and general interest to deserve our special examination. Hippuric acid we have already discussed somewhat fully, while the consideration of uric acid I must postpone to my next lecture. There remain, then, only leucine and tyrosine; but, before adverting to the natural occurrence of these bodies in the living and dead body, let me direct your attention for a short time to certain allied products obtainable from nitrogenous tissue by artificial processes. When flesh, for instance, is submitted to the action of the oxidising agent most commonly employed by chemistsnamely, a mixture of sulphuric acid with either bichromate of potassium, or peroxide of manganese-there are produced a considerable number of monobasic acids, and several of their associated aldehydes and nitriles. The relationship of an aldehyd to its corresponding acid and alcohol is very simple, and may be exemplified by common or vinic aldehyd among fatty, and by benzoic aldehyd among aromatic compounds. Thus, when vinic alcohol is submitted to oxidation, it does not simply take up an additional dose of oxygen, but instead gives up a portion of its hydrogen to the oxygenant, being thereby converted into alcohol dehydrogenatus or aldehyd, thus:Alcohol. Oxygen. Water. C2HO + O The resulting aldehyd is a much more readily oxidisable substance than the original alcohol, and, upon exposure to air, is rapidly convertedby direct absorption of oxygen

into acetic acid, thus:

=

Aldehyd.

H2O + CHO.

=

H2O +

Benz-aldehyd. CHO;

the destructive distillation of castor oil, which contains the 7-carbon or œnanthic aldehyd, the whole becomes, you observe, a semi-solid white mass, from the instantaneous combination of the two bodies with one another to form enanthal-sulphite of sodium C,H,,O.HNaSO3. But even this property of uniting with the acid sulphites, which enables us so easily to recognise and isolate the aldehydes, is less characteristic than their acidifiability by direct absorption of oxygen; so that, considered as products of oxidation, the aldehydes may be looked upon as incompletely formed acids. When, therefore, we find that by treating muscle with an oxidising agent we obtain aldehydes together with their corresponding acids, it only shows that our oxidising agent is employed in deficiency, or rather that the products, being readily volatile, are not left in contact with the heated oxidising mixture sufficiently long to be entirely converted into acids.

But in addition to aldehydes and acids, certain nitriles, more particularly formio-nitrile and valero-nitrile, have been obtained by muscle oxidation. You may remember that I have already, in previous lectures, made mention of prussic acid, cyanide of hydrogen, or formio-nitrile; of cyanide of methyl, or aceto-nitrile; of cyanogen, or oxalo-nitrile, &c. Now, the majority of nitriles are procurable either by the action of the simplest organic nitrile, namely, formio-nitrile or prussic acid, upon the preceding alcohol, or by the action of ammonia upon the co-equal acid, with elimination of water, as shown below in the case of valero-nitrile :

The first process is a true synthesis, or passage from a lower to a higher carbon group, as explained in my last lecture when speaking of general synthetic methods;

Benz-aldehyd. Oxygen. Benzoic acid. C-H6O + 0

=

C-H6O2.

Oxygen, then, which removes hydrogen from the alcohols, attaches itself directly to the aldehydes, and thereby distinguishes the one class of compounds from the other; even when, as in the case of allyl alcohol and propionic aldehyd, the two bodies have the same ultimate composition, represented in their case by the formula C2HO. Now, although the characteristic property of the aldehydes is to absorb oxygen with conversion into acids, they may nevertheless be rehydrogenised into alcohols, as by the process of Wurtz referred to in my last lecture, thus :Benz-aldehyd. Hydrogen. Benzyl-alcohol. C-H6O + H2 C-H2O.

Or, still more curiously, one moiety of the reacting aldehyd may be oxidised into the corresponding acid or its salt, and the other moiety simultaneously hydrogenised into the alcohol, as in Cannizzaro's well-known process :-Benz-aldehyd. Potash.

