The discovery of a biological gatekeeper that prevents genetic code from fraying with age has won a trio of American scientists this year's Nobel prize for medicine.
The prestigious award – and the 10m Swedish kronor (£818,000) prize money – is shared by Elizabeth Blackburn, 60, Carol Greider, 48, and Jack Szostak, 56. It is the first time the prize has honoured two women at once.
The researchers identified one of the most critical and intriguing processes in living organisms, one that has deep implications for understanding ageing, a variety of cancers and inherited diseases.
Announcing the award at the Karolinska Institute in Stockholm, the Nobel assembly said the discoveries "added a new dimension to our understanding of the cell".
Blackburn, a biochemist at the University of California in San Francisco, made headlines once before when she was fired from President George W Bush's council on bioethics for criticising his opposition to embryonic stem cell research. She said later the administration had the "strange impression that science was the enemy of morality".
She was born in Tasmania and received a PhD from Cambridge University before carving out a career in the US. Greider, a geneticist at Johns Hopkins University in Baltimore, was Blackburn's student when the two made their discovery. Szostak, the third winner, was born in London and grew up in Canada. He moved to the US and joined Harvard Medical School in 1979.
Blackburn received the news in a 2am phone call. "It's lovely to have the recognition and share it with Carol Greider and Jack Szostak," she told Associated Press.
Szostak said: "When we started the work, we were really just interested in the very basic question about DNA replication, how the ends of chromosomes are maintained. At the time we had no idea there would be all these implications.
"This process of maintaining the ends of DNA molecules is very important and plays an important role in cancer and ageing, which are really still being fully worked out," he added.
Their experiments solved one of the great mysteries of biology, one scientists had wrestled with since the dawn of genetics. They revealed how cells make a faithful copy of their chromosomes when they divide. Chromosomes are strands of DNA that carry genes, and there are 23 pairs in almost every cell in the body.
The first hint of a breakthrough came when Blackburn was studying chromosomes in a simple pond-dwelling organism called tetrahymena. She noticed that at the end of each of the creature's chromosomes was a repeating sequence of DNA, spelt out by the letters CCCCAA. What it meant was not clear.
Her work caught the eye of Szostak. He had developed "mini-chromosomes" from strands of DNA and was investigating what happened when he injected them into yeast cells. The problem he encountered was that each time the cells divided, the mini-chromosomes degraded, until eventually they vanished completely.
The two decided to join forces and make mini-chromosomes with the CCCCAA sequences at either end. When these were injected into yeast, the DNA sequence protected the chromosomes when they were copied, just as the plastic tips at the ends of shoelaces stop them from fraying.
The researchers called the genetic caps "telomeres", from the Greek for "end part". Two years later, in 1984, Greider, who was working as Blackburn's PhD student, discovered "telomerase", the enzyme in the body that makes telomeres.
Further studies revealed that healthy telomeres delay the ageing process in cells, a finding that prompted a flurry of research into potential anti-ageing treatments. Related studies investigated whether overactive telomerase made cells immortal, causing them to grow out of control and form cancers.
Some rare inherited diseases are now known to be caused by defects in the telomerase enzyme, including certain forms of aplastic anaemia, in which faulty cell division in bone marrow stem cells leads to anaemia.
The Nobel prize for medicine has been awarded to 10 women since it was established in 1901, but this is the first time two women have shared the prize.
"It was their work that has opened up the whole field of telomere biology, with all its promise for cancer cures and prolonging life span," said Thomas Vulliamy, a molecular biologist at Queen Mary, University of London. "Closer to home, it has been important for us in helping to explain how a debilitating inherited disease, which worsens in each generation, comes about through impaired telomere maintenance."
