Albert Lasker Award Laureate: Paul Nurse
The adult human body consists of approximately one hundred trillion cells. Every second, millions of those cells are dividing to create new cells, a task that is accomplished by an intricately orchestrated sequence of events known as the cell cycle. The cell cycle is the process by which a fertilized ovum develops into an organism, and by which many parts of the mature organism — hair, skin, blood and certain internal organs — are renewed. In the 1970s and 1980s, scientists applying genetic approaches to the study of cell biology demystified this crucial biological process when they identified the molecules that control it, genes and proteins that ensure that each biochemical step of the cycle is completed correctly before allowing the next step to begin. Paul Nurse, British biochemist and Rockefeller’s president emeritus, identified two of the molecular key-holders of the cell cycle. For his contribution to the revolution in cell biology and cancer research, Dr. Nurse received the 1998 Albert Lasker Basic Medical Research Award.
It has long been understood that the cell cycle is divided into two main phases: interphase, during which the cell grows larger, stores up nutrients that will be needed in the second phase and duplicates the DNA in its chromosomes; and mitosis, during which the cell divides into two separate daughter cells. Interphase can be broken down into three distinct stages, each of which supports the next. During G1 phase, the first of those stages, the cell ramps up production of enzymes that will be used for the DNA replication that defines the subsequent S phase. Finally, in G2 phase, the cell produces proteins called microtubules, which will be used to align the chromosomes for equal cell division. During mitosis, which is itself divided into five distinct molecular events, the cell’s nucleus and cytoplasm split and the original single cell becomes two cells. This process can take anywhere from 10 to 30 hours in mammals.
Dr. Nurse chose fission yeast, Schizosaccharomyces pombe, as a model system. By observing mutation-based defects in different mechanisms of the cell cycle, he discovered cdc2, a gene that acts as gatekeeper for the cell’s transition from its G1 phase to its S phase, in 1976. He later found that the gene has a broader function, also ushering the cell from the G2 phase into mitosis. In 1987, Dr. Nurse isolated CDK1, a human version of the cdc2 gene, which encodes a protein called cyclin-dependent kinase (CDK). One of the most common classes of kinases, CDK guides the cell cycle along by phosphorylating — and thus activating or deactivating — the cellular proteins required to complete each stage of the cycle. To compare the yeast and human versions of the gene, Dr. Nurse then placed CDK1 in yeast cells and observed that the human gene was fully functional in the yeast cells, proving that the CDK mechanism had been conserved in eukaryotic cells through more than one billion years of evolution, from yeast to humans. Since Dr. Nurse’s discovery, six different CDK molecules have been discovered in human cells.
Disruptions in the cell cycle can lead to numerous diseases, particularly cancer. The demonstration of cell cycle universality provided an easier model system by which to study cancer, and further research in this vein has shown not only that genes that encode for CDKs can also function as oncogenes, but also that CDK molecules cooperate with tumor-suppressor genes during the cell cycle. Observation of increased levels of CDK in some tumors has also led to new cancer diagnostic techniques as well as new principles for the design of CDK-targeted cancer therapies. Dr. Nurse shared the 1998 Lasker Award with Leland Hartwell of the Fred Hutchinson Cancer Research Center and Yoshio Masui of the University of Toronto.
Dr. Nurse, a native of the United Kingdom, graduated from Birmingham University in 1970 and received his Ph.D. in cell biology and biochemistry from the University of East Anglia in 1973. He did postdoctoral work at universities in Bern, Switzerland, Edinburgh, and Sussex, and joined the Imperial Cancer Research Fund (ICRF) in London in 1984. In 1988 he moved to the University of Oxford as chair of its department of microbiology, and he returned to ICRF in 1993 as director of research. He became director general in 1996 and in 2002 was appointed chief executive of Cancer Research UK, formed when ICRF merged with the Cancer Research Campaign. He was president of The Rockefeller University from 2003 to 2011, when he became director of the Francis Crick Institute in London.
Dr. Nurse is a member of The Royal Society and a foreign associate of the U.S. National Academy of Sciences. He received The Royal Society’s Royal and Copley Medals and the Legion of Honor in 2002 and the Nobel Prize in Physiology or Medicine in 2001. In 1999 he was honored with knighthood in Great Britain for services in cancer research and cell biology. Since 2000, he has been a member of CST advising the UK Prime Minister on science and technology.