The 2009 Nobel Prize in physiology or medicine is shared by three grantees of the National Institutes of Health (NIH): Elizabeth H Blackburn, of University of California, San Francisco; Carol W Greider, of Johns Hopkins University School of Medicine; and Jack W Szostak, of Massachusetts General Hospital, Harvard Medical School and Howard Hughes Medical Institute. The three researchers, supported by NIH funding for decades, are honoured for discovering how chromosomes are protected against degradation by telomeres through the enzyme telomerase. Their discoveries added a new dimension to the scientific community's understanding of the cell, shed light on disease mechanisms, and introduced new directions for the development of potential new therapies.
Cancer and aging research merge in the study of telomeres, the tails at the ends of chromosomes that become shorter as a cell divides. All telomeres have the same short sequence of DNA bases repeated thousands of times. Rather than containing any genetic information, these repetitive snippets help keep chromosomes intact. The enzyme telomerase, which builds telomeres, enables the entire length of the chromosome to be copied without missing the end portion.
"The question of how cellular aging relates to abnormal cell division, such as cancer, and the aging of organisms continues to be the focus of rigorous study, thanks to the insights of Dr Greider, Dr Blackburn and Dr Szostak," said NIH director Francis S Collins. "These NIH grantees' discoveries offer a classic example of how basic science research driven by investigators' curiosity can illuminate our understanding of health and disease."
Dr Blackburn has received NIH funding since 1978, Dr Greider since 1990, and Dr Szostak since 1980. The NIH has provided a total of more than $32 million to the three researchers for their study of telomeres, telomerase, and the molecular functions of cells.
The NIH's National Institute of General Medical Sciences (NIGMS) has provided more than $13 million to support the work of Dr Blackburn, more than $6 million to support the work of Dr Greider, and more than $3 million to support the work of Dr Szostak.
"Driven by their curiosity, these researchers answered fundamental questions about a basic biological process now known to be involved in cancer and cellular aging," said NIGMS director Jeremy M Berg. "Their work has been an important breakthrough for many fields."
In addition, the NIH's National Cancer Institute (NCI) and National Institute of Dental and Craniofacial Research (NIDCR) provided more than $2 million and $400,000, respectively, to support the research of Dr Blackburn. Dr Greider has also received more than $7 million in support from the National Institute on Aging (NIA). She is also the recipient of a Method to Extend Research In Time (MERIT) Award, a grant mechanism initiated by NIA and the National Advisory Council on Aging to provide long-term support to outstanding, experienced investigators.
During cell division, the ends of the chromosomes are not completely copied, so telomeres become progressively shorter. Over time, scientists theorize, telomeres become so short that their function is disrupted, and this, in turn, leads the cell to stop proliferating. Average telomere length, gives some indication of how many divisions the cell has already undergone and how many remain before it can no longer replicate.
"The work of the three Nobel Prize winners on telomeres has critical implications for the study of aging at the cellular level and has provided key avenues for investigators to pursue," said NIA director Richard J Hodes.
In cancer cells, telomeres act abnormally-they no longer shrink with each cell division. Dr Blackburn and Dr Greider discovered the enzyme telomerase, which is not active in most adult cells but becomes active in advanced cancers, enabling cells to replace lost telomeric sequences and divide indefinitely. This finding has led to speculation that if a drug could be developed to block telomerase activity, it might aid in cancer treatment. In addition, some inherited diseases are now known to be caused by telomerase defects, including certain forms of congenital aplastic anaemia, and some inherited skin and lung diseases.
"The work by Dr Greider, Dr Blackburn and Dr Szostak has been truly groundbreaking and has given researchers worldwide a much better understanding of how telomeres and telomerase affect the life-span of a cell and, in turn, how a cell can become immortal, which is a hallmark of a cancer cell," said NCI director John E Niederhuber.
The office of the director, the central office at NIH, is responsible for setting policy for NIH, which includes 27 Institutes and Centers. This involves planning, managing, and coordinating the programmes and activities of all NIH components.