that the disease in monkeys is less violent and less painful than it is
in man. By the help of these experiments, Flexner and Jobling
were able to prepare a serum for the treatment of the disease, in
the same way as the serum is prepared which has been such a
blessing to the world in cases of diphtheria. This serum for the
treatment of epidemic meningitis was first used in the spring of
1907.
The contrast between cases without serum treatment and cases with serum treatment is very plain. We may first give the records before the use of the serum. Of 4000 cases in New York in 1904, 75% died; Baker reports from Greater New York 2113 cases with 36 deaths, giving 77.4% mortality; Chalmers reports from Glasgow (1907) 998 cases with 683 deaths, giving 68.4% mortality; Bailie reports in Belfast (1907) 623 cases with 493 deaths, giving 79.2% mortality; Ker reports that in the Edinburgh epidemic there was 78% mortality; Robertson reports from Leith (1907) 62 cases with 74.4% mortality; Turnour reports from the Transvaal 200 cases with 74% mortality. Amongst patients treated in hospitals death-rate was no better. Of 202 cases in Ruchill Hospital, Glasgow, 79.2% died; of 108 cases in Edinburgh Fever Hospital, 80.5% died; of 275 cases in Belfast Fever Hospital, 72.3% died; and Dunn reports that in the Boston Children's Hospital, during the eight years 1899-1907, the mortality varied from 69% to 80%. Contrast with these the results in cases treated with Flexner's and Jobling's Serum:—
Cases.
Died.
Mortality
per cent.
City Hospital, Cincinnati 45 14 31.1
Dr Dunn, Boston 40 9 22.5
Johns Hopkins Hospital, Baltimore 22 4 18.1
Rhode Island Hospital 17 6 35.2
Lakeside Hospital, Cleveland 29 11 37.7
Edinburgh Fever Hospital 33 13 43.3
Mount Sinai Hospital (Children) 15 2 13.3
Municipal Hospital, Philadelphia 21 9 42.7
Belfast Fever Hospital 98 29 29.6
These figures speak for themselves. Similar results have been obtained with similar treatment in France and Germany. “From these figures,” says Dr Robb, “it will be seen that the death-rate in cases not treated with serum averaged some 75%. This has been reduced in cases treated with the serum to less than half, and in many instances much below that figure.” “My own experience has been that of 275 cases under my care in hospital, before the use of the serum was commenced, 72.3% died; while of the 98 cases treated with serum 29.6% died. No selection of cases was made: every case sent into hospital since September 1907 has been treated in this way. No change in the severity of the attack was observed: in the three months immediately before the serum arrived with us 45 cases came under treatment, of whom 37, or 82%, died; and in the first four months after we began its use in hospital 30 cases were treated, of whom 8 died, a mortality of 26.6%; while of the 34 cases occurring in the city in the same period, but not sent into hospital, and not treated with the serum, over 80% died. Great as this change in the death-rate has been, it is not more striking than the improvement in the course run by the cases; for whereas it was common to have cases running on into weeks and even months, such cases are no longer met with ” (R. D. S. pamphlet, 1909).
13. Malaria.— Laveran, in 1880, discovered the Plasmodium malariae, an amoeboid organism, in the blood of malarial patients. In 1894 Manson took, as a working theory of malaria, the old belief that the mosquito is the intermediate host of the parasite. In 1895 came MacCullum's observations on an allied organism, Halteridium. In 1897, after two years' work, Ross found bodies, pigmented like the Plasmodium, in the outer coat of the stomach of the grey or “dapple-winged” mosquito, after it had been fed on malarial blood. In February 1898 he started work in Calcutta: “Arriving there at a non-fever season, he took up the study of what may be called ‘bird malaria.’ In birds, two parasites have become well known—(1) the Halteridium, (2) the Proteosoma of Labbé. Both have flagellate forms, and both are closely allied to the Plasmodium malariae. Using grey mosquitoes and proteosoma-infected birds, Ross showed by a large number of observations that it was only from blood containing the proteosoma that pigmented cells in the grey mosquito could be got; therefore that this cell is derived from the proteosoma, and is an evolutionary stage of that parasite” (Manson, 1898). These pigmented cells give issue to innumerable swarms of spindle-shaped bodies, “germinal rods”; and in infected mosquitoes Ross found these rods in the glands of the proboscis. Finally, he completed the circle of development, by infecting healthy sparrows by causing mosquitoes to bite them. It would be hard to surpass Ross's work, and that done in Italy by Grassi and others, for fineness and carefulness. He says, for instance, “out of 245 grey mosquitoes fed on birds with proteosoma, 178, or 72%, contained pigmented cells; out of 249 fed on blood containing halteridium, immature proteosoma, &c., not one contained a single pigmented cell. … Ten mosquitoes fed on the sparrow with numerous proteosoma contained 1009 pigmented cells, or an average of 101 each. Ten mosquitoes fed on the sparrow with moderate proteosoma contained 292 pigmented cells, or an average of 29 each. Ten mosquitoes fed on the sparrow with no proteosoma contained no pigmented cells.”
