A Russian Jewish family in rural France
André Michel Lwoff was born on May 8, 1902, in Ainay-le-Château, a small town in the Allier department of central France, into a Jewish family of Russian-Polish origin. His father, Solomon Lwoff, was a psychiatrist who had come to France from the Russian Empire and directed the psychiatric hospital at Ainay-le-Château. His mother, Marie Siminovitch, was an artist and sculptor.
Growing up among the patients and staff of a psychiatric hospital and in a home full of art, Lwoff developed two lifelong passions: science and the visual arts. Colleagues remembered his love of painting, sculpture and music, which he called the things that awaken the spirit.
A student of single-celled life
Lwoff studied science and medicine in Paris. In 1921, at nineteen, he began working with the great protozoologist Édouard Chatton, who introduced him to the Institut Pasteur in the laboratory of Félix Mesnil, where parasites of tropical diseases were studied. He remained Chatton’s colleague for seventeen years, studying the life cycles and development of ciliates, tiny single-celled organisms covered in hair-like cilia. He earned his medical degree in 1927 and his doctorate in science in 1932.
In 1925 he married Marguerite Bourdaleix, a microbiologist who became his closest research partner for decades. Marguerite Lwoff co-authored much of his work, although, as Wikipedia notes, he received considerably more recognition than she did.
Marguerite made important discoveries of her own. She showed that haematin could replace blood in the diet of the flagellate Crithidia, an observation that launched the couple’s research on growth factors, and in 1944 she was appointed head of a laboratory at the Institut Pasteur. Together the Lwoffs established how much of a growth factor a microbe needs and how precisely its chemical structure must match.
Vitamins as the tools of cells
Lwoff’s first major research programme asked what nutrients microbes need to grow. With Rockefeller Foundation grants he worked in 1932 and 1933 in Heidelberg in the laboratory of Otto Meyerhof, studying haematin, a growth factor needed by certain flagellates, and in 1936 at Cambridge with David Keilin, where he and Marguerite identified “factor V,” a growth requirement of the bacterium Haemophilus influenzae, as the coenzyme cozymase, now called NAD.
This work helped establish a general principle: that vitamins and other growth factors needed in tiny amounts act as parts of coenzymes, the small helper molecules that enzymes require. It also showed how microbes that lose the ability to make such molecules must take them from their surroundings, which Lwoff saw as a form of evolution by loss of function. In 1938 he was appointed head of a department of microbial physiology at the Institut Pasteur.
Science and the Resistance
When Germany occupied France in 1940, Lwoff, a Jew by origin, was in danger, yet he stayed in Paris and kept working at the Institut Pasteur. He joined the Cohors-Asturies Resistance network led by the philosopher Jean Cavaillès and collaborated with British intelligence. Cavaillès was later captured and shot by the Germans. After the war Lwoff was awarded the Medal of the Resistance for his work in the French underground.
His department, in the attic of the Pasteur Institute, also became a refuge for young scientists who would change biology. Jacques Monod joined him as early as 1938, and in 1950 a young former Free French medical officer, François Jacob, talked his way into the laboratory. With Élie Wollman and others, they formed the extraordinary group from which French molecular biology was born.
The virus that hides
Since the 1920s researchers had known that some strains of bacteria carry bacteriophages, viruses that infect bacteria, without seeming to be infected. Every so often a few cells in a culture would burst and release viruses, while the rest grew normally. This phenomenon, called lysogeny, was so puzzling that many scientists doubted it was real.
From 1949 Lwoff attacked the problem by watching single bacteria under the microscope, one at a time, through many generations. He showed that lysogenic bacteria do not continuously release viruses; instead, they carry the virus in a hidden, non-infectious form that is copied along with the bacterium’s own genes each time it divides. Only occasionally is the hidden virus switched on, and then it multiplies and kills its host. He called the dormant form the prophage. In 1950, with Louis Siminovitch and Niels Kjeldgaard, he discovered that ultraviolet light could switch on the prophage in almost all the bacteria in a culture at once, proving that its activation is triggered by outside factors.
From prophage to gene control
Lwoff’s explanation raised a new question: what keeps the hidden virus silent? Jacob and Wollman, working in his department, traced the prophage to a specific place on the bacterial chromosome, and Jacob and Monod went on to show that genes are controlled by repressor molecules that switch them off until a signal releases them. The same logic explained both how bacteria turn on the enzymes to digest a sugar and how a prophage stays dormant until disturbed.
