Certainly, nowadays, hunting for viruses may not seem like the best of ideas but, for Renato Dulbecco, following step by step the Polyomavirus was the solution to understand how some of these pathogens are capable of inducing the formation of tumors. We are talking about the category of oncoviruses, today responsible for about 1 tumor on 6 in the world, and that among its ranks includes the Papillomavirus (cause of cervical cancer), Hepatitis B and C (which instead attack the liver). Dulbecco discovered that the integration of the viral genome with that of the host is responsible for the generation of tumors, earning a place among the Nobel Prizes for Medicine in 1975.

Let's rewind the tape of time: Dulbecco was born in 1914 in Catanzaro, he spends his childhood summers playing meteorologist but, as a young adult, decides to study medicine. Among his closest acquaintances stand out the names of Rita Levi-Montalcini and Salvatore Luria, two other illustrious Italian Nobel laureates. They will be the ones to stir his ambitions and spur him to embark for the United States in 1947, to pursue the vanguards of modern biology.

In his early years in the New World, he studied bacteriophages (or just phages), viruses that attack bacteria and exploit them to reproduce until they explode. Dulbecco discovers "photoreactivation": a phenomenon of phage DNA repair carried out by ultraviolet light, which had led him to repeatedly observe more "plaques" of dead bacteria (indicative of increased virus activity) in plates left under the direct light of the lamp in his laboratory compared to others placed in the shade.

Then hired at CalTech (California Institute of Technology), Dulbecco shifts his interest towards animal and human viruses. In that period Poliomyelitis was a serious social problem affecting many children, causing nervous system damage and paralysis of the limbs. Dulbecco develops a technique for culture and accurate measurement of the virus, providing the basis for the development of the polio vaccine that later occurred thanks to Albert B. Sabin.

It was the 1950s when Dulbecco became interested in oncoviruses and elected Polyomaviruses as an exemplary study model for this category. The mechanism of initiation of tumors eluded scientists: once entered the cells, the virus "disappeared" leaving its hosts apparently healthy, only after a short period these changed becoming cancer cells.

"The idea was that this virus would introduce some thing that would persist, in order to give changed but constant characteristics to the cells "

To put him on the right track is the discovery, made by him and his colleague Marguerite Vogt, that the genetic information of this virus was written in DNA, as for us, and possessed a circular structure. By following its tracks, they discover that the virus releases this circular DNA inside the infected cell, and not only: the ring opens, becoming a linear string that is inserted into the host's genome. This is therefore the key step that alters the normal expression of the cell's genes, to which are added those of the virus causing their malignant transformation and abnormal proliferation. The mechanism ofintegration of the viral genome turned out to be true for all oncoviruses, even those with an RNA genome (which, however, have an additional conversion step from RNA to DNA) as discovered by the studies of Howard M. Temin and David Baltimore who also won the Nobel Prize with Dulbecco in 1975.

In the 80s and 90s, Dulbecco becomes one of the first promoters of the Human Genome project (aimed at mapping all our genes), and returns home to coordinate the Italian participation in the project, then canceled due to lack of funds. Anyhow, satisfied to have largely contributed to the scientific Renaissance of the twentieth century by revolutionizing key concepts of virology, oncology and genetics, he retires to San Diego to devote himself to writing and the playing piano. Dulbecco leaves us in 2012 at the age of 98 years.

Image: created by kjpargeter @Freepik.com

Sources:

https://www.nobelprize.org/prizes/medicine/1975/dulbecco/biographical/

https://www.webofstories.com/play/renato.dulbecco/1

Italian Encyclopedia Treccani: Fabio De Sio – The Italian Contribution to the History of Thought - Sciences (2013)

Renato Dulbecco: a Renaissance scientist. DOI: 10.1016/j.cell.2012.03.013.

Statistics on tumors caused by oncoviruses: DOI: 10.1089/vim.2016.0109; DOI: 10.1016/j.chom.2014.02.011