Supplement to "Nature" December 23, 1922 



The Influence of Pasteur on the Development of Bacteriology and the Doctrines 

 of Infection and Immunity. 



By Prof. William Bulloch, F.R.S. 



TO the ancients the cause of plagues and epidemics 

 was a great mystery. Such visitations were 

 regarded either as punishments administered by the 

 Omnipotent to chastise his erring creatures, or as the 

 foul work of a spirit or demon who possessed the powers 

 of evil over men. It was natural that human beings 

 who possessed the ability to ward off the avenging 

 hand or to neutralise the deadly effects of a cacodemon 

 should be esteemed or, indeed, venerated. This was, 

 no doubt, the origin of the ^Esculapian worship in 

 ancient times, and was the source of charms, the use 

 of which is not extinct even now. In any case, t be- 

 cause of disease was believed to be something super- 

 natural, and this was the current doctrine down to 

 the Middle Ages, to be replaced by the view that the 

 cause must be sought in some natural phenomenon 

 rather than a vague supernatural element. Among 

 natural causes of disease were reckoned deleterious 

 changes in the air from miasms emanating from the 

 soil, the effluvia given off from unburied bodies, and 

 such like. Changes in weather were also believed to 

 be effective, and a vague " epidemic constitution "- 

 a " genius epidemicus " — was utilised to explain the 

 repeated appearance of diseases like small-pox, measles, 

 influenza, and scarlet fever. There were also those 

 who believed that telluric influences like earthquakes 

 and floods, or celestial phenomena like the conjunction 

 of planets or eclipses, were responsible for the sub- 

 sequent outbreaks of epidemic disease. 



The idea that disease could be contracted by contact 

 with the sick, although ancient, was never popular 

 and played no important part in the evolution of 

 medical doctrine until the sixteenth century, when its 

 main elements were clearly formulated by Jerome 

 Fracastori (1483-1553) whose work " De Contagione " 

 (1546) constitutes a great landmark in medical history. 

 He clearly differentiated (a) contagion by contact, 

 (b) contagion by fomites, and (c) contagion at a 

 distance. The starting point of his work was the 

 appearance of syphilis, which spread over Europe as 

 a great pandemic at the end of the fifteenth and the 

 beginning of the sixteenth century. In addition to 

 syphilis, small-pox, itch and hydrophobia were clearly 

 recognised as contagious. Contagion, however, did 

 not explain all epidemic diseases. For example, it 

 was < lear that, although malaria affected large numbers 

 of people, it was not dangerous for the healthy to come 

 even in remote contact with the sick. Such a disease 

 was believed to be due to some pollution of the air — 



a miasm, mal aria, emanating from marshes. In this 

 way miasmatic were differentiated from contagious 

 diseases, while later, a group of miasmatic-contagious 

 diseases was included. In all cases the miasm, which 

 was not believed to be transmissible directly, was 

 regarded as undergoing some process of maturation 

 in soil, air, or water. At this period, indeed, the 

 influence of the soil and air was regarded as paramount. 



By degrees, however, the doctrine of infection 

 clearly emerged and passed through three phases. 

 At first there was the idea that the disease cause was 

 poison was not more nearly defined. The poison was 

 then regarded as the action of a ferment, and the name 

 zymotic still persists. Lastly, in the nineteenth 

 century, the idea became prevalent that the disease 

 cause is not a vague chemical ferment but a living 

 fermenting agent — a contagimn vivum. The foundation 

 of this great advance is to be sought in the classical 

 observations of Cagniard-Latour (1836) and Theodor 

 Schwann (1837) that yeast — a substance known from 

 time immemorial — is a living organism reproducing 

 itself by a process of budding and producing chemical 

 changes in certain substances termed fermentable. 

 Schwann, in particular, showed that while no yeast 

 cells are to be found in fresh grape juice, their addition 

 to such grape juice is followed by the infallible signs 

 of fermentation and the production of gas. This 

 view, opposed as it was to the prevailing teaching of 

 chemistry, was at first ardently opposed, but in due 

 course was accepted as indicating the truth. 



One of the earliest investigators to realise the 

 possibilities of the work of Schwann was Henle the 

 anatomist, and so long ago as 1840 he developed the 

 idea, on theoretical grounds, that microscopic living 

 beings might be the causes of disease ; with a remark- 

 able prescience he set forth the principles whereby 

 this might be experimentally proved. Indeed, his 

 suggestions constituted the nucleus on which, forty 

 years later, the whole modern fabric of the etiology 

 of infective diseases was erected. Even so far back 

 as 1835, Agostino Bassi, of Lodi, showed that the 

 muscardine disease of silkworms was due to infection 

 by a fungus. In 1839, Schonlein demonstrated the 

 existence of the Achorion fungus in favus, and Gruby 

 (1843) found the Trichophyton fungus in ringworm. 



A new stream of discovery had set in, no longer 

 characterised by vague philosophical speculation but 

 by hard facts established by experiment. To this 

 advancing current Louis Pasteur was the main con- 



