LINDAU, Germany—Drab details dominate most academic conferences, but here at the 61st Meeting of Nobel Laureates, the hundreds of young scientists in attendance want and get a lot more—including career tips and snappy anecdotes about the twists and turns of how science actually happens.
Elizabeth Blackburn, who shared the Nobel Prize in physiology or medicine in 2009 with Carol W. Greider and Jack W. Szostak, kicked off the laureate presentations—the hallmark of this event—on June 27 with a deceptively breezy tour-de-force overview of her decades-long effort to understand the biology of chromosome endings, or telomeric DNA. Like many of the eminent speakers here, she urged students to pursue research questions even when no one else thinks the answers are attainable or important, and to seek out passionate colleagues throughout one's career.
"Find PhD students who want to go for what they think is the most interesting project in the lab even though it might not be one that generates results," she advised the audience as she showed a slide of Greider working as a graduate student in Blackburn's lab—and wearing a Mickey Mouse Club hat.
Blackburn and Greider's work has involved discovering the biochemistry of how chromosomes are protected by end caps called telomeres, as well as discovering the enzyme telomerase and its role in maintaining telomeres. Over the years, the senior researcher has had to learn the hard way about how to talk to potential funders of her research.
"You can't tell them, 'I think I'm going to study a new enzyme.' It doesn't really work well that way," Blackburn said, drawing laughter from the audience.
And Blackburn blew up the myth that tenure provides total freedom, valuable information for a room full of undergraduates, graduate students and post-doctoral researchers, who straddle the worlds of students and scientists. "I'm studying protein-dissociated telomeric DNA. Then I got tenure and had my grant," she explained. "I felt really brave. 'I can do anything I like. I've got tenure I've got a grant.' I realized later that's not really true. You can't do everything you'd like."
The biologist also referred to the painstaking efforts required to piece together extremely short sequences of DNA from her research organism, a humble pond protozoan called Tetrahymena thermophila, when she worked in the 1970s lab of laureate Fred Sanger. "You couldn't believe how impossible it was to sequence DNA in those days," she said.
She studied the short repeated sequences found at the organisms' chromosome endings and tried to figure out why DNA replication worked so poorly at these sites. The answer was found in when she and her colleagues started to understand the workings of the enzyme telomerase.
"It sounds as if it fell out of the sky or we stumbled on it. It didn't really work that way," she said. Instead she ended up accidentally disabling telomerase in an experiment and noticed an unexpected outcome: the absence of the enzyme meant a progressive shortening of the chromosomes and the eventual death of cells.
"Always look at what the organism is telling you," she advised. "I hadn't designed that experiment with that in mind but it turned out to answer the question of whether you need telomerase. I inadvertently made an experiment that killed the activity of the enzyme in cells. That enabled me to ask questions, and it looks as if I planned to do this experiment but I actually lucked into it."
Her subsequent work continues to elucidate exactly how that the cellular phenomenon of shortening telomeres plays out in our lifetimes. Cancer, pulmonary fibrosis, cardiovascular disease, vascular dementia, osteoarthritis, osteoporosis, diabetes, obesity and insulin resistance are all characterized by shortened telomeres. And researchers now know that telomerase is highly activated in cancer cells. Genetic mutations cause an excess proliferation of these cells, such that they ignore signals to cease multiplying and to go to the "wrong places" in the body.
More recent advances have also shown that adverse childhood events and chronic psychological stress, such as pessimism or hostility, result in shorter telomeres, whereas education and exercise are associated with longer telomeres.
Blackburn concluded with a strong position regarding the 61st meeting's focus on biomedicine as a solution for diseases such as malaria, AIDS and tuberculosis. "Once we have solved these acute problems and major infectious disease problems, why not look ahead for next decade?" she said. "We are left with these other chronic diseases. We should think about how we look at the very complicated problem of preventing them. These are the diseases that we will be left with after we survive the acute and chronic infectious diseases."
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