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Ask most students who discovered DNA and they will say Watson and Crick. They described its structure in 1953. The molecule itself had been found 84 years earlier, by a young Swiss doctor working in a castle kitchen with bandages from a surgical clinic. This post covers what Friedrich Miescher did, how he knew his substance was new, a worked calculation that shows why phosphorus gave it away, and what you can take from how he worked.
Who was Friedrich Miescher?
The Museum of the University of Tübingen gives his dates as 1844 to 1895. Its page on the Castle Laboratory explains that the former kitchen of Hohentübingen Castle became one of the first biochemical laboratories in the early nineteenth century. Felix Hoppe-Seyler named haemoglobin there, and it was there that Miescher discovered nucleic acid in 1869. His test tube of nucleic acid still survives and is on display.
According to the historian of science Ralf Dahm, writing in Developmental Biology (2005), Miescher had just finished training as a physician when he moved to Tübingen. His aim was to work out the building blocks of life, and he chose white blood cells (leucocytes) as his material.
How did Miescher find nuclein?
Leucocytes were easy to get in quantity from pus. Nature Education's Scitable article on the discovery of DNA explains that Miescher arranged for a local surgical clinic to send him used, pus-coated bandages. He washed out the cells and set out to study their proteins.
That plan did not go as expected. Dahm's later review in Human Genetics (2008) describes what happened in the winter of 1868-69. Miescher noticed a precipitate of an unknown substance. Its behaviour during isolation, and its resistance to digestion by protein-splitting enzymes, showed it was not a protein or a lipid. Elemental analysis then showed that, unlike proteins, it contained large amounts of phosphorus, and Miescher later confirmed that it had no sulphur. Because it came from the cell nucleus, he named it nuclein. That name survives inside "deoxyribonucleic acid".
Why did phosphorus prove nuclein was new? A worked example
Miescher did not know the structure of DNA, but we can use it to see why his phosphorus result was so telling. Each DNA nucleotide carries one phosphate group. Using the formula of each nucleotide unit as it sits in the chain and standard atomic masses (C 12.011, H 1.008, N 14.007, O 15.999, P 30.974):
The four units have masses of about 313.2 (A), 329.2 (G), 289.2 (C) and 304.2 (T).
The average is (313.2 + 329.2 + 289.2 + 304.2) / 4 = 309.0.
Each unit holds one phosphorus atom, so the phosphorus fraction is 30.97 / 309.0 = 0.100, or about 10% by mass.
Typical proteins contain little or no phosphorus but do contain sulphur, in the amino acids cysteine and methionine. A substance with about a tenth of its mass as phosphorus and no sulphur could not be a protein. That is the logic Miescher's analysis followed, decades before anyone knew what a nucleotide was.
Common mistakes with this kind of reasoning:
Using the free nucleotide mass. A free nucleotide carries an extra water molecule that is lost when units join, so use the chain unit.
Forgetting the counter-ions. Real DNA preparations are usually sodium salts, which lowers the phosphorus percentage a little. Miescher's crude nuclein also held impurities.
Treating "contains phosphorus" as proof of DNA. Some proteins carry phosphate groups. It was the high phosphorus together with the lack of sulphur and resistance to protein digestion that mattered.
What else did Miescher work out?
Dahm's 2008 review says Miescher went on to show that nuclein was a characteristic component of all nuclei. He suggested that its abundance in a tissue might be linked to the tissue's state, with increases in "nuclear substances" coming before cell division. He even speculated that it might help transmit hereditary traits, but later rejected the idea.
Later he isolated nuclein from salmon sperm. In 2021 a team including Dahm reproduced his methods and tested a historic sample of his salmon nuclein. They reported in Biological Chemistry that it contained significant uracil, a base found in RNA, so Miescher had isolated both DNA and RNA.
Why was Miescher forgotten?
The NCERT Class 12 Biology chapter on the molecular basis of inheritance credits him (spelt "Meischer") with first identifying DNA in 1869 and naming it nuclein. Few people outside textbooks know his name. Dahm and Banerjee, in BioEssays (2019), argue that discoveries can come before the world is ready for them, and that how a scientist communicates also matters: findings that are not publicised well can be "overwritten" by later researchers. The story of DNA as genetic material was told decades later, through the work of Griffith and then Avery, MacLeod and McCarty.
What can a student take from Miescher's way of working?
Notice the result you were not looking for. Miescher set out to study proteins. The precipitate that did not fit was the discovery.
Test what a thing is not. He ruled out protein and lipid by how the substance behaved, then confirmed it by elemental analysis. In biology answers, eliminating options with evidence is often the strongest argument.
Write it up clearly. His own story shows that a discovery can be overlooked if it is not explained well.
When a chapter like the molecular basis of inheritance feels like a list of names and dates, it helps to see how the ideas connect. The Fermi Concept Library covers every concept in physics, chemistry, biology, mathematics and computing, each with its own lesson and its place in the map. For the full NEET chapter, read our guide to the molecular basis of inheritance.
Try it now: use the same method to work out the percentage of phosphorus in an RNA nucleotide unit, and compare it with DNA.
