courtesy of André Luiz Perondini/IB-USP
Article about genetic amplification, from 1955, and notes by Marta Breuer about Rhynchosciara puffscourtesy of André Luiz Perondini/IB-USPOn March 7, 1953, Francis Crick (1916-2004) and James Watson (1928) made scientific history. The result of the research carried out by the pair was that the structure of the DNA molecule is in the form of a double helix. The genetic revolution, which paved the way for unimaginable advances, such as the Human Genome Project in the 1990s, was just in the very early stages. In 1995, a mere two years after the famous article by the pair of scientists, Crodowaldo Pavan published a paper on DNA in-vivo replication, in the German journal Chromosoma.
Today, more than 50 years later, in any minimally equipped genetics laboratory in the world you have what is referred to as PCR (Polymerase Chain Reaction). This technique amplifies the DNA molecule in vitro. Because this is extremely basic, during a degree course a biology student learns to perform this procedure. This method is used, for example, to identify genetically modified organisms and for many other purposes that involve the study of genes.
“Obviously, Pavan’s work on DNA replication is what draws most of the attention”, states Carlos Menck, a researcher from the University of São Paulo (USP) and currently one of the leading figures in Brazil in the area of genetics. In the 1970s, the USP scientist attended Pavan’s classes during his undergraduate studies. “In the 1950s, just two years after Watson and Crick’s paper , Pavan was already engaged in cutting-edge molecular biology with his studies of DNA replication,” says Menck. “This was at a time when we barely understood that DNA was in reality the molecule that stores the genetic information.” In his opinion, a glance at the 1950s given what we know today just reinforces the idea that Pavan was truly a pioneer. “It should be stressed that the work on genetics that he carried out was really very advanced for the period, at least in Brazil.”
The biochemist Hugo Armelin, a professor at USP’s Chemistry Institute, has also conducted an in-depth study of the work that Pavan did during the latter half of the 1950s. He is in full agreement with Menck that this research was extremely important for the history of the molecular biology studies carried out in Brazil. “In my opinion, his most important work was the discovery of the DNA puffs in [giant] polytenic chromosomes.”
Although he has tracked the work of the Pavan the researcher, Armelin stresses that he was not influenced either directly or indirectly by it. The biochemist was a member of the group of another USP professor, Francisco Lara. “The work developed and carried out in the second half of the 1950s was very much the starting point for Professor Lara’s laboratory projects. However the scientific approach of the two groups from that point onwards was different, and the work in the 1960s was developed in a totally independent way between the two laboratories,” emphasizes Armelin.
The research into gene amplification, in particular, and into molecular genetics, in a more general sense, did not just help to train people. These paths ended up influencing other laboratories’ research projects. A process that, from the standpoint of an overview, culminated in new approaches and lines of research that were also innovative. Without being aware of it, with his research Pavan was consolidating the pillars of Brazilian genetics.
At the cutting edge
Nowadays Brazil has various research groups that are working at the forefront of genetics knowledge. Part of this is due to the seeds sown by Pavan and a number of his contemporaries and students, such as Francisco Salzano and Ernesto Paterniani, in the 1950s and 1960s. As explained by the USP geneticist Lygia da Veiga Pereira, one of the key figures in the first wave of Brazilian research into embryonic stem-cells, if Gregor Mendel virtually inaugurated what we know today as classic genetics, Watson and Crick, with the revolution they started, laid the foundations for modern molecular genetics. “Instead of links between the descendants based merely on the observation of the phenotypes [the individual’s gene-based characteristics], scientists began to study the gene itself”, explains Lygia.
Although classical genetics, based almost entirely on the method of trial and error, still exists today, it left some room on the battlefield for the entry of molecular genetics. According to Lygia, there are currently at least two very clearly defined scientific developments that result from this. “It has become possible to study the genes that are producing a particular phenotype, and not just the contrary. Additionally, transgenic elements also appeared, which are organisms that have received at least one gene from another species in order to arrive at a pre-programmed specific response,” compares Lygia, who is also an admirer of Pavan.
These are two of the scientific pillars that allow the world to now discuss, for example, synthetic biology – which is nothing more than the construction of a totally new organism, based on duly studied and identified genes. For instance, at least in the case of genetically modified organisms, all one needs to do is to consult the archives from the last annual meetings of the Brazilian Society for the Advance of Science (SBPC), from 2008 and earlier, in order to learn Pavan’s invariably vehement position on this theme. Provided that the security aspects were considered, he was in favor of experiments with genetically modified organisms. After all, back in the 1950s, the pioneering studies about genetic amplification somehow contributed to what is now being sought in Brazil’s genetics laboratories.
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