In the winter of 1869, a 24-year-old Swiss chemist named Friedrich Miescher walked to a nearby surgical clinic in Tübingen, Germany, and collected buckets of used bandages soaked in pus. He soaked them in dilute salt solutions, dissolved away the debris, and eventually isolated a strange, phosphorus-rich substance from the nuclei of the white blood cells. He called it nuclein. It was DNA.
Nobody would understand what he had found for the better part of a century.
The story is one of the strangest in the history of biology: the molecule that carries the instructions for every living thing on Earth was first pulled out of infected surgical rags by a young man who was worried he’d be a bad doctor because he couldn’t hear his patients properly. According to a National Geographic account of Miescher’s life, a childhood bout of typhus had left him partially deaf, and he had turned to laboratory work instead of clinical medicine.
The bandage problem
Antiseptic surgery barely existed in 1869. Joseph Lister had only published his carbolic acid paper two years earlier, and most European hospitals had not adopted his methods. Wounds routinely became infected. The bandages that came off patients at the surgical clinic near the University of Tübingen were saturated with pus — which is, essentially, a slurry of dead and dying white blood cells.
For Miescher, this was raw material. He had come to Tübingen in 1868 to work in the laboratory of Felix Hoppe-Seyler, the German physiologist widely credited with founding biochemistry. Hoppe-Seyler wanted his young researcher to study the chemistry of white blood cells. Miescher wanted to understand life at the molecular level — an almost absurdly ambitious goal for a scientist working before the word “biochemistry” had really settled into use.
White blood cells were a good starting point because, unlike cells locked into tissue, they float free. Pus was the easiest place to find them in bulk. So Miescher took bandages, washed the cells off, and got to work.
What came out of the nuclei
Miescher expected to find the three biomolecules chemists already knew about: proteins, lipids, and carbohydrates. He found those. But he also kept isolating something that behaved like none of them.
He tried digesting it with pepsin, an enzyme that shreds proteins. The substance survived. He stained it with iodine to test for carbohydrates. Nothing. He washed it with alcohol and ether to strip lipids away. It remained. Whatever it was, it was chemically unlike anything on the accepted list. It was acidic. It was rich in phosphorus, which was strange — phosphorus was not something anyone expected to find at the heart of a living cell in that quantity.
And it came specifically from the nucleus. Miescher had developed a method to strip away the cytoplasm of the white blood cells and leave the nuclei intact, then break those open. The mystery substance sat inside. He named it nuclein, from the Latin for kernel or nut. As The Times of India summarised the episode, he was, without knowing it, the first person to hold DNA in a test tube.
Two years of waiting
Miescher wrote up his results and sent them to Hoppe-Seyler. His mentor did not publish them. Instead, he held the paper for two years and repeated the experiments himself, because a previous student had once claimed to find a new substance that turned out to be a chemical illusion. Hoppe-Seyler wanted to be sure.
By the time the paper finally appeared, in 1871, it carried the title On the Chemical Composition of Pus Cells. The most consequential biochemical discovery of the nineteenth century was buried on page 19 of a 20-page report on the analysis of infected wound fluid. A reader had to wade through pages of dry chemistry to find the moment where Miescher notes, almost in passing, that he has isolated something entirely new.
The molecule was invisible, abstract, and — to the readers of 1871 — apparently pointless. Nobody knew what it was for. Miescher himself later suggested it might have something to do with the transmission of hereditary information, an idea that a coauthored history in The Conversation credits as remarkably prescient, but he backed off from the claim. In an era when proteins were assumed to be the machinery of life, phosphorus-rich acid from a cell nucleus did not seem like a candidate for the secret of inheritance.
Salmon sperm and Rhine winters
After Tübingen, Miescher took a professorship at the University of Basel in 1872. He needed a better source of nuclein than pus-soaked bandages, and he found one in the salmon that swam up the Rhine to spawn. Salmon sperm cells are almost entirely nucleus. They were, chemically speaking, tiny packets of nuclein wrapped in a thin coat of protein.
Miescher would fish before dawn in the freezing river, carry the salmon back to his unheated laboratory, and work in near-freezing conditions to keep the delicate molecule from breaking down. He was, by all accounts, unrelenting. One of his students, Fritz Suter, later said Miescher had nearly missed his own wedding because he could not tear himself away from the bench.
From the salmon work he began to grasp that nuclein was enormous — a long, thread-like acid rather than a small compound. He noted that the ratios of its chemical components stayed remarkably consistent from sample to sample, a hint of internal structure he could not decode.