1

Pot. benzoate. Benzyl-alcohol. 2C, HO + KHO C,H,KO2 + C2HO Correlated, then, with every alcohol and acid is an intermediate aldehyd, several of which bodies, in addition to benz-aldehyd, are familiarly known to us in the form of essential oils. Thus, essential oil of chamomile contains angelic aldehyd convertible by exposure into angelic acid. Oil of cinnamon, again, contains cinnamic aldehyd convertible by exposure into cinnamic acid. Oil of spirœa constitutes salicic aldehyd convertible by oxidation into salicic acid; while oil of rue contains methyl-rutic aldehyd, convertible by oxidation into rutic acid. Moreover, the bodies known as acroleine, acetone, propione, glyoxal, &c., belong to the same class of compounds, all of which are characterised by the property of forming sparingly soluble crystalline compounds with the acid- or bi-sulphites of alkali-metal (Bertagnini). Thus, on mixing a solution of a cid-sulphite of sodium with the product of

into its dehydrated ammonia salt. By treatment with caustic alkalies, the several nitriles or organic cyanides to which they respectively appertain, thus:— absorb water to reproduce ammonia and a salt of the acid

=

=

Valero-nitrile. Potash. Water. Ammonia. Pot. valerate. CH.N + KHO + H,O H2NC,H,KO.. Prussic acid. Potash. Water. Ammonia. Pot. formiate. CHN + KHO + H,O H2NCH KO2. Accordingly, the occurrence of nitriles in addition to acids and aldehydes, only shows that certain oxidationproducts of the carbo-hydrate constituents of muscle exist partly in combination with an ammonia-residue derived from its nitrogenous constituents, whereby, instead of the normal acids, we obtain in some cases their dehydrated ammonia salts; whence it follows that the nitriles, like the aldehydes, do not call for any separate consideration, but may be discussed with their respective acids, of which, indeed, they constitute mere varieties.

The following acids, then, in the state of acids, aldehydes, and nitriles, have been obtained by the oxidation of flesh with a mixture of sulphuric acid, and peroxide of manganese,--as now taking place in the retort upon the

in contact with it for so great a length of time-are subjected to such a prolonged process of oxidation-that they become more or less completely destroyed, or, in other words, converted into carbonic acid.

Now, there are two special points of interest connected with the above list of muscle-acids, which are arranged, you observe, in the order of simplicity, instead of complexity, as heretofore. The first point to which I would direct your attention is, that even the most complex of these acids is comprised among the simpler members of its particular series. Thus, while by the direct or indirect oxidation of fat, we may obtain acids with eight, nine, ten, and even sixteen atoms of carbon, the most complex acids as yet obtained by the artificial oxidation of flesh, are those with five, six, and seven atoms, for the production of toluic acid is at any rate very doubtful. Now, although this oxidation of flesh has not been performed with sufficient frequency or variety of process to warrant our laying much stress upon the results obtained, still less of affirming that no more complex aplone molecules than those with seven atoms of carbon are in any case procurable, nevertheless the above observation, taken in conjunction with other facts, has an interest which must not be overlooked. Thus among all the products of tissue-metamorphosis occurring in the living body, with the possible exception of indigo, which, like toluic acid, contains eight carbon atoms; among all the products of the putrefactive decomposition of dead animal tissue; among all the products obtainable by its direct oxidation as just referred to; and among all the products obtainable by its indirect oxidation with acids or alkalies, not a single aplone molecule with more than seven atoms of carbon has yet been positively observed. Comparing the ascertained constitution of oleine, for instance, with the hypothetical constitution of some protein body, we know that the molecule of oleine contains 57 carbon atoms, and that these atoms pertain to the residues of four distinct aplone molecules, namely, three molecules of oleic acid, containing each 18 carbon atoms, and one molecule of glycerine, containing 3 carbon atoms. Accordingly, by the breaking up of oleine we may obtain aplone molecules with as many as 18 atoms of carbon, and with successively fewer and fewer atoms, according to the degree of oxidation, until finally we get such bodies as succinic acid CHO4, oxalic acid ̊C,H2O4, and carbonic acid CH2O3; while, among intermediate compounds, the palmitic acid with 16, the sebacic and rutic acids with 1o, and the suberic acid with 8, are certainly, and other acids with from 1 to 18 carbon atoms, in all probability, procurable. On the other hand, the composition of the molecule of albumen is at present undetermined, but assuming, according to the balance of authority, that it contains 72 carbon atoms, what is the number and what the complexity of the aplone molecules between which these 72 carbon atoms are divided? All we can say is that no aplone molecule with more than 7 or 8 carbon atoms has hitherto been produced by its natural or artificial decomposition, so that its constituent residues probably appertain to simpler molecules, than do the residues of ordinary fat.

