for the structure of DNA also relied on the assembly of possible three-dimensional structures based upon known molecular distances and bond angles, a technique advanced by American biochemist Linus Pauling, and some crucially important X-ray crystallography work by English researchers Rosalind Franklin and Maurice Wilkins.

In 1962, Watson, Crick, and Wilkins jointly received the Nobel Prize in Physiology or Medicine for their 1953 determination of the structure of DNA. Franklin did not.

An X-ray Crystallography Pioneer

Rosalind Elsie Franklin was born July 25, 1920, in London, the second of four children in her family. She excelled in science at London’s St. Paul’s Girls’ School before studying physical chemistry at Newnham College, University of Cambridge.

“After graduating in 1941, she received a fellowship to conduct research in physical chemistry at Cambridge,” writes Britannica. “But the advance of World War II changed her course of action: not only did she serve as a London air raid warden, but in 1942 she gave up her fellowship to work for the British Coal Utilisation Research Association, where she investigated the physical chemistry of carbon and coal for the war effort.”

Franklin eventually earned a Ph.D. in physical chemistry from the University of Cambridge in 1945 then spent three years working with Jacques Méring at the State Chemical Laboratory in Paris. There, she learned X-ray crystallography leading to her research on the structural changes caused by the formation of graphite in heated carbons—work that proved valuable for the coking industry.

Upon her return to England in 1951, Franklin worked as a research associate at King’s College London, focusing on the structure of DNA. “When she began her research at King’s College, very little was known about the chemical makeup or structure of DNA,” Britannica writes. “However, she soon discovered the density of DNA and, more importantly, established that the molecule existed in a helical conformation.”

The same year, Watson attended a lecture by Franklin in which she revealed DNA can exist in two forms depending on the relative humidity in the surrounding air. From this discovery, Franklin deduced that the phosphate part of the molecule was on the outside.

“Watson returned to Cambridge with a rather muddy recollection of the facts Franklin had presented,” PBS writes. “Based on this information, Watson and Crick made a failed model. It caused the head of their unit to tell them to stop DNA research.

“Franklin, working mostly alone, found that her X-ray diffractions showed that the ‘wet’ form of DNA (in the higher humidity) had all the characteristics of a helix. She suspected that all DNA was helical but did not want to announce this finding until she had sufficient evidence on the other form as well.”

Wilkins shared Franklin’s research with Watson in January 1953, apparently without her knowledge or consent. Crick later said he and his fellow researchers, “Used to adopt – let's say, a patronizing attitude toward (Franklin)."

Photograph 51: A Picture Is Worth A … Noble Prize?

Armed with Franklin’s research that was provided to them by Wilkins, “Watson and Crick took a crucial conceptual step, suggesting the molecule was made of two chains of nucleotides, each in a helix as Franklin had found, but one going up and the other going down,” writes PBS. “Crick had just learned of Chargaff's findings about base pairs in the summer of 1952. He added that to the model so that matching base pairs interlocked in the middle of the double helix to keep the distance between the chains constant.”

Watson and Crick demonstrated that each strand of the DNA molecule serves as a template for the other. When the cells divide, the two strands split apart and a new “other half” is constructed on each strand, exactly like the one before. This process allows DNA to replicate itself without altering its structure, except for sporadic errors or mutations.

One of the most critical pieces of Franklin’s research was Photograph 51, her fifty-first X-ray diffraction pattern of DNA which was taken on May 6, 1952. It is one of the most famous scientific images in history and was taken using X-ray crystallography, a technique that involves shining X-rays through a crystallized sample and analyzing the resulting diffraction pattern.

Photograph 51 “presents a clear diffraction pattern for B-Form DNA,” writes Arizona State University’s Embryo Project Encyclopedia. “The outermost edge of the diffraction pattern consists of a black diamond shape “The diamond has rounded corners with the darkest corners situated at the top and bottom of the film. The diamond shape of the DNA diffraction pattern is not made of fine, definite lines, but rather thick, fuzzy borders that vary in darkness such that the borders fade on the left- and right-hand sides of the film.

“Inside the diamond is a cross shape like the letter ‘X.’ The X shape is not made of continuous lines. Instead, along each line of the X are four horizontal dashes, called spots that become darker as they move closer to the center of the film. There is a hole at the center of the film, with dark spots lining the outside of the center hole.”

From Photograph 51, Franklin was able to deduce important information about the structure of DNA, such as its helical nature and the dimensions of the helix. Her analysis of the photograph suggested that the phosphate groups were located on the outside of the DNA molecule.

Furthermore, the distance between the dark bands in Photograph 51 indicated that the nitrogenous bases were stacked in the center of the DNA molecule. Franklin’s measurements from the photograph provided key dimensions of the DNA helix, including the distance between the turns of the helix and the angle of the helical structure.

Photograph 51 provided critical evidence supporting the idea of a helical structure for DNA. This evidence was instrumental in the eventual elucidation of the DNA double helix by Watson and Crick.

The circumstances surrounding the sharing of Franklin's data and the extent of its influence on Watson and Crick’s model remain controversial. Some argue that Franklin’s contribution was not fully acknowledged, while others believe that her data was just one of several factors that led to the discovery of the DNA structure.

Despite the controversy surrounding its use, Photograph 51 remains a landmark image in the history of science and has contributed to our understanding of the molecular basis of life. In recent years, there has been greater recognition of Franklin’s role in the discovery of DNA's structure, and Photograph 51 is often cited as evidence of her significant contributions to science.

