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Hambardzumyan was born into an Armenian family in Tiflis on 5 September 1908. His father, Amazasp Asaturovich Hambardzumyan, was a philologist and writer, translator of Homer's Iliad from Ancient Greek into Armenian.
In 1924 he entered the Physics and Mathematics Department of the Leningrad Pedagogical Institute and a year later transferred to Leningrad University. As a student, in 1926, he published his first scientific paper on solar flares. After graduating from the University at the age of 20, Hambardzumyan studied at the postgraduate course of Pulkovo Observatory under the supervision of A.A. Belopolsky from 1928 to 1931.
In 1930 he married Vera Fyodorovna Ambartsumyan (née Klochikhina, from the village of Lysva, Solikamsk District, Perm Province).
In 1934, after four years at Leningrad University, Hambardzumyan founded and headed the first Astrophysics Department in the USSR. In 1939-1941. Hambartsumyan was director of the Astronomical Observatory of Leningrad University.
In 1939 Hambardzumyan was elected a corresponding member and in 1953 a full member of the Academy of Sciences of the USSR.
The Great Patriotic War found him as pro-rector of the Leningrad University. At the very beginning of the war, in 1941, the scientific laboratories of the University were evacuated to the city of Elabuga, far from the front, in Tatarstan, where Hambardzumyan spent four years heading the evacuated laboratories.
During the most difficult period of the war, in 1943, the Academy of Sciences of the Armenian SSR was founded. This was probably done as a thank-you to Armenia for its devotion during the years of war hardship. I.A. Orbeli was appointed President and Hambardzumyan was appointed Vice-President of the Academy. In 1947 Hambardzumyan was elected president of the Armenian Academy of Sciences and was re-elected to the post till 1993, when he became honorary president.
In 1946 Hambardzumyan founded the Byurakan Observatory, of which he was the permanent director until 1988.
From 1961 to 1964 Hambardzumyan was the president of the International Astronomical Union. He was twice elected the President of the International Council of Scientific Unions (1966-1972).
V.A. Ambartsumyan passed away on August 12, 1996 and is buried in Byurakan, near the Big Telescope Tower.