André Lwoff Biography (1902-1994)
André Lwoff was a French microbiologist whose 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. An erudite manwho painted and was well versed in philosophy and literature, Lwoff was oneof the foremost teachers and mentors to guide a generation of scientists whowould move biology to a new frontier. Lwoff, who was Jewish, actively participated in the French Resistance during World War II.
André Michel Lwoff was born in Ainay-le-Château, in central France, on May 8, 1902. His parents were Russian immigrants who had come to France in the late nineteenth century. His father, Solomon Lwoff, was a physicianin a psychiatric hospital; his mother, Marie Siminovitch, was a sculptor. Although Lwoff--who early on loved to paint, listen to music, and read--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. Lwoff spent most of his younger years in a rural community near Paris.
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. Lwoffspent 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, atthe 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 worktoward 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 termsof their role in putrefaction, fermentation, and the biological factors involved in disease. Lwoff, however, was more interested in the general biologicalproperties 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 vitaminsvitamins.
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 hehad 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 remarkable intuitive approach to research and demonstrated the unity of biochemical actionin all living things. In 1938, the Pasteur Institute made Lwoff the chief ofa new program focusing on the emerging field of microbial physiology.
During the 1930s, Lwoff developed a friendship with Eugène Wollman, apioneer researcher of lysogenic bacteria, which have the hereditary power toproduce bacteriophage , or bacterial viruses. In effect, these bacteriophageparasitize other bacteria and can cause bacterial lysis or cell destruction,which releases a host of bacteriophage particles, or phages. Initial interestin 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 maybe types of "lethal genes" that were reintroduced into the genetic makeup ofan organism.
By the early 1940s, however, lysogeny had become an area that was consideredof 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. The advance of World War II further disrupted the study of lysogeny. The Wollmans, who were Jewish, were captured by the Gestapo in Paris in 1943 and sent to the notorious Auschwitz concentration camp in Poland, never to be heard from again. Lwoff, meanwhile, had joined a resistance group in France that focused primarily on gathering intelligence for the Allies. He managed to escape capture when his underground networkwas destroyed by the Gestapo, who arrested many of Lwoff's compatriots. But Lwoff was soon involved in another underground network. He also hid American airmen in his apartment as they tried to make their way to unoccupied France after having being shot down over Nazi territory. After the war, Lwoff was awarded the Médaille de la Résistance, and was made Commander of the Légion d'Honneur for his efforts in resisting the Nazi occupation of France.
At war's end, Lwoff chose to continue the work of his friends the Wollmans. 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 lysogenicbacteria 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 theorizedthat cells in cultured lysogenic bacteria carry "free" phages on their surface, which further strengthen the phage-host association that render bacteriaresistant to later viral destruction. He believed that the increase of phagesin 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 indiameter--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, Lwoffhad not explained what actually took place during lysogeny. He did, however,go on to confirm Wollman's earlier finding that when the enzyme lysozyme wasused 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 theproduction of bacteriophage . After months and months of experiments, Lwoff and his colleagues at the Pasteur Institute decided to irradiate the bacteriawith ultraviolet light, which normally kills bacteria and bacteriophages. Totheir 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 researchshowed 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 Lwoffto study poliomyelitis 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 for physiology or medicine in 1965 for hislysogeny studies. He shared the award with fellow Pasteur Institute scientists Jacques Lucien Monod and François Jacob. These three were the first French scientists to win the Nobel Prize in thirty years, and Lwoff and his fellow Nobel Prize winners were largely unknown in France untilthey received the award. But this was not the case in the United States, where Lwoff had traveled and conducted some of his most important scientific dialogues. Soon, many young scientists came from the U.S. to visit Lwoff and learn as much about his expertise in the field of microbiology as possible. Theywere also drawn to Lwoff because his line of research was fundamentally similar to that used in studying the genetic manipulation of microorganisms. Lwoff's influence was also enhanced because he spoke fluent English.
Unfortunately for many of his devotees, Lwoff was in no position to take themunder his wing. His quarters in the attic of the Pasteur Institute were cramped and crowded with equipment. At the Institute, Lwoff was not obligated toteach and preferred to dedicate his time to his research. Even François Jacob had to plead with Lwoff on several occasions to work with him at theInstitute. Despite this obstacle, many students and fellow scientists formedclose relationships with Lwoff over the years. Lwoff had also helped Monod early in his career by allowing Monod to work with him in his laboratory at theInstitute. In one series of studies, scientist Alice Audureau isolated a genus of bacterium taken from the gut of Lwoff; Monod eventually named the genusMoraxella lwoffii in Lwoff's honor.
In the book Of Microbes and Life, many of Lwoff's former students andcolleagues contributed essays in celebration of the "fiftieth anniversary of[Lwoff's] immersion in biology." In the book, Salvador Edward Luria aptly described Lwoff's Renaissance nature, which made him so interesting to so many of his fellow scientists. "André Lwoff--scientist, painter, master of language, leader of one of the great schools of biology--is a prototype scientist-humanist, in whom the 'two cultures,' supposedly divergent and losing touch of each other, remain happily married." Lwoff was also noted for his marvelous sense of humor and enthusiasm, which, to the careful reader, would oftenshine through in even his most scientific papers. Lwoff retired from the Pasteur Institute in 1968 and became director of the Cancer Research Institute at Villejuif, near Paris, a position he held until 1972. He died in October 1994.