Was Franklin’s Data Stolen?

In 2015, according to The Guardian, Nobel laureate Tim Hunt said, “Let me tell you about my trouble with girls … three things happen when they are in the lab … You fall in love with them, they fall in love with you, and when you criticize them, they cry.” The ensuing controversy led to his resignation from several key research and policy positions, including the European Research Council, and a temporary withdrawal from public life and professional activities.

It also led The Guardian to explore sexism in science, particularly the possibility that Watson and Crick – with the help of Wilkins – stole Franklin’s data. “The four protagonists would make good characters in a novel – Watson was young, brash, and obsessed with finding the structure of DNA; Crick was brilliant with a magpie mind, and had struck up a friendship with Wilkins, who was shy and diffident,” writes The Guardian. “Franklin, an expert in X-ray crystallography, had been recruited to King’s in late 1950. Wilkins expected she would work with him, but the head of the King’s group, John Randall, led her to believe she would be independent.”

While Photograph 51 provided a vital clue about the double helix, “Watson and Crick needed precise observations from X-ray crystallography. Franklin unwittingly provided those numbers herself, included in a brief informal report that was given to Max Perutz of Cambridge University.”

According to The Guardian, Perutz’s report was passed on to Sir Lawrence Bragg, the head of the Cambridge lab where Watson and Crick were working. Bragg passed the report on to Watson and Crick and the two researchers had the information they needed to complete their discovery.

“The report was not confidential, and there is no question that the Cambridge duo acquired the data dishonestly,” The Guardian writes. “However, they did not tell anyone at King’s what they were doing, and they did not ask Franklin for permission to interpret her data (something she was particularly prickly about).”

The Guardian blames the “myth” that Franklin’s data was stolen on Watson’s memoir, The Double Helix, which “included frank descriptions of his appalling attitude toward Franklin, whom he tended to dismiss, even down to calling her ‘Rosy’ in the pages of his book – a nickname she never used. The epilogue to the book, which is often overlooked in criticism of Watson’s attitude to Franklin, contains a generous and fair description by Watson of Franklin’s vital contribution and a recognition of his failures with respect to her – including using her proper name.”

Despite a Nobel rule that no more than three people can be awarded a prize, The Guardian theorizes that Franklin, along with Watson, Crick, and Wilkins, could have been recognized had she not died four years earlier. “The simple expedient would have been to award Watson and Crick the prize for Physiology or Medicine, while Franklin and Watkins received the prize for Chemistry.”

A Life Cut Short

Franklin became friends with Crick and his wife, Odile, after moving to her Cambridge laboratory where she undertook dangerous work on the poliovirus, writes Science History Institute. Wilkins went on to apply X-ray techniques to the structural determination of nerve cell membranes and RNA while rising in rank and responsibility at King’s College.

“Watson’s subsequent career eventually took him to the Cold Spring Harbor Laboratory (CSHL) of Quantitative Biology on Long Island, NY, where as director from 1968 onward he led it to new heights as a center of research in molecular biology,” Science History writes. “From 1988 to 1992 he headed the National Center for Human Genome Research at the NIH. Afterward, he returned to CSHL as chancellor. Watson’s racist remarks about the intelligence of Africans in 2007 led the CSHL to force him into retirement.”

Franklin’s X-ray diffraction images, particularly Photograph 51, provided crucial evidence of the helical structure of DNA, serving as the foundation for Watson and Crick’s model of the DNA double helix. As noted, despite her significant contributions, Franklin's role in the discovery of DNA’s structure was initially overlooked.

Her life, however, was much more than Photograph 51 and the controversy surrounding her lack of credit. She left King’s College in 1953 and worked in the Crystallography Laboratory at Birkbeck College, London for the next five years.

“While there she completed her work on coals and DNA and began a project on the molecular structure of the tobacco mosaic virus,” writes Britannica. “She collaborated on studies showing that the ribonucleic acid (RNA) in that virus was embedded in its protein rather than in its central cavity and that this RNA was a single-strand helix, rather than the double helix found in the DNA of bacterial viruses and higher organisms.”

Known for her meticulous diligence and her skill in interpreting complex data, Franklin remained a resolute scientist who often worked long hours in the laboratory where her colleagues respected her as a brilliant but sometimes reserved scientist.

Remembering Rosalind Franklin

Franklin never knew about the 1962 Nobel Prize won by Watson, Crick, and Wilkins having died four years earlier, at the age of 37, of ovarian cancer. However, her work in X-ray crystallography paved the way for advancements in molecular biology and biophysics and continues to be celebrated and studied by scientists around the world.

Her story has been the subject of numerous books, articles, and documentaries and several institutions and awards have been named in her honor, including the Rosalind Franklin University of Medicine and Science in Illinois.

The Rosalind Franklin Mars rover, part of NASA's Mars exploration program, was named even in her honor and the Rosalind Franklin Award, established by the Royal Society, honors outstanding contributions to the advancement of women in STEM fields.

Franklin’s research has had a lasting impact on our understanding of the molecular basis of life. Whether she received credit or not, she remains an iconic figure in the history of science, particularly for her contributions to the discovery of DNA’s structure which also helped lay the foundation for the Human Genome Project and other initiatives aimed at understanding and treating genetic diseases.