published an exhaustive report, of 215 pages, on 119 cases of the
disease, giving all historical, clinical, pathological, chemical and
experimental facts; but out of 215 pages there is but half a page
about treatment, of the useless old-fashioned sort. In 1890 Horsley
published the suggestion that a graft of thyroid gland from a
newly killed animal should be transplanted beneath the skin in
cases of myxoedema: “The justification of this procedure rested on
the remarkable experiments of Schiff and von Eisselsberg. I only
became aware in April 1890 that this proposal had been in fact
forestalled in 1889 by Dr Bircher in Aarau. Kocher had tried to
do the same thing in 1883, but the graft was soon absorbed; but
early in 1889 he tried it again in five cases, and one greatly
improved.” In 1891 George Murray published his Note on the Treatment
of Myxoedema by Hypodermic Injections of an Extract of the
Thyroid Gland of a Sheep. Later, the gland was administered in food.
At the present time tabloids of thyroid extract are given. We could
not have a better example how experiments on animals are necessary
for the advancement of medicine. Now, with little bottles of tabloids,
men and women are restored to health who had become degenerate
in body and mind, disfigured and debased. The same treatment
has given back mental and bodily growth to countless cases of
sporadic cretinism. Moreover, the action of the thyroid gland has
been made known, and the facts of “internal secretion” have been
in part elucidated. (Claude Bernard, speaking of the thyroid,
the thymus and the supra renal capsules, said: “We know
absolutely nothing about the functions of these organs; we have not
so much as an idea what use and importance they may possess,
because experiments have told us nothing about them, and anatomy,
left to itself, is absolutely silent on the subject.”)
18. The Action of Drugs.—Even in the 18th century medicine was still tainted with magic and with gross superstition: the 1721 Pharmacopoeia contains substances that were the regular stock-in-trade of witchcraft. Long after 1721 neither clinical observation, nor anatomy, nor pathology brought about a reasonable understanding of the action of drugs: it was the physiologists, more than the physicians, who worked the thing out—Bichat, Magendie, Claude Bernard. Magendie's study of upas and strychnine, Bernard's study of curare and digitalis, revealed the selective action of drugs: the direct influence of strychnine on the central nerve-cells, of curare on the terminal filaments of motor nerves.
Two instances may be given how experiments on animals have elucidated the action of drugs. A long list might be made—aconite, belladonna, chloride of calcium, cocain, chloral, ergot, morphia, salicylic acid, strophanthus, the chief diuretics, the chief diaphoretics—all these and many more have been studied to good purpose by this method; but it must suffice to quote here (1) Sir Thomas Fraser's account of digitalis, and (2) Sir Thomas Lauder Brunton's account of nitrite of amyl:—
“1. Digitalis was introduced as a remedy for dropsy; and on the applications which were made of it for the treatment of that disease, a slowing action upon the cardiac movements was observed, which led to its acquiring the reputation of a cardiac sedative. . . . It was not until the experimental method was applied in its investigation, in the first instance by Claude Bernard, and subsequently by Dybkowsky, Pelikan, Meyer, Böhm and Schmiedeberg, that the true action of digitalis upon the circulation was discovered. It was shown that the effects upon the circulation were not in any exact sense sedative, but, on the contrary, stimulant and tonic, rendering the action of the heart more powerful, and increasing the tension of the blood vessels. The indications for its use in disease were thereby revolutionized, and at the same time rendered more exact; and the striking benefits which are now afforded by the use of this substance in most (cardiac) diseases were made available to humanity.”
“2. In the spring of 1867 I had opportunities of constantly observing a patient who suffered from angina pectoris, and of obtaining from him numerous sphygmographic tracings, both during the attack and during the interval. These showed that during the attack the pulse became quicker, the blood-pressure rose and the arterioles contracted . . . It occurred to me that if it was possible to diminish the tension by drugs instead of by bleeding, the pain would be removed. I knew from unpublished experiments on animals by Dr A. Gamgee that nitrite of amyl had this power, and therefore tried it on the patient. My expectations were perfectly answered.”
