5 Pioneers Receive Lasker Medical Prizes
By LAWRENCE K. ALTMAN
Published: September 14, 2008
Akira Endo, a Japanese scientist whose discovery of the first cholesterol-lowering statin drug helped extend the lives of millions of people, is one of five winners of this year's Lasker Awards for medical research, it was announced Saturday.
An American microbiologist, Stanley Falkow of Stanford University, was honored for greatly expanding knowledge of disease-causing microbes, ranking him as ''one of the greatest microbiologists of all time,'' the Albert and Mary Lasker Foundation said in making the awards.
A third award went to two Americans and a Briton for their pioneering look into a previously unknown universe of potent molecules, tiny ribonucleic acids known as micro-RNAs. The Americans are Victor R. Ambros, 54, of the University of Massachusetts Medical School in Worcester and Gary B. Ruvkun, 56, of Massachusetts General Hospital in Boston. The Briton is David C. Baulcombe, 56, of the University of Cambridge.
RNA is DNA's close chemical cousin. These scientists found that snippets of RNA act as genetic regulators governing many activities in animals and plants. Scientists now have implicated micro-RNAs in viral infections, heart failure, cancer, other diseases, and normal functions like muscle action and blood cell specialization.
Dr. Endo, 74, was chosen for ushering in a new era in preventing and treating coronary heart disease, the leading cause of death in the United States and many other countries, said Dr. Joseph L. Goldstein, chairman of the 24-member scientific jury that selects the Lasker recipients.
For two years beginning in 1971, Dr. Endo grew more than 6,000 fungi as a microbiologist working for a Japanese drug company. He was seeking a natural substance that could block a crucial enzyme involved in the body's production of cholesterol, which occurs largely in the liver. Cholesterol is a crucial component of cells and serves as a raw material for some hormones and nerve sheaths. But it is also a major contributor to coronary artery disease.
At the time, many scientists were skeptical about the safety of lowering the amount of cholesterol because it was an essential body chemical. But by 1980, Dr. Endo's team found that the statin lowered the LDL, or ''bad'' cholesterol level, in the blood by 17 percent.
Dr. Endo went on to identify other statins, and his work led the American pharmaceutical company Merck to start a program to develop them as drugs.
Merck manufactured lovastatin (Mevacor), the first statin to be licensed, in 1987. Since then, statins have become among the most widely prescribed drugs in the United States, taken by an estimated 25 million Americans to treat high levels of LDL cholesterol.
Dr. Falkow, 74, was honored for his discoveries that grew out of an extraordinary ability to imagine himself as a bacterium so he could view the world from the microbial perspective.
That talent helped him discover the molecular nature of antibiotic resistance; forge new laboratory tools that revolutionized the way scientists think about how microbes cause disease; and train a number of students who have become scientific leaders in infectious diseases.
Over his 51-year professional career, Dr. Falkow has also developed techniques to help identify disease-causing bacteria that cannot be grown in the laboratory; show how bacteria pass certain traits to one another; pave the way for recombinant DNA technology that has wide use in drug production and in the laboratory; and help untangle mysteries about how bacteria survive and spread.
Dr. Falkow said his research was conducted at the Walter Reed Army Medical Center, Georgetown University, the University of Washington and then Stanford.
The three winners in the basic research category were honored for expanding the versatility of RNA, long regarded as DNA's poor cousin. Previous scientific convention held that proteins, not RNAs, governed gene activity in animal cells.
''The notion that small RNAs could control gene expression was unheard of,'' said Dr. Goldstein, the Lasker jury chairman, who works at the University of Texas Southwestern Medical Center in Dallas.
The scientists' discovery of micro-RNAs was an accidental finding in research conducted for other reasons.
Dr. Ambros and Dr. Ruvkun were studying how a roundworm, C. elegans, develops from newly hatched larva to adult. The worm serves as a model animal for many geneticists.
Earlier research on flies showed that certain genes instructed embryos where to place wings, legs and other body parts. Suspecting that other genes specified the timing of such developmental events, Dr. Ambros focused on lin-4, a gene that allows immature worms to advance past a particular development stage. Animals with a defective version of lin-4 cannot pass that hurdle.
Dr. Ambros discovered that animals with a different gene, lin-14, skip early steps in development and prematurely acquire characteristics that normally appear later. The two genes exerted opposite effects in worm cells.
Dr. Ambros and Dr. Ruvkun went on to show how the genes collaborated; at an appropriate time, lin-4 blocks lin-14 activity, allowing worms to continue normal development.
In a series of additional steps, the researchers found that they were dealing with very small strands of RNA. At the time, the smallest RNA known to be of importance in cells consisted of 75 nucleotide building blocks. The RNA they found was composed of 22 nucleotides.
Dr. Baulcombe, in a seemingly unrelated line of research in England, expanded the scope of micro-RNAs' crucial functions by finding that they silenced genes in plants. He called them silencing RNAs and showed that earlier experiments were not intended to find micro-RNAs because their size was much smaller than scientists had imagined.
Now it seems that micro-RNA provides a sophisticated way of adjusting production of amounts of proteins that are needed at one stage of life but must be absent in others.
Recent studies suggest that the human genome contains more than 500 micro-RNAs and that, collectively, they might control a third of all protein-producing genes. Researchers are now trying to develop drugs that work by blocking micro-RNAs.
The winners will received their Lasker Awards at a luncheon on Sept. 26. The prize in each category is $300,000.
PHOTOS: This year's Lasker Awards went to, from left, Akira Endo of Japan; David C. Baulcombe of England; and three Americans, Gary B. Ruvkun, Stanley Falkow and Victor R. Ambros.