The Swiss physician and biologist Friedrich Miescher isolated nuclear extracts and named them "nuclein". He took the first step on the path of DNA and genetic material exploration in human history.
How did Friedrich Miescher discovery "nuclein" (crude extract of DNA)？
The primary task assigned to him by Hoppe Seyler was studying the biochemical components of lymphocytes. However, it is difficult to extract pure lymphocytes from the lymph glands. Therefore, he focused on the biochemical components of white blood cells. A nearby clinic provided him with discarded bandages where the fresh pus was an ideal source of white blood cells.
Miescher treated white blood cells in bandages with various salt solutions and chemical reagents. One day, he discovered a strange insoluble extract that was unlike any known protein. Friedrich Miescher suspected this substance originated from cell nucleus because almost everything from cytoplasm had been removed by hydrochloric acid. Later another experiment was conducted meticulously by him in order to confirm his point. The bandages that had non-degraded cells were selected by him under microscope. Cells were washed by sodium sulfate that didn’t damage them. Since centrifuges were not available at the time, cell were allowed to settle to the bottom of a beaker. Finally, he re-examined sediment by a microscope to ensure nearly all the cells were intact.
The next step was to extract cell nucleus substance. This step had to be conducted in winter when the DNA would not degrade. Miescher treated these cells with a thousand times diluted hydrochloric acid for several weeks. Lipids and proteins in cell membrane was destroyed by acid. Nucleus component was released into solution. Finally, he vigorously shook cell nuclear substance with water and ether to remove lipids. The precipitate in aqueous phase was the mysterious substance he sought. Since it came from cell nucleus, Friedrich Miescher named it "nuclein". Undoubtedly, he had obtained the first crude nucleic acid extract in human history. "Nuclein" acquired by this method was too little for chemical analysis, so he improved extraction technique. The pus was washed by ethanol. Then cytoplasm and proteins were digested by pig pepsin. Remove lipids by ether was still necessary.
Friedrich Miescher used salmon sperm to study "nuclein" and extracted protamine.
Friedrich Miescher was a biological professor at Basel University since 1872. During breeding season, swarms of salmon swam upstream to the upper reaches of Rhine River. He often fishes near university in the early morning and brings them to his lab.
Most of sperm head was occupied by nucleus, while proteins were concentrated in its tail. Therefore, sperm was very suitable for studying "nuclein". Analysis showed that "nuclein" did not contain sulfur. Moreover, he accurately calculated the quantity of phosphorus after it was burnt. The 22.5% P₂O₅ was contained, a figure very close to actual ratio of 22.9%. He also discovered an alkaline protein that was closely bound to "nuclein". It was named protamine by him. However, he did not delve deeply into its property.
His interest in genetic material began to wane after 1875. More energy and time was devoted to fertilization and teaching. Giving classes to students and being perfectionist about work made him take less and less time off. Even most of his vacations was spent in lab, so he became exhausted and weak in the later year. He infected tuberculosis in the early 1890s and died in 1895.