Élie Metchnikoff was a Russian-born zoologist and microbiologist. He received (with Paul Ehrlich) the 1908 Physiology or Medicine for his discovery in animals of amoeba-like cells that engulf foreign bodies such as bacteria - a phenomenon known as phagocytosis and a fundamental part of the immune response.
Background
Ethnicity:
Élie Metchnikoff is of Moldavian, Russian and Jewish ancestry.
Élie Metchnikoff was born Ilya Ilich Mechnikov on May 16, 1845, in Ivanovka, Kharkov Province, Russian Empire (now Kharkivs'ka Oblast', Ukraine). He was the youngest of the five children of Ilia Ivanovitch Mechnikov, a remnant of an old Moldavia boyar family and Emilia Nevakhovich, the daughter of the Polish-Jewish writer Leo Nevakhovich. His paternal ancestor was Nikolai Spathari. His mother played an important role in the boy’s education and encouraged his scientific career. Metchnikoff demonstrated from an early age a passionate interest in science. He used his first microscope at age fifteen and thereby began a lifetime study of microorganisms.
Education
A tutor to the family stimulated Metchnikoff to become interested in the wonders of natural history at an early age. In 1856 he enrolled in the 2nd Kharkov Men's Gymnasium, where he made a splendid academic record, his main passion being biology. At this time he read Buckle’s History of Civilization in England, and throughout his life strongly adhered to one of Buckle’s main tenets, that through science would come man’s advancement.
Metchnikoff’s mother dissuaded him from the study of medicine because she believed that he was too sensitive for such a career. He did win her approval to study physiology and zoology, to which he increasingly devoted his life. The seventeen-year-old student was especially interested in the subject of protoplasm and decided to go to Würzburg lo study with Koelliker. The German term did not begin in September. Disappointed, lonely, and bewildered in the strange city, Metchnikoff hurried back home, content to study for two years at the university in Kharkov. In 1864 he studied the sea fauna on the North Sea island of Heligoland, a naturalist’s paradise. Here the botanist Ferdinand Cohn gave Metchnikoff friendly guidance and advised him to continue his work with Rudolf Leuckart at Giessen. Metchnikoff made his first real scientific discovery in Leuckart’s laboratory when he found an interesting example of alternation of generations (sexual and asexual) in nematodes. In Giessen, Metchnikoff also read Fritz Müller’s Für Darwin. The German enthusiasm for the theory of evolution greatly influenced him. He worked feverishly and began to suffer from severe eyestrain. This malady prevented him for a time from using his chief research tool, the microscope.
In 1865 Metchnikoff went to Naples, where he began a systematic study of the development of germ layers in invertebrate embryos, a subject less well understood at the time than the similar development in vertebrate embryos. Metchnikoff devoted many years to studying the comparative development of the embryonic layers of lower animals. Like many zoologists of the immediate post-Origin of Species period, Metchnikoff’s constant aim was to show that in their development the lower animals follow a plan similar to that of the higher animals. He thus attempted to establish a definite link between the two divisions and to add to the theory of evolution. In Naples, he befriended another young Russian zoologist, Aleksandr Kovalevsky, with whom he collaborated on several embryological studies.
Because cholera was epidemic in Naples in the autumn of 1865, Metchnikoff decided to continue his studies in Germany. He went to Göttingen where he briefly worked with W. M. Keferstein and then with Henle. In the following summer, he went to Munich to study with Siebold. After again doing research together in Naples, Kovalevsky and Metchnikoff returned to Russia in 1867 to obtain their doctoral degrees in St. Petersburg.
After completing their doctorates Metchnikoff and Kovalevsky shared the prestigious Karl Ernst von Baer prize, presented by the discoverer of the human ovum for their work on the development of germ layers in invertebrate embryos. Metchnikoff also received a faculty position at the new University of Odessa. At age twenty-two, the instructor was younger than some of his pupils. He soon was embroiled in a controversy with a senior colleague over attendance at a scientific meeting. The conflict was resolved, but Metchnikoff thought the atmosphere at the university in Saint Petersburg would be more conducive to work and teaching and when he was offered a job there in 1868 he gladly accepted. The move proved a disappointment, for the working conditions, were, if anything, worse than in Odessa. Metchnikoff was barely able to make ends meet, and he led a lonely existence.
After the period of tragedy and exhaustion connected with his first wife's death, Metchnikoff slowly returned to his scientific work, but his eyesight was not sufficiently restored to allow microscopic work. Instead, he planned an anthropological trip to the Kalmuk steppes, where he observed the natives and carried out comparative physical measurements. He concluded that the development of Mongol natives was arrested in comparison with that of the Caucasian race, although relative bodily proportions were the same. He ascribed the growth lag of the Kalmuks to a state of slight but chronic intoxication, which was the effect of the habitual drinking of fermented milk.
