André Lwoff's seminal work in the genetic control of virus synthesis helped guide successive generations of scientists toward a new outlook on cell physiology. Lwoff's primary contributions have come from his study of the biology of viruses, including the genetics of bacteria and the mechanisms of viral infection and replication.
Lwoff was born in Ainay-le-Château, in central France to Russian immigrant parents. His father, Solomon Lwoff, was a physician in a psychiatric hospital; his mother, Marie Siminovitch, was a sculptor. Although Lwoff inherited his mother's artistic temperament, his interest in science was cultivated by his father, who often took the boy with him on his daily rounds. On the advice of his father, Lwoff attended the University of Paris (the Sorbonne) to study medicine, a field in which he could earn a comfortable living. But his real interest lay in his other major field of study, biology. Lwoff spent his summers at the Marine Biology Laboratory at Roscoff, in Britanny. He graduated with a bachelor's degree in the natural sciences in 1921 and, at the age of nineteen, became an assistant at the Pasteur Institute in Paris, working under microbiologists Édouard Chatton and Félix Mesnil. While conducting research part-time at the Institute, Lwoff continued to work toward his medical degree, which he received in 1927. He received his doctorate in natural science in 1932.
Lwoff's keen intellect was first applied to morphological studies of protozoa, one-celled animals that often live as parasites on other animals. Lwoff focused specifically on ciliates, which are covered with cilia (hair-like structures), and discovered a new species of ciliated protozoa. These studies eventually culminated in the discovery of the extranuclear inheritance characteristic of these organisms and earned Lwoff recognition as a leader in protozoology. Lwoff next turned his attention to an even simpler form of life, bacteria. The scientific community at that time primarily studied bacteria in terms of their role in putrefaction, fermentation, and the biological factors involved in disease. Lwoff, however, was more interested in the general biological properties of bacteria. Focusing on the ways such simple organisms get nutrition, he discovered how to produce chemically defined media for their growth--a discovery that led him to identify specific growth factors identified as vitamins.
Lwoff's discovery astounded the scientific community because it pointed to the bacterium as an organism much like higher organisms that need nutritional factors to grow and survive. Lwoff continued his research on vitamins, analyzing how vitamin deficiencies cause interruptions at certain points during metabolic processes. In 1936, in collaboration with his wife, Marguerite, whom he had married in 1925 and with whom he worked throughout his life, Lwoff published what was to become an extremely influential paper on how vitamins function as coenzymes, small molecules that help the larger enzyme molecules perform their catalytic functions. These discoveries revealed Lwoff's intuitive approach to research and demonstrated the unity of biochemical action in all living things. In 1938, the Pasteur Institute made Lwoff the chief of a new program focusing on the emerging field of microbial physiology.
During the 1930s, Lwoff developed a friendship with Eugène Wollman, a pioneer researcher of lysogenic bacteria, which have the hereditary power to produce bacteriophage, or bacterial viruses. In effect, these bacteriophage parasitize other bacteria and can cause bacterial lysis or cell destruction, which releases a host of bacteriophage particles, or phages. Initial interest in bacteriophages stemmed from scientists who thought it might be possible to use bacteriophages to fight specific diseases. Although this approach was, for the most part, ineffective, scientists were intrigued by the phenomenon since the appearance and disappearance of phages was highly unpredictable. Wollman, working with his wife, Elisabeth, had theorized that bacteriophages may be types of "lethal genes" that were reintroduced into the genetic makeup of an organism.
By the early 1940s, however, lysogeny had become an area that was considered of little importance by the young school of American bacterial virologists and many others, who now focused their work on T strains of Escherichia coli, in which lysogeny did not occur.
During World War II, Lwoff was decorated for his work with the French Resistance. Afterwards, Lwoff chose to continue the work of his friends, the Wollmans, who had disappeared after arrest and deportation by the German Gestapo. At the time, scientists who still worked in the field of bacterial lysogeny maintained that the haphazard release of phages probably occurred because of one of two reasons: the release of phages either resulted from bacteria mutation that spontaneously created phages (virus particles), or that the lysogenic bacteria leaked the phages without bursting. Furthermore, Félix Hérelle had hypothesized that bacteria are resistant to phages released by other bacteria and only absorb the phage from like bacteria. He also theorized that cells in cultured lysogenic bacteria carry "free" phages on their surface, which further strengthen the phage-host association that render bacteria resistant to later viral destruction. He believed that the increase of phages in a lysogenic bacterial culture was due to a few susceptible, or phage-sensitive, bacteria.
Lwoff began working with a lysogenic strain of soil bacteria called Bacillus megaterium and a second strain of bacteria susceptible to phage infection. Lwoff exhibited remarkable dexterity and skill in the extremely difficult procedure of growing individual bacteria in a microdrop and then fishing out the newly divided bacteria with a capillary pipette--only a few microns in diameter--without contaminating the specimen. He would then transfer the bacteria to a new non-contaminated medium. Although the approach was time-consuming and cumbersome, Lwoff was able to show that, contrary to D'Hérelle's theory, lysogenic bacteria could multiply for nineteen successive generations without the intervention of exogenous, or cell surface, phages. These successive generations were also lysogenic, which proved that lysogeny was a genetic trait. Lwoff's discoveries once again made lysogeny a viable area of study. Lwoff had also dispelled the notion that the host-virus relationship was one that always ended in morbidity, showing that the two could coexist.
Through his experiments, Lwoff also determined that lysogenic bacteria release the phages they produce by lysing, or breaking down, the cell. Still, Lwoff had not explained what actually took place during lysogeny. He did, however, go on to confirm Wollman's earlier finding that when the enzyme lysozyme was used to artificially break open lysogenic bacteria without affecting the phages, no phage particles could be found. He soon discovered what he called "prophages," which, unlike normal bacteriophages, were noninfectious. Furthermore, Lwoff discovered that the prophages acted as "bacterial genes" that integrated themselves into the chromosome of the host, where the genes are located. Reproduction of the phage particle was halted by a regulatory gene in the phage DNA.
Lwoff next theorized that some external environmental stimulus could interfere with the dormant merger of phage particles and host DNA and thus cause the production of bacteriophage. After months and months of experiments, Lwoff and his colleagues at the Pasteur Institute decided to irradiate the bacteria with ultraviolet light, which normally kills bacteria and bacteriophages. To their surprise, they found that ultraviolet light caused the phage to multiply and eventually destroy the bacterial cell. Lwoff would later note this discovery as one of the most thrilling of his scientific career. Further research showed that other stimuli, including chemicals that were known to cause cancers, could produce the same effect.
Lwoff's studies of lysogeny provided a viable model for a viral theory of cancer; and, in 1953, Lwoff proposed that "inducible lysogenic bacteria" might serve as a way of testing cancerous and noncancerous activity in cells. Although this proved difficult and engendered much debate over the possible viral origins of some cancers, Lwoff was correct in postulating that viruses' protein coats contain carcinogenic properties that can be activated by outside factors such as ultraviolet light. His research on lysogeny also led Lwoff to study oliomyelitis virus. He demonstrated that, unlike vaccine strains of the virus, some strains of the polio virus were not affected by temperature fluctuations.
Lwoff was awarded the Nobel Prize in physiology or medicine in 1965 for his lysogeny studies. He shared the award with fellow Pasteur Institute scientists Jacques Lucien Monod and François Jacob. In 1968, Lwoff retired from the Pasteur Institute in and became director of the Cancer Research Institute at Villejuif, near Paris, a position he held until 1972. Lwoff died in 1994, at the age of 92.
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