The 75-year silence
In 1889, twenty years after the original discovery, Miescher’s own student Richard Altmann renamed the substance nucleic acid. The new term stuck, and the shift subtly detached the molecule from its discoverer. Miescher died of tuberculosis in 1895, aged 51, still largely unrecognised outside a small circle of German-speaking biochemists.
The chemistry advanced slowly. Albrecht Kossel, working in Berlin, identified the four nitrogenous bases — adenine, guanine, cytosine, and thymine — that hang off the phosphate-sugar backbone. His work, described in a Hindu retrospective on the chemical basis of heredity, won him the Nobel Prize in Physiology or Medicine in 1910. But even then, most biologists thought proteins carried genetic information. The reasoning was simple: proteins were complex, made of twenty different amino acids arranged in intricate sequences. Nucleic acids had only four bases. Four letters seemed too poor an alphabet to write out the instructions for a living creature.
This belief hardened into orthodoxy. When Frederick Griffith, an English microbiologist, published his 1928 experiments showing that dead Streptococcus pneumoniae bacteria could transfer virulence to living ones through some “transforming principle,” as Nature Scitable documents, nobody assumed the transforming principle was DNA. Griffith himself could not identify it.
It took Oswald Avery, Colin MacLeod, and Maclyn McCarty at Rockefeller University until 1944 to prove that the transforming principle was DNA — by treating extracts with enzymes that destroyed protein, RNA, or DNA in turn, and showing that only the DNA-destroying enzyme abolished the effect. That is 75 years after Miescher first held the molecule in his hands.
Even then, resistance held. Many biologists thought Avery must have missed a contaminating protein. It was not until Alfred Hershey and Martha Chase ran their radioactive labelling experiments with bacteriophages in 1952, and until James Watson and Francis Crick worked out the double helix in 1953, that the molecule Miescher had scooped out of bandages was finally, unambiguously, understood as the carrier of life’s instructions.
Why the delay
Part of the answer is aesthetic. The double helix, when Watson and Crick finally revealed it, was gorgeous — two spiralling strands, base pairs stacked like rungs, self-complementary and self-copying. It looked like something. Miescher’s nuclein looked like nothing. According to a Chemistry World feature on the road to the helix, DNA in Miescher’s era was a smear of gelatinous substance in a beaker, resistant to every chemical test, without an obvious shape or function. There was nothing to point at.
Part of the answer is disciplinary. In the late nineteenth century, biology, chemistry, and what would become genetics were separate worlds. Gregor Mendel’s pea experiments — published in 1866, three years before Miescher’s bandage work — sat unread until 1900. Nobody was yet in a position to connect an abstract Austrian monk’s inheritance ratios with a Swiss chemist’s phosphorus-rich pus extract. The concepts had not yet been forced into contact with each other.
And part of the answer is that Miescher himself, cautious and self-critical, refused to overreach. He suspected the molecule might carry hereditary information, but he did not push the claim. He wrote to a friend that he often felt like a schoolboy who had not done his homework, a Sisyphus endlessly pushing the same rock uphill.
What his rock became
The molecule Miescher pulled out of surgical bandages now underwrites a research enterprise that costs tens of billions of dollars a year. Every genome sequence, every PCR test, every ancestry kit, every gene therapy, every criminal-forensics case, every genetically modified crop traces back through Watson and Crick, through Avery, through Kossel, through Altmann, to the young man in the cold Basel laboratory who was patient enough to wait for salmon.
DNA analysis now reveals surprises that would have been unthinkable in 1869. Science Blog has covered shared genetic origins linking ALS and schizophrenia, findings that depend on reading the exact sequence of nucleotides Miescher first isolated as an undifferentiated goo. Every one of those studies is, in a technical sense, an elaboration of his 1871 paper.
Miescher’s name is on a small research institute in Basel. His portrait is not on stamps. Schoolchildren memorise Watson, Crick, sometimes Rosalind Franklin, occasionally Mendel. Almost nobody learns the name of the man who first held the molecule.
He died the year Wilhelm Röntgen discovered X-rays and the year the Lumière brothers projected the first film. Neither he nor anyone else knew that the substance he’d been coaxing out of Rhine salmon for a quarter century was the code every cell in his own body was busy transcribing as he lay dying of tuberculosis — a disease caused, it would later turn out, by a bacterium whose DNA carried the instructions for its own lethality.
The bandages, long since incinerated, had contained the answer all along.