The trip helped Metchnikoff to recover from the hardships of the previous five years and restored his eyesight. He again returned to his job in Odessa, to which he had been recalled in 1872. Metchnikoff was already well established in the scientific world by this time. He had published twenty-five papers, most of which dealt with the development and characteristics of invertebrates, and Odessa afforded him ample material for collecting sea fauna. Moreover, he was a successful and popular lecturer.
In 1880 the Metchnikoffs spent the summer on Mine Metchnikoff’s family farm. A beetle infestation was destroying the grainfields, and Metchnikoff studied the insects and found that some had died from a fungus infection. He conceived the idea of starting an epidemic among the beetles. After experimenting with the idea in the laboratory, he had some success in its implementation in the fields. This study was the starting point for his interest in infectious diseases. A remarkably similar chain of events occurred in the career of Pasteur, who would in future years play a significant role in Metchnikoff’s life.
By 1882 the unrest in Russia, and at the University of Odessa in particular, was so great that the nonpolitical Metchnikoff wished to leave for the quiet atmosphere of Messina, where he could better devote himself to science. In Messina he made his greatest scientific discovery, the role of phagocytes in the defense of the animal body; but the related strands of this concept of the cellular mechanism of immunity had begun to take shape somewhat earlier.
While working in Giessen in 1865, Metchnikoff had studied and observed intracellular digestion in roundworm (Fabricia). He compared this type of digestion to that found in some protozoans and saw in the similarity one more proof of a genetic connection between a lower and somewhat higher animal form. A dozen years later he published another paper that dealt with the digestive process and in 1880 “Über die intracellulär Verdauung bei Coelenteraten.” Here he showed that endodermal and mesodermal cells take up carmine granules suspended in water. He did not discover the exact mode of uptake of dye by the cell.
This phenomenon was not an original discovery by Metchnikoff. In 1862 Ernst Haeckel had described in his monograph on Radiolaria white blood cells ingesting dye particles. Several other investigators reported similar results, but it was Metchnikoff who made the proper interpretation and who realized the significance of the link between phagocytic digestion and the body’s defense.
In Messina in 1882 Metchnikoff observed that the mobile cells in a transparent starfish larva surrounded intruding foreign bodies, a phenomenon similar to the inflammatory response in animals with a vascular system. These mobile cells were derived not from the endoderm, the layer that gives rise to the digestive system, but from the mesoderm. Metchnikoff reasoned correctly that these mesodermal cells might serve in the defense of the animal against intruders and that this observation had very wide implications. He devoted the next twenty-five years to the development and popularization of his theory. As he later explained, “Thus it was in Messina that the great event of my scientific life took place. A zoologist until then, I suddenly became a pathologist.”
Both Kleinenberg and Virchow, who were in Messina that summer of 1882, encouraged Metchnikoff. Carl Claus in Vienna urged Metchnikoff to publish his findings, and in 1883 the first of many papers appeared in which Metchnikoff explored the newly developing field of immunology. In Claus’s Arbeiten, Metchnikoff first used the term phagocyte, derived from the Greek, instead of Fresszellen (eating cells). Metchnikoff had been studying the evolution of the alimentary tract. One question that had arisen was whether the lower metazoa retained the power of using mesodermal and also endodermal cells for digestion. He observed that in starfish larvae the wandering or mobile cells of mesodermal origin were active in the metamorphosis of the larva. These cells resorbed the parts of the larva that were no longer used. By simple experiment, Metchnikoff showed that it was but a short step from resorption of useless parts to a similar role when a foreign particle was introduced into the organism.
In the next years, Metchnikoff showed that the mobile cells (the white blood corpuscles) of the higher animals and man also developed from the mesodermal layer of the embryo and were responsible for ridding the body of foreign invaders, especially bacteria. Although Virchow supported him and published Metchnikoff’s papers in his Arehiv für pathologische Anatomie und Physiologie und für klinische Medizin, the phagocyte theory ran counter to many commonly held theories of the time.
By 1886 Metchnikoff was well known as a biologist and also as a microbiologist and pathologist, and was invited back to Odessa, where he had taught from 1873 to 1882. The city had established a bacteriological institute similar to the Pasteur Institute of Paris. In Odessa there was to be a combination of basic research and the production of antirabies vaccine.
