From the foregoing table it appears that there has been a slight decrease in the mortality from consumption, a marked decrease in that of smallpox, measles, scarlet fever, typhoid fever, and diphtheria, and a slight increase in that of cancer. The decrease in consumption and increase in cancer have in neither instance been so great as that of Northern European countries or the United States.

Vital Statistics of England.-From the advance sheet published by the Registrar-General of England for 1898 the following figures are obtained relating to the vital statistics of England for that year. These figures are usually found to be nearly, but not quite, as accurate as those which are published in the annual volume a year later. Estimated population of England, in the middle of the year 1898, 31,397,078. Marriages, 254,955; marriage-rate per 1000 persons married, 16.24. Births, 922,873; birth-rate, 29.39. Deaths, 552,040; death-rate, 17.58. Ratio of male to female births, 1032 males to 1000 females. Birth-rate of London, 29.4. Death-rate of London, 18.3.

The Increase of Cancer.-R. J. Moore, M. P.,' as the result of inquiries among farmers, states that cancer is more common among cattle than tuberculosis, and that the meat of cancerous cattle is generally sold as food; and suggests this as a cause of cancer in man. The British Medical Journal answers this statement by a reply from McFadyean, that cancer is much less common in cattle than tuberculosis. He had never seen a case of cancer in the udder of the cow, and thinks the possibility of human beings contracting it by eating the meat of such animals is not worthy of consideration. Williams attributes the spread of cancer to increase of eating meat. He says meat consumption in England has more than doubled in 50 years, and now amounts to 126 pounds per capita per year. He also attributes the increase to insufficient bodily exercise and insufficient nourishment with fresh vegetables. The death-rate from cancer in 1840 was 177 per million; in 1896, 764 per million population. The mortality of men has increased in England 167%, and that of women 0.91%, from 1851 to 1890.

The sixtieth report of the Registrar-General of England,3 in commenting on the increase of cancer, states that the increase is greater among males than among females. He says the increase in the recorded deaths from this disease is the resultant of 3 factors: 1. Possible changes in the actual mortality from cancer. 2. Improvements in medical diagnosis. 3. A recent system of inquiry respecting deaths certified as due to "tumor." Men are more liable than women to cancer of the larynx, trachea and lungs, mouth, tongue, throat, and esophagus, as well as of the jaw, lips, face and neck, bladder and urethra. Among females the mammæ and generative organs are specially liable to cancer. All death certificates from this cause should specifically state the organ affected. 1 Food and Sanitation, Sept. 30, 1899, p. 473. Lancet, July, 1897, p. 50.

36 M

3 * London, 1899, p. 25.

2

PHYSIOLOGIC CHEMISTRY.

BY WALTER JONES, PH.D., AND REID HUNT, M.D.

OF BALTIMORE, MARYLAND.

Distribution of Urea in the Animal Organism.-Schöndorff 1 gives the results of determinations, made by an original method, of the percentage of urea in the organs of a dog which had been given a meal rich in proteid. The various organs, with the exception of the skeletal muscles, the heart-muscle, and the kidney, were found to contain about the same amount of urea as the blood: viz., about 0.12%. The skeletal muscle contained 0.0884%; since the time of Liebig it has been a matter of doubt whether urea occurred in muscle at all. The amount of urea in the organs of a dog weighing 32 kilos was nearly 17 gm.; the weight of the organs studied made up 53% of the animal's weight. This work has important bearings upon the question of the action of foods, drugs, etc., upon the production of urea; it is by no means easy to determine whether the increased excretion of urea which follows the administration of a drug is due to an increased production of urea or simply to an increased excretion of the urea already present in the body. In a second paper Schöndorff 2 reports the determinations of urea in a few animal liquids; he finds that the percentage of urea in human milk and in the amniotic liquid is about the same as that of blood; the amount in blood increases as the amount of proteid in the food increases.

Cholesterin of the Blood.-Hürthle showed that cholesterin occurs in blood-plasma in the form of esters of palmitic and oleic acids. Brown has found the same to be true of the blood-serum of the hen and other fowls. Hepner 4 has made a series of experiments to determine in what form the cholesterin of the corpuscles occurs, and finds that it is free; as is also, at times, at least a part of that of the plasma. A few experiments on fasting animals indicated that the amount of cholesterin was independent of the food. Brown also obtained cholesterin crystals directly from the bird's corpuscles by extraction with ether.