19. Snake Venom.—Sewall (1887) showed that animals could be immunized, by repeated injection of small doses of rattlesnake's venom, against a sevenfold fatal dose. Kanthack (1891) immunized animals against cobra venom: afterward Eraser, Calmette and many others worked at the subject. Eraser's work on the antidotal properties of the bile of serpents is of the very highest interest and value, both in physiology and in sero-therapy. Calmette's work is an admirable instance of the delicacy and accuracy of the experimental method. The different venoms were measured in decimal milligrammes, and their action was estimated by the body-weights of the animals inoculated; but of course this estimate of virulence was checked according to the susceptibility of the animals; guinea-pigs, rabbits and especially rats being more susceptible than dogs.
“The following table gives the relative toxicity, for 1 kilogramme of rabbit, of the different venoms that I have tested”:—
| 1. Venom of Naja | 0.25 milligramme per | ||
| kilogramme of rabbit. One gramme of this venom kills 4000 kilogrammes of rabbit: activity = 4,000,000. | |||
| 2. Venom of Hoplocephalus | 0.29 | 3,450,000. | |
| 3. Venom of Pseudechis | 1.25 | 800,000. | |
| 4. Venom of Pelias herus | 4.00 | 250,000. | |
By experiments in vitro Calmette studied the influence of heat and chemical agents on these venoms; and, working by various methods, was able to immunize animals:—
“I have got to immunizing rabbits against doses of venom that are truly colossal. I have several, vaccinated more than a year ago, that take without the least discomfort so much as forty milligrammes of venom of Naja tripudians at once. Five drops of serum from these rabbits wholly neutralize in vitro the toxicity of one milligramme of Naja venom. . . . . It is not even necessary that the serum should come from an animal vaccinated against the same sort of venom as that in the mixture. The serum of a rabbit immunized against the venom of the cobra or the viper acts indifferently on all the venoms that I have tested.”
In 1895 he had prepared a curative serum: “If you first inoculate a rabbit with such a dose of venom as kills the control-animals in three hours; and then, an hour after injecting the venom, inject under the skin of the abdomen four to five cubic centimetres of serum, recovery is the rule. When you interfere later than this, the results are uncertain; and out of all my experiments the delay of an hour and a half is the most that I have been able to reach.”
In 1896 four successful cases were reported in the British Medical Journal. In 1898 Calmette reports:—
“It is now nearly two years since the use of my antivenomous serum was introduced in India, in Algeria, in Egypt, on the West Coast of Africa, in America, in the West Indies, Antilles, &c. It has been very often used for men and domestic animals (dogs, horses, oxen), and up to now none of those that have received an injection of serum have succumbed. A great number of observations have been communicated to me, and not one of them refers to a case of failure” (Brit. Med. Journ., May 14, 1898; see also Boston Medical and Surgical Journal, April 7, 1898).
It is of course impossible that “antivenene” should be always at hand, or that it should bring about any great decrease in the number of deaths from snake-bite, which in India alone are 30,000 annually; but at least something has been accomplished with it.
The account given above of the chief discoveries that have been made by the help of experiments on animals, in physiology, pathology, bacteriology and therapeutics, might easily have been lengthened if we added to it other methods of treatment that owe less, but yet owe something, to these experiments. Nevertheless the facts quoted in this article are sufficient to indicate the great debt that medicine owes to the employment of vivisection. (S. P.)
VIZAGAPATAM, a town and district of British India, in the Madras presidency. The town stretches 3 m. along the coast, and has a station on a short branch of the East Coast railway, 484 m. N.E. of Madras. Pop. (1901) 40,892. It lies on a small bay, the south extremity of which is bounded by a promontory known as the Dolphin's Nose, and its northern extremity by the suburb of Waltair. The town or fort, as it is called, is separated from the Dolphin's Nose by a small river, which forms a bar where it enters the sea, but is passable for vessels of 300 tons during spring tides. An English factory was established here early in the 17th century, which was captured by the French in 1757, but shortly afterwards recovered. The town owes much to the munificence of the neighbouring raja of Vizianagram. A water supply has been provided at a cost of £30,000. Waltair is the European quarter. There is a considerable Roman Catholic population and a branch of the London Mission. The exports by sea include manganese ore, rice and sugar. Some weaving is carried on, and there is a specialty of ornamental boxes, &c., carved out of sandalwood, horn, ivory, porcupine quills and silver.
The District of Vizagapatam has an area of 17,222 sq. m., being one of the largest districts in India. It is a picturesque and hilly country, but for the most part unhealthy. The surface is generally undulating, rising towards the interior, and crossed by streams, which are dry except during the rainy season. The main portion is occupied by the Eastern Ghats. The slopes of these mountains are clothed with luxuriant