Metchnikoff headed the Institute in 1886 and pari of 1887, but found that the internal strife among the members and his inability to carry out immunizations himself, because he was not a physician, combined to make life and work there unpleasant. He and his wife traveled to various centers in Europe in search of a congenial place to settle. It was Pasteur in Paris who made them most welcome and who gave Metchnikoff a laboratory in which to work. In 1888 the Metchnikoffs moved to Paris, where Elie worked for the last twenty-eight years of his life. This was an honorary position because Metchnikoff had sufficient income from his parents-in-law’s estate to live without salary.
Metchnikoff quickly became a revered member of the small circle of the Institute, where friendships and working relationships were close. He began to attract students to his laboratory and set most of them to work answering the various objections to the theory of phagoevtosis, elucidating ways in which the white blood cells were attracted to and ingested bacteria, or determining how, in general, the mechanism of immunity worked. Among his many talented students was Bordet, who in 1919 received the Nobel Prize for his work on complement fixation.
Metchnikoff also gave public lectures. In 1891 he delivered a series of talks on inflammation. In these talks, Metchnikoff dealt with the history of the various theories of inflammation and their investigation, and chiefly with the role of phagocytes in the animal kingdom. The lectures were well-attended and Pasteur himself came. The series was published as Leçons sur la pathologie compurée de l’inflammation in 1892 and in English translation in the following year.
Metchnikoff continued his research in immunity and also into the problem of fever and the mechanisms of infection. While attending the International Medical Congress in Paris in 1900, he realized that there should be a summary of his and his antagonists’ different theories. He began to write a large and comprehensive book, L’immunité dans les maladies infectieuses (1901). This book was a magnificent review of the entire field of both comparative and human immunology. The work was also, of course, a defense of the theory of phagocytosis, which the humoral theory of immunity seriously challenged. The work of the German bacteriologists, especially Emil Behring, Paul Ehrlich, and Robert Koch, which led to the discovery of many new bacteria, toxins, and antitoxins, strengthened the beliefs of those who held to a noncellular theory of immunity. Even before the English edition of Immunity in Infectious Diseases was issued in 1905, two British investigators, A. E. Wright and S. R. Douglas, put forth their theory of opsonins, which postulated that something in the fluid portions of the blood helped the white blood cells to digest bacteria. Hence a compromise was beginning to take shape. In 1908 Metchnikoff and Ehrlich shared the Nobel Prize for their researches illuminating the understanding of immunity.
Élie Metchnikoff is credited with the discovery of phagocytes (macrophages) in 1882. This discovery turned out to be the major defense mechanism in innate immunity. He and Paul Ehrlich were jointly awarded the 1908 Nobel Prize in Physiology or Medicine "in recognition of their work on immunity". He is also credited by some sources with coining the term gerontology in 1903, for the emerging study of aging and longevity. He established the concept of cell-mediated immunity, while Ehrlich established the concept of humoral immunity. Their works are regarded as the foundation of the science of immunology. In immunology, he is given an epithet the "father of natural immunity". He received Copley Medal in 1906, Nobel Prize in Physiology or Medicine in 1908, Albert Medal in 1916.
In addition to the Nobel Prize, Metchnikoff received numerous awards, including an honorary doctorate from Cambridge University, and was elected to various international academies of science, scientific societies, and institutes.
Metchnikoff adhered to atheistic views, despite the strict religious education in childhood. Attributing himself to the supporters of rationalism, Metchnikoff criticized religious, idealistic and mystical views.
Politics
Metchnikoff stayed out of politics. He nevertheless was a strong opponent of the revolutionary movement.
Views
Julius Cohnheim, a pupil of Virchow’s, had shown that the pus cells of the inflammatory process were derivatives of the bloodstream, and not of the surrounding connective tissue, as Virchow had claimed. Cohnheim further maintained that without blood vessels to bring the while blood cells, there could be no inflammation. Metchnikoff claimed that the action of mobile cells in clearing an organism of foreign material or no-longer-useful parts was a form of inflammation. According to Metchnikoff, furthermore, one could observe this action in starfish larva altogether lacking a vascular system.
A serious objection to this new theory of bodily defense was the currently held idea that the white blood cells took up invading particles or bacteria and spread them throughout the body. These phagocytes of Metchnikoff were then far from salutary and were believed to be helpful to the invader rather than to the host. There was also the usual resistance to major innovations in thought or approach.
Metchnikoff had been in a number of scientific and personal fights in his early career, and it was natural that he now became a staunch defender of his new theory. He devised new experiments and new arguments and warded off one attack after another upon his brainchild. Much of his voluminous writing in the years 1883 to 1910 was dedicated to elaboration or modification of the role of phagocytes in inflammation and immunity, but he always held tenaciously to the underlying idea of the central role of the phagocytes.
Metchnikoff also gave public lectures, for he believed the popularization of science to be important.
