Friedrich Miescher found DNA in pus washed from discarded surgical bandages, nearly 75 years before researchers proved that DNA carries hereditary information. The National Human Genome Research Institute credits his 1869 work as the first isolation of DNA.
He was 24 years old and was not searching for the molecule of heredity. He was trying to answer a more basic question: what are cells physically made of?
A doctor’s son who turned away from medicine
Miescher was born in Basel in 1844 into a family of physicians and university professors. He completed his medical degree in 1868, but partial hearing loss left by typhoid fever made him doubt that he could practise clinical medicine effectively, according to a biographical account from the Linda Hall Library.
Instead, he travelled to Tübingen to study under Felix Hoppe-Seyler, one of the founders of physiological chemistry. Hoppe-Seyler’s laboratory occupied rooms in Hohentübingen Castle, including a former kitchen that the Museum of the University of Tübingen now preserves as the site where nucleic acid was discovered.
The laboratory had stone walls, basic glassware and none of the centrifuges or automated instruments that modern biologists take for granted. Miescher’s assignment was enormous in scope: separate a cell into its chemical parts and determine what each part contained.
Why pus was perfect
To analyse cells chemically, Miescher needed large quantities of material that could be separated without grinding apart an entire organ. White blood cells offered what he needed, but obtaining enough of them was difficult.
Pus solved the supply problem. It contains enormous numbers of leukocytes, particularly neutrophils, and the nearby hospital regularly discarded bandages saturated with material from infected wounds.
Miescher washed the cells from the cloth with salt solutions, eventually finding that a dilute sodium sulphate mixture released them without immediately destroying them. He allowed the cells to settle, isolated their nuclei and used pepsin obtained from pig stomachs to digest much of the remaining protein.
He then treated the nuclear material with alkaline solutions and caused a new substance to precipitate by adding acid. His surviving 1871 paper describes the method and the substance, although his terminology and purification procedures belonged to an age before modern molecular biology.
The substance that did not fit
The material behaved differently from the proteins, fats and carbohydrates familiar to 19th-century chemists. It precipitated under acidic conditions, dissolved again under alkaline ones and remained after protein-digesting enzymes had broken down much of the surrounding cellular matter.
Most strikingly, it contained an unusually large amount of phosphorus and no detectable sulphur. Those results persuaded Miescher that he had isolated a previously unknown class of biological substance rather than an unusual protein.
Hoppe-Seyler was not immediately convinced. He repeated parts of Miescher’s work himself before allowing the findings to appear in the fourth volume of his journal, a verification process that delayed publication until 1871.
The paper carried the restrained title On the Chemical Composition of Pus Cells. It reported that the nuclei of those cells contained a phosphorus-rich substance unlike any established group of organic compounds.
Miescher named it nuclein because it came from the nucleus. The name survives inside the modern term deoxyribonucleic acid, even though later researchers would refine the chemistry, distinguish DNA from RNA and separate nucleic acids from the proteins attached to them.
From bandages to salmon sperm
After working for a time in Carl Ludwig’s laboratory in Leipzig, Miescher returned to Basel and continued studying nuclein. He became a professor of physiology at the University of Basel in 1872, not 1871, as the Friedrich Miescher Institute records.
He also found a cleaner and richer source of nuclear material. Salmon sperm contains densely packed nuclei and relatively little cytoplasm, allowing him to extract quantities of nuclein that were difficult to obtain from pus cells.
Miescher acquired Rhine salmon around dawn and worked in cold conditions that helped preserve his material. Later accounts say he nearly missed his wedding in 1878 while finishing an extraction, although the safer version of the story is that colleagues had to remind the absorbed researcher to leave his laboratory, not physically drag him to a church.
How close he came to heredity
Miescher understood that nuclein was unusual, concentrated in nuclei and especially abundant in sperm. Yet he initially argued against the idea that it carried hereditary information because its chemistry seemed too uniform to encode the immense variety of living organisms.
Like many researchers of his era, he considered proteins more plausible carriers of heredity because proteins appeared far more structurally diverse. In private correspondence from 1892 and 1893, however, he speculated that variations within a large molecule might encode biological differences in something resembling an alphabet, an idea examined in a later historical analysis in Genetics.
He never firmly identified nuclein as that molecule. Miescher died of tuberculosis in Davos in 1895, aged 51, knowing that he had discovered an important component of the cell but not its central role in inheritance.
In 1944, Oswald Avery, Colin MacLeod and Maclyn McCarty demonstrated that DNA could transfer inherited characteristics between bacteria. On April 25, 1953, James Watson and Francis Crick published their double-helix model in Nature, alongside related work by Maurice Wilkins and colleagues and by Rosalind Franklin and Raymond Gosling.
By then, Miescher’s modestly titled German-language paper was separated from the new molecular biology by eight decades of discoveries. Researchers including Albrecht Kossel, Phoebus Levene, Erwin Chargaff, Avery, Franklin, Wilkins, Watson and Crick had added so many layers to the story that the person who first isolated the material was easily pushed into its opening footnote.
What sits inside your cells
In a typical nucleated human cell, the DNA that descends from Miescher’s nuclein would stretch about six feet if unwound and laid end to end, according to the National Human Genome Research Institute. It is not present as a full nuclear genome in every human cell, because mature red blood cells and platelets lack nuclei.
The molecule now underlies forensic identification, PCR-based testing, gene editing and the reconstruction of extinct populations. Researchers use it to build three-dimensional maps of folded genomes, trace the genetic history of Ice Age populations and assemble increasingly ambitious synthetic genomes.
Miescher’s original preparations were not pure DNA in the modern laboratory sense. They nevertheless contained the newly identified nucleic material, and his combination of nuclear isolation, chemical analysis and repeated testing established that cells held a phosphorus-rich substance that was not simply another protein.
The discovery began with wet cloth carried uphill from a hospital to an old castle kitchen. The bandages disappeared, but the nuclein remained, first as a pale precipitate in Miescher’s glassware and later as the molecule folded inside nearly every nucleated cell of every person who has heard his name.
