Dr Andrew Z. Fire was awarded the Dr H.P. Heineken Prize for Biochemistry and Biophysics 2004 for his discovery of RNA interference.
Andrew Fire has discovered that introducing double-stranded RNA in a cell will shut down any given gene. His discovery has far-reaching implications. Protein synthesis, the basis for virtually all biological processes, is controlled by the genes, but without the messenger, RNA (ribonucleic acid), the instructions – the genetic code – would never reach the ribosomes, the cellular particles where proteins are produced. Genes are ‘expressed’ (as geneticists put it) only when RNA has delivered the instructions. An RNA molecule normally carries a copy of one of the two strands of DNA of a particular gene, but experiments conducted in the mid-eighties showed that the other strand of RNA (known as the antisense RNA) is sometimes capable of inhibiting RNA activity.
Fire in cooperation with his colleague Dr Craig Mello discovered in 1998 that double-stranded RNA is very effective at ‘interference’, i.e. at blocking protein synthesis. RNA interference takes place outside the laboratory as well, however, and not only in C. elegans, the roundworm that Fire uses in his research. It has been shown to be a well-preserved evolutionary mechanism that plays a key role in the natural development of all fungi, flora and fauna, and that is, for example, of huge importance in an organism’s defence against viral infection.
This fundamental understanding of natural processes has led to a powerful new technology for identifying the function of genes. Although researchers have described a large number of complete genomes in the past few years, they are far from knowing the purpose of the individual genes. Using the new technology, they can explore the effect of silencing or inhibiting a single gene at cellular level and in that way uncover the role of that gene. Researchers are now also attempting to inhibit specific genes in living organisms. There is growing hope and indeed the expectation that the discovery of RNA interference will lead to new treatments against cancer, genetic disorders and viral diseases.
Fire A., Xu S., Montgomery M.K., Kostas S.A., Driver S.E., Mello C.C., Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegance, Nature 391 (6669): 806-811, 1998 Timmons L., Fire A., Specific interference by ingested dsRNA, Nature 395 (6705): 854, 1998
Andrew Z. Fire was born in Santa Clara County, California (USA) in 1959. He majored in mathematics at the University of California, Berkeley, where he obtained his degree in only three years, but genetics were to become his life’s work. At the age of 19 he went to the Massachusetts Institute of Technology in Cambridge, Massachusetts, to work in the laboratory of Professor Philip Sharp (a later Nobel Prizewinner) on a new area of cell biology: the biochemistry that underlies gene expression in mammalian cells. After obtaining his Ph.D. (the subject of his 1983 dissertation was the genetics of adenoviruses), Fire left for Cambridge in the United Kingdom, where he worked with one of the fathers of molecular biology, Nobel Prizewinner Professor Sidney Brenner, on the DNA of the C. elegans worm, which has played a key role in his research since then.
Between 1986 and 2003, Andrew Fire was a member of staff of the Carnegie Institution of Washington, Department of Embryology (Baltimore, USA), where he supervised dozens of students, Ph.D. candidates and post-docs. In 2003 he moved his laboratory to Stanford University School of Medicine (Departments of Pathology and Genetics); in addition, he is an adjunct professor at Johns Hopkins University in Baltimore. Fire has been the recipient of many scholarships and prizes, for example the Maryland Distinguished Young Scientist Award (1997) and the National Academy of Sciences Award in Molecular Biology (2003, together with Dr Craig Mello). In 2006 he won the Nobel Prize in Physiology or Medicine, together with Dr Craig Mello. His colleagues praise his creativity and originality.