When most people hear about the discovery of DNA, they picture James Watson and Francis Crick in 1953, triumphantly holding up a model of the double helix. But DNA鈥檚 story doesn鈥檛 begin, or end, there. In fact, the molecule that carries our genetic code had been sitting quietly in lab notebooks for almost a century before Watson and Crick entered the scene. The journey from obscure cellular 鈥済unk鈥� to the blueprint of life is a tale full of false starts, overlooked heroes, and more than a little scientific drama.
The Accidental Beginning
Our story starts in 1869 with Swiss chemist Friedrich Miescher, who wasn鈥檛 even looking for DNA. He was trying to study proteins in white blood cells, so he did what any 19th-century scientist might: he asked a nearby hospital for their used surgical bandages (yes, really). When he analyzed the cells, he stumbled upon a mysterious substance in the nuclei that didn鈥檛 behave like proteins. It had a ton of phosphorus and resisted being broken down by enzymes. Miescher dubbed it 鈥渘uclein,鈥� and while he knew he had found something important, almost no one else cared. For decades, nuclein languished in obscurity, a chemical curiosity without a purpose.
The First Blueprints
Fast forward to the early 20th century, when Phoebus Levene began teasing apart what nuclein (by then renamed nucleic acid) was actually made of. Levene figured out that nucleic acids were strings of smaller units, which he called nucleotides. Each nucleotide was a neat three-part package: a sugar, a phosphate group, and one of four nitrogenous bases. He even proposed a repeating 鈥渢etranucleotide鈥� structure, which turned out to be wrong, but his bigger idea, that DNA was a long chain of these nucleotides, was absolutely right.
Levene鈥檚 model was like giving future scientists the Lego blocks to build DNA, even if he didn鈥檛 quite know what the finished structure looked like.
The Smoking Gun: DNA as the Genetic Material
For years, proteins were the leading candidates for the hereditary material, given that they were complex, versatile, and already linked to biological functions. With its monotonous structure, DNA looked far too dull to hide life鈥檚 greatest secrets.
That assumption unraveled thanks to some . In 1928, British bacteriologist Frederick Griffith showed that harmless bacteria could be 鈥渢ransformed鈥� into deadly bacteria by a mysterious substance from dead cells. When he mixed heat-killed virulent bacteria with living harmless ones, the harmless strain somehow acquired the deadly traits. He didn鈥檛 know what the substance was, but he knew it carried instructions powerful enough to change one cell into another.
It wasn鈥檛 until 1944 that Oswald Avery, along with Colin MacLeod and Maclyn McCarty, tracked down the culprit. Working with heat-killed virulent bacteria, they painstakingly stripped away proteins, sugars, and RNA through a series of purification steps, each time testing whether the mysterious 鈥渢ransforming principle鈥� was still active. What remained behaved exactly like DNA. It gave a positive result in chemical tests for nucleic acids, carried the expected phosphorus-to-nitrogen ratio, and, most convincingly, lost all transforming power when treated with DNA-destroying enzymes. This revelation was seismic: heredity could be written in nucleic acids, not proteins. Still, many scientists remained skeptical, holding fast to the idea that genetic material lay within proteins, until further proof arrived.
Cracking the Code鈥檚 Logic
One of the people who took Avery鈥檚 work seriously was Erwin Chargaff. By the late 1940s, he noticed that DNA wasn鈥檛 the monotonous tetranucleotide pattern Levene imagined. Instead, its base composition varied from species to species, and always followed a peculiar rule: the amount of adenine (A) matched thymine (T), and cytosine (C) matched guanine (G). These pairings, later immortalized as 鈥淐hargaff鈥檚 rule,鈥� set the stage for solving DNA鈥檚 structure.
Rosalind Franklin鈥檚 Lens
Enter Rosalind Franklin, a master of X-ray crystallography. Her precise experiments revealed that DNA came in two forms (A and B) and that the B form had the repeating patterns of a helix. Contrary to the myth that she 鈥渕issed鈥� the double helix, Franklin understood a great deal about DNA鈥檚 structure. Her data, especially the now-famous 鈥淧hotograph 51鈥�, provided crucial evidence that complemented Chargaff鈥檚 base-pair rules.
Unfortunately, her contributions were downplayed for decades, in part because Watson鈥檚 memoir The Double Helix painted her as an unwitting outsider. has shown she was not a sidelined observer, but an equal contributor whose insights were essential.
The Double Helix Emerges
By early 1953, Watson and Crick, spurred on by competition with American chemist Linus Pauling, were busy shuffling cardboard cutouts of bases on their desks. When they realized A pairs with T and C pairs with G (just as Chargaff鈥檚 ratios predicted) the pieces finally clicked. Add Franklin鈥檚 X-ray data and a dash of trial-and-error modeling, and the elegant double helix emerged: two sugar-phosphate backbones spiraling in opposite directions, joined in the middle by complementary base pairs.
In April 1953, Nature published three papers: one from , one from , and one from , together unveiling DNA鈥檚 structure.
The Legacy
The double helix didn鈥檛 just explain heredity; it opened the floodgates of modern biology. Understanding DNA鈥檚 structure made it possible to uncover how genetic information is copied, passed on, and even manipulated. Today, the same molecule that Miescher found on pus-soaked bandages lays at the heart of everything from ancestry tests to CRISPR gene editing to precision medicine.
Watson and Crick may have gotten the glory, but the story of DNA is a relay race, not a solo sprint. Miescher, Levene, Griffith, Avery, Chargaff, Franklin, Wilkins, and many others each carried the baton, often without knowing what the finish line would look like.
Sophie Tseng Pellar recently graduated from 9I制作厂免费 with a Bachelor of Science (BSc) degree in the physiology program. She will be continuing her graduate studies in the Surgical and Interventional Sciences program at 9I制作厂免费. Her research interests include exercise physiology, biomechanics and sports nutrition.
Part of the OSS mandate is to foster science communication and critical thinking in our students and the public. We hope you enjoy these pieces from our Student Contributors and welcome any feedback you may have!