By these and the like observations it was made practically certain that malaria is transmitted from man to man by a special kind of mosquito. Then came the final experiments on man. In 1900 Sambon, Low and Terzi made their famous experiment on themselves in the neighbourhood of Ostia. They put up a little mosquito-proof hut in a neighbourhood “saturated with malaria.” In this little hut they lived through the whole of the malaria season, without taking a grain of quinine, and not one of them had a touch of the fever. Then another experiment was made. A consignment of mosquitoes containing blood from a case of malaria was sent from Rome to the London School of Tropical Medicine. Dr Manson and Dr Warren then submitted themselves to being bitten by these mosquitoes, and in due time suffered malarial fever. On these proven facts was founded the whole plan of campaign against malaria. The nature, habits and breeding-places of the mosquito of malaria (Anopheles maculipennis) have been studied with infinite care, and are now thoroughly recognized. The task is to destroy its eggs and its larvae, to break the cycle of its life, and to do away with its favourite breeding-places.
14. Yellow Fever.—A special mosquito (Stegomyia) conveys yellow fever from man to man. The germ, like the germ of rabies, has not yet been made visible under the microscope. It is probably a very minute spirochaete, which undergoes a slow evolution in the body of the mosquito told off for that purpose. The earlier experiments (1810-20) made on themselves by Chervin, Potter, Firth and others were truly heroic, but proved nothing. Finlay (1880-1900) experimented with mosquitoes on himself and other volunteers, and certainly proved the transmissibility of the fever through mosquitoes. Sanarelli (1898) prepared an immunizing serum which gave good results: but the germ which he took to be the specific cause of the fever, having found it in cases of the fever, is not now accepted by bacteriologists as specific. But the great work, which proved to the world the way of infection of yellow fever, was done by the Army Commission of the United States (1900). This Commission was sent to Havana, and the experiments were carried out by Drs Walter Reed, Carrol, Lazear and Agramonte in the Army Camp in Havana. A hut was constructed with two compartments, divided from each other by a wire mosquito-proof screen. In one compartment they placed infected mosquitoes, which had bitten a yellow fever patient within the first three days of the fever. More than twenty volunteers offered themselves for experiment. In one set of experiments, clothing and other material, soiled by the vomit or blood or excretions from cases of the fever, were placed in one of the rooms, and some of the experimenters slept for 21 consecutive nights in contact with these materials, and in some cases in the very sheets on which yellow fever patients had died. Not one of these experimenters took the fever. In another set of experiments, 22 of the experimenters submitted themselves to be bitten by the infected mosquitoes, and in each instance they took the disease. It was thus proved, past all reasonable doubt, that yellow fever cannot be conveyed by ordinary infection, but must be transmitted from man to man through the agency of the mosquito. It might be said, by the opponents of all experiments on animals, that the discovery of these facts has nothing to do with “vivisection.” But, as Professor Osier said in his evidence before the Royal Commission (vol. iv. p. 158), these experiments would never have been thought of if it had not been for previous experiments on animals. “The men who made these investigations spent their lives in laboratories, and their whole work has been based on experimentation on animals. They could not otherwise, of course, have ventured to devise a series of experiments of this sort.” Out of this work came the wiping out of yellow fever (q.v.) from Cuba after the Spanish-American War, and from the area of the Panama Canal.
15. Sleeping-Sickness.—Experiments on animals have proved that sleeping-sickness is due to specific germs carried by tse-tse flies from man to man. By measures taken to prevent this way of infection, legions of human lives have been saved or safeguarded.
16. Infantile Paralysis.—Flexner, of the Rockefeller Institute, has proved, by experiments on animals, the infective nature of this disease, and its transmissibility by inoculation: a discovery of the very utmost value and significance.
17. Myxoedema.—Our knowledge of myxoedema, like our knowledge of cerebral localization, began not in experimental science but in clinical observation (Gull, 1873; Ord, 1877). In 1882-1883 Reverdin and Kocher published cases where removal of the thyroid gland for disease (goître) had been followed by symptoms such as Gull and Ord had described. In 1884 Horsley, by removal of the thyroid gland of monkeys, produced in them a chronic myxoedema, a cretinoid state, the exact image of the disease in man: the same symptoms, course, tissue-changes, mental and physical hebetude, the same alterations of the excretions, the temperature and the voice. In 1888 the Clinical Society of London
