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Andre LwoffNobel Prize in Physiology or Medicine 1965 jointly with François Jacob and Jacques Monod
Date of Birth: 08.05.1902
Country:  France |
Content:
- André Michel Lwoff: A Pioneer in Molecular Biology
- Research and Discoveries
- Genetics of Bacteria and Viruses
- Molecular Biology and Regulation
André Michel Lwoff: A Pioneer in Molecular Biology
Early Life and EducationAndré Michel Lwoff was born on May 8, 1902, in Ainay-le-Château, a small village in central France. His parents, Salomon and Marie (Siminovitch) Lwoff, were Russian emigrants who had fled to France at the end of the 19th century. Salomon Lwoff was a psychiatrist and chief medical officer of a psychiatric hospital, while Marie pursued a career in sculpture.
When Lwoff was a young child, his father was appointed to a new hospital in Neuilly-sur-Marne, near Paris. Growing up in the countryside, Lwoff enjoyed swimming, playing tennis, and marksmanship. His father often took him on hospital rounds to foster his interest in medicine, and they also visited other medical facilities. During one such visit, Lwoff met his father's friend, the Russian biologist Ilya Ilyich Mechnikov, who showed him typhoid bacteria under a microscope.
Lwoff vividly recalled the outbreak of World War I when he was 12 years old. Fighting came within 20 miles of his home. "The anti-aircraft machine guns were very close, and the shrapnel was whistling and hitting the roof," he recounted. "I listened with curiosity to this strange music, not at all aware of the danger... I was not yet old enough to grasp the folly and tragedy of war."
Although Lwoff yearned to study biology and become a researcher, his father advised him to pursue medicine to ensure a steady income. At the age of 17, Lwoff entered the Faculty of Science of the University of Paris (Sorbonne) to study medicine and biology. He spent the following three summers at the Roscoff Marine Biological Laboratory in Brittany.
In 1921, Lwoff became an assistant at the Pasteur Institute in Paris, where he worked under the guidance of renowned microbiologists Édouard Chatton and Félix Mesnil. That same year, he was awarded a Rockefeller Fellowship, which allowed him to work part-time at the institute while completing his medical studies. His doctoral dissertation, based on research conducted at the Roscoff Marine Laboratory, focused on the eye pigment of copepods, a group of small crustaceans.
Research and Discoveries
Throughout the 1920s, Lwoff's research centered on ciliates, single-celled organisms covered in hair-like structures called cilia. He investigated their nutrition and morphology (the formation of organs and tissues). At the Pasteur Institute, he met microbiologist Marguerite Bourdale, whom he married in 1925 and with whom he would collaborate on many research projects over the years.
In 1927, Lwoff received his medical degree from the University of Paris. Two years later, he was appointed head of a laboratory at the Pasteur Institute, and in 1932, he obtained his Doctor of Science degree from the University of Paris. With the support of another Rockefeller grant, he spent the following year working with Otto Meyerhof at the Kaiser Wilhelm Institute for Medical Research in Heidelberg, Germany.
Around two decades earlier, in 1911, Polish chemist Casimir Funk had coined the term "vitamins" to describe unknown substances essential for human and animal life. However, by the early 1930s, only a few of these substances had been isolated and studied. In Heidelberg, Lwoff investigated heme, a growth factor for flagellates, another type of protozoan. This research led to the first definition of growth factors as "specific substances which the organism cannot synthesize, and which are required for growth and multiplication."
Lwoff's subsequent research focused on the biochemistry of thiamine (vitamin B1) in protozoa and the physiology of nicotinamide (vitamin PP, part of the B-complex). He demonstrated that nicotinamide was present in colostrum, the fluid produced in small quantities by female mammary glands in the last months of pregnancy and the early days after childbirth before breast milk appears.
With another Rockefeller grant in 1936, Lwoff continued his work on growth factors at the Molteno Institute in Cambridge, England. It was known at the time that heme, designated as growth factor X, was essential for the growth of Haemophilus influenzae bacteria. Lwoff isolated the growth factor X and showed that it was the limiting factor for their growth.
Upon his return to Paris in 1938, Lwoff was appointed head of the Division of Microbiology at the Pasteur Institute. He held this position throughout World War II. After the war, in 1946, Lwoff played a significant role in a conference on the nomenclature of microorganisms at Cold Spring Harbor, helping to create a classification system based on energy sources and synthesis processes.
During the 1940s, Lwoff also wrote two books: "Problems of Morphogenesis in Ciliates" and "Biochemistry and Physiology of Protozoa." In his earlier research in the 1930s, Lwoff had elucidated the characteristics of a previously misclassified genus of bacteria and proposed a new name for it: Moraxella. One species of this genus was later named in his honor: Moraxella lwoffi.
Genetics of Bacteria and Viruses
Towards the end of the 1940s, Lwoff shifted his research focus to the genetics of bacteria and viruses. The advent of genetics had begun in 1866 when Gregor Mendel published his work on the laws of heredity, proposing that physical characteristics of an organism are determined by "elements" later called genes. By the early 20th century, genes were found to reside within chromosomes, strands of genetic material located in the nucleus of cells. However, it was not until the 1940s that genes were identified as being composed of deoxyribonucleic acid (DNA).
By this time, the first generation of virologists had characterized the life cycle of bacteriophages. These viral particles could infect bacterial cells and, after a latent phase, begin to replicate within them, causing lysis, or their death. Bacteria that had been infected with phage particles were termed lysogenic, and the process was known as lysogeny.
With the assistance of two Pasteur Institute collaborators, François Jacob and Jacques Monod, Lwoff embarked on the study of lysogenic bacteria and lysogeny. In 1950, he made a groundbreaking discovery. By placing a lysogenic bacterium in a culture medium, he followed its division through 19 generations and showed that the daughter cells also exhibited lysogeny, indicating that this trait was inherited. He also discovered that the phage particles of lysogenic bacteria and noninfectious, or temperate, phages were distinct. He coined the term "prophage" for the noninfectious phage.
Lwoff and his colleagues further showed that through exposure to ultraviolet (UV) radiation, the noninfectious prophage could become activated, leading to the breakdown and disintegration of the cell. Phage particles, like most other viral particles, consist of an inner DNA-containing core and an outer protein coat. In 1952, Alfred Hershey demonstrated that phage reproduction involved replication of their inner DNA.
Molecular Biology and Regulation
In their quest to understand the organization and regulation of phage genes, Lwoff, Monod, and Jacob discovered that, upon infection of a bacterial cell, the prophage particle attached to the cell's chromosome, where genes were typically located, and, in Lwoff's words, "behaves like a bacterial gene." The phage DNA contained two types of genes: structural and regulatory. Structural genes transmitted the genetic code from one generation to the next. In the prophage state, the structural gene activity was repressed by the regulatory gene, preventing the phage particle from reproducing. Lwoff found that UV radiation and other stimuli could counteract the action of the regulatory gene
