Boston geneticist shares Nobel

Jack W. Szostak, a professor of genetics at Harvard Medical School and an investigator at Massachusetts General Hospital, will split the $1.4 million prize equally with Elizabeth H. Blackburn of the University of California at San Francisco and Carol W. Greider of Johns Hopkins University School of Medicine.

All three were honored for the pivotal roles they played in revealing a mechanism that explains how chromosomes, which carry genes, are protected from degrading.

“What started off as work on a really basic question has turned out, to our pleasant surprise, to have much broader implications,’’ Szostak said yesterday at a press conference, where colleagues welcomed him with a long standing ovation. “This is the highest scientific honor. It’s great to receive that kind of recognition.’’

Szostak, 56, was awakened shortly before 5 a.m. by a phone call from Stockholm. His wife, Tel McCormick, described picking up the phone in the dark, handing it to her husband, and waiting until the conversation ended before she started screaming with excitement.

Then, she said, her husband asked her, “How do you hang this up?’’

In anticipation of his arrival at work, colleagues placed balloons and streamers around Szostak’s seventh-floor laboratory in a Mass. General research building. They also hung photocopies of the first page of the landmark paper that started him on his track to the Nobel - a 1982 journal article called “Cloning Yeast Telomeres on Linear Plasmid Vectors’’ - with the words “Congrats, Jack!’’ scrawled over it.

The cause for celebration is a seminal finding in biology: Repetitive sequences of DNA on the tips of chromosomes formed a kind of molecular “cap’’ that keeps chromosomes from unraveling - often compared to the plastic tip that keeps a shoelace from fraying. That cap is built by a special enzyme, which ensures that as cells divide, the chromosomes are completely copied.

“It’s become textbook stuff. Where it’s keeping the field going is sorting through all the biological implications of this,’’ said Jeremy Berg, director of the National Institute of General Medical Sciences, who noted that the National Institutes of Health has provided the three scientists with $33 million in funding over their careers. “Cancer, cellular aging . . . with implications for stem cells . . . that’s the aspect of it that’s still very vibrant.’’

In 1980, Szostak and Blackburn collaborated to try to plug a hole in scientists’ understanding of an essential process of life: the copying of DNA when cells divide. When a cell divides, the very end of a strand of DNA cannot be copied, which means chromosomes should get shorter, eventually eliminating critical genes. But they don’t usually, so the two scientists reasoned that something must be preventing the chromosome from degrading.

They took chromosome tips - called telomeres - from a pond-dwelling organism called Tetrahymena. They spliced that repetitive sequence of DNA into yeast and found that it played a protective function in this completely different organism, a result that suggested the same basic molecular machinery was protecting chromosomes in most plants and animals.

Later, Blackburn and Greider found an enzyme called telomerase that caused the tips to rebuild, and Szostak discovered a protein fundamental to that enzyme. They also began to understand what purpose the telomeres played, finding that if telomeres are shortened, cells age. Some scientists speculate that telomeres could also play a role in the aging of organisms as a whole.

As time has passed, the molecular machinery the scientists uncovered has become of greater interest. The telomerase enzyme appears to be overactive in most human tumor cells, turning the cells immortal and allowing them to grow out of control. Some efforts are now being made to turn that idea into a cancer therapy, including vaccines against cells with overactive telomerase.

“This is a huge victory, yet again, for basic science. You have someone asking a very fundamental question about how Tetrahymena - pond scum - or yeast maintains their chromosomes, and setting out a set of basic scientific principles that taught us something basic about chromosome biology without a clue as to its relevance to human disease,’’ said Dr. Ron DePinho, director of the Belfer Institute for Applied Cancer Science at the Dana-Farber Cancer Institute. “It turns out to be very, very important.’’

Szostak said the work would not have been possible without his colleagues, adding that it was a special honor to win the award with Blackburn and Greider. Szostak began working with Blackburn after meeting her at a conference, sparking a transcontinental collaboration.

Greider was a graduate student in Blackburn’s lab when they did the work isolating the enzyme.

Szostak was born in London. He went to McGill University in Montreal for his undergraduate education, and received a doctorate in biochemistry from Cornell University. He has taught at Harvard Medical School for 30 years.

Now, in the lab festooned with balloons and streamers, Szostak works on a completely different area - trying to understand how life began on earth.

“It was pretty clear that a lot of people were going to enter the field and explore all the ramifications for medical application’’ of the chromosome research, Szostak said. “So I thought the questions that were open would be taken care of, and therefore I could safely move on and think about some other things.’’

Carolyn Y. Johnson can be reached at cjohnson@globe.com.