496 



NATURE 



[August i6, 191 7 



two diseases had been locally endemic for long i>eriods 

 in some districts, we may come to the same conclusion 

 as is reached in many cases of the geographical dis- 

 tribution of animals and plants. When a form intro- 

 duced into a continental area rapidly spreads over 

 that area, its previous absence is to be exiplained as 

 due to the fact that the form in question originated 

 at some period after the separation of the different 

 continental areas. In this very war two new diseases, 

 hitherto unknown, have made their appearance — 

 trench fever and trench shin. 



How, then, can we picture to ourselves the evolu- 

 tion of an infectious disease? In the first place, it is 

 to be noted that pathogenic microbes are singularly 

 diverse in their affiliations — there is scarcely a genus 

 of micro-organism but has its representative or repre- 

 sentatives among the pathogenic organisms — moulds, 

 yeasts, lission-fungi, spirochaetes, filterable viruses 

 and chlamydozoa, amoebae, flagellate and ciiiate pro- 

 tozoa. Every pathogenic microbe has closely related 

 species differing from it in little beyond that the one 

 is virulent, the other not. 



Next, the allied sf>ecies are found suggestively grow- 

 ing in the cavities or on the surfaces of the body in 

 the same habitat as the virulent forms, or, again, in 

 the water and foodstuffs taken by the animal. This 

 leads to the conclusion that pathogenic microbes at 

 some period or periods have originated from forms 

 saprophytic on the body surfaces, or in the foodstuffs, 

 that they have originated by adaptation of these forms 

 to growth, not on, but within, the tissues. 



We possess abundant examples of experimental 

 adaptation of bacteria to new foodstuffs, to foreign 

 sugars, glucosides, fats, etc., from Pasteur onwards. 

 The observations of Penfold, Twort, Massini, and 

 others upon the accustomance of bacteria to new 

 sugars and their acquirement of the power of ferment- 

 ing the same may be' mentioned. The bacilli taking 

 on these new powers were not mutants, the outcome 

 of chance variation, but the acquired new property 

 was definitely the result of a particular environment. 

 Major F. B. Bowman has prepared a simple experi- 

 ment which demonstrates that not some, but all, the 

 members of a culture of bacilli, subjected to the same 

 environment in a fluid medium of growth containing 

 a foreign glucoside — isodulcite — acquire the new pro- 

 perty. 



Here, then, contrary to Bateson, we have evidence 

 of positive acquirements from without, and, contrary 

 to the Lankesterian dogma, we can so arrange our 

 experiment as to obtain, not evidence of variation in 

 many directions, but evidence that organisms placed 

 in a given environment all vary in one identical direc- 

 tion with clockwork regularity. 



If this be true regarding other properties, it must 

 be true regarding the acquirement of virulence. As a 

 matter of fact, Thiele and Embleton, at University 

 College, had experimentally taken a harmless sapro- 

 phytic form, the B. mycoides, accustomed it gradually 

 to grow at the temperature of the body, and then, em- 

 ploying the dead bacilli to induce anaphylaxis and 

 increased susceptibility, had, upon making a second 

 injection, succeeded in obtaining the active growth of 

 the bacilli in the tissues of the guinea-pig — and with 

 this found that the bacillus was now virulent, killing 

 other animals when injected into them. With these 

 examples for consideration, is it possible for medical 

 men not to believe in direct adaptation? 



The Adaptation to Disease-producing Agencies in 



the Higher Animals. 



It is in respect to these new acquirements in the 



higher animals that we obtain the deepest insight into 



the processes involved, and that through the abundant, 



not to say overwhelming, studies of the last thirty 



NO. 2494, VOL. 99] 



years upon immunity. Yet although every man and 

 woman of the day discusses familiarly- matters such 

 as typhoid inoculation, diphtheria antito.xin, and tuber- 

 culin, not a single general biologist has dwelt seri- 

 ously upon the significance of these studies. 

 Immunisation is direct adaptation. Take the familiar 

 examples (to medical men) of immunisation to the 

 phytotoxins, abrin, the active principle of the jequirity 

 bean, and ricin, of the castor oil plant. The rabbit 

 and guinea-pig have never come across these in nature. 

 They are, in fact, intensely poisonous. One gram of 

 ricin is adequate to kill 1,500,000 guinea-pigs. Feed 

 these small animals with minute and progressively 

 increasing doses, and eventually they can be given 

 100 times the fatal dose. And now I c.c. of the 

 blood serum of the immunised animal will destroy 

 ten, one hundred, or one thousand times the fatal 

 dose, according to the grade of immunity induced. 

 Clear!)', the blood serum now contains antitoxic sub- 

 stances, bodies which combine with the toxin, render- 

 ing it inert and harmless. The antitoxin has been 

 elaborated and excreted into the blood by certain cells 

 of the animal, and once these cells have acquired the 

 property of elaborating an antiricin, they continue to 

 produce it for weeks and months. Here is the acquire- 

 ment of a new property— the acquirement is some- 

 thing positive, something added ; there can be no alter- 

 native hypothesis of loss of inhibitory factors. Nor 

 is it a chance variation : the power can be produced 

 in any mouse or rabbit or guinea-pig with absolute 

 certainty. Nor is it a matter of the survival of the 

 fittest. The case of diphtheria and tetanus toxins, and 

 the production of antitoxins against these toxins is 

 absolutely parallel. The tissues can be educated to 

 elaborate, and elaborate in excess, a body substance 

 which neutralises the toxin, and, once started, they 

 continue for weeks and months to elaborate the anti- 

 toxin. It has been shown that it is the cells that 

 take up and fix ihe toxins which elaborate the anti- 

 toxins. It is, however, only a minority of the patho- 

 genic bacteria that form and excrete ectotoxins, 

 poisons which are discharged into the fluid of growth ; 

 the majority do not excrete toxic substance. Never- 

 theless the body can be immunised against these also, 

 though here the immunity is of a different order. It 

 is bacteriolytic — a. process of digestion. The fluids of 

 the body gain the power of dissolving and digesting 

 these bacteria That power has been acquired by the 

 millions of soldiers subjected to anti-typhoid inocula- 

 tions. 



This fact of the acquirement of a pDwer on the 

 part of the body fluids to digest the bacteria can easily 

 be demonstrated. Every student of medicine has 

 heard of Pfeiffer's reaction, in which the peritoneal 

 fluid of a guinea-pig given progressive injections of 

 the typhoid bacillus or the cholera spirillum, instead of 

 forming a favourable culture medium for these bac- 

 teria now causes a rapid swelling up and dissolution, 

 so that they melt away like sugar in water. Clearly, 

 in the process of immunisation certain tissues of the 

 body have gained "the property of elaborating ferments 

 which digest and dissolve the bacterial bodies, so that 

 now, with little or no general reaction, the animal ; 

 withstands many times the fatal dose of these patho- 

 genic organisms. And this reaction is in general j 

 narrowly specific, so that it is employed to distin- 

 guish, for example, between closely related specif' 

 of spirilla. 



Nor is this necessarily merely a temporary acquire- 

 ment on the part of the individual. For months after ^ 

 a man has been given one or two doses of dead 

 typhoid bacilli his blood serum has a different physical 

 constitution, or, as we are accustomed to term it, 

 contains specific "anti-bodies" — ^agglutinins. T^ 

 whole British Army now agglutinates the specifi 



