Alexander Varshavsky (Moscow, Russia; 1946) completed a PhD in Biochemistry in 1973 at the Institute of Molecular Biology in Moscow, staying on there as a research fellow until 1976. In 1977, he was issued with a visa to travel to the United States and secured the post of assistant professor at the Massachusetts Institute of Technology (MIT). From there he progressed to associate professor (1980-1986) and finally Professor of Biology. In 1992 he moved to the California Institute of Technology (Caltech) to take up the post of Howard and Gwen Laurie Smits Professor of Cell Biology.
He is a member of the American Academy of Arts and Sciences, the U.S. National Academy of Sciences, the European Molecular Biology Organization, the American Association for the Advancement of Science and Academia Europaea. Among the distinctions earned in the course of his career, he holds the Max Planck Award of the Max Planck Society and the Alexander von Humboldt Foundation (2001), the Wilson Medal of the American Society for Cell Biology (2002) and the Breakthrough Prize in Life Sciences (2014).
Speech
Biomedicine, 4th edition
One August evening in 1977, an American and a Russian met in Helsinki’s railway station. They embraced. The American wore an overcoat with the collar up, like in a spy film, his friend would later relate. The Russian had just been conversing with Francis Crick, co-discoverer of the double helix structure of the DNA molecule. The two men made their way to the port and from there caught a ferry to Stockholm, despite the Russian not having a visa. On arriving in Sweden, they took a taxi straight to the United States embassy.
And so, at the age of thirty, Alexander Varshavsky began his life on the other side of the Iron Curtain, dreading the reprisals that his defection might mean for family members, but driven by the desire to continue his research free of the constraints of a political regime that cut him off from the rest of the scientific community. “My mother a physician and my father a scientist, I was insulated from physical privation. But living in a Communist country was psychologically difficult for trouble-prone characters like mine, with hopes and reality on different planets. Such people trap themselves by their dreams.”
Varshavsky, we can safely say, has realized his own dreams. The winner of the BBVA Foundation Frontiers of Knowledge Award in the Biomedicine category, currently a U.S. national and professor at the California Institute of Technology (Pasadena, United States), has made a vital contribution to the biological advances of the last few decades. More specifically, he is author of a discovery with fundamental implications for the understanding of basic cell function and indeed all of medicine: the mechanism of protein degradation and its role in regulating the cell cycle.
In the 1980s, protein degradation in the cell was believed to be “a simple process, serving largely to clear the cell of ‘aged’ or damaged proteins.” But his work showed that it is in fact a complex mechanism that goes far beyond mere cellular cleaning. The controlled destruction of proteins ensures that each one is present at the right time in the right quantity; an essential process in normal cell functions ranging from the control of gene transcription, protein synthesis and DNA repair to cell division and the response to stress.
So important is this mechanism that its malfunction underlies a large number of conditions, from cancer to immune system and neurodegenerative diseases. Indeed the search for therapies and drugs based on the mechanism described by Varshavsky is today a particularly thriving area.
Varshavsky’s scientific life dates to his adolescence when he first felt intensely drawn to the world of science. His father, a physicist and chemist, was doing work related to Russia’s atomic bomb program, which entitled him to an extra bottle of milk daily. The talk of the scientists who gathered at the Varshavsky home sparked a lifelong fascination in the young Alik. “By 16, I wanted to do all of science and also dreamt of being a writer; I felt that all of it was possible.”
In 1964, after gaining straight As in the entrance exam, he became a chemistry student at Moscow State University. He wanted to be a biologist, but to learn physics, mathematics and chemistry as well. His first “scientific idea” came to him in 1967, and with it the conviction that his future must lie in research – the same determination that would later lead him to spend night after night in the laboratory. It had recently been discovered that certain genes repressed the activity of others. And this, for Varshavsky, begged the question of what regulated the repressors, and whether they themselves might inhibit their own synthesis. “I skipped all my classes and buried myself in the library,” he relates. That particular adventure ended with the publication of his first scientific paper, but a string of fails in his remaining subjects came close to earning him expulsion and immediate drafting into the Soviet army.
In 1970, he joined the Institute of Molecular Biology in Moscow. As a result of his publications in international journals, he began to receive invitations to congresses. But he could only accept those from Communist-bloc countries. Then in 1977 he was finally allowed to attend a congress in London. Despite his eagerness to do so, the young Varshavsky did not defect; a decision which earned him the trust of the Soviet intelligence agency, the KGB. So when the agency needed a scientist to report back on the development of a possible new weapon, genetic engineering, they called in an astonished Varshavsky. In August 1977, in his new espionage role, he left for a congress in Helsinki. This time never to return.
A few months later, with the help of Francis Crick, among others, Varshavsky had a laboratory at the prestigious Massachusetts Institute of Technology (MIT), where he would remain for seventeen years. “My first year at MIT was happiness itself.” His devotion to science was absolute: “I didn’t perceive it as a profession at all, but as the only thing I would ever wish to do.”
His interest in protein degradation mechanisms dates back to 1980, and one of those light bulb moments. That year some groups had discovered that ubiquitin, a small protein, attached itself to others targeted for destruction. He was quick to intuit the importance of this process as a cell cycle regulator, and spent the next four years investi-gating his hypothesis. Finally, he was able to demonstrate it in two papers published to widespread acclaim in the journal ‘Cell’.
The next step was to explain how the protein knows who to label for destruction. Varshavsky found that ubiquitins attach themselves to proteins that are due to be destroyed through ubiquitin-ligases, one of a large and varied family of enzymes, which give this mechanism its selectivity. There is still considerable excitement around the area. “One amazing thing about the ubiquitin field is that it refuses to age,” as Varshavsky puts it. He personally has just uncovered an entirely new pathway of protein degradation, potentially as important as that mediated by ubiquitin. The scientist who came in from the cold still has many challenges before him.
