Shared the 2009 Nobel Prize in medicine for the discovery of telomeres.
"There was something completely different about the DNA ends."
Although he gave up his Canadian citizenship to become an American in the mid-1990s, biochemist and geneticist Jack Szostak was still a Canadian when he performed the seminal experiments that led to him winning the Nobel Prize in Physiology and Medicine in 2009.
It was the summer of 1980, and Szostak — who grew up between Ottawa and Montreal, and attended McGill University for his undergraduate studies — saw a presentation that would change his career. At the Gordon Research Conference on nucleic acids that year, Elizabeth Blackburn, of the University of California, Berkeley, presented some intriguing data on the bizarre DNA of a single-celled pond creature called Tetrahymena. The freshwater organism, Blackburn told attendees of the meeting, contained thousands of very short chromosomes with unusual, repetitive DNA sequences at the ends called telomeres that acted like the tips of shoelaces, protecting the DNA from any damage.
Szostak, then a 27-year-old new faculty member at Harvard Medical School in Boston, was studying DNA repair in baker’s yeast, and had never seen anything like Blackburn’s findings in the broken DNA molecules he was looking at. “It was amazing to me because here were DNA ends that just didn’t do any of the things that we were studying,” he recalls. “There was something completely different about them.” So, he cornered Blackburn at the meeting, and the two agreed to team up for an unusual project. Their idea: to take the chromosome tips from Tetrahymena and transplant them into yeast to see if they remained stable in another organism.
“We didn’t think really it was likely to work because Tetrahymena and yeast are pretty far apart in an evolutionary sense,” says Szostak. “But we thought it was worth a try because if it did work it would say that that biochemical machinery must be very highly conserved.”
Blackburn sent Szostak an envelope in the mail containing some DNA from Tetrahymena’s chromosome tips. Szostak attached the telomeres to a piece of yeast DNA that he had converted into a linear stretch. He inserted the hybrid DNA molecule into living yeast cells, and, to his surprise, the experiment worked. The Tetrahymena ends indeed kept the yeast DNA intact. “It was a pretty dramatic experiment,” says Szostak.
That discovery, published in 1982 in the journal Cell, led to a number of follow-up experiments. In 1984, Szostak and Blackburn showed that yeast has its own distinct telomeres, and that the yeast cells were adding a unique DNA sequence onto the transplanted Tetrahymena tips. This finding suggested that an enzyme was building up the telomeres — and, indeed, a year later Carol Greider, then a graduate student in Blackburn's laboratory, isolated the enzyme and named it telomerase. Szostak, Blackburn and Greider won the Nobel Prize in 2009 for this work.
Szostak worked on telomeres for a couple more years, but eventually moved on to other things. Nowadays, he studies the origin of life on Earth by trying to construct artificial cells using chemicals in the lab.
Szostak was born in London, England, during the great fog of 1952, but sailed to Canada with his parents when he was less than a year-old. He grew up between Ottawa and Montreal, and attended high school in Pierrefonds, Quebec, where he developed an early interest in science. His first experiments took place in his basement where he grew a hydroponics garden and tinkered with a small chemistry set. “I blew things up periodically,” he recalls.
In 1968, Szostak began undergraduate studies at McGill University with the intention of becoming a chemist. His first laboratory work involved helping a graduate student purify cholesterol from large sacks of gallstones for synthesizing more complex organic compounds called sterols. But “it didn’t inspire to go into chemistry at that time,” he says, “so I ended up doing things that were more biological.” He spent a summer at the Jackson Laboratory in Bar Harbor, Maine, analyzing thyroid hormones in various strains of mutant mice. However, after a large number of mouse dissections, Szostak soon realized that he didn’t like working with animal models.
Back at McGill, Szostak spent the next summer testing out new lab experiments for a plant physiology course, and, for his senior thesis, he studied the environmental conditions that trigger a particular species of green alga to initiate sexual reproduction. That work landed him his first scientific publication in the Journal of Phycology, in 1973.
Story by Elie Dolgin.
In the 1930s, the American geneticist Hermann Muller first noticed that the ends of chromosomes had some sort of unique property that helped them maintain their genetic integrity. In experiments with fruit flies irradiated with X-rays, he observed many animals with genetic abnormalities, but he never found flies with mutations in the chromosome tips. “The terminal gene must have a special function, that of sealing the end of the chromosome, so to speak,” Muller told attendees of a 1938 lecture at the Woods Hole Marine Biological Laboratory in Massachusetts. “And that for some reason, a chromosome cannot persist indefinitely without having its ends thus sealed.” He thus named these ends telomeres, from the Greek words telo, meaning “end,” and mere, meaning “part”.
Thanks to the work of Jack Szostak and his colleagues, scientists now know that Muller was only partially correct. (Still, not a bad hypothesis given that Muller’s lecture came 15 years before the discovery of DNA.) Telomeres do stabilize the ends of chromosomes, but, instead of active genes, telomeres contain a string of highly repeated DNA sequences that act as disposable buffers to prevent vulnerable chromosomes from deterioration.
During cell division, enzymes that duplicate DNA cannot reach all the way to the ends of chromosomes. If cells divided without telomeres, necessary genetic information would get lopped off with each round of division. Fortunately, telomeres are nonsense DNA that do not encode essential proteins, so there are no immediate consequences when telomeric sequences are lost. Yet this telomere shortening can eventually lead to cancer or even cell death — which explains why telomeres have been linked to the ageing process.
To maintain telomeres in rapidly growing cells, however, cells contain an enzyme called telomerase that can synthesize telomeric DNA directly onto chromosome ends. In this way, the original length of the telomere sequence is restored, which in turn helps keep chromosomes intact longer. This function has also earned telomerase the nickname ‘the immortalizing enzyme’.
Illustrations and layout: Annika Röhl, Bengt Gullbing, courtesy of The Nobel Committee for Physiology or Medicine at Karolinska Institutet.
Ten years from now we'll be learning more and more about earth-like planets orbiting sun-like stars elsewhere in our galaxy. Some of these will be relatively close to us, say within 100 light years or so. Students studying astronomy will be figuring out ways of learning more about these other planets, trying to see if they could support life, or even trying to get evidence that there is (or isn't) life out there. Students studying planetary sciences will be modeling these alien earths, trying to understand their environments, and students studying chemistry will be trying to figure out what clues to look for in the atmospheric chemistry of these distant earths. Perhaps some adventurous students will even be thinking about how we might send robotic missions to investigate other solar systems and send information about them back home to us.
“The thing to do is just to take opportunities to get involved in doing research,” says Szostak. “People who run labs are almost always interested in having new, young excited people join the lab and learn how to do things.” But he cautions against specializing too much too soon. As a student, Szostak worked in chemistry, physiology and biochemistry labs — and all those experiences, he believes, helped with his research later on. “It’s good to move around,” he says, noting that one of the best ways to discover something new is to take ideas from widely differing fields and bring them together to create never-before-imagined experiments. “Learning a lot of different things is a really good thing to do, and it’s more interesting and fun.”