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Dogma overthrown

Crodowaldo Pavan, who has died aged 89, overturned the concept that the amount of DNA was constant in all cells

Collection Commission Memory IB/USPPavan, Brito da Cunha (standing), Dobzhansky and his daughter, Sophie in Vila AtlânticaCollection Commission Memory IB/USP

The team of researchers which left São Paulo on excursions to the south coast of the state to collect examples of drosophila, the fruit fly, found something different in that summer of 1952. When Crodowaldo Pavan turned over the trunk of a banana tree, the group leader found a mass of hundreds of larvae of another type of fly and decided to take them to the laboratory for analysis. There he began a study that would overturn a paradigm of biology. Until the middle of the 1950s it was believed that the amount of DNA was constant in all cells. In an article he published with Marta Breuer, in 1955, he showed that there were genes that duplicated themselves constantly. Even before this discovery Pavan was already one of the pioneers in genetic research in Brasil from his studies with drosophilae. He died on April 3 in São Paulo, at 89 years old, as a result of multiple organ failure.

“Pavan showed that at certain moments the cell synthesizes DNA”, explains Professor Luiz Edmundo Magalhães, a biologist who was a student of the geneticist from 1949 and with whom he carried out field research, including research in Vila Atlântica, in Mongaguá, on the São Paulo State coast, where the larvae of the Rhynchosciara angelae (today called Rhynchosciara americana) fly were collected. He also showed that in some tissues of the organism certain genes do not function, something that was unknown. The observations were made about the larvae of Rhynchosciara, a fly that lays its eggs all at one time and then dies. “The larvae evolve together in a synchronized way, which is great because we can monitor their development until they become flies, as if it were a single individual, dissecting one of them a day.”

The larva has a pair of salivary glands with large chromosomes. Pavan observed that some strands of chromosomes of the larva multiply, a phenomenon called puffing, and then condense. At the time he found out that Belgian researcher Jean Brachet was using a method of injecting a radioactive substance, tritiated thymidine, into the larva. He then placed the material on a sheet and covered it with a photographic film for some days in the dark. The radiation made an impression on the film, which allowed a photographic image of the chromosome to be seen and changes in DNA to be monitored. At the request of Pavan, Brachet sent an assistant, Adrianne Ficq, to teach him the method. “It was with the help of, Marta Breuer, his extremely skilled German lab. technician  who was living in Brazil, and Adrianne that Pavan made the discovery that overthrew this dogma of genetics and, right away, began doing molecular biology in the country using Brachet’s method”, says Magalhães. It was proved that the number of chromosomes was constant, but the amount of DNA could vary.

In an interview with journalist, Ricardo Zorzetto, for the book Scientists of Brazil (SBPC, 1998), Pavan recalled that time: “It took eight years for my hypothesis – that the number of genes within the chromosome could change as the animal developed – was accepted. At the time I presented the data and they said, ‘Your data is good, but this is an exception. It’s an insect'”. Later it was proved that the phenomenon was common in man. “His suggestion, that DNA was replicated within the cell, was something completely different from what was thought at the time”, says Professor Hugo Aguirre Armelin, a researcher from the Chemistry Institute of the University of São Paulo (USP).

Archive of Luiz Edmundo MagalhãesThe geneticist in his officeArchive of Luiz Edmundo Magalhães

Although Rhynchosciara was the star of Pavan’s main research, it was drosophila that received most of the attention during his scientific life. He was born in Campinas and entered the then Faculty of Philosophy, Science and Letters of USP in 1938, taking a natural history course. When he graduated he was invited to be an assistant in the Department of General Biology, a post he accepted. His mentor at the time was André Dreyfus, from the group of notable people who created USP and one of those who introduced the study and teaching of genetics and evolution into Brazil. Another enormous influence was Ukrainian, Theodosius Dobzhansky, a geneticist recognized worldwide. Harry Miller Jr., from the Rockefeller Foundation, admired the work of Dreyfus and suggested the scientist should come to Brazil in 1943.

Dobzhansky accepted and in São Paulo taught his research techniques with drosophila, which for a long time was the study model in genetics and evolution and unknown in Brazil “During the Ukrainian’s second visit in 1948 and 1949, Dreyfus and Pavan created study groups with young researchers not only from São Paulo, but from Rio de Janeiro, Rio Grande do Sul and even from Argentina and Switzerland and established systematic programs in this area”, says Magalhães. It was no accident that a brilliant generation of geneticists sprang up, like Antonio Brito da Cunha and Magalhães himself, in São Paulo, Newton Freire-Maia, from Minas Gerais, Antonio Rodrigues Cordeiro, from Rio Grande do Sul, Oswaldo Frota-Pessoa and Chana Malogolowkin, from Rio, and others.

Pavan did post-doctorate studies in Dobzhansky’s laboratory in Columbia University in New York, between 1945 and 1947. In 1952, with the death of Dreyfus, he took over the chair of the Department of Biology. In 1965 he was hired by the Oak Ridge laboratory in the United States where he founded and directed a cytogenetic laboratory. From 1968 to 1975 he was a full professor of the University of Texas, following which he returned to Brazil.

Institutional action
Apart from his intensive scientific work, Pavan was heavily involved in the political and administrative areas of science support institutions. He was a member of the first board of directors of FAPESP, between 1961 and 1963, when he played an important role in consolidating the institution that started functioning in 1962. Between 1981 and 1984 he was back in FAPESP, this time as the executive president of the technical and administrative board. He was President of the National Council of Scientific and Technological Development (CNPq), from 1986 to 1990, when he was responsible for some significant activities, like the creation of the Science Station in São Paulo, and the National Synchrotron Light Laboratory (LNLS), in Campinas.

Archive of Luiz Edmundo MagalhãesPavan (writing), with researchers: experiment in Pirassununga, in 1952Archive of Luiz Edmundo Magalhães

On three occasions between 1981 and 1986 he was the president of the Brazilian Society for the Progress of Science (SBPC). He became an emeritus professor at USP in 1989 and at the State University of Campinas in 1991. When he died he was a voluntary researcher at the Institute of Biomedical Sciences at USP, a coordinator of Scientific Disclosure at the José Reis Nucleus of the School of Communication and Arts of USP and President of the Brazilian Association of Scientific Disclosure.

“FAPESP deeply regrets the death of a great man in Brazilian science and is very grateful for the legacy he has left us”, said Celso Lafer, President of FAPESP. “It’s important to highlight the fundamental work he did in supporting Brazilian research and development, whether at the level of institutions, like at FAPESP and the CNPq, or at the civil society level, for the time he was at the head of the SBPC.” Sergio Rezende, Minister of Science and Technology, also remembered the contribution of he biologist. “Pavan will live on in the history of science in Brazil as one of the pioneers in genetics and a teacher-scientist”, he said. “Few scientists have dedicated themselves with more tenacity to attracting young people to careers in science.”