perfect insensibility. The peculiarity of action is slowness. When the sleep has been produced, it lasts a considerable period, and is undisturbed, but the respiration is slow and heavy. There is no marked excitement and no vomiting. If the action were less prolonged, methylal would rank amongst the best of anesthetics. It is a very agreeable vapour to inhale.

3

FORMIATE OF ETHYL.

The last agent which I tested was the formiate of ethyl. The composition of the formiate is C, H, O, the boiling-point 130°, the vapour-density 370. It is made by distilling alcohol with formic acid. In the vapour of this substance animals fall into a stupor, but do not actually sleep. They have considerable muscular excitement, and vomiting is easily excited. The vapour is also irritating to the throat and to the air-passages of the lung.

My chief object in testing the formiate of ethyl was to compare its action with that of the acetate of methyl, with which it is isomeric. The action of the two is different; the acetate produces deep stupor without muscular excitement.

ON THE NEUTRALIZATION OF SOME POISONS BY THE METHYL AND ETHYL SERIES. The last line of research to which I shall refer in this Report relates to the employment of the members of the methyl and ethyl series for the purpose of neutralizing alkaloidal poisons. From the fact that iodide of potassium and iodide of methyl produce very definite curative effects in some forms of disease, it occurred to me that possibly they underwent change of constitution in the body, forming, with a foreign and injurious agent, a new compound.

This view was confirmed by an observation made some years ago while conducting experiments on the synthesis of cataract. I found then, and recorded the fact in Brown-Sequard's Journal in 1860, that while chloride of potassium and chloride of sodium would produce a synthesis of cataract, the corresponding iodide salts would not. Hence I concluded that the iodides, even in organisms so low as frogs, were decomposed. The question, therefore, came before me, whether the iodides would neutralize in the organism the action of some of the better known poisons of the alkaloidal type.

To test this the following research was made; it dated from the 24th of October last year, 1867.

Three solutions were prepared. One consisted of 2 minims of iodide of ethyl, mixed with 30 of water. Two consisted of 30 minims of water and alcohol, holding the of a grain of strychnia. Three consisted of of a grain of strychnia with 2 minims of iodide of ethyl and 30 of alcohol and

water.

A frog was injected with the solution number 1. It became tetanic in one minute and a half. Another frog was injected with the solution number 3, i. e. the solution of strychnia and iodide of ethyl. This frog also be'came tetanic in one minute and a half.

The frog number 1 was now injected with a solution containing 5 minims of the iodide of ethyl; within ten minutes the spontaneous tetanus had ceased, and spasm produced under the influence of irritation was very much less. In twenty minutes there was entire relaxation, but with faint twitches when the skin was touched.

The frog number 2 was next injected with a solution containing 1 minim of iodide of ethyl. There was immediate relaxation of the tetanic spasm, and irritation brought on no spasm.

One hour after this the frog number 1 still twitched when touched, while

frog 2 remained relaxed and living, but paralyzed. Both frogs died on the following day, retaining their symptoms to the end.

It was clear in these two cases that the iodide of ethyl exerted an antidotal action to the poison, but as the animals died with different classes of symptoms, a further research was made.

A large frog was injected with 10 minims of the iodide simply. It seemed quite unaffected for some hours, but on the following day it died, presenting symptoms of general paralysis similar to the frog that had received the five-minim injection after the strychnia. Thus the question had to be solved whether any precise formula of neutralization could be arrived at. In one experiment I had not used enough iodide to overcome the spasm, in another I had thrown in so much of the iodide as to more than neutralize. and, in fact, to kill by the iodide itself. Can, then, any known quantities for exact neutralization be arrived at in a living body?

I believe they can, but up to this time I have failed, after the most careful study, to find the quantity. I can certainly prolong life twenty-four and even twenty-eigh hours after a terribly intense dose of strychnia, but ultimately there is death.

Iodide of methyl acts in precisely a similar way as the iodide of ethyl, as do also the bromides of methyl and ethyl.

Another series of experiments were at the same time made with nicotin. On October the 26th, 1867, two minims of nicotin were injected subcutaneously into a large rabbit. The animal died in twenty-five seconds.

A second rabbit was injected with two minims of nicotin and two of iodide of ethyl. It died also in twenty-five seconds.

A third rabbit was injected with one minim of nicotin and ten of the iodide. It died in one minute and fifty-one seconds.

A guineapig and a rabbit were treated with ten minims of the iodide only. They remained well for several hours, but both died next day. Again, varied experiments were carried out to get at the neutralizing proportions of these two agents. and guineapigs were made to replace the rabbits; but the point was never reached. The effect of a large dose of nicotin was modified, i. e. the convulsive action was prevented, but in the end there was death.

In my Report at the Meeting at Birmingham, I suggested that possibly it would be practicable to make new chemical compounds, substitution-compounds, in the living body. While I have been thinking and trying to work out this idea, Drs. Fraser and Crum Brown have been conducting the most singularly beautiful series of research bearing on the same question, but carried on differently. These experimentalists have shown conclusively that an intensely poisonous dose of strychnia can be rendered inert by first converting the alkaloid into a methyl-iodide.

This is a wonderful advance. But the question remains, can the same thing be done within the living body? Can a new chemical compound be produced there? When we consider the circumstances under which the substitution-compounds are made in the laboratory, I confess I am hardly prepared to see that they can be formed in the body. On the other hand, we have now evidence that to a certain extent iodide of methyl and ethyl are directly antidotal to strychnia or nicotin.

In the body, however, there are two distinct actions to be considered, the physiological action and the chemical. The antidotal effects of the methyliodide might, therefore, be due, not to chemical union or substitution, but to physiological neutralization.

To approach a conclusion on this particular point I moved from the iodides altogether, and from the monocarbon series altogether, and repeated some experiments, which I had commenced as early as 1864, with various nitrites of the bodies of which carbon is the base. I began with nitrite of amyl, passed to nitrite of ethyl, and next to the nitrite and nitrate of methyl. The results are rich in interest; for each one of these substances proves to be singularly antidotal to the acute action of strychnia. So remarkably is this true in respect to nitrite of amyl, that in a frog tetanized with strychnia I was able to hold back every convulsion for three days by the simple experiment of keeping the animal on a bed of moist moss, covering it with a bell-jar, and by introducing into the jar two minims of the nitrite every eight hours on a strip of paper.

But here came the singular fact, and in different degrees it was seen in all the other experiments; so soon as the bell-jar was removed, and the antidote was able to escape from the body of the animal, the strychnine tetanus returned. In one case, however, by great care in the experiment, a slightly tetanized frog was kept long enough under the nitrite to allow the effects of the tetanic poison to cease, and this animal recovered.

These truths are so convincing that I can have no hesitation in confirming another suggestion I made at the Birmingham Mecting, for the careful employment of the nitrite of amyl, by inhalation, in the treatment of tetanus in the human subject. The remedy can be inhaled from the alcoholic solution which I have already placed before the Section, and it may be applied, under cautious or, rather, careful administration, whenever there is spasmodic paroxysm.

But what is the action? I do not think there can be any doubt on the point in the case of the nitrites. It is clear that the action is purely physiological, because when the antidote is not renewed the action of the strychnine returns. I am bound at this moment to confine myself to the strict narration of this fact, without applying it by inference to the iodides, bromides, or other bodies of the organic series. Next year, after a new course of experimental research, I shall, I trust, be able to show the possession of some more definite knowledge on the subject.

I conclude. It is not a practice of mine to trespass beyond cue bounds on the patience of an audience, and if on this occasion I may appear to have broken a wholesome ruie, I really cannot apologize. The subject I have had to treat goes to the root of principle in the study of means for the cure-I am bold to say the cure, by true and certain scientific methods, of the diseases which most severely scourge the human family and many of the lower families in the scale of living organization.

Gradually, but surely as gradually, the curer of bodies will learn from the chemist and the practical physiologist that his remedies, rapid in action, easy in administration, positive in result, must all come from the organic compounds, which are of themselves a part of the organic nature.

Thus learned, the physician will exchange dogmatism for wisdom, faith for knowledge, and doubt for certainty. He will compete with his fellows by the pure struggle of intellect; he will be responsible for results without evasion, and his duties will be more solemnly his own; but he will stand, where he never stood before, a conscious master in his art; he will know in what he doth believe, and the world, assured by his exactitude, will soon learn to know none but him in his vocation.

Report of the Edinburgh Committee on the Action of Mercury on the Biliary Secretion. By J. HUGHES BENNETT, M.D., F.R.S.E., Chairman and Reporter.

Ar the Meeting of the Association in Dundee (1867), I read as a communication some of the results arrived at by a Committee which had been investigating the action of mercury as a holagogue. The inquiry originated in a suggestion made by myself, in the annual address in medicine I delivered to the British Medical Association at Chester in 1866. The physiological department of Section D considered the results so interesting and important that a grant of money was voted in aid of the Committee's researches, with the understanding that a full report was to be made on the whole inquiry at the next Meeting of the Association to be held in Norwich. The Committee consisted of Dr. Hughes Bennett, Professor of the Institutes of Medicine and Physiology in the University of Edinburgh, the Chairman and Reporter, Dr. Christison, Professor of Materia Medica, Dr. Maclagan, Professor of Medical Jurisprudence, Dr. James Rogers, formerly of St. Petersburg, Dr. W. Rutherford, assistant to the Professor of Physiology, Dr. Gamgee, assistant to the Professor of Medical Jurisprudence, and Dr. Fraser, assistant to the Professor of Materia Medica, Edinburgh.

The first meeting of the Committee was held November 16th, 1866. On proceeding to consider by what method the action of mercury on the biliary secretion was to be accurately ascertained, the conclusion was arrived at that no kind of examination of the fæces could yield trustworthy results. Supposing that the chief and characteristic constituents of the bile found their way into the alvine evacuations unchanged, imperfection in the analytical methods at our disposal render their quantitative analysis impossible. The plan of ascertaining bile-acids indirectly by means of nitrogen and sulphur determinations of the alcoholic extract, while most unsatisfactory in the case of pure bile, is still more so when applied to the alcoholic extract of fæces. The method of Professor Hoppe-Seyler of Tübingen, who calculated the amount of bile-acids from the effect which their solutions exert upon the ray of polarized light, presents such complexity and difficulty as to render its systematic employment in any series of analyses altogether inapplicable. As to the colouring-matters of bile, there is no direct method known by which they can be estimated. But it was further argued that, did we even possess proper means of estimating the bile-products, it is only a small portion of such as are secreted by the liver which can be found in the alvine discharges. Bidder and Schmidt ascertained that the amount of unoxidized sulphur in them only represented one-eighth part of the total sulphur which the liver secretes, and that of the other constituents of the bile the larger proportion are absorbed. Indeed the utter impossibility of detecting the constituents of bile in the fæces is admitted by one of the most reliable physiological chemists of Europe, viz. Professor Hoppe-Seyler. That under the influence of purgatives unchanged bile is occasionally discharged from the bowel is true; but this furnishes no proof of any increase of that secretion; for under ordinary circumstances it is decomposed and absorbed in the alimentary canal, and any cause which increases the rapidity of its passage there, must render absorption and decomposition less complete.

As it was evident that no accurate information concerning the amount of bile secreted by the liver was to be obtained by an examination of the fæces, the Committee arrived at the conclusion that the formation of biliary fistula in living animals, and collecting the bile directly through such fistulæ from

the gall-bladder, was the only means open to them of determining how far mercury influenced that secretion.

HISTORY.

It next became necessary to ascertain what had been made out by previous observers as to the amount of bile secreted by the liver, under varied circumstances, through biliary fistula. For literary researches into this matter, the Committee are greatly indebted to Dr. Rogers. He informs the Committee, in his report on this branch of the inquiry, that efforts to establish biliary fistula and to collect the bile have been attended with extreme difficulty in the hands of all experimenters, and have led to a large mortality among the animals operated on. Of 18 dogs operated on for this purpose by Professor Schwann of Louvain, 10 died within a week after the operation, from its immediate effects; six in from eight to eighty days from inanition, although the appetite remained good. In 2, the choledic diet was reestablished. Some years afterwards he operated on 12 other dogs, so that the total number operated on amounted to 30; and Bidder and Schmidt inform us that of these one lived four months, and another a whole year, after the operation. The last-mentioned authors say, "We shall not take into account the unsuccessful cases, of which the number at the commencement of our investigation of this subject was not very small." Again, they say, "After ten or twelve unsuccessful attempts to establish permanent biliary fistula in cats, we were obliged to have recourse to dogs." Dr. Flint, in his paper on a New Function of the Liver, does not mention the number of dogs on which he performed the operation; but it is evident that a great number perished. He says, " All the experiments made during the winter 1860-61 were unsuccessful, no animal surviving the operation more than three days." After a number of trials during the following winter, which were not more successful than the previous ones, he succeeded at last with one animal. There is every reason to believe that, had other experimenters informed us of their failures, the number of these would have been equally great. In the few cases which have succeeded, however, it is important to remember that a large amount of valuable information regarding the bile has been obtained that never would have been arrived at without them.

The operation performed by physiologists on animals in order to establish biliary fistula has, with a few modifications, been essentially the same, and will be subsequently described when detailing the experiments of the Committee.

The results arrived at may be divided into:-1, the amount of the biliary secretion in health, and the circumstances which influence it; 2, the special effect of mercury on the secretion of bile.

1. Previous Researches to determine the amount of Bile Secreted in Dogs, and the Circumstances which influence it.

HALLERT.-In Haller's Physiology,' reference is given to several cases in which attempts had been made to ascertain the quantity of bile secreted in a given time by experiments on living dogs. The description of them, however, is so very vague and general that they possess little interest for the physiologists of the present day. Van Reverhord found the quantity of bile secreted by a dog in twenty-four hours to be 6 oz.; and Haller, estimating the secretion in the human subject at four times that in the dog, suggested 24 oz. Verdauungs-Säfte und der Stoffwechsel, 1852, page 125. + Physiologia, tom. vi. page C05.