“In 1874 Miescher observed that a large proportion of the dry weight of the sperm of the Rhine salmon consisted of a ‘nuclein’”

…a rather odd sentence that starts the section on histidine in Vickery and Schmidt’s 1931 history of the discovery of the amino acids.1 It really highlights just how odd chemistry was as a profession back in the 19th century. I can’t help but imagine a meeting of the Royal Society where they all sat around and tried to out-do each other with tales of the weirdest thing that they have plucked from nature and boiled up in the lab. The sperm of the Rhine salmon feels like a pretty good contender!

We now know that Miescher’s ‘nuclein’, which became known as protamine, is one type of negatively charged protein that neutralises the positive charge on DNA and allows it to be tightly wrapped up.

Miescher found that protamine was combined in the sperm with an organic base containing a high proportion of nitrogen. Little was established about this substance until the German biochemist Albrecht Kossel followed up on these observations in 1896.1,2 For convenience, he opted to investigate the sperm of the sturgeon rather than the Rhine salmon and isolated a similar substance, designating the two examples sturine and salmine. Kossel hydrolysed his sturine, and isolated a precipitate he stated “contains a previously unknown base, for which I suggest the name histidine”.2

Reading this part of Kossel’s work in isolation does not yield any explanation as to where he got this name from, and it is tempting to try to rationalise it with no further context. However, the key thing to note is that Kossel, who later won the 1910 Nobel Prize “in recognition of the contributions to our knowledge of cell chemistry made through his work on proteins, including the nucleic substances”, had also discovered and named the histones. Notice a theme?

In the 1884 report in which Kossel isolates these nuclear proteins for the first time, from avian red blood cell nuclei, he once again does not given his reasoning for this naming.3  However, he notes in the introduction to the paper that the advantage of working with red blood cells is that they are “histologically homogenous”; the majority of the cell body is soluble in water, making it easy to isolate the nucleus. The use of the word “histologically” is a good clue (histology is the study of the microscopic structure of tissues). This term is derived from the Greek word histos meaning a web, or anything stood upright, and histo- is used as an appropriate root to describe animal tissues, or structural elements of the animal body. It seems reasonable that Kossel would borrow this prefix to describe a key nucleic protein.

Moving back forwards to 1896, it seems like Kossel had a favourite prefix, and used is once again to name histidine. It may be a reasonable assumption that this was because he isolated it by hydrolysis of his histones. However, it was actually Miescher’s protamine that was his starting material, and he was aware of there being a difference between the two. However, in the paper he highlights the importance of the basic substances in the nucleus, and it is perhaps the level of importance and the similar role, rather than a chemical relationship, that leads him to assign the same prefix to histidine:

“The widespread distribution of these basic substances in the cell nucleus suggests that they are no less important components of the cell nucleus than the nucleic substances they oppose as acids. The elucidation of the chemical nature of these basic substances is, therefore, a step towards the knowledge of the peculiar chemical conditions of the cell nucleus”.  


1.          Vickery HB, Schmidt CLA. The History of the Discovery of the Amino Acids. Chem Rev. 1931;9(2):169-318. doi:10.1021/cr60033a001.

2.          Kossel A. Über die basischen Stoffe des Zellkerns. Sitzungsberichte der Königlich Preuss Akad der Wissenschaften zu Berlin. Published online 1896:403-408. doi:10.1515/bchm2.1897.22.2.176. URL:https://biodiversitylibrary.org/page/29351956

3.          Kossel A. Ueber einen peptonartigen Bestandtheil des Zellkerns. Zeitschrift für Physiol Chemie. 1884;8(6):511=515.

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