Oct. 6 (Bloomberg) -- It was Christmas Day, 1984, and Carol Greider, a 23-year-old first-year graduate student at the University of California, Berkeley, couldn’t stay away from the lab where she and assistant professor Elizabeth Blackburn were trying to untangle a genetic mystery.

Greider had been testing an enzyme, one of the proteins that start chemical reactions in the body, and was impatient to check results. What she saw was “the first clear evidence” of how cells make telomeres, small parts of human DNA that allow genes to be replicated without the loss of protein-making information, Greider said in an interview yesterday. Her comments came just hours after she and Blackburn became the first two women to share a Nobel Prize for medicine.

The enzyme, which Greider and Blackburn named “telomerase” is key to controlling unbridled cellular growth, the hallmark of cancer, as well as to age-linked disease, subsequent research has found. Blackburn, already an established scientist at age 35, often debated with her student how best to proceed. In the end, they created scientific history.

“A brave student was needed to make this project drive along, and Carol was very willing to do that,” Blackburn said yesterday in an interview. “It was a great, fun kind of adventure because we didn’t know the answer. There was no chart telling us what to do.”

Greider, now 48, is a molecular biologist with her own lab at Johns Hopkins University in Baltimore. Blackburn, 60, is at the University of California, San Francisco. The two women shared the Nobel Prize for Physiology or Medicine with Jack Szostak, 56, of Harvard Medical School in Boston, who began collaborating with Blackburn on the telomere research in 1980.

Sharing the Prize

The three scientists will share the 10 million Swedish kronor ($1.4 million) prize equally, the Nobel Assembly in Stockholm said.

Blackburn said the honor for her and Greider is “a hopeful sign” for women. In the future, people will say, “Oh yes, it’s not too unusual to have women getting Nobel prizes,” Blackburn said in an interview. “Two got one this year. I hope it becomes very normal.”

Research over the past decade suggests that telomeres are just one component in the complicated process of aging, said Leonard Guarente, a researcher at Massachusetts Institute of Technology, in Cambridge, Massachusetts. On the other hand, cancer cells, which divide and grow indefinitely, may be highly dependent on telomerase, he said.

Combating Cancer

“The biology of telomerase is critical to the cancer cell,” said Guarente, a scientific adviser to London-based GlaxoSmithKline Plc’s Sirtris Pharmaceuticals unit, the developer of anti-aging drugs, in a telephone interview. “Understanding this and developing ways to intervene may be one of the viable ways to combat cancer.”

Diseases that have been linked to defects in telomerase activity include inherited forms of aplastic anemia, when the bone marrow doesn’t produce enough blood cells, and genetic forms of skin and lung ailments. The most intense research has been in cancer, where malignant cells have the ability to divide indefinitely, and in aging, which has been linked to short telomeres.

Merck & Co., a drugmaker based in Whitehouse Station, New Jersey, and Menlo Park, California-based biotechnology company Geron Corp. began testing a cancer vaccine last year that targets telomerase in patients with solid tumors, including lung and prostate cancer. Geron is testing another telomerase inhibitor in breast and plasma cell cancer.

Repeating Pattern

Blackburn, born on the island of Tasmania in Australia, became curious about telomeres in 1970s. She found they had a repeating pattern of six DNA building blocks, called bases, and wanted to find out how they were made.

“The DNA was acting in ways that were completely unprecedented according to the textbooks, and so we knew something new was going on,” she said yesterday in an interview in San Francisco.

The collaboration between her and Harvard’s Szostak began when Blackburn was studying a single-celled organism, called Tetrahymena, with an unusually large nucleus that made it easy to observe the DNA. Blackburn was studying the telomeres at the end of their chromosomes, trying to understand their structure.

Szostak heard Blackburn present her findings at a medical meeting in 1980, and the two decided to combine their efforts. Blackburn isolated the DNA sequence from the single-cell pond organism, which Szostak linked to genetic strands called mini- chromosomes he had been working with.

DNA Cap

Blackburn’s DNA cap, now called a telomere, protected the mini-chromosome from damage, the researchers found.

That was when Greider entered the picture, looking for the unknown enzyme that could be responsible for making telomeres. A native of Davis, California, Greider had overcome dyslexia to study biochemistry, according to her biography in the Proceedings of the National Academy of Sciences.

The student worked 12-hour days and learned DNA cloning techniques to find the enzyme. She and Blackburn frequently debated research problems. They would eventually learn that the enzyme seen by Greider that Christmas day allows the entire chromosome to be copied before cell division begins.

“This really is a tribute to curiosity-driven basic science,” Greider said yesterday in a press conference at John Hopkins. “We didn’t know at the time that there were any particular disease implications, we were just interested in the fundamental biology.”

Stopwatch on Lifespan

Some scientists hypothesized that telomeres, in effect, put a stopwatch on the lifespan of an organism by limiting the number of times that its cells can replicate before DNA damage ensues. Michael West founded Menlo Park-based Geron in 1990 with the goal of extending extend human life expectancy into the hundreds of years.

“I used to say at Geron that between 5 and 95 percent of human aging is in the telomere,” said West, now president and chief executive officer of BioTime Inc., in Alameda, California. “Now I’d say it’s probably about 80 percent.”

MIT’s Guarente credited Blackburn for making the study of telomeres one of the scientific fields that is most friendly to women. About half of the researchers in the field are women, said Titia de Lange, a professor of cell biology and genetics at Rockefeller University in New York, who studies aging.

“It would be great if, in the future, women got 50 percent of all the awards,” she said in a telephone interview. “What’s needed is gender equality in the upper echelons of science.”

800 Nobelists

More than 800 people have been awarded Nobel Prizes from 1901 through 2008, and 36 of them have been women, according to the Nobel Web site. The relative lack of prizes for women discourages young female researchers, said Phoebe Leboy, president of the Association for Women in Science, in Washington.

“It’s one of the major issues faced by women in science,” she said in a telephone interview. “When a really bright graduate student wants to work with someone, they’re looking for someone with power and prestige.”

With fewer prizes, women are less likely to get the top students, who are more likely to write ground-breaking papers, working for them, Leboy said. She has a grant for $800,000 to study why women are often shut out of science prizes and how to correct it.

“When scientists are sitting around a table thinking about who deserves an award, a lot of the guys don’t think of women,” she said. “Men have been habituated not to think about women when they think of prizes.”

Persistent Bias

While women’s status in the laboratory has improved over the past few years, there are still many signs of persistent bias, said Gioia De Cari, who got a master’s degree in mathematics at MIT in the late 1980s. She had dropped writing a one-woman play about her experiences in male-dominated academia until she heard that former Harvard University President Lawrence H. Summers said in January 2005 that innate differences might explain women’s lack of success in math and science.

“I thought, ‘Maybe this isn’t so passé,’” she said in telephone interview. “He was an unlikely muse for a woman playwright.”

De Cari’s play, “Truth Values: One Woman’s Romp Through MIT’s Male Math Maze,” will be performed at the City University of New York Graduate Center for one night, Oct. 9, in Manhattan.

To contact the reporters on this story: John Lauerman in Boston at jlauerman@bloomberg.net; Rob Waters in San Francisco at rwaters5@bloomberg.net; Michelle Fay Cortez in London at mcortez@bloomberg.net.

Last Updated: October 6, 2009 00:00 EDT