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ene and naphthalene in the tar, and an this turned into ester with ethyl bromide, analogous proposition may be true for the and then a new hydrazide and azide to be proteins. Later, however, this important combined with glycine, as before. These generalization was reached; it matters little steps will lead to benzoyl diglycylglycine, how the decomposition is effected, the prod- and by using alanine, leucine or other uets of protein destruction are essentially amino acid it will be seen that by repeat-. the same as long as brought about in the ing the processes extremely complex groups presence of water, and all seem to be in the may be finally built up. Curtius has carnature of hydrolytic cleavages. The action ried the reaction to the formation of benof boiling acid or alkali, steam under pres- zoyl hexaglycylglycine, sure, pepsin and hydrochloric acid, trypsin C.H.CO. (NHCH.CO) NHCH,COOH. and weak alkalies, all lead to nearly the same resultant products, and among these
Hippuryl and three alanine groups have certain a-amino acids are always the most
also been condensed to form benzoyl glyabundant. The conclusion follows, there
cyldialanylalanine. fore, almost of necessity, that these are the
Fischer has worked from a different true nucleus groups and the question nat
standpoint. The study of various hydrourally suggests itself, is it possible to put
lytic products from proteins, already rethese things together and build up any
ferred to, and the isolation of certain other thing like a true protein. An answer to
groups by Fischer himself, led to the belief the question has been slow in coming, but
that the complex molecules in the proteins a beginning has been made, and especially
must be built up by the union of amino through the experiments of Curtius and
acid groups. Various attempts had been Fischer. The condensation method fol
made to condense some of the simple amino lowed by the former is a general one,
acids in anhydride form, but without much through which a large number of amino
success, until the first experiments were groups have already been combined. It
made by Fischer in 1901. The starting depends first on the production of hydra
point of the series of condensations was zides, then azides, which are very reactive,
found in the product obtained from the and take on additional amino groups with
glycine anhydride described in 1888 by loss of hydronitric acid. For example, the
Curtius and Goebel. This may be looked ethyl ester of hippuric acid condenses with upon as formed by the union of two molehydrazine hydrate to form the hydrazide:
cules of glycine with loss of two molecules
of water, and when digested with strong C,H,CO.NHCH,CO.NH.NH,;
hydrochloric acid suffers a peculiar decomthis with nitrous acid gives the azide position and yields a body to which Fischer C.H.CO.NHCH,CO.NZ.
has given the name glycylglycine. By treatment with glycine under certain
CO OH H HNCH, conditions this reaction follows:
CH, NHн ноос
+ H2O=NH,CH,CONHCH, COOH In other words we have started with hen. NA·Chl, . . zoylglycine and have obtained benzoylgly- Glycylglycine may be considered as the cylglycine. This in turn may be used as a first anhydride of glycine and is the charnew starting point. A silver salt is made, acteristic group in the hippuryl glycine from which Curtius 'has made the deriva- been split by the ferments, and these, it will tives referred to above. In the same connec- be remembered, are among the most importion Fischer explained that a similar reac- tant of the fractions secured by the hydroltion follows with the anhydrides of alanine ysis of the true proteins. The method of and deucine, from which alanylalanine and producing these polypeptides seems to be leucylleucine must result. To carry the without limit and doubtless much more process farther and obtain more complex complex aggregations will be secured. groups proved practically difficult. An- Molecular weights of over 500 have already other method was finally developed which been reached. may be illustrated by some of the simplest Closely related to the question of the syncases described by Fischer. On bringing thesis of the polypeptides is that of the together a halogen acid chloride, for ex- composition of the simplest proteins. The ample chloracetyl chloride, with an ester work of Kossel and others in this direction of glycylglycine, chloracetylglycylglycine has furnished most interesting results. ester results,
For several of the protamines and histones CIC'IL.CO.NHCH.CO.NHCH,C00C,H,
the content of hexone bases has been found which on saponification yields the acid.
with a fair degree of accuracy, and of The latter in turn when treated with
many of the more complex proteins the strong ammonia gives up chlorine for the
amounts of both mono- and diamino acids amino group and diglycylglycine results.
present have been found. The numbers With a-brompropionyl bromide employed
secured must be looked upon, however, as as the halogen compound, alanylglycylgly
minimum values because of the practical cine is obtained, and with a-bromisocapro
difficulties in the way of quantitative sepanyl chloride leucylglycylglycine is secured ration and identification. in the same manner.
Several improved processes have been deIt will be seen that while the processes veloped for the separation of amino acids of Fischer and Curtius follow different from digestion or other mixtures. A lines they lead usually to the same ends. method first suggested by Curtius for the A considerable number of the Curtius in production of ethyl esters of the amino vestigations have been published in Vol. 70, acids, and which has been referred to above, N. F., 1904, of the Jour. prakt. Chem. has been perfected by Fischer. From mixunder the title of Condensations of tures the esters are distilled off under Amido Acids,' while the Fischer work has greatly reduced pressure. From the distilcome out in recent volumes of the Berichte late some are separated by solvents, while under the general title of ‘Syntheses of the others, after conversion to acids, are sepaPolypeptides.' This work seems to be rated by fractional crystallization. It has more directly concerned with the building been found that B-naphthalene sulphochloup of bodies of physiological interest; the ride combines with many of the amino acids Curtius work is somewhat more general. to form compounds of very slight solubility Of many of the Fischer compounds it has and Fischer and Bergell have developed a been shown that ready hydrolysis with ac- method of separation based on this fact. tive pancreatic juice follows. The biuret Both general methods have been applied reaction is also given in many cases, but also in the detection and estimation of apparently not always. Groups containing amino acids in urine which is likely to betyrosine, cystin, leucine, alanine, etc., have come a matter of considerable clinical interest, as these acids must represent degen- claims of Pawlow, although the doctrines erative or otherwise abnormal products of the latter have been put in very strong having their 'origin in the liver and other light. organs.
To Pawlow we owe, also, the discovery of Unquestionably one of the most impor- a new group of ferments which he calls tant fields of effort in physiological chem- kinases, or activators. The most thoristry at the present time is the study of the oughly studied of these is the enterokinase soluble ferments, and we have here for con- which converts the inactive pancreatic juice sideration not only certain newly discov- into an active ferment secretion. As to ered enzymes, but, perhaps, of more im- the value of the other kinases much less is portance, a great advance in our knowledge known. of those already known. It was not many About four years ago Cohnheim deyears ago that we considered the question scribed, under the name of erepsin, a pecuof the gastric enzymes as practically set- liar ferment in the intestinal walls which tled. The presence of both pepsin and has the power of splitting peptones and rennin no one could have doubted, but the proteoses, but not albumins. This discovwork of Pawlow and his school in the last ery grew out of an investigation to deterfive years has thrown entirely new light on mine the fate of the peptone bodies of the subject and it would appear that one proteolysis, it being long known that no apand the same ferment, working under dif- preciable amount of these substances apferent conditions, is responsible for both pears in the circulation after digestion. A classes of observed phenomena. Pawlow theory grew up to the effect that in the has compared the digesting and milk curd- intestinal walls, just before absorption, ling power of ferment secretions from the they were converted back into true albutrue pepsin and pyloric glands of the mins. According to the views now adstomach, from the pancreas and from Brun- vanced by Cohnheim and others this can ner's glands, and has found them perfectly not be the case to any large extent. The parallel under proper conditions of experi- peptones break down with liberation of the ment; any cause which operates to destroy carbon and hydrogen excess, which serves as one power, destroys also the other according a source of energy, while the nitrogen fracto Pawlow. But in any given extract or tions go over into the form of amino acids, preparation the conditions must be prop- to be further broken down by the liver. erly chosen to show both effects. A com- This coincides with the view that very little mercial rennet, for example, may exhibit protein is actually needed by the body. On the milk curdling action very strongly, yet the other hand, it is held by several physiolappear to be wholly inert toward fibrin. ogists that the erepsin katabolism does not Pawlow holds that in all such cases simple go so far, but merely to the production of dilution with very weak hydrochloric acid amino compounds which are ready for a is all that is called for to show the peptic synthesis not yet understood. power. A valuable résumé of this work If time permitted I should like to go is given in a recent number of the Zeit- into the question of enzymes in other direcschrift für physiologische Chem. (Vol. 42, tions, especially with reference to the work p. 415, 1904)..
in the liver and the action of the so-called It is proper to say that the physiologists autolytic ferments, the behavior and genof the Hammarsten school do not admit the eral importance of which are still very obscure. A large and interesting literature Pfeiffer and others, these doctrines aphas grown up around the discussion. A peared from the chemical standpoint wholly word must be said, however, about the im- visionary and intangible, but in the last portant discussion started two years ago few years a great change has followed in by Cohnheim when he announced the rela- the attitude of chemists and now some of tion of two distinct ferments to the oxida- the phrases of the immunity theory of tion of carbohydrates in the body. The Ehrlich have become part of the language bearing of this on the question of diabetes of organic chemistry. was immediately recognized and numerous It was early recognized that toxins and investigations were launched to throw more antitoxins act on each other in a manner light on the subject. According to Cohn- suggesting combinations in definite chemheim the pancreas furnishes one of these ical proportions, and attempts were soon enzymes and the muscle substance the made to work out the laws of the union. other. One may serve as a kinase or acti. The earlier Ehrlich experiments seemed to vator for the other and the effect of the point to simple combinations like those betwo is to facilitate oxidation in the muscles. tween an acid and a base, the union folThe subject is immensely important, but the lowing to complete saturation. It was latest studies do not seem to fully confirm recognized later, however, in many cases, all the Cohnheim statements.
