All parts of an organism are essential for life. Only with this in mind
does it make sense to say that the most important part of the cell is
its nucleus. From the nuclei of cells in pus and in salmon sperm, Johann
Friedrich Miescher (1811-1887) obtained a peculiar kind of substance,
which he named nuclein (1868). Its phosphate content was easily
discovered, but to find the exact proportions and the nature of the
other components required special methods of separation from
phosphatides and other proteins. It was difficult to develop such
methods at a time when little was known about the properties, and
particularly the stability, of a nuclein. For preparing nuclein from
yeast cells, Felix Hoppe-Seyler (1825-1895) described the following
details: Yeast is dispersed in water to extract soluble materials, like
salts or sugars. After a few hours, the insoluble material is separated,
washed once more with water, and then extracted with a very dilute
solution of sodium hydroxide. The slightly alkaline solution, freed from
insoluble residues, is slowly added to a weak hydrochloric acid. A
precipitate forms which is separated by filtration, washed with dilute
acid, then with cold alcohol, and finally extracted by boiling alcohol.
The dried residue is the nuclein.[32] It contains six percent
phosphorus. A little more washing with water, a slightly longer
treatment with acid or alcohol gives products of lower phosphorus
content. Many experimental variations were necessary to establish the
procedure that leads to purification without alteration of the natural
substance.
This was also true for the methods of chemical degradation, carried out
in order to find the components of nucleins in their highest state of
natural complexity. It was learned for example, that the special kind of
carbohydrate present in nucleins was very susceptible to change under
the conditions of hydrolysis by acids. Phoebus Aaron Theodor Levine
(1869-1940), therefore, used the digestion by a living organism. With E.
S. London, he introduced a solution of nucleic acid into, e.g., the
gastrointestinal segment of a dog through a gastric fistula and withdrew
the product of digestion through an intestinal fistula. Fortunately, the
products obtained in such degradations were not new in themselves. The
carbohydrate in this nucleic acid proved to be identical with D-ribose,
which Emil Fischer had artificially made from arabinose and named ribose
to indicate this relationship (1891). The nitrogenous products of the
degradation were identical with substances previously prepared in the
long study of uric acid. In the course of this study, Emil Fischer
established uric acid and a number of its derivatives as having the
elementary skeleton of what he called "pure uric acid," abbreviated to
purine. Out of Adolf Baeyer's work on barbituric acid came the knowledge
of pyrimidine and its derivatives.
[Illustration: Figure 15.--ALBRECHT KOSSEL (1853-1927) received the
Nobel Prize in Medicine and Physiology in 1910 for his work on nucleic
substances, which contain a high proportion of phosphorus. The chemical
bonds of this phosphorus in the molecules of nucleic substances were
determined in later work. (_Photo courtesy National Library of Medicine,
Washington, D.C._)]
From these findings, together with what Oswald Schmiedeberg (1838-1921)
had established concerning the presence of four phosphate groups in the
molecule (1899), Robert Feulgen (1884-1955) constructed the following
scheme of a nucleic acid. Feulgen's formula of 1918 is:
Phosphoric acid--Carbohydrate--Guanine
Phosphoric acid--Carbohydrate--Cytosine
Phosphoric acid--Carbohydrate--Thymine
Phosphoric acid--Carbohydrate--Adenine
Of the four basic components on the right, thymine occurs in the nucleic
acid from the thymus gland. Yeast contains uracil instead. The
difference between these two bases is one methyl group: thymine is a
5-methyluracil. In all of these basic substances, the structure of urea
NH_{2}
/
C=O
\
NH_{2}
is involved, and they form pairs of oxidized and reduced states: