Every one knows that in exciting reflex action in the limb of a decapitated frog, it is perfectly immaterial to which branch of the sensory nerve the irritation is applied. There is thus no difficulty in accounting for the liver being excited to secrete sugar when an irritation is applied to the pulmonary branches of the pneumogastric; and we are not necessarily forced to believe that they are the branches which normally call into action the peculiar function of the organ referred to. Indeed, if such be in reality the case, how does it happen that while the respiration, and consequently the stimulus, continue at about the same rate during the entire day, the secretion, which is said to be the result of the stimulus, varies at different times? At one hour it is known to be exceedingly active; at another, a somewhat later one, almost dormant. Such a result has no parallel in any other organ of the body. A certain amount of stimulus, cæteris paribus, invariably calls forth a similar and definite amount of action; and upon what grounds are we warranted in considering the function of the liver an exception to the general rule? I need scarcely detain the reader at present with further arguments against what appears to me an untenable hypothesis, as I believe the results of the subjoined experiments clearly indicate, that if the pneumogastric is the nerve which carries the stimulus to the brain, to be from thence transmitted by the spinal cord and splanchnic nerves to the liver, the point of departure of the stimulus is most probably in the liver itself, and that the cause of the reflex action may originate in the stimulating effect of the portal blood upon the hepatic branches of the pneumogastric nerve. If, for example, the stimulating effect of the blood of the portal vein be imitated as much as possible by injecting into that vessel substances such as alcohol, ether, chloroform, methylated spirit, or ammonia, the liver is excited to secrete an excess of sugar, and the animal operated upon is for a time rendered diabetic. The following experiment illustrates this fact very clearly:

I injected ten cubic centimètres of sulphuric ether, mixed with thirty cubic centimètres of water, into one of the branches of the portal vein of a full-grown Newfoundland dog, half-an-hour after he had been fed. When he rose up after the operation he appeared intoxicated, and staggered a little as he moved about. This effect, however, soon disappeared, and in a few hours the animal looked as if nothing had been done to him. In two hours after the injection was made I passed a catheter into his bladder, but did not obtain sufficient urine to enable me to satisfy myself whether it contained sugar. Some hours afterwards, when I had obtained enough urine, I found that it readily reduced the copper in Barreswil's liquid, thus indicating the presence of saccharine matter. To assure myself that this effect was not due to the presence of any other substance, I boiled the urine in order to coagulate the albumen, of which it contained a little, then evaporated it almost to dryness, dissolved the residue in boiling alcohol, and filtered. The filtered liquid was next evaporated to drive off the alcohol, and an aqueous solution made. On testing the latter for

The experiment is very easily performed by using a sharp-pointed syringe, which can be pushed with facility through the coats of one of the large mesenteric veins.

sugar with the sulphate of copper solution, its presence was clearly indicated. Although by this method the existence of saccharine matter was rendered almost undeniable, I still wished to convince myself of its presence by some other means. The urine which the dog passed the next day was therefore fermented, and carbonic acid gas and a trace of alcohol were obtained, thus placing beyond a doubt the existence of sugar in the urine. In consequence of the dog break-. ing his chain and escaping, I am unable to state how long he remained diabetic; but he was certainly in that condition forty-eight hours after the injection of the sulphuric ether.

The following case, of which I shall speak very briefly, proves the presence of sugar in the urine until the third day after the operation : A very large dog (the largest I ever saw) was treated in the same way as the preceding one, but he appeared to suffer much more from the operation. His urine was so loaded with bile that I was forced to decolorize it before testing it for sugar with the tartrate of potash and copper, which however it readily reduced. I also fermented the urine, and was able to convince myself of the existence of saccharine matter in it until three days after the injection had been made.

In another case I injected nine cubic centimètres of ether, mixed with thirty cubic centimètres of water, into the portal vein of a small dog. He became insensible, and continued so during a few minutes. Twenty-four hours afterwards he was killed by section of the medulla oblongata, and in his urine the presence of sugar was detected, both by the fermentation and by the copper test.

The following case shows how ammonia has the same power as ether in causing the liver to secrete an abnormal amount of saccharine matter:

Into the portal vein of a good-sized dog, in full digestion, I injected fifteen drops of liquor ammonia, diluted with forty cubic centimètres of water. In twenty hours afterwards, on the animal being killed, his bladder was found enormously distended with urine, which not only reduced the copper in the liquid of Barreswil, but fermented most rapidly.*

I have on several occasions repeated the experiment with ammonia, and have not yet met with a single unsuccessful case. Attempts with chloroform, on the other hand, are not invariably successful, as they sometimes result in the death of the animal, especially if the dose be considerable, as the following example proves:

Into the portal vein of a large sheep-dog I injected a mixture of three grammes of chloroform, ten cubic centimètres of ether, and fourteen cubic centimètres of water. He died three hours after the operation. Notwithstanding this untoward circumstance, I found that the urine remaining in his bladder after death contained a certain amount of sugar. In operating with chloroform, it is best to use only a few drops, as then the animals seem to suffer but little inconvenience.

In another experiment I injected into the portal vein of a small

This and the preceding experiment I had the honour of performing at the College of France, before a commission appointed by the Société de Biologie, and consisting of Profs. Bernard, Robin, and Verdeil.

dog ten cubic centimètres of a liquid composed of equal parts of alcohol and water. Two hours afterwards I examined the urine, and found that it contained sugar, but in small quantity. As I had great difficulty in obtaining the urine of this animal, I ceased making any further observations on him.

Into the portal vein of another dog, of the Skye-terrier breed, I injected ten cubic centimètres of the common methylated spirit, diluted with thirty cubic centimètres of water, six hours after he had eaten a full meal. For a few minutes after the operation he appeared to be intoxicated; but this effect soon disappeared, and on the following day he seemed perfectly well. When he was killed, his bladder was found distended with pale-coloured urine, which contained a considerable amount of sugar, as was seen by the quantity of copper it reduced, and the facility with which it fermented.*

It may be here mentioned that all the dogs so treated vomited after the operation, from the irritation, no doubt, of the pneumogastric

nerves.

These experiments are selected from a number of others, which it is quite unnecessary to cite, as the results obtained were identical. From the total of my experiments upon this point, I conclude— firstly, that a flow of saccharine urine can be induced by means of stimulants introduced into the portal circulation, even in animals that have been fasting during twenty-four hours; and secondly, that the introduction of these stimulants sometimes produces albuminuria and an increased discharge of bile, as well as of saccharine urine.

The question now to be considered is, "In what manner do the stimulants act—is it directly, by exciting the tissue of the hepatic organ, or indirectly, through the nervous system ?"

The assertion, that an organ like the liver can be excited to perform its function without the intervention of the nervous system, may appear to some as unwarranted. Indeed, were it not that we already know muscles to possess a contractile power altogether independent of nervous influence, I should not have dared to hazard such an opinion. Bernard, however, has clearly demonstrated, on frogs poisoned with wourali, that although the influence of the nervous system can be totally destroyed (as is seen by the muscle not contracting when the nerves are galvanized), galvanism, applied directly to the muscular fibre itself, excites immediate and violent contraction. I have frequently had occasion to repeat this experiment, and am well satisfied of the justness of Bernard's conclusions. In the case of the muscle we have, therefore, indubitable proof that the specific property does not exist in the nerves, but in the muscle itself. And I see no reason for doubting that the various internal organs of the animal body are constructed for the performance of a special and peculiar office, and possess within themselves their specific properties, altogether independently of nervous agency; and I am further of opinion, that when we shall be as able to separate the nerve agency from the internal organs, as we are to part it from the muscles, we shall be equally suc

* Some of the gentlemen who attended my class last summer may perhaps recollect this experiment. It was performed on the dog with an artificial gastric fistula.

cessful in calling their functions into action, by the direct application of electricity, or any other stimulus, to the tissue of the organs themselves. Professor Bernard seems to take a similar view of the subject, for, speaking of my experiments, he observes that the stimulants may have acted immediately on the tissue of the liver.*

There is certainly another, and apparently a more simple, mode of explaining the influence of the stimulants injected into the portal circulation upon the glucogenic function of the liver, and one which will, moreover, be more readily acceded to, because it does not oppose any of our old views regarding the specific properties of organs or of nerves. The stimulants may act by exciting the hepatic branches of the pneumogastric nerve to transmit an impression to the nervous centre, to be from thence reflected to the liver through the splanchnic nerves, and cause an increased secretion of saccharine matter; and if this be the correct explanation of their mode of action, the normal secretion of sugar is very probably caused by the stimulating effect of the nutritive materials in the portal blood. In those cases where the vena portæ is either accidentally or intentionally obliterated, the nutritive materials absorbed by the mesenteric veins will take a circuitous course towards the liver, and in that case the blood of the hepatic artery will excite the secretion of sugar. The following facts materially strengthen the view of the normal secretion of sugar being the result of a stimulus applied to the hepatic branches of the pneumogastric nerve.

During the time of digestion, the blood of the vena portæ must of necessity prove most stimulating, as it is then loaded with nutritive materials; and this happens to be exactly the period at which the greatest quantity of sugar is formed. On the other hand, the blood of the portal vein of a fasting animal contains very little nutritive material; it is therefore but feebly stimulant, and consequently during this period the secretion of sugar ought to be lessened. This, in fact, is exactly what occurs, for in a fasting animal the secretion of sugar has invariably been found to be at its minimum.

M. Bernard has pointed out that the liver of a dog nourished entirely on fat does not secrete more sugar than if the animal had received no food at all; and this is precisely what might be à priori expected if the above theory be correct. For in consequence of the fats, which are scarcely if at all stimulating, being absorbed by the lacteals, and entering the general circulation by the thoracic duct, without passing through the vena portæ and liver, the blood of the portal vein of a dog nourished exclusively on fat does not contain more nutritive material than that of a fasting one. It cannot, therefore, be more stimulating in the one case than in the other, and consequently the production of sugar ought in both cases to be at the minimum. This agrees perfectly with the facts already cited.

These data show that the foregoing hypothesis of the reflex action,

See Leçons de Physiologie Expérimentale, par M. C. Bernard, vol. i. pp. 345, 347. It may be asked, perhaps, "whether the blood of the hepatic artery would not in this case, as in that of obliteration of the portal vein, excite the saccharine secretion ?" It is not very probable that it would do so: firstly, because the quantity of fats in the blood is very limited; and, secondly, on account of their feebly stimulating properties.

which normally produces the secretion of sugar, is not based on illogical grounds. There exists, indeed, but one argument against the theory-namely, that while section of the pneumogastric nerves in the neck at once arrests the secretion of sugar, division of the same nerves below the point at which they send branches to the lungs is not followed by a similar result. This, too, is the very fact upon which Bernard founds his theory of the reflex action originating in the lungs. And upon a cursory view of the subject, it might be considered equally valid as an objection to the former, and as a commendation to the latter hypothesis. If we examine the point of argument, however, we shall find that the mere fact of the disappearance of sugar from the liver after section of the cervical, and not after division of the thoracic pneumongastrics, is in reality of little value, since it can be readily accounted for on other grounds. The liver ceases to secrete sugar in all cases where animals are subjected to severe operations,* whether of the pneumogastric or of any other nerve. Indeed, whenever a febrile state of the system is set up, the glucogenic function of the liver becomes immediately disturbed; section of the cervical pneumogastrics is moreover one of the severest operations to which an animal can be subjected: it is not, therefore, in the least degree surprising, that the saccharine secretion should be arrested. The same thing occurs after a variety of severe operations on different parts of the body, entirely unconnected with the nerves supplying the liver. Besides this, the slow asphyxia to which animals with divided cervical pneumogastrics are subjected, is sufficient of itself to account for the disappearance of sugar from the liver.t

On the other hand, since division of the pneumogastric nerves below the lungs in general entails neither the death of the animal, nor gives rise to any symptoms of asphyxia, it is not in the least surprising that the glucogenic function of the liver should in that case suffer but a slight derangement. Another fact in favour of the statement, that the disappearance of the sugar from the liver after section of the cervical pneumogastrics is simply dependent upon the severity of the operation, is to be found in the observation that an equal amount of injury done to the pneumogastric below the lungs is followed by a similar result. If, for example, the nerves are ligatured instead of divided, the animals frequently die, and in those cases no sugar is found in the liver. On examining the livers of two dogs, one of which died within sixteen, the other within twenty hours after ligature of the pneumogastrics at their entrance into the abdomen, I found that the saccharine secretion had been arrested, just as happens when the pneumogastrics are divided in the neck, and probably from an identical cause, the severity of the operation.

Thus it is seen that there really exists no valid objection to the idea of the glucogenic function of the liver being excited by means of a reflex action, originating in the hepatic organ. On the other hand,

See some interesting remarks upon this point at p. 360 of Bernard's Lectures. In proof of this statement I need but quote a single sentence from Bernard's Lectures. He says," Si encore on asphyxie un animal lentement, les angoisses de l'agonie font encore disparaître le sucre." (vol. i. p. 360.)