In 1965 Lwoff, Jacob and Monod shared the Nobel Prize in Physiology or Medicine “for their discoveries concerning genetic control of enzyme and virus synthesis.” The Nobel presentation said their work had laid the foundations of molecular biology in the true sense of the term, and noted that some tumour viruses appeared to enter normal cells in the same way, turning them into tumour cells.
The Nobel presenter, Sven Gard, compared the systems they had found to the control circuits of a television set: chemical switches, linked together, that let a single cell produce an enzyme when it is needed and stop when it is not. A bacteriophage, he explained, carries its own complete control circuit, and as long as its repressor signal is being sent, it behaves like a harmless part of the cell; when the signal is interrupted, the virus awakens and kills its host. Lwoff’s patient observations of single cells had revealed the first example of this logic.
Why it matters
Lwoff’s discovery that a virus can insert its genes into a host and lie dormant is one of the keys to modern virology and medicine. Many human viruses persist in similar ways. HIV inserts a DNA copy of its genome into the chromosomes of immune cells as a provirus, which is why it cannot yet be cured; herpes viruses, including those causing cold sores and shingles, lie latent in nerve cells and reactivate years later; and the integration of certain human papillomavirus genes into cells is a step toward cervical cancer. Understanding latency is the starting point for vaccines, antiviral drugs and the search for cures for these infections.
The gene-control systems revealed by the prophage also became basic tools of biotechnology. The bacteriophage lambda, the classic lysogenic virus, was used to build early cloning vectors, and the switches that control it became textbook models of how genes are turned on and off, knowledge used throughout genetic engineering. In 1954 Lwoff turned to poliovirus and showed that the virus’s ability to multiply depends strongly on temperature, suggesting that fever can be part of the body’s defence. In 1957 he wrote an influential essay, The Concept of Virus, distinguishing viruses from living cells, and he helped devise one of the first systematic classifications of viruses in 1962.
Teacher, director and humanist
His honours included honorary degrees from Chicago and Oxford in 1959, Glasgow in 1963 and Louvain in 1966, the Leeuwenhoek Medal of the Royal Netherlands Academy in 1960 and the Keilin Medal of the British Biochemical Society in 1964, and election as a foreign member of the Royal Society and an associate of the US National Academy of Sciences. France made him a commander of the Legion of Honour in 1966, and he was later raised to its highest rank.
In 1959 Lwoff became professor of microbiology at the Faculty of Sciences in Paris, the Sorbonne. In 1968 he left the Institut Pasteur to direct the cancer research institute of the CNRS at Villejuif, which he led until 1972 and helped to modernise. He served as president of the International Association of Microbiological Societies and of the Federation of European Microbiological Societies, which now awards the FEMS-Lwoff Award in his honour.
He was known as an independent spirit; one colleague wrote that his total lack of conformity and diplomacy often made him enemies. He campaigned against capital punishment, which France abolished in 1981, and in May 1980 he sat on the jury of an international tribunal in Amsterdam held on behalf of the imprisoned Soviet Jewish dissident Anatoly (Natan) Sharansky, alongside figures such as the former US ambassador to the United Nations Andrew Young. He was made a Grand Cross of the Legion of Honour.
Death and legacy
André Lwoff died in Paris on September 30, 1994, at the age of 92, the last survivor of the three 1965 laureates. Marguerite Lwoff had died in 1979.
His legacy is the idea that a virus can become part of its host. By patiently watching single bacteria divide, he showed that viral genes can hide in a cell, be inherited silently, and later awaken. That insight runs through modern medicine, from the treatment of HIV and herpes to the study of virus-driven cancers, and through the science of gene regulation that he helped to found.
Sources & further reading
André Lwoff, Biographical, NobelPrize.org · Award ceremony speech, Nobel Prize in Physiology or Medicine 1965, NobelPrize.org · André Lwoff, Encyclopedia.com · LWOFF André (1902-1994), Encyclopædia Universalis · André Michel Lwoff, Wikipedia · Researched from the sources above and checked against them. Spotted an error? Tell us.
A life of tikkun olam. This is part of tikkun olam, the Jewish idea of repairing the world, and every one of us can add to it.