Louis Willems (1822-1907) and the immunization against contagious bovine pleuropneumonia. An evaluation

Louis Willems's name is intimately linked with the history of prophylactic immunization in the nineteenth century. When he obtained his medical degree in 1849 contagious bovine pleuropneumonia or lung sickness was raging among the cattle population in most European countries. As the son of a cattle fattener Willems was confronted directly with the problem in his father's stables and decided to study the disease and to search for a remedy to combat it. The disease is caused by Mycoplasma mycoides and subspecies mycoides, but in the middle of the nineteenth century during the battle between the miasmatists and the contagionists, many had doubts about its contagiousness. Willems defended from the start the contagiousness of the disease and noticed that animals who had survived an infection did not contract it a second time. He demonstrated that inoculation of the serous fluid from the lungs or from the pleural cavity of affected animals into healthy cattle led to pronounced local reactions. When these inoculated animals later on came into contact with diseased cattle they were shown to be immune. In his first trials he inoculated at the base of the tail or around the nostrils but this led to very severe reactions and frequently to death. He then started inoculating at the tip of the tail with much better results. Most animals showed a more or less pronounced reaction at the inoculation site and about seven percent lost their tail partially or completely through necrosis, but the mortality remained very limited. The local reactions were caused by the etiological agent itself. The lesions in the connective tissue of the tail showed much resemblance to those in the interlobular septa of the lungs and contained strong accumulations of serous fluid. The tip of the tail was obviously a good choice; this was confirmed later by many authors and the procedure is still being used today in areas where the disease is still prevalent. Inoculation at other sites of the body such as the neck or the dewlap, led to very severe reactions often followed by death. Willems also demonstrated that local inoculation at the tip of the tail not only immunized the animals against infection via the respiratory tract resulting from contact with diseased animals, but also against a second inoculation in the tail, in the neck or elsewhere. Material harvested from the inoculation site in the tail (so-called secondary "virus") could also be used as inoculum. Animals who showed no reaction to the first inoculation received a second one after a few weeks. Immunization as a result of inoculation was proved repeatedly experimentally as well in Willem's lifetime, by himself and by his contemporaries, as later in more recent trials. Failures were usually attributable to inoculation of already infected animals or to the use of badly stored or purulent inocula. Inoculation during the incubation period did not provide protection. Willems' concepts about the mechanisms of immunity were understandably vague and ill-defined. He considered pleuropneumonia as an affection of the whole body with process in the lung in case of natural infection; following inoculation this process took place somewhere else and one created as it were a typical lung infection at another site of the body. Through the introduction of the "virus" a "dynamisation" of the whole body took place by which the blood and other organs became insensitive to reinfection. This explained why the inoculation protected not only the inoculation site, but the whole organism; Willems thought that the infection did not spread from inoculated to non-inoculated animals; this opinion was supported by some other workers in the field but opposed by others. The publication of his results created enormous interest in his country and abroad. In several countries commissions were created, trials were initiated and several foreign observers came to visit Willems in Hasselt. In general his results were confirmed abroad at least