that the reaction is not complete and that In connection with the subject of enzymes the saturation curve is far from being a reference must be made to the considerable straight line. These observations led to number of papers which have appeared in various speculations. Ehrlich assumed the last few years on the question of the that in the ordinary toxin mixtures we relation of the ferments to the simple in- have certain modified forms known now as organic katalytic agents. Beginning with toxoids and toxons, which, while non-toxic, the work of Tammann published in the have saturating power resembling that of Zeitschrift für physikalische Chemie many the toxins. Hence the amount of antiattempts have been made to express the toxin added to a toxin solution to destroy velocity of enzyme reactions by equations its toxicity would have to be sufficient to analogous to those suggested by Wilhelmy combine, not only with the real toxin, but for the inversion of sugar. The extended with any toxoid or toxon present also; just investigations of Tammann led in general as in neutralizing free sulphuric acid by to formulas which were more complicated sodium carbonate the amount of the latter than those corresponding to the simple necessary would have to be increased if logarithmic curve. Some of the more re- some salt decomposable by sodium carboncent work, especially that of Henri, has led ate, such as alum, is likewise present. In to more definite results. This whole dis- the one case as in the other the simplicity cussion has been well reviewed by Bredig of the reaction would be obscured by comin volume 1 of the Ergebnisse der Physiol. plexity of the mixture. ogie.
Arrhenius and Madsen, and others folOne of the most interesting developments lowing them, have been led also to study in recent physiological chemistry is in the these extremely important phenomena and discussion of theories of immunity and the have given a different interpretation. Acrelations of toxins and antitoxins. As first cording to the notions of the physical chempresented by Buchner, Bordet, Ehrlich, ists these reactions are more or less per
present may better serve in the advance of investigation.
J. H. LONG. NORTH WESTERN UNIVERSITY MEDICAL SCHOOL,
fectly reversible, which certain experiments seemed to prove, and resemble somewhat the union of an alcohol and an acid which combine to reach a condition of equilibrium. They assume for the toxin-antitoxin reaction the perfect applicability of the Guldberg-Waage mass action formulas, and for a number of relations have calculated the value of the constant k. It is interesting to note that a number. of the leading physical chemists have taken part in the discussion About a year ago Michaelis reviewed the subject in a long article in the Biochemisches Centralblatt and this has recently appeared in expanded book form under the title, ‘Die Bindungsgesetze von Toxin und Antitoxin.' Michaelis does not accept the Arrhenius work as satisfactory or convincing, and points out several conditions necessary for the applicability of the mass action laws which do not obtain in the cases in question; for. example, the mixtures are not homogeneous and the degree of reversibility is extremely limited, if it really exists.
On the other hand, the doctrine of the toxoids and toxons appears to explain the apparent discrepancies and in certain mixtures secured in the experiments of Keyes and Sachs, known to be free from these bodies, the toxin and antitoxin combination followed in proportions represented by an almost perfect straight line.
It remains to add that this whole discussion can not fail to have an important influence on the attitude of medical men to the rapidly developing physiological chemistry. The Arrhenius theory seemed to simplify the question somewhat and make it
i analogy with other well-known phenomena. The facts more recently adduced by the Ehrlich workers do not seem to permit this theoretically preferable solution. The toxoid and toxon hypotheses are necessarily chemical, however, and for the
SCIENTIFIC BOOKS. The Evolution of Man. By ERNST HAECKEL.
Translated from the fifth German edition by JOSEPH McCabe. 2 vols., 8vo. New York, G. P. Putnam's Sons. 1905.
In the two stately and richly illustrated volumes before us we have a translation of the fifth edition of Haeckel's ' Anthropogenie,' and coming as they do from the pen of one who may now be regarded as a Nestor of zoology and the most vigorous exponent of the historical method of investigation, they present not a little interest. They profess to give in their course of some nine hundred pages an account of the embryological and comparative anatomical evidence bearing on the origin of man, a subject of perennial interest not only to the laity, but also to professional zoologists, since it involves the problem of the origin of the vertebrates.
The work opens with a chapter upon the biogenetic law, or, as it is termed, “the fundamental law of organic evolution, and then follow five especially interesting chapters devoted to a history of the development of embryology and phylogeny. To these succeed an extended account of the principal embryological stages of the vertebrates and a discussion of their significance, in which the germ cells, segmentation, gastrulation, the germ layers, metamerism, the fetal membranes and the development of the general form of the body, are all considered from the standpoint of their bearings on the ancestral history. This completed, the author passes on to a consideration of the recent representatives of the ancestral stages and concludes with several chapters devoted to the phylogeny of the various organs of the human body.
It would require much space to consider adequately the entire contents of the volumes, and the purpose of this review will, perhaps, be best served by indicating briefly the line of descent which Haeckel advocates. It is essentially the same as that presented in earlier