The other point of interest connected with the artificial oxidation of flesh is, that the acids and aldehydes produced thereby belong to both our primary series, namely, the fatty and the aromatic; so that while the oxidation of muscle in the laboratory yields us the same series of fatty acids that are producible by the similar oxidation of fat, it yields in addition certain acids of the aromatic series which are not producible by the oxidation of fat. This result acquires additional importance from the consideration that chemists are at present quite unable to transform fatty into aromatic compounds, or vice versa, by any definite reaction. It is true that when certain bodies of the fatty class are subjected to a full red heat, some products belonging to the aromatic class are formed; but this transformation is one which we cannot trace. It belongs to

that class of reactions which are called destructive or indefinite, in contra-distinction to those easily traceable and definite reactions which we call more especially metamorphic. By no ordinary treatment with reagents, and certainly not by any of the modes of treatment to which muscle has been subjected, are we able to pass from the fatty to the aromatic class of bodies; and accordingly, when we find, by treating flesh, &c., with sulphuric acid and manganese, that both aromatic and fatty acids are produced, we have a right to infer that, be the exact composition of flesh, &c., what it may, it certainly contains, in addition to its ammonia residues, one or more residues of compounds belonging to the fatty, and one or more residues of compounds belonging to the aromatic class. This conclusion becomes even more irresistible when we consider that not only by the direct oxidation of nitrogenous tissue now taking place on the table, but by its indirect oxidation, through the agency of acids and alkalies, as well as by its post-mortem putrefactive decomposition, and its antemortem natural transformation, compounds belonging to both the aromatic and fatty class simultaneously make their appearance.

Among these compounds, leucine and tyrosine demand our special attention-leucine being an ammoniated term of the 6-carbon fatty, and tyrosine an ethyl-ammoniated term of the 7-carbon aromatic acid group. These two bodies occur in association with one another under the following circumstances :-In the first place, they result from the putrefaction of flesh, cheese, white of egg, gluten of wheat, &c. They have also been detected in fresh blood, and occur very generally in glandular tissue and secretionleucine, however, in much the larger proportion, so that in some cases where it has been recognised, the tyrosine probably accompanying it has been overlooked. Leucine, more particularly, has been found in the spleen, thymus, thyroid, and lymphatic glands; and, indeed, from its occurrence in the two former, received at one time the names of lienine and thymine.

Both leucine and tyrosine are met with most abundantly in the pancreas and its secretion, but they also occur in the liver and bile, and in the kidneys and urine, particularly in certain pathological conditions. Leucine has also been recognised in the salivary and intestinal glands and their secretions, and is, according to Badcker, an ordinary constituent of pus.

That leucine and tyrosine pre-exist in the living body, and are not merely post-mortem products, is evident from the circumstance of their having been detected in the urinary, pancreatic, and, in the case of leucine, purulent and salivary secretions of living animals. But more than this. A long time back, De ia Rue noticed that tyrosine existed pre-formed in the dried cochineal insect, and Staedeler has more recently recognised the presence of both tyrosine and leucine in invertebrata belonging to all the principal non-infusorial classes, by crushing up the living animals in a mortar with a mixture of powdered glass and alcohol. Thus it is manifest that leucine and tyrosine are possessed of a very extensive natural distribution. But they have not as yet been detected in the juice of flesh, a circumstance, however, which appears the less surprising when we remember that even urea itself, an undoubted product of muscular metamorphosis, has never been satisfactorily recognised in healthy muscular tissue, probably on account of its rapid removal by the circulation.

Artificially, leucine and tyrosine may be produced from flesh, blood-albumen, white of egg, gluten, casein or cheese, gelatin, chondrin, elastic tissue, horn, nails, feathers, hair, hedgehog-spines, cockchafer-elytra, &c., &c., by one or other of two well-known indirect processes of oxidation, which consist in boiling the above-named substances for many hours with some mineral acid, or in fusing them gently with caustic alkali. Now, these two apparently opposite processes are the same in principle. In each case, the acid

or alkali merely enables the protein or gelatinoid substance to react with water H2O, whereby one portion of it becomes oxidised into leucine, tyrosine, &c., while another portion is hydrogenised into divers products. The nature of this action is best exposed by considering the case of some tolerably simple well-characterised substance-such, for instance, as benz-aldehyd, or essential oil of bitter almonds. When this body is treated with caustic potash, one-half of it becomes oxidised into benzoic acid, which appears in the form of an alkaline benzoate, and the other half is hydrogenised into benzyl-alcohol, as I mentioned a few minutes ago :Benz-aldehyd. Water. 2C-H6O + H2O C-H6O2 + C-H2O When, however, a large excess of alkali is used, and the action allowed to become more violent, the hydrogen does not enter into any combination, but is simply liberated in the gaseous state, thus:

