The Nucleo-proteids.—This progress in the characterization and specification of the proteids required in the first place a knowledge of two particular compounds, the nucleins and the histones. This did not become possible until after the researches of Miescher and Kossel on the nucleins, which went on from 1874 to 1892, and those of Lilienfeld and d’Yvor Bang on the histones, from 1893 to 1899. The complete albuminoids are constituted by the combination of two kinds of substances—albumins or histones on the one hand, and nucleins on the other. By combining solutions of albumins or histones with solutions of nuclein, the synthesis of the proteid is effected. The study of the properties and characteristics of these nucleo-albumins and nucleo-histones is going on at the present moment. It is being carried out with much method and with wonderful patience by the German school.
All the proteids contain phosphorus in addition to the five chemical elements, carbon, oxygen, hydrogen, nitrogen, and sulphur, which are common to the other albuminoids. Another interesting feature in their history is that the action of the gastric juice divides them into their two constituents:—the nuclein, which is deposited and resists the destructive action of the digestive liquid, and the albumin or histone, which on the contrary experiences this action with the usual consequences. Thus the gastric juice furnishes a process which is very simple and very convenient in the analysis of the proteids.
Localization of the Nucleo-Proteids.—What we said before as to the important physiological rôle of the cellular nucleus may arouse the expectation that in it will be found the living matter which is chemically the most differentiated, the albuminoids of highest rank—i.e., the nucleo-proteids and their constituents. Not that they would not be found in the protoplasm of the rest of the cell, but there is certainly a risk that they would be less concentrated there and more blended with accessory products; they are there connected with much more secondary vital functions. This conclusion inspired the early researches of Professor Miescher, of Basle, in 1874, and, twenty years later, those of Professor Kossel, one of the most eminent physiological chemists in Germany.
In fact, these compounds have been found in all tissues which are rich in cellular elements with well-developed nuclei. The white globules of the blood furnished to Lilienfeld the first nucleo-histone ever isolated. The red globules themselves, when they possess a nucleus, which is the case in birds and reptiles as well as in the embryo of mammals, contain a nucleo-proteid which was easily isolated by Plosz and Kossel. Hammarsten, the Swedish chemist, who has acquired a great reputation from his researches in other domains of biological chemistry, prepared the nucleo-proteids of the pancreas in 1893. They have been obtained from the liver, from the thyroid gland (Ostwald), from brewers’ yeast (Kossel), from mushrooms, and from barley (Petit). They have been detected in starchy bodies and in bacteria (Galeotti).
§ 2. Constitution of Nucleins.
Constitution of Nucleins.—Our path is already marked out if we wish to penetrate farther into the constitution of these proteids, which are the immediate principles highest in complexity among those which form the living protoplasm. We must analyze the two components, the albumins and the histones on the one hand, and the nucleins on the other. As for the nucleins, this has already been done, or very nearly so.
Kossel, in fact, decomposed the nuclein by a series of very carefully arranged operations, and has reduced it step by step to its crystallizable organic radicals. At each stage that we descend in the scale of simplification a body appears which is more acid and more rich in phosphorus. At the third stage we come to phosphoric acid itself. The first operation divides the nuclein into two substances: the new albumin and nucleinic acid. After separating these elements they can be reunited: a solution of albumin with a solution of nucleinic acid reconstitutes the nuclein. A second operation separates the nucleinic acid in its turn into three parts. One is a body of the nature of the sugars—i.e., a carbohydrate. The appearance of a sugar in this portion of the molecule of nucleinic acid is an interesting fact and fertile in results. The second part is constituted by a mixture of nitrogenous bodies, well known in organic chemistry under the name of xanthic bases (xanthin, hypoxanthin, guanin, and adenin). The third part is a very acid body and full of phosphorus—thymic acid. If in a third and last operation the thymic acid is analyzed, it is finally separated into phosphoric acid and into thymene, a crystallizable base, and thus we are brought back to the physical world, for all these bodies incontestably belong to it.
§ 3. The Constitution of Histones and Albumins.
Constitution of Histones.—But we are only half-way through our task. We are acquainted in its origin with one of the genealogical branches of the proteid, the nucleinic branch. We must also learn something of the other branch, the albumin or histone branch. But on this side the problem assumes a character of difficulty and complexity which is admirably adapted to discourage the most untiring patience.
The analysis of albumin for a long time baulked the chemist “Here,” said Danilewsky, “we come to a closed door which resists all our efforts.” We know how vastly interesting what is taking place on the other side must be, but we cannot get there. We get a mere glimpse through the cracks or chinks which we have been able to make.