The color of your hair, the hue of your skin, the length of your ring finger, the shape of your lips; all of the complexities that make you a unique organism, the things that make you human, were bestowed upon you by a tiny chemical alphabet. In fact, just four chemical letters wedged between groups of sugar and phosphate can define a species. These chemical letters can write an Albert Einstein, or a house mouse—with only a 2.5% ‘code’ difference separating the two. It seems too simple. How can just a combination of four letters code the template for humankind, or every other living creature, for that matter?
In 1953, James Watson and Francis Crick published a theory and model that would answer that question. They posited that those four chemical letters comprised DNA, and that DNA was arranged in a double helix. A double helix resembles the shape of a twisted ladder. They suggested that the backbone of DNA (each side of the ladder) was made up of alternating sugar and phosphate groups, and that the ‘rungs’ were comprised of nucleic acids (letters), 10 rungs per helix. They stated that each rung was a combination of adenine, cytosine, guanine or thymine (A, C, G, T), with A always paring with T, and C always pairing with G.
Why is this important?
Well, identifying the structure of DNA allowed scientists to draw two ground-breaking conclusions. First, unzipping the strands of DNA provides template strands that can create two identical ‘daughter molecules.’ Second, the order of the bases on each strand creates a digital message that codes for specific traits. If DNA had a helical structure capable of replication, it would explain how our bodies make proteins, how our cells inherited genetic material and, thus, set the stage for the fields of genetics, molecular biology and biotechnology, genomics and so much more. In other words, this was no small feat. In fact, the discovery of the structure of DNA and the chemical explanation of heredity is considered one of the most critical scientific breakthroughs of all time. Watson and Crick received the Nobel Prize in Physiology or Medicine in 1962, along with Maurice Wilkins, an X-ray crystallographer.
Their award-winning discovery was important for a less scientific reason, as well. Let’s take a step backward—back to 1953. How did Watson, Crick and Wilkins know what DNA looked like? What information did they work from to develop their theory? How did they build a model? After all, DNA was an elusive subject, not easily obtained, observed or photographed. In fact, to this day, scientists are creating new ways to view stands of DNA. Behind the Nobel Prize winners stood a self-assured woman, the only individual in the group to actually possess a degree in chemistry, whose data was utilized by Watson, Wilkins and Crick without her consent.
Enter: Rosalind Franklin.
Rosalind Franklin was the product of a wealthy London banking family, where each child was expected to engage in both personal and professional development. From an early age, Franklin displayed academic aptitude. She went on to obtain a fellowship and attended Newnham College, a college for women, at Cambridge University. After completing her degree in 1941, she pursued graduate work with Ronald Norrish, who would later receive a Nobel Prize. Franklin spent one year in Norrish’s lab before his drinking and inability to assist her with a research project drove her to pursue new endeavors. It would be Franklin’s research on coal porosity and density at the British Coal Utilisation Research Association (BCURA) that would earn her a PhD in physical chemistry from Cambridge. Her work at BCURA helped scientists accurately predict coal performance for fuel development and the production of wartime devices. If you recall, World War II took place during the years where Franklin was earning her PhD. Amazingly, not only did she conduct graduate-level research during wartime, she also aided war efforts by offering her services as an Air Raid Warden, often making rounds to check on citizens during air raids.
After the war ended, she began pursuing jobs, marketing herself as “a physical chemist who knows very little physical chemistry, but quite a lot about the holes in coal.” She was quickly paired with Jacques Meringat at the Laboratoire Central des Services Chimiques de l’État in Paris. Meringat was an X-ray crystallographer who taught Franklin how to use X-ray diffraction on amorphous—aka, no clearly defined shape or form—objects (X-ray crystallography allows one to determine the structure of an object after it’s hit with X-ray beams and the beams scatter in predictable patterns). In 1950, Franklin transferred from Paris to King’s College with a new skill set that allowed her to study the structure of proteins, lipids, and DNA fibers. It was her job to improve crystallography techniques in such a way that researchers could observe the structure of DNA. Maurice Wilkins, a fellow PhD researcher at King’s, and an experienced X-ray crystallographer, initially proposed the study of DNA using X-ray diffraction. However, it would be Franklin who would drastically improve the process, in spite of limitations imposed by rudimentary equipment. Her skills were such that Maurice Wilkins asked how she perfected her crystallography techniques. Whatever her answer, it clearly offended Wilkins, who wrote that Franklin possessed an “air of cool superiority.” In short, the relationship between Wilkins and Franklin was a tense one. Nevertheless, thanks to Raymond Gosling, a PhD student assigned to assist Franklin, the duo obtained the first clear photo of DNA through X-ray diffraction, making the development of a DNA model plausible.
“Photo 51,” the X-ray diffraction image taken of DNA by Franklin and Gosling, inadvertently became crucial evidence in determining its structure. Although the photo could not help elucidate the number of strands or the exact chemical organization of a DNA molecule, this image provided the first clear evidence of the double helix structure. Maurice Wilkins took the image to Watson and Crick, without the knowledge or approval of Franklin. Watson and Crick then used the photo to develop the chemical model of the DNA molecule, beating King’s college researchers to the finish line. The resulting Watson-Crick manuscript, an article by Wilkins and two colleagues, and a co-authored paper by Gosling and Franklin on the structure of DNA, were all published together in Nature in 1953. Watson and Crick acknowledged Gosling and Franklin in a footnote, stating that they were “…stimulated by a general knowledge of Franklin and Wilkins’ “unpublished” contribution.”
It would not be until years later that the theory of the double helix was widely accepted and Nobel Prize awarded. Sadly, by this time, Franklin had succumbed to ovarian cancer at a very early age. Franklin worried she was ill when bulges in her abdomen prevented her from zipping her skirts. Although there was no rule forbidding a posthumous Nobel Prize award, the Nobel Committee did not typically bestow posthumous awards, either.
Some historians have debated the significance and contribution of “Photo 51” to the work of Watson and Crick, and there is also debate regarding whether Franklin would have deduced the structure of DNA on her own, based on the diffraction image. These arguments were contested hotly after Watson’s initial critique of Franklin in his book The Double Helix, stating Franklin was “difficult to work with” and “careless with her appearance.” He later backtracked, noting in his epilogue that Franklin made a number of significant achievements that should be applauded. Indeed, Franklin’s achievements were remarkable, especially considering she did much of her work solitarily. The absence of her name on the Nobel Prize recipient list is no reason to forget about her ‘noble’ work and significant contribution to science. Her X-ray diffraction and crystallography work was arguably better than Wilkins, and her understanding of DNA structure was equal to that of Watson and Crick. It is the author’s opinion that instead of critiquing her self-assurance and lack of interest in fashion, men of the era would have been better served celebrating her brilliance and mourning a life cut far too short.
If you are interested in learning more about the race to the double helix, I highly suggest “Raymond Gosling: the man who crystallized genes” accessible for free online. This is an elaborate, wonderful interview with Gosling that contains much more information.
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