=

Benzoic acid.

Benzyl-alcohol.

Benz-aldehyd. Water. Benzoic acid. Hydrogen. C2H&O + H2O C7H6O2 + H2. Now, in fusing the above-mentioned animal substances with caustic alkali, a greater or less proportion of gaseous hydrogen from the decomposed tissue-water is similarly liberated; whereas, in boiling them with mineral acids, this same hydrogen, instead of being liberated, effects certain hitherto unexamined combinations or reactions; while, in both cases, the oxygen of the decomposed water effects the production of leucine and tyrosine. Here are specimens of leucine and tyrosine obtained in this way by the action of sulphuric acid on feathers, and here a fine specimen of tyrosine extracted from cochineal, all kindly lent me by Dr. Hugo Müller.

Thus the conclusion that nitrogenous tissue contains a something related to the fatty group and a something related to the aromatic group, suggested by the results of its direct oxidation with peroxide of manganese or chromic acid, is confirmed by the results of its indirect oxidation with acids and alkalies. Among fatty compounds, we obtain, in the one case, caproic acid, and, in the other, amido-caproic acid, or leucine; while among aromatic compounds we obtain, in the one case, benzoic acid, and, in the other, ethyl-amido-salicic acid, or tyrosine. Now, let us consider the constitution and respective relationships of these two bodies.

Starting from our primary fatty acids, we may obtain the following series of chlorine derivatives:

2

B-Acids.

CH (HO)O, Carbonic. CH, (HO)O, Glycolic. CH (HO)O, Lactic. CH (HO)O2 Bulatic. CH, (HO)O Phocic. CH(HO)O2 Leucic.

11

y-Amides.

CH (HN)O, Carbamic? CH (HN)O2 Glycocine. CH, (IIN)O2 Alanine. CH, (HN)O, Bulatine. CH, (HN)O2 Phocine. C&H (H2N)O, Leucine. Excluding the mono-carbon compounds, whose behaviour in other cases is frequently different from that of their more complex homologues, the B-acids and y-amides may be obtained from the corresponding fatty acids through the intervention of their a-chloro-derivatives as above described. Excluding, again, the mono-carbon compounds, by acting upon any of the y-amides with nitrous acids, we obtain the B-acids, whereas by acting on them

with an electro-negative chloride and water, we obtain the a-chloro-acids, convertible into the normal acids by treatment with nascent hydrogen. Moreover, the y-amides are producible and decomposible in a variety of other ways. The relation, therefore, of glycocine to the glycolic and chlor-acetic acids, and of leucine to the leucic and chloro-caproic acids, is merely the relation of ammonia H.H,N, to water H.HO, and to chlorhydric acid H. Cl, as I explained to you more fully in my first lecture.

Glycocine I have referred to on several previous occasions. It is produced together with leucine and tyrosine by the action of acids or alkalies upon nitrogenous, and more particularly gelatigenous, tissues, whence its original name of sugar of gelatine. It exists as a constituent residue of sarcosine and kreatine, as well as of the hippuric and glycocholic acids. The next body, alanine, is obtainable from acet-aldehyd by treatment with aqueous prussic acid in the same way that leucine is obtainable from valer-aldehyd, as mentioned also in my first lecture. By analogy it should be called lactine, were not this appellation otherwise appropriated-namely, by milk sugar CH12O6, whose formula, you observe, is exactly twice that of lactic acid CHO,, a compound to which It is curious that while lactic acid exists so largely in milk sugar is in some way or other very closely related. been recognised in any natural or artificial product of flesh-juice, gastric juice, &c., alanine should never have animal tissue. I am not aware that bulatine has yet been been noticed upon one occasion only by Gorup-Besanez obtained from any source whatever; while phocine has in the pancreas of an ox. Leucine, on the other hand, as I have already remarked, exists naturally in, and is producible artificially from, a great variety of animal and vegetable bodies.