Thiocyanic Acid in the Saliva.-Thiocyanic acid is, according to Krüger, a constant and normal constituent of human saliva; it does

3

5

1 Pflüger's Archiv, lxxiv., p. 307.

Amer. Jour. of Physiol., ii., p. 306.

2 Ibid., lxxiv., p. 357.

4 Pflüger's Archiv, lxxiii., p. 596. 5 Zeitschrift f. Biologie, xxxvii., p. 6.

562

not result from a partial decomposition of the saliva or from carious teeth. The saliva of smokers was found to contain 2 or 3 times as much of the acid as that of nonsmokers. The quantity of saliva secreted in 24 hours (250 to 300 cc.) was not markedly influenced by cigaret smoking.

Iron Absorption.-Hofman 1 reached the conclusion, from microchemic studies of the intestinal walls, that the chief absorption of iron takes place in the duodenum; he believes that inorganic salts of iron are absorbed. A similar result has been reached by Honigman 2 by chemic methods; the observations were made upon a patient with a fistula in the lower ileum. After the administration of nearly a half gram of ferrum citricum oxidatum in 2 days, only 18% was recovered from the feces voided at the fistula, and practically none from the urine; 0.328 gm. of "inorganic iron" had been absorbed in 2 days. Swirski, 3 studying the question in guinea pigs by microchemic methods, believes that iron is absorbed along the entire length of the alimentary tract with the exception of the stomach; it seems probable that some iron is eliminated through the respiratory mucous membrane. Austin, on the other hand, experimenting on dogs and using quantitative chemic methods, obtained results which he interprets as showing that inorganic iron (ferrous sulphate) is not absorbed; the iron of raw meat was, however, readily absorbed.

Iron in Liver and Spleen in Malaria.-The following table, from analyses of Dutton,5 shows how great may be the deposition of iron in the liver and spleen in malaria :

Microchemic tests also showed a large amount of iron.

6

Inorganic Compounds in the Human Fetus.-According to analyses of Hugounenq, a fully developed fetus contains about 100 gm. of inorganic compounds, but only 0.294 gm. of this is metallic iron. The absorption of inorganic salts, especially of iron, is very great during the last 3 months of fetal life,―much more so than during any previous period,—and the advisability of giving the mother at this time a diet rich in iron is suggested.

Products of Gastric Digestion.-Within the last 4 or 5 years a large number of writings have appeared which describe the attempts made by various experimenters to separate the products of an artificial gastric digestion of proteids. Each experimenter uses a method of separation which produces what are apparently well-characterized products, and which, when applied to the substances obtained by his

1 Virchow's Archiv, cli., S. 488.

2 Ibid., clii., S. 191.

3 Pflüger's Archiv, lxxiv., S. 466. * Boston Med. and Surg. Jour., cxl., p. 204. 5 Jour. of Path. and Bacteriol., v., p. 331. Compt. rend., cxxviii., 1054.

predecessors, shows that each of these is capable of being resolved into at least 2 constituents. The object of most of these experiments has been to show the relation that each of these products bears to every other and to the common mother substance, and it seems never to have occurred to one of these experimenters that the mother substances may themselves be very complex mixtures, and that there is, consequently, no direct chemic relation between the products. The latest contribution on the subject is by E. P. Pick, who, by fractional precipitation of Witte's peptone with ammonium sulphate, has obtained what he believes to be 4 well-characterized albumose fractions, and has also isolated 2 peptones from the part of the material which is not capable of forming a precipitate with ammonium sulphate.2 There are thus 6 fractions to which the author proposes to devote his attention, and if we are to judge the 5 contributions that are to appear by the first instalment, his work alone will constitute a library on the subject.

