Nicolle,Charles Jules Henri
NICOLLE,CHARLES JULES HENRI
(b. Rouen, France, 21 September 1866; d. Tunis, Tunisia, 28 February 1936)
Nicolle grew up in Rouen, where his father, Eugène Nicolle, was a physician at the municipal hospital and professor of natural history at the École des Sciences et des Arts. Following family tradition, he studied medicine although he considered himself more gifted in literature than in science. Nicolle prepared for his medical examinations at Rouen and at Paris, where he passed the competitive examination for a medical residentship in 1889. His older brother Maurice (1862-1932), who had become a noted bacteriologist and pathologist, persuaded him to enroll at the Pasteur Institute. There, under the supervision of Émile Roux and drawing on the teaching of Metchnikoff, Nicolle wrote his doctoral dissertation(1893)on the pathology and etiology of the soft chancre, a venereal disease caused by Ducrey’s bacillus.
After obtaining his medical degree, Nicolle returned to Rouen, where he married Alice Avice; they had two children, Marcelle and Pierre, both of whom became well-known physicians. Nicolle was a member of the municipal hospital staff as well as assistant lecturer at the medical school. He also was in charge of a bacteriology laboratory, in which he inoculated monkeys with Ducrey’s bacillus and improved techniques for making antidiphtheria serum. Nevertheless, he was disappointed at being unable to create a major center of medical research at Rouen. An enthusiastic man with an unshakable faith in humanistic ideals, and stubborn whenever questions of principle were at stake, Nicolle often found himself in conflict with an inactive and meddlesome bureaucracy. In addition, the deafness from which he had suffered since the age of eighteen created difficulties in his medical practice and in his professional contacts. In 1902, discouraged by the indifferent reception accorded his efforts at Rouen, he accepted the post of director of the Pasteur Institute at Tunis.
When Nicolle arrived in Tunisia, the Pasteur Institute existed only on paper. Through his energetic and devoted work, however, a dilapidated antirabies vaccination unit was transformed into a prestigious institution equipped for large-scale manufacture of vaccines as well as for scientific research. Nicolle remained director of the institute until his death. Built according to his ideas, it became a training ground for bacteriologists and specialists in tropical medicine.
Nicolle’s principal discovery, for which he received the Nobel Prize in 1928, was the experiment proof of the role of lice in the transmission of exanthematous typhus. While visiting the native hospital in Tunis, he observed that an outbreak of typhus in the city did not seem to be reflected by any spread of the disease within the wards of the hospital. In his Nobel Prize acceptance speech and in his lectures at the Collège de France he later described how the idea suddenly occurred to him that the factor that ceased to act at the hospital threshold could only be an ectoparasite-in this case, the louse. This initial hypothesis was confirmed by rigorous experiments, the results of which Nicolle reported to the Académie des Sciences in July 1909. He first infected a chimpanzee by injecting it with blood taken from a man ill with typhus. He demonstrated that the disease could be transmitted from this animal to other monkeys only by lice. This discovery had an immense practical significance because of the prophylactic procedures that followoed from it. The effectiveness of systematic delousing to combat rickettsiosis, which traditionally plagued armies, was dramatically demonstrated during World War I.
Nicolle’s research was not confined to exanthematous typhus. He also examined most of the germs causing infectious diseases in the Mediterranean region. The extraordinary value of his work was due to the combination of imagination and a talent for careful observation. He formulated bold hypotheses, which he scrupulously tested in the light of experimental data. An introvert by nature, Nicolle dreaded social gatherings because his deafness excluded him from the conversation. He divided his time among scientific research, writing, and his family.
Nicolle described African infantile leishmaniasis and differentiated it from kala-azar, generally found in India. He discovered leishmaniasis in the dog, which was thus recognized as the reservoir and vector of this disease; and he developed a culture medium that made it possible to study various types of Leishmania(1908). In collaboration with L. Manceaux, he isolated a previousluy unknown parasite of Tunisian rodents. Toxoplasma gondii (1908). Other researchers later established that toxoplasmosis is also a human disease. Nicolle elucidated the mechanisms by which lice spread the infection caused by Obermeir’s spirillum and determined the precise role of ticks in epidemics involving certain spirochetes, and of flies in the tranmission of trachoma. In addition, he demonstrated the viral nature of influenza. In 1931 he participated in studies of the murine typhus found in Mexico.
Having discovered that injection with serum from a convalescing victim of exanthematous typhus can protect others who have been exposed to the disease, Nicolle sought to apply this finding to other diseases. With the aid of his friend E. Conseil, he won a major victory in the fight against measles; and his work in this area became the point of departure for the use of gamma globulin in preventive medicine.
Nicolle’s chief theoretical contribution was the elaboration and utilization of the concept of unaparent infection. On the basis of experiments in which guinea pigs were inoculated with typhus, he and C. Lebailly established that a germ can go through its entire life cycle in an organism that apparently remains healthy. In its broader generalization, this idea of a disease without clinical symptoms has proved very useful in epidemiology.
During his last years, especially after his nomination to the chair of experimental medicine at the Collège de France in 1932, Nicolle began increasingly to consider scientific methodology, the major lines of the historical evolution of diseases, and human destiny. While retaining his post in Tunis, he lectured at the Collège de France every year from 1932 to 1935. These lectures were published in several volumes and were widely read by the French scientific community. Of particular interest are his views on the moral responsibility of scientists and on the biological foundation of creativity. For Nicolle, the birth of an idea is comparable to biological mutation. His statement that scientific creation is essentially similar to poetic inspiration was based on personal experience: he had also distinguished himself as the author of several novels and collections of stories.
I. Original Works. Nicolle’s papers include “Recherches expérimentales sur le typhus exanthématique,” in Annales de l’lnstitut Pasteur. 24 (1910), 243-275 : 25 (1911), 97- 144; and 26 (1912), 250-280, 332-335. His most important books are Naissance, vie et mort des maladies infectieuses(Paris, 1930); Biologie de l’invention (Paris, 1932); Destin des maladies infectieuses (Paris, 1933; new ed., Geneva, 1961) ; L’expérimentation en médecine (Paris, 1934); Responsabilités de la médecine, 2 vols. (Paris-Tunis, 1935-1936); and La destinée humaine (Paris, 1936).
II. Secondary Literature. See “Hommage à Charles Nicolle.” the special commemorative issue of Archives de l’lnstitut Pasteur de Tunis,25 (1936); and the obituary by F . Mesnil, in Bulletin de l’Académie de médecine,115 (1936), 541-548. Besides the popularized account by G . Lot, Charles Nicolle et le biologie conquérante (Paris, 1961), see the pref. to the new ed. of Destin des maladies infectieuses (Geneva, 1961),written by Pierre Nicolle’s son Charles; and the biography of Nicolle’s brother Maurice. written by the latter’s son. Jacques Nicolle, Maurice Nicolle, un homme de la Renaissance à notre époque (Paris, 1957).
M. D. Grmek