Jack Szostak

Biochemistry

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.

 

As a young scientist ...

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.

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