MEDICINE, RECENT ADVANCES IN. 



351 



it is very probable that a new therapeutic agent 

 of considerable value has been discovered. 



Antitoxins and Serum Therapy. It was 

 recognized early in the history of medicine that 

 certain diseases occur only once in the same in- 

 dividual that is, that the effect of the disease on 

 the system in some way protects it from subse- 

 quent attacks. When it was found that a mild 

 attack of smallpox could be induced by inoculat- 

 ing the contents of a pustule into a healthy sub- 

 ject, and that this mild attack conferred im- 

 munity just as effectively as when the disease was 

 contracted in the ordinary way, the antitoxin 

 treatment was inaugurated. This method of 

 treating smallpox was introduced into England 

 by Lady Mary Wortley Montagu in 1721; but it 

 is probable that it was used by the Indians and 

 the Chinese hundreds of years before. Many 

 dangers were connected with the direct transfer- 

 ence from person to person of the infective mate- 

 rial. The smallpox patient might be suffering 

 from syphilis, for instance, and this disease might 

 be inoculated along with the smallpox. Again, 

 the result of inoculation was to produce an attack 

 of true smallpox, which was infectious, and could 

 be transferred to other individuals by ordinary 

 infection, and cause dangerous attacks. So the 

 method met with considerable opposition. In 

 1798 Jenner published his account of the protect- 

 ive action of cowpox. This proved to have all the 

 advantages of the direct inoculation, and none of 

 the latter's dangers, and its wide-spread use has 

 practically stamped out smallpox. The theory 

 of the action of the cowpox vaccine is that cow- 

 pox is a disease caused by the entrance into the 

 cow of a specific infection, and that its passage 

 through the latter animal, which is little sus- 

 ceptible to the disease, weakens its virulence, or 

 attenuates it to such an extent that it is not 

 dangerous to man, although its inoculation into 

 his system gives him all the immunity against 

 true smallpox that a severe attack of the disease 

 confers. It has been discovered that other human 

 disease germs may be diminished in virulence by 

 this same method of passing them through ani- 

 mals that are only slightly susceptible to the dis- 

 ease. Several other methods of lessening the viru- 

 lence of disease germs have been discovered recent- 

 ly. If they are exposed to temperatures above that 

 at which they grow best, or to direct sunlight, or 

 to the electric current, or to the action of chemicals 

 such as carbolic acid, it is found that their viru- 

 lence is much diminished. Anthrax vaccine is 

 obtained by growing cultures of the germs, ob- 

 tained from cases of the disease, at somewhat 

 higher temperatures than their normal, and using 

 these for inoculating patients, in doses of gradu- 

 ally increasing virulence. Still another method of 

 decreasing bacterial virulence is by drying. This 

 is the device used by Pasteur for making his 

 rabies vaccine. He found that for each day of 

 drying the brain of a mad dog, which if injected 

 when fresh into the brain of another dog produces 

 hydrophobia, it lost a certain amount of its viru- 

 lence; and that after fourteen days it had en- 

 tirely lost the power of producing the disease. In 

 treating a case of " mad-dog " bite, unless it is 

 very urgent, the first injection is made with a 

 well-dried or weak virus; each subsequent in- 

 jection is a little more virulent, until finally the 

 full strength is inoculated and the individual has 

 become immune to hydrophobia. 



In still other cases the products of the growth 

 of microorganisms or extracts of the dead germs 

 themselves can be used to secure artificial immu- 

 nity in man. Koch's tuberculin belongs to the lat- 

 ter class, as does also Haffkine's antiplague serum. 



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Another, and perhaps the most n 

 the antitoxin methods (with the 

 Jenner's vaccine), is that used in ti 

 diphtheria. Ernil Behring, in IS'.M), < 

 the blood and serum of animals lluii l,, ,' ;,,..,, 

 rendered artificially immune to di|.j> 

 graduated injections of the germ |>o.-s< --<<! pi*, 

 nounced antitoxic properties When in jeered. j M t<, 

 human beings. The subsequent investigations <>i 

 Ehrlieh, Roux, and others have standardized this 

 antitoxin, which is now commonly made by im- 

 munizing horses and using their serum. The UM; 

 of this serum has very markedly reduced the mor- 

 tality from diphtheria, and it is now the routine 

 treatment for the disease. 



The two antitoxins that have received the most 

 attention recently are those used against typhoid 

 fever and plague. The method of obtaining the 

 antityphoid serum used by Dr. A. E. Wright, of 

 Netley, is as follows: A virulent mass of typhoid 

 germs is allowed to grow at about 37 C. for two 

 weeks, and is then heated at 60 C. until the 

 germs are killed. A small quantity of lysol, an 

 antiseptic, is now added. The resulting fluid con- 

 tains the poisons produced by the growth of the 

 bacteria, as well as the portions of the latter's 

 bodies which are soluble. The injection of 5 

 cubic centimeters of this fluid will kill a small 

 guinea-pig in less than twenty hours. The 

 amount used for injection into human beings is 

 two-fifths of that necessary to kill a guinea-pig 

 weighing 250 grams. A second dose of double the 

 quantity may be given in a week. The effects 

 produced by the injection of this antitoxin are 

 fever (up to 102 or 103), severe headache, loss 

 of appetite, and in some cases vomiting. The 

 reaction subsides in three or four days. There is 

 still considerable difference of opinion among 

 students as to the value of this serum. Dr. A. E. 

 Wright, who has experimented extensively with 

 it, gives the following statistics. In 1900, of 11,- 

 295 individuals under observation in India, one- 

 fourth were inoculated. Of the inoculated, 0.95 

 per cent, contracted the disease, and a mortality 

 of 0.2 per cent, resulted. Of the uninoculated 2.5 

 per cent, had the disease, with a death-rate of 

 0.34 per cent. In the British army in Bengal, for 

 the period of Oct. 22, 1899, to Oct. 22, 1900, of 

 the inoculated 0.55 per cent, had the fever, with a 

 mortality of 0.27 per cent.; of the uninoculated, 

 6.14 per cent, took the disease, and 3.35 per cent, 

 of these died. Among the British troops in Egypt 

 and Cyprus in 1900, of the inoculated 0.14 per 

 cent, had typhoid, with a mortality of 0.14 per 

 cent.; of the uninoculated, 2.5 per cent, had the 

 disease, and 0.4 per cent, of these died. During 

 an epidemic of typhoid at a large insane asylum 

 in Dublin, Ireland, 511 persons were inoculated 

 and 114 not inoculated. In the inoculated, 7 

 cases developed; in the uninoculated, 29. There 

 are several plague sera Haffkine's Yersin's, 

 Roux's, Lustig and Galleoti's, and Calmette's. Of 

 these Haffkine's and Calmette's have been the 

 most extensively tested. Haffkine's serum is ob- 

 tained by simply killing cultures of the plague 

 bacillus \Bacillus pestis) by continued heating at 

 70 C., and using the resulting fluid for injection 

 into man. Considerable success has attended the 

 use of this serum in India. Dr. Calmette, of the 

 Pasteur Institute in Paris, obtains his antitoxin 

 by first establishing immunity in the horse, as 

 is done in the case of the diphtheria antitoxin, 

 and then \ising the latter's serum for human in- 

 jection. He gives very favorable statistics. 



Dr. Calmette has also devised a snake-bite anti- 

 toxin, which he calls antivenine. It has proved 

 valuable when used immediately after the occur- 



