The 2009 Nobel Prize in Physiology or Medicine

Source: Nobelprize.org

The 2009 Nobel Prize in Physiology or Medicine has been awarded to Elizabeth Blackburn (UCSF), Carol Greider (Johns Hopkins) and Jack Szostak (Harvard) for their discovery of the enzyme telomerase and its role in human health and disease.

This prize was highly predictable because the trio's discovery is of obvious and fundamental importance to an understanding of living systems. DNA replication is a very high fidelity event where new nucleotides are added to the new DNA helix being synthesized with an error rate of only 1 in 10*9. Highly efficient repair enzymes act on damaged or wrongly structured DNA strands and repair them with impressive accuracy. And yet the process has some intrinsic problems. One of the most important problems concerns the shortening of one of the two newly synthesized strands of the double helix during every successive duplication. This is an inherent result of the manner in which the two strands are synthesized.

This shortening leads to shortened ends of chromosomes, termed telomeres. As our cells divide in every generation, there is progressive shortening of the chromosomal ends. Ultimately the chromosomal ends become too short for the chromosomes to remain functional and the cell puts into the motion the machinery of apoptosis or cell death which eliminates cells with these chromosomes. The three recipients of this year's prize discovered an enzyme called telomerase that actually prevents the shortening of chromosomes by adding new nucleotides to the ends. Greider was actually Blackburn's PhD. student at Berkeley when they did the pioneering work (not every PhD. student can claim that his or her PhD. thesis was recognized by a Nobel Prize). The group not only discovered the enzyme but actually demonstrated through a series of comprehensive experiments that mutant cells and mice lacking the enzymes had shortened life spans and other fatal defects, indicating the key role of the enzyme in preventing cell death. At the same time, they and other scientists also crucially discovered that certain kinds of cancers, brain tumors for instance, had high levels of telomerase. This high level meant that cancer cells repaired their chromosomes more efficiently than normal cells, thus accounting for their increased activities and life spans and their ability to outcompete normal cells for survival (As usual, what's beneficial for normal cells unfortunately turns out to be even more beneficial for cancer cells; this need to address similar processes in both cells is part of what makes cancer such a hard disease to treat)

The work thus is a fine example of both pure and applied research. Most of the work's implications lie in an increased understanding of the fundamental biochemical machinery governing living cells. However, with the observation that cancer cells express higher levels of telomerase the work also opens up possible chemotherapy that could target increased levels of telomerase in such cells using drugs. Conversely, boosting the level of the enzyme in normal cells could possibly contribute toward slowing down aging.

The prize has been awarded for work that was done about twenty years ago. This is quite typical of the Nobel Prize. Since then Jack Szostak has turned his focus on to other exciting and unrelated research involving the origins of life. In this field too he has done pioneering work involving for instance, the synthesis of membranes that could mimic the proto-cells formed on the early earth. Blackburn also became famous in 2004 for a different reason; she was bumped off President Bush's bioethics council for her opposition to a ban on stem cell research. Given the Bush administration's consistent manipulation and suppression of cogent scientific data, Blackburn actually wore her rejection as a proud label. Catherine Brady has recently written a fine biography of Blackburn.