The author first investigates the primary products of digestion-the so-called primary albumoses. He claims that the methods hitherto employed for the separation of these substances from each other, and for separating both from the secondary products, are inadequate, since saturation with sodium chlorid always throws out some deuteroproteose, and subsequent dialysis always leaves some heteroproteose in solution. These difficulties were overcome by treating a solution of the protoproteose and heteroproteose with strong alcohol until the solution contains alcohol in such strength as has been determined by numerous experiments to be more than sufficient for completely throwing down heteroproteose and yet is capable of holding all of the protoproteose in solution. He thus obtains two substances which he considers purer than any heteroproteose or protoproteose that has been described. Analysis of the compounds shows that they are both richer in carbon and nitrogen, but poorer in oxygen, than Hammarsten's fibrin; and, in marked contrast to the mother substance, neither product contains any fast-bound sulphur. While in many respects the 2 substances behave very much alike, their decomposition products show that they are very differently constituted. Thus, the heteroproteose contains 39% of its nitrogen in the basic form, while the protoproteose contains only 25%. The protoproteose yields a large quantity of tyrosin by pancreatic digestion, or yields indol and skatol by heating with alkalies, but only a trace of leucin and no glycocoll. The heteroproteose, on the contrary, yields very little tyrosin, indol, or skatol, but a large quantity of leucin and a reasonable amount of glycocoll.

The author's experiments are also in accord with the generally accepted conclusion that the two proteids are formed from fibrin contemporaneously, and not successively.

E. Zunz 3 has shown also that by fractional precipitation with zinc sulphate there can be isolated from among the products of gastric digestion of proteids 4 well-defined albumoses. These 4 substances

1 Zeits. f. physiol. Chem., xxviii., S. 219.

3 3 Zeits. f. physiol. Chemie, xxvii., S. 219.

2 Ibid., xxiv., 246.

not only differ sharply in the limits within which they may be thrown out of a solution in water by the addition of zinc sulphate, but also differ qualitatively in many of their chemic reactions. These 4 fractions are believed by Zunz to be identical with the 4 albumoses that were obtained by Pick by fractionally precipitating with ammonium sulphate.

Protamins.-The researches of Kossel and his co-workers on the protamins and their decomposition products proceed with vigor. The latest addition to this most important group of compounds is a substance called cyclopterin, which Morkowin1 has obtained from the spermatozoa of cyclopterus lumpus (lump-sucker). This substance responds to Millon's reaction, a property not possessed by the other protamins, and, therefore, in all probability contains the atomic grouping which in the proteids gives rise to tyrosin. Kossel gives an abstract of the results which he has hitherto obtained, together with his views on the relation of the protamins to other proteids, in a speech before the meeting of the British Scientific Association, held in Dover during the summer of 1899. After noting the many points of resemblance between the protamins and the more complex proteids, he says: "Protamins, however, differ from other proteid bodies chiefly in that they present strongly marked basic characteristics and furnish chiefly basic bodies as a result of cleavage: that is, they contain little else than the basic moiety of the complex proteid molecule. We can, therefore, regard the ordinary proteids as bodies having originated by the addition of tyrosin or leucin groups to the original sturin molecule. On the other hand, a preponderance of protamin groups in the proteid molecule will endow it with prominent basic characteristics. We can produce such artificial combinations by adding certain albuminous bodies to protamins in alkaline solution. Under these circumstances compounds are formed which possess the properties of complex proteids, and in which basic characteristics prevail. These artificial substances are identical with certain compounds found in the body, and named histons. These histons are widely distributed in animal cells, and appear to belong chiefly to the cell-nucleus. We can, therefore, consider them as proteid bodies in which the basic moiety of the molecule -the protamin group-outweighs the others. Thus, we see that the proteid molecule must possess duplex properties: on the one hand, it is to be regarded as of an acid, and on the other hand, as of a basic constitution. But it cannot be doubted that, in addition to these two kinds of affinity, the proteid molecule also possesses others, by means of which it is enabled to effect combinations both with organic and inorganic atomic groups. This many-sided property of the proteid molecule is that which enables it to fulfil its widely different physiologic functions in cell-life.

"One may aptly apply to the proteid molecule the Greek description of the Sphinx-the front, a lion; the middle, a dragon; and behind,

1 Zeits. f. physiol. Chem., xxviii., 313.