David Baltimore, who shared the Nobel Prize with Renato Dulbecco and Howard Temin in 1975, said it best in his memorial tribute at the time of Dulbecco's death: "A gentle superman," Baltimore wrote. Renato was truly a superman, although when I first met him, in his late seventies, stylish, sharp-as-a-razor scientist, he reminded me more of James Bond than of a comic book character. But indeed, superhero he was.
Back in my own postdoc times at the Salk Institute, when Dulbecco was also there, I was too poor to own a car, plus it never rained in San Diego. I used to park my motorcycle in the Institute's incomparable parking lot on the bluffs above the Pacific Ocean. After a glimpse at the breathtaking view, I would note, parked in the first row, a cool convertible late '70s Mercedes, pea-green in color. "Ah, Renato is in," I used to tell myself. If I had some cool results to show or needed advice on what to do next, I headed straight for his office in my semi-official San Diego attire—t-shirt, shorts, and flip flops. Despite Renato's sartorial style, matched only by his intellect, and my gone-native outfit, I never felt he was condescending or paternalistic. He always listened carefully before speaking. If there was something he was not sure about, he wouldn't guess or bluff. Go ask so and so, he would tell me. He was a Great Man of Science, even then, but one possessed of an even greater intellectual honesty.
I miss those Salk days, but those times came back to me last week when I was asked to speak at an event in Washington, DC, organized by the Italian Ambassador to the United States, His Excellency Claudio Bisogniero, to commemorate the one-year anniversary of Renato's death and to speak about the American and the Italian legacies of his remarkable career. The speakers came from all over—some by videoconference from Italy and the Salk, some present in person at the embassy—to examine Renato's great contributions to science during the 20th century.
Renato is a common name in Italy; its literal meaning is born-again. It was given to him after his mom had lost a child at a very early age. Taking his name almost faithfully, Renato brought modern microbiology to a new birth. Salk Institute scientist Inder Verma, a colleague and close friend of Renato, reminded the audience of young graduate students and postdocs how Dulbecco discovered the lysis plaque method to count and titer bacteriophages, which are viruses that attack bacteria. Today this is something graduate students do routinely in any lab around the world but before Renato, not being able to titer a virus was a constant obstacle in biology. He then moved on to study cell transformation in order to understand how certain viruses, like polioma virus, stimulate cellular DNA. He was the first to propose that the viral DNA could integrate into the cellular DNA.
This important discovery paved the way for Harold Varmus and Michael Bishop (who were also awarded the Nobel Prize) to define cancer as a genetic disease, opening the door to so many of the current treatments available in oncology. Finally, Renato was among the first, if not the very first one, to propose the idea of sequencing the human genome, a proposal initially met with a great deal of pushback. I think many of those who pushed back at the time are now pushing their own research programs forward, thanks to the sequencing of the human genome, which has fundamentally changed the way molecular biology is done in the lab, and opened the doors to the future of personalized medicine.
Last week at the Italian Embassy, it was a Renato Dulbecco love fest! Speakers remembered Renato's towering contributions to science but also talked about their own new projects and approaches, which would certainly have grabbed Renato's attention. Alberto Bardelli, a researcher at the University of Turin, where Dulbecco received his MD in the 1930s, is developing a system for detecting cancer mutations at very early stages, without the need for biopsying the tumor itself, through a blood test. Interestingly, this system can also detect somatic mutations, which are present in the tumor, but not necessarily in other cells of the body. Given the importance that somatic mutations have, not only for cancer, but for many other diseases as well, I think this technique could soon prove a major breakthrough in diagnosing cancer.
We also heard of a "mouse hospital" at Harvard Medical School, where Pier Paolo Pandolfi conducts cancer co-clinical trials. The idea of co-clinical trials is to replicate in mice the exact same conditions of how a given experimental drug is tested in human clinical trials—same active principle, same dosage, and same administration method. Often only a subset of patients respond to a drug and once data are averaged, the size of the effect tends to be small. We are being fooled by the statistical average, so that if one person eats two chickens and one none, both appear to have had dinner. Because of this, larger and larger trials are needed to detect smaller and smaller effects, greatly slowing the regulatory process of drug approval by the Food and Drug Administration. Modeling the problem in animals (note: I am not saying mouse model) by replicating the trial conditions, makes the analysis of large numbers easier. Equally important, it makes possible the rapid identification of subpopulations of "mouse patients" who respond to the drug versus those who do not. This approach reveals the genetic and mechanistic reasons at the basis of heterogeneity, which then inform the human trial.
We also discussed workforce issues and how different the situation is today from when Renato was a student. Today, only 26% of biomedical PhDs obtain tenure-track positions. What was proposed? Well, since that was my talk, stay tuned, I will discuss it in a future blog. For now suffice it to say that training the next generation of scientists was something Renato was passionate about. In 1999, Renato agreed to serve as the co-host of the Sanremo Festival, a musical competition in Italy that draws as much attention and glamour as the Academy Awards in the United States. Renato was criticized for sacrificing the dignity of science by lending his presence to such a frivolous event. The contest lasted four nights, and on the fourth night, he announced that he was donating his engagement fees to the Fondazione Telethon specifically to fund research projects of young scientists. And then on TV, Renato explained the importance of this basic research. Never had such a wide audience in Italy (we are talking about 50% TV audience share) heard about genetic research or why the general public needs to support it. So, Renato also became the face of science advocacy in Italy, and a role model for us, science advocates at ASCB. Bravo!
Renato, we miss you, but your legacy lives on, and motivates us to promote basic science even in these difficult times. In the face of threats of unprecedented cuts in U.S. research funding, we also see unprecedented opportunities to cure devastating diseases. That was also part of the Dulbecco superman approach, to see beyond the immediate difficulty to the promise of taking the next step.
- Baltimore D (2012). Retrospective. Renato Dulbecco (1914-2012). Science 335(6076), 1587.
- Dulbecco R (1986). A turning point in cancer research: sequencing the human genome. Science 231(4742), 1055-1056.
- Insel TR (2007). From animal models to model animals.Biol Psychiatry 62(12), 1337-1339.
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