After the Immunity book was finished, Metchnikoff turned his attention to the problems of aging and the idea of death. With his friend and co-worker Émile Roux, he began to study syphilis, one disease that was known to be implicated in cardiovascular pathology. In 1903 Metchnikoff and Roux discovered that syphilis was transmissible to monkeys, thereby destroying the old theory that the disease was exclusively human and inaccessible to experiment. They also showed the importance and efficacy of early treatment of the primary lesion with mercurial ointment.
In a series of books and lectures between 1903 and 1910 Metchnikoff developed his thoughts on the prolongation of life. He stressed proper hygienic and dietary rules. His idea of orthobiosis, or right living, included careful attention to the flora of the intestinal canal. He believed that intestinal putrefaction was harmful and that the introduction of lactic-acid bacilli, as in yogurt, accounted for the longevity of the Bulgars. He introduced sour milk into his own diet and thought that his health improved. Although his name became associated with a commercial yogurt preparation, he had not endorsed it and realized no profit from it.
In his Nature of Man Metchnikoff argued that when diseases have been suppressed and life has been hygienically regulated, death would come only with extreme old age. Death would then be natural, accepted gratefully, and robbed of its terrors.
The outbreak of World War I in 1914 was a profound shock to Metchnikoff. Not only was there an interruption of the work of the Pasteur Institute, but Metchnikoff was forced to acknowledge that science had not yet brought man to that stage of civilization which he had envisioned.
In a number of works, Metchnikoff addressed general theoretical and philosophical problems, including the problem of the meaning of human life. He attributed the main role in the progress of mankind to science. Metchnikoff believed that in the future, science will save people from the fear of death if it manages to arouse in people "the instinct of natural death", which, according to Metchnikoff, "nests in the depths of human nature in a hidden state." Metchnikoff believed that first of all, science will change human old age, significantly improving, thanks to the progress of medicine, the quality of life in this period; the ultimate goal of science would be “the extension of life until it is saturated with and the feeling of the need for non-existence.”
Quotations:
"The duration of the life of men may be considerably increased. It would be true progress to go back to the simple dishes of our ancestors. Progress would consist in simplifying many sides of the lives of civilized people."
"In the ancient world and, above all, among the Greeks, human nature was held in high esteem."
"The Greek conception of a life in harmony with nature found its most complete development in the rationalism of the Renaissance and of the centuries that followed it."
"Whatever concerns health is of real public interest."
"Inflammation as understood in man and the higher animals is a phenomenon that almost always results from the intervention of some pathogenic microbe."
Membership
Élie Metchnikoff was a member of the Royal Society, the Saint Petersburg Academy of Sciences, the American Academy of Arts and Sciences, and the Academy of Medicine in Paris.
Royal Society
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United Kingdom
Saint Petersburg Academy of Sciences
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Russia
American Academy of Arts and Sciences
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United States
National Academy of Medicine
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France
Personality
Metchnikoff felt that the decade 1895-1905 was the happiest period of his life. He and his wife lived outside of Paris in Sèvres, and he came to the Institute each morning by train. When he became ill and weaker in the summer of 1916, he faced death placidly, according to the tenets of his own philosophy.
Physical Characteristics:
Political pressures, student unrest, and Olga’s severe bout of typhoid fever in 1880 led Metchnikoff to a second suicide attempt. He injected himself with the spirochete of relapsing fever. A long illness resulted, but he recovered with a renewed zest for life. Cardiac disturbances, from which he suffered in his last years, seem to have begun with his bout of relapsing fever, but the eyestrain, a great cause of worry and inconvenience in earlier years, never did return.
Interests
Philosophers & Thinkers
Charles Robert Darwin
Connections
Metchnikoff met Ludmila Feodorovitch, who on one occasion nursed him during an illness. They were married in 1869. Trouble was already on the horizon. The bride was disabled by severe “bronchitis,” and she had to be carried to the church in a chair. For the next five years, Metchnikoff devoted himself to caring for his wife, who subsequently died of the tuberculous disease already present on her wedding day. To enable him to lake Ludmilla to a warmer climate, he did translations besides his teaching and researches. His eyesight again weakened, and he became extremely distraught. In the winter of 1873, he hurried to Madeira to see Ludmilla, who by now was extremely sick. She died in April 1873, and Metchnikoff collapsed. He did not attend the funeral and on his way back to Russia attempted suicide. He swallowed a large dose of morphine, which caused him to vomit, thereby sparing his life.
In 1875 Metchnikoff married Olga Belokopytova, a young student who lived with her large family in the apartment directly over Metchnikoff’s. It was a happy marriage, and his wife was a devoted companion and co-worker for the remainder of his life.