In commencing the study of the constitution of tyrosine we are at once struck by the great resemblance which its formula bears to that of hippuric acid. You observe that the molecule of tyrosine differs in ultimate composition from the molecule of hippuric acid, by an excess of two atoms of hydrogen, thus :

CH, NO, CHNO

Hippuric acid. Tyrosine.

Since, however, complex molecules of this description are built up of the residues of several simpler molecules, it may happen, and indeed not unfrequently does happen, that the number of the atoms of carbon, hydrogen, oxygen, and nitrogen in two or more complex bodies, approximate very closely to, or are even identical with, one another; whilst the bodies themselves are built up of very different residues, and accordingly have no real relationship of proximate constitution. Such, however, is not the case with hippuric acid and tyrosine. Each of these ammonia residue, a 2-carbon residue, belonging to the fatty, bodies is composed of three constituent residues-namely, an and a 7-carbon residue, belonging to the aromatic class. That the aromatic residue of tyrosine, however, differs from the hippuric acid residue, in belonging to the salicic instead of the benzoic sub group, is evident from a variety of considerations pointed out by Schmitt and Nasse, whose recently published views on the constitution of tyrosine, if not demonstrated with absolute certainty, are so probable in themselves, and so supported by collateral testimony, as to leave us in very little doubt as to their substantial correctness. Thus tyrosine agrees with other salicic compounds in the characteristic properties of yielding phenol by distillation, and chloranil by chlorination, and, after suitable treatment, of striking a purple colour with persalts of iron, as you perceive. This last reaction constitutes Piria's well-known test for tyrosine. Now, according to Schmitt and Nasse, the particular member of the salicic sub-group which enters into the constitution of tyrosine is salicic acid, whose formula, you observe, differs from that of benzoic acid by an excess of one atom of oxygen. More.

stituting a residue of glycocine for the atom of chlorine in chlorobenzoic aldehyd C-H5(C1)O, the relationship of hippuric acid and tyrosine to one another and to the benzoic and salicic acids is shown by the following formulæ, the parentheses of which are merely intended to point out the exchanged portions of the original and derived bodies:

Benzoic acid.

C,H,(HO)O

Salicic acid.

C-H5(H)O3

Hippuric acid. C7H5(C2H3O2.HN)O

Tyrosine.
C,H,(C2H,.HN)O3

Now, alcohol is directly convertible into glycolic acid, and hence ethylamine indirectly convertible into glycocine, by oxidation, whereas salicic acid is convertible into benzoic acid by hydrogenation; so that the fatty 2-carbon constituent of hippuric acid is more highly oxidised than that of tyrosine, while the aromatic 7-carbon constituent of tyrosine is more highly oxidised than that of hippuric acid. Doubtless, therefore, the natural production of the two bodies by tissue metamorphosis takes place under different conditions. Their joint occurrence in the urine, however, together with that of indigo and phenol, confirms the inference we have already drawn-that be the chemical constitution of nitrogenous tissue what it may, there exist in its molecule one or more groupings belonging to the fatty family, and yielding fatty oxidation-products, together with one or more groupings belonging to the aromatic family, and yielding fatty oxidation-products. In my next lecture we shall consider the intimate constitution of uric acid and its congeners.

BRITISH ASSOCIATION. Birmingham Meeting, President, Professor PHILLIPS, M.A., &c., &c.

President's Address, delivered September 6.

(Continued from page 119.)

The greater our progress in the study of the economy of nature, the more she unveils herself as one vast whole; one comprehensive plan; one universal rule, in a yet unexhausted series of individual peculiarities. Such is the aspect of this moving, working, living system of force and law, such it has ever been, if we rightly interpret the history of our own portion of this rich inheritance of mind, the history of that earth from which we spring, with which so many of our thoughts are co-ordinated, and to which all but our thoughts and hopes will again

return.

