Discovering the Structure of DNA

Now the race was on to figure out the structure of DNA. It’s a rather complex story involving many different scientists, primarily in the U.S. and England. 
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Join DNA Dan each month as he dives deep into the world of genetics, genomics, DNA, and the future of precision genomic medicine. Dan discusses health and ancestry genetic testing, forensic genetics, genetics and mental health, common myths about genetics, and more. 

DNA Dan, SCU Professor of Genomics, Dan Handley, M.S., Ph.D., shares his knowledge from his over 30 years of experience in the world of advanced genomics research and biotechnology. 

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Tune in each month as DNA Dan dives into the evolving world of genetics, from ancestry and health testing to genetics in mental health and forensics. With over 30 years of experience in genomics, SCU Professor Dan Handley, M.S., Ph.D., brings unique insights into how genetics shapes our lives and the future of precision medicine.

Please visit our website for more information about Southern California University of Health Science's Master of Science Program in Human Genetics & Genomics. https://bit.ly/SCU-DNA_Dan

Transcript

In previous episodes, I explained how DNA was discovered to exist and then how it was determined to be the substance responsible for the inheritance of traits. That process took nearly a hundred years. Now the race was on to figure out the structure of DNA. It’s a rather complex story involving many different scientists, primarily in the U.S. and England. An in-depth account of it is chronicled in James B. Watson’s classic book, the Double Helix. For those who want far more detail, I recommend reading it. It’s only about 250 pages long, and it’s a fascinating read. However, it does give the tale from Dr. Watson’s personal perspective. As of the date of this recording. Dr. Watson is still alive and active.

Now on to an abridged account of the discovery of the structure of DNA.

Remember that DNA had been determined to be the molecule carrying the information of inheritance. Also, remember Chargaff’s findings that As and Ts were always found in the same amounts in a species and the same for Cs and Gs. 

Now the time is the early 1950s at Cal Tech in Los Angeles, California, and simultaneously at Cambridge University in England. Nobel Laureate Linus Pauling was at Cal Tech. He gained fame by discovering the structure of proteins. He found that proteins are made up of strings of different sequences of amino acids, not unlike a string of differently shaped pearls. He had a student, Max Perutz, who used a technique called X-ray crystallography to decipher the structure of hemoglobin, the molecule in red blood cells that transports oxygen to our tissues and removes carbon dioxide.

X-ray crystallography involves taking a highly purified substance that can be crystallized, meaning it forms a three-dimensional regular structure or lattice. One of the simplest crystals we encounter in daily life is common table salt or sodium chloride. By shining a thin beam of X-rays at a crystal and capturing the X-ray refraction pattern on photographic film, rather complex mathematics can be used to figure out the three-dimensional structure of the crystalline substance. The key to the success of this process is to ensure that the substance under study is exceedingly pure and that it has been prepared in a way as to assumes a highly regular crystalline lattice structure.

In Cambridge, professor Maurice Wilkins ran a laboratory performing X-ray crystallography studies. Working in his lab was Rosalind Franklin, who was known for her exacting techniques in performing X-ray crystallography. While Maurice Wilkins made some rather crude X-ray diffraction photographs of DNA crystals in 1951, Rosalind Franklin produced by far the clearest, most precise images. DNA, as it turns out, has an affinity for water, even pulling water vapor out of the air. This distorts its structure and makes it difficult to study with X-rays. Rosalind Franklin figured out how to get extremely pure DNA crystals devoid of water. Her images strongly suggested that DNA had to be a helical molecule, like a spiral staircase.

Across the pond, as they say, Linus Pauling was stuck on the idea that DNA had to have some kind of molecular spiral backbone on the inside of its structure, with nucleic acids lined up on the outside. He, like many others, also thought that DNA consisted of three long twisting spiral molecules.

Back in Cambridge, Francis Crick and James Watson worked together to try to figure out the structure of DNA from the existing evidence. They puzzled over it for months, but it was only when they decided to create a physical model of DNA that they started to make a breakthrough. They asked the university machine shop to make sheet metal pieces that resembled the shapes they believed each of the four DNA nucleic acids had. They also used wire to form what they believed to be the backbone that held the nucleic acids in place.

By this time, Rosalind Franklin had moved on to another institution. Maurice Wilkin showed Rosalind Franklin’s X-ray crystallography photos of DNA – the clearest one being denoted number 51, to Watson and Crick. This was done without her knowledge or permission.

In any case, having dimensional information derived from the X-ray crystallography photograph and remembering Chargaff’s rules, Watson and Crick devised an elegant solution to the structure of DNA that was consistent with all the experimental evidence to date. In their proposed structure, DNA consists of a double helix, a dual outside spiral backbone made of linked phosphate groups. Attached on the inside were the nucleic acids. As lined up with Ts exclusively, and Cs with Gs. This allowed for a regular linear structure that essentially could go on endlessly. The dimensions fit all the known atomic size and bonding parameters, as well as the dimensions extrapolated from Rosalind Franklin’s X-ray photograph number 51. Watson and Crick published their findings in a one-page journal article in 1953.

The double helix not also conformed to and explained Chargaff’s findings but also suggested an elegant way for DNA to be duplicated in chromosome form and evenly distributed to daughter cells arising from mitosis. Being a double helix, the helix would unwind to form single strands, and new, complementary strands would be synthesized. Single As connecting with Ts on the existing single, Ts with As, Cs with Gs, and Gs with Cs. In the end, two unwound single DNA strands would give rise to four strands with the identical, although inverted or complementary order. In this way, the double helix model showed how not only As, Ts, Cs, and Gs could be ordered in sequences that formed a code, but how that code could be duplicated and propagated faithfully during cell division as well as passed from generation to generation.

While, like many scientific discoveries, at first, many scientists rejected Watson and Crick’s explanation of the structure of DNA. However, it soon became apparent that it was a rock-solid model and was eventually accepted by the greater scientific community.

In later years, many have said it was among the most significant scientific discoveries in human history. However, the complexity of the discovery process, the rivalry between the famed and prominent Linus Pauling versus the obscure Watson and Crick, and the roles that Wilkins and Franklin played make the story very complex. 

After many years of confirmatory evidence, it turns out that the DNA structure Watson and Crick proposed was essentially correct, although we now know that DNA can form other types of dual helix structures. However, the original central principle of A-T and C-G binding in DNA still stands in those cases as well. For decades and even now, the A-T and C-G base-pairing scheme in DNA is usually referred to in textbooks as Watson-Crick base pairing. More recently, more publications refer to it as Watson-Crick-Wilkins base pairing. And occasionally, giving Rosalind Franklin more credit for the role she played, now it’s more commonly called Watson-Crick-Wilkins-Franklin base pairing.

And by the way, I think it’s worth pointing out that the discovery of the structure of DNA was not the product of the so-called scientific method taught in high school science books. Rather, the discovery was a convoluted piecemeal process involving many people with different talents, knowledge, personalities, and motives. Not to mention a lot of trial-and-error and sometimes heated arguments. Watson and Crick used their intuitions, given the known evidence at the time. They played trial-and-error with a makeshift metal model not unlike a child’s Tinkertoys, if you’re old enough to know what those are. In any case, the point is that there was little methodical about the discovery process. Skill, competitiveness, intuition, luck, playing with physical models, and many would say skullduggery, each played a major role in the discovery of the structure of DNA. 

In the next episode, I’ll discuss in further detail the controversy surrounding Rosalind Franklin and the credit or lack of credit about her role in determining the structure of DNA. It’s an important story.