The structure of DNA was elucidated in 1953, but it was actually discovered in 1868 in a small laboratory in Germany by a Swiss scientist named Friedrich Miescher.
Today, when I ask most people the simple question of “Who discovered DNA?”, I will get one of two answers: “I don’t know” or “Watson and Crick”.
In most basic science textbooks, the names that primarily pop up when the history of DNA comes into question are James Watson, Francis Crick and Maurice Wilkins. Their Nobel Prize—awarded in 1965—is lauded in these textbooks beside a classic picture of Watson and Crick staring admiringly at the double helix model. Their Nobel Prize was awarded “for their discoveries concerning the molecular structure of nucleic acids and its significance for information transfer in living material.” The words worth noting there are molecular structure, but that isn’t the whole story, as they didn’t actually discover the molecule.
The 19th Century: the story of DNA begins
In the late 19th century, one of the most widely researched questions was how life existed and how information was passed down between generations. Very little was known about the nucleus, but interest was building. Many people were taking a more cellular and molecular view of life. Charles Darwin and Alfred R. Wallace gave us the theory of natural selection in 1859, and in 1866, Ernst Haeckel proposed that the nucleus contained hereditary components. A decade later, Walther Flemming described chromosomes during mitosis and Theodore Boveri supported the idea that chromosomes contained the hereditary material of a cell. Most championed the idea that proteins held the key to life. Amongst all this excitement and enlightenment, DNA was discovered by a Swiss scientist in Germany.
Friedrich Miescher was born into a family immersed in science on August 13, 1844 in Switzerland. Both his father and uncle, Johann F. Miescher and Wilhelm His, respectively, were renowned physicians, anatomists and professors at the University of Basel. Miescher showed a keen interest in science and took up studying medicine in Basel, but later decided that research would satisfy his curiosity about the natural world.
What is this precipitate?
The story of DNA begins in 1868, when Friedrich Miescher joined Felix Hoppe-Seyler’s lab some 85 years before Watson and Crick discovered the structure of DNA. Miescher’s research aim was to determine the chemical composition of cells and Hoppe-Seyler’s lab provided him with the opportunity and guidance to do so. Using pus from fresh surgical bandages sourced from a nearby clinic, Miescher obtained leucocytes, his cells of choice to work with.
Miescher was a meticulous scientist, recording every detail and methodically carrying out his work with great caution. This patient approach, amidst his working with proteins and lipids, allowed Meischer to detect something odd. While performing tests, he noticed that a substance precipitated in acidic conditions. Excited and intrigued, he set out to explore this unusual precipitate.
He did several experiments to precipitate the substance out of solution. This unknown precipitate dissolved under alkaline conditions, but precipitated when the solution was neutralized. Even when the solution was made acidic, the substance did not dissolve back into solution.
About protein precipitation
Proteins carry both positive and negatively charged molecules in their structure. Depending on the pH of the solution, these molecules may either be negatively charged or positively charged. At a pH where a protein has a net positive or negative charge, it will remain dissolved in solution. The ions in water can interact with these charged species on the protein, which keeps the protein in solution. However, at a particular pH, the net charge on a protein is 0, meaning that it is neutrally charged. At this pH level, the protein molecules begin to interact among themselves, instead of with the surrounding ions, and therefore precipitate out. This pH is called the isoelectric point or pI. Once the pH is changed in either the acidic or basic direction, away from its pI, it will dissolve back into the solution.
Knowing this, the fact that Miescher’s unknown precipitate did not dissolve under a variety of acidic pHs showed him that this was probably not a protein.
To be sure, Miescher performed several more tests. Upon burning the precipitate, he found all the usual organic elements – oxygen, carbon, hydrogen and nitrogen, but he found no sulphur, which is usually present in proteins. Additionally, he found that the precipitate had an appreciable amount of phosphorus within it.
He also subjected the precipitate to proteases, enzymes that break down proteins into their building blocks—amino acids. The precipitate was not affected by protease, further cementing his view that this was not a protein. He also knew, based on previous work, that the substance was found in the nucleus, so he named it nuclein.
The paper highlighting Miescher’s discovery came in 1871. After this, Miescher continued to work on nuclein, preferring to use salmon sperm as the material. His work on nuclein showed that all the phosphorus contained in nuclein is present as phosphoric acid, and that the molecule must have a high molecular weight, as it diffused poorly. He stated that this nuclein was present with another basic molecule, which he called protamine. Together, these substances constituted the mass of the sperm heads he was studying. Miescher was right about all of this!
DNA after Miescher
The great task of studying DNA began shifting from Miescher’s hands—who altered his research focus and became burdened by his other responsibilities—to other scientists. Many chemists, especially those who knew Miescher and Hoppe-Seyler, began working on nuclein. Albrecht Kossel, a researcher in Hoppe-Seyler’s lab (and a later Nobel Prize winner) found that nuclein was composed of four bases and sugars. Eduard Zacharias, a botanist, merged the concept of chromosomes with nuclein, demonstrating that nuclein was an important component of chromosomes.
Even so, DNA still received little attention from the scientific community at the time. Most experts, including Miescher, believed that proteins were the hereditary components, rather than nucleic acids (as they were later renamed by Richard Altmann). Many reasoned that nucleic acids were chemically too simple to yield such dynamic variety amongst life. Proteins, on the other hand, were composed of 20 different amino acids and were complex enough to provide the variation of life we see around us.
This caused nucleic acids to be neglected to a large degree. Work on the molecule faltered and the focus primarily shifted to proteins. All of this changed when a sequence of experiments—first by Griffith in 1928, then by Avery, MacLeod and McCarthy in 1944, and finally by Hershey and Chase in 1952—proved that DNA was the genetic material in cells.
However, the deal had still not been clinched! Without understanding the structure of DNA, it was difficult to say with certainty (or as much certainty as science allows) that DNA was irrefutably the life-giving molecule. Watson and Crick at Cambridge, Wilkins and Rosalind Franklin and her student Raymond Gosling, as well as Linus Pauling (of protein alpha helix fame) were all working to discover the structure of DNA. Through a combination of luck, ingenuity and inspiration, Watson and Crick reached the finish line first.
Since their discovery and the validation of DNA structure, the world of nucleic acids has never been the same. Work on the molecule skyrocketed and in the next 3 decades, an incredible amount of ground-breaking work had been done.
Upon Friedrich Miescher’s death at 51 from tuberculosis, his uncle Wilhelm His wrote in the introduction of Miescher’s collected works, “The appreciation of Miescher and his work will not diminish; on the contrary, it will grow and his discoveries and thoughts will be seeds for a fruitful future.” Today, we are still probing DNA and other nucleic acids for the secrets of evolution, health, and the beginning of life on Earth, so those words ring true, and Miescher will always hold a renowned place in the history of DNA!