How should we prize this history! and exult in the thought that in our own days, within our own memories, the very foundations of the series of strata, deposited in the beginning of time, have been explored by our living friends, our Murchison and Sedgwick, while the higher and more complicated parts of the structure have been minutely examined by our Lyell, Forbes, and Prestwich!* How instructive the history of that long series of inhabitants which received in primeval times the gift of life, and filled the land, sea, and air with rejoicing myriads, through innumerable revolutions of the planet, before in the fulness of time it pleased the Giver of all good to place man upon the earth, and bid him look up to Heaven. Wave succeeding wave, the forms of ancient life sweep across the ever-changing surface of the earth; revealing to us the height of the land, the depth of the sea, the quality of the air, the course of the rivers, the extent of the forest, the system of life and death-yes, the growth, decay, and death of individuals, the beginning and ending of races, of many successive races of plants and animals, in seas now dried, on sand-banks now raised into mountains, on continents now sunk beneath the waters.

Had that series a beginning? Was the earth ever un*The investigations of Murchison and Sedgwick in the Cambrian and Silurian strata began in 1831; the views of Sir C. Lyell on Tertiary periods were made known in 1829.

inhabited, after it became a globe turning on its axis and revolving round the sun? Was there ever a period since land and sea were separated—a period which we can trace —when the land was not shaded by plants, the ocean not alive with animals? The answer, as it comes to us from the latest observation, declares that in the lowest deposits of the most ancient seas in the stratified crust of the globe, the monuments of life remain. They extend to the earliest sediments of water, now in part so changed as to appear like the products of fire. What life? Only the simpler and less specially organised fabrics have as yet rewarded research among these old Laurentian rocksonly the aggregated structures of Foraminifera have been found in what, for the present at least, must be accepted as the first deposits of the oldest sea. The most ancient of all known fossils, the Eozoon Canadense of Sir W. Logan, is of this low, we may even say lowest, type of animal organisation.

Then step by step we are guided through the old Cambrian and Silurian systems, rich in Trilobites and Brachiopoda, the delights of Salter and Davidson; with Agassiz, and Miller, and Egerton we read the history of the strange old fishes of the Devonian rocks; Brongniart, and Göppert, and Dawson, and Binney, and Hooker unveil the mystery of the mighty forests now converted to coal; Mantell, and Owen, and Huxley restore for us the giant reptiles of the Lias, the Oolite, and the Wealdon; Edwards and Wright almost revive the beauteous corals and echinodermata; which with all the preceding tribes have come and gone before the dawn of the later periods, when fragments of mammoths and hippopotami were buried in caves and river sediments to reward the researches of Cuvier and Buckland, Prestwich and Christy, Lartet and Falconer.

And what is the latest term in this long series of successive existence? Surely the monuments of ever-advancing art-the temples whose origin is in caverns of the rocks; the cities which have taken the place of holes in the ground, or heaps of stones and timber in a lake; the ships which have outgrown the canoe, as that was modelled from the floating trunk of a tree, are sufficient proof of the late arrival of man upon the earth, after it had undergone many changes and had become adapted to his physical, intellectual, and moral nature.

Compared with the periods which elapsed in the accomplishment of these changes, how short is the date of those yet standing monoliths, cromlechs, and circles of unhewn stone which are the oldest of human structures raised in Western Europe, or of those more regular fabrics which attest the early importance of the monarchs and people of Egypt, Assyria, and some parts of America! Yet tried by monuments of natural events which happened within the age of man, the human family is old enough in Western Europe to have been sheltered by caverns in the rocks, while herds of reindeer roamed in Southern France,† and bears and hyænas were denizens of the South of England. More than this, remains of the rudest human art ever seen are certainly found buried with and are thought to belong to races who lived contemporaneously with the mammoth and rhinoceros, and experienced the cold of a Gallic or British winter, from which the woolly covering of the wild animals was a fitting protection.

Our own annals begin with the Kelts, if indeed we are entitled to call by that historic name the really separate nations, Belgian, Iberian, and Teutonic, whom the Roman writers recognise as settlers in Britain; § settlers among a really earlier family, our rudest and oldest forefathers,

See the memoirs of M. Lartet on the "Caves of the Dordogne," 1863-4.

In the caves of Gower, Devon, and Somerset, flint flakes occur with several extinct animals.

§ Gallic or Belgian on the south-east coast; Iberian in South Wales; German at the foot of the Grampians.-(Tacitus, Vita Agricolæ.)