Identification of Nucleic Acids
Miescher and Kossel
Friedrich Miescher identified ‘nuclein’ in 1869, which is the combination of DNA and associated proteins.
Friedrich Miescher was born into the intellectual elites of Switzerland. His father was a physician that taught anatomy, and his uncle was a renowned embryologist. Miescher excelled in the classroom, despite several challenges with personality and health. Miescher went to medical school following his family traditions, although he had toyed with becoming a priest. He eventually joined the laboratory of Hoppe-Seyler, the first in Germany to focus on the chemistry of tissues in the human body. While many of their colleagues were debating the nature of a ‘cell,’ Hoppe-Seyler and his lab were isolating the fundamental molecules in cells. Miescher was tasked with studying white blood cells and determining their molecular makeup.
White blood cells are produced in the bone marrow and so were very hard to isolate. However, it was noticed that a large quantity of white blood cells was present in the pus from patient infections. So Miescher collected used bandages from the nearby hospital and collected the pus. This ended up being a wonderful and relatively pure source of white blood cells for his research.
Miescher characterized the basic lipids, but at the time, proteins were thought to be the primary component of cells, so he focused his work on these. Unfortunately, the lack of sophisticated equipment and methodologies hindered his work, and much of the protein analysis that we do these days was well beyond his capability. However, he did notice a substance that precipitated out of the cells when he washed the cells with acids and then followed by another wash with an alkaline solution. This substance did not act like a protein, and thus he identified it as something different. We recognize now that he had a crude isolation of DNA. The DNA that he was extracting was impure and had many proteins attached to it. He called this substance ‘nuclein’.
Through numerous tests, Miescher identified that nuclein was composed of organic molecules, such as hydrogen, oxygen, carbon, and nitrogen. However, he noticed a lack of sulfur, something that is essential to many proteins. Instead, nuclein had high levels of phosphorus. This confirmed to Miescher that nuclein was not something that had been reported before.
Unfortunately, Hoppe-Seyler was unconvinced. Instead of throwing the results out, Hoppe-Seyler repeated all of the experiments for over a year before he was convinced that Meischer had identified something new.
Albrecht Kossel (1853-1927)
Nobel Prize in Physiology or Medicine 1910
Kossel is known for identifying the five nitrogen bases of nucleic acids (both DNA and RNA): adenine, cytosine, guanine, thymidine, and uracil.
Ludwig Karl Martin Leonhard Albrecht Kossel was born into a merchant family in 1853. His father was the Prussian consul of the same name. Kossel thrived in academic society, eventually attending the newly founded University of Strassburg to study Medicine. It was here that he was heavily influenced by Hoppe-Seyler. Kossel would eventually join Hoppe-Seyler’s lab.
Kossel’s work, similar to Meischer’s, was in physiological chemistry, or the study of chemistry in the human tissues. Kossel focused on the discovery of nuclein and worked on the foundational building blocks of nuclein. Kossel decided to get his nuclein from a local slaughterhouse rather than the pus from bandages, which turned out to be a major factor in his success. The extraction of nuclein from pus yielded very small amounts, and Kossel was going to need large amounts. It has been estimated that the extraction and isolation of nucleic acids required 100 kilograms of cow pancreas.
Originally Kossel was able to isolate two nucleic acids, one of which was already identified: guanine. The other he named adenine, which combines the Greek word for ‘gland’ (aden) and the suffix (-ine) which is ‘derived from.
Then the slaughterhouse changed the organ it delivered. This time it sent him the ‘gullet sweetbread’ or thymus. This is a special gland that generates, matures, and trains the T cells that are part of the immune system. From this tissue, Kossel isolated the nucleic acid that we now call thymine. One year later, he identified the nucleic acid called cytosine, named for the Greek word for ‘cell’ (Cyto). Unfortunately, when he identified the last nucleic acid, it too had already been named: uracil.
This sets the groundwork for the A (adenine), C (cytosine), T (thymine), and G (guanine) that we use today.
http://www.dnaftb.org/15/bio.html
https://www.sciencedirect.com/science/article/pii/S0012160604008231
https://www.nobelprize.org/prizes/medicine/1910/kossel/facts/
https://geneticsunzipped.com/news/2020/2/27/from-poop-to-pus-the-discovery-of-dna
