In the News...
In Switch, Scientists Share Data to Develop Useful Drug Therapies
by Sharon Begley
Wall Street Journal
January 20, 2006
Brian Popko makes mice in varieties that nature hasn't gotten around to. He makes mice missing a gene or with an added gene, mice with cells that glow or that get the rodent version of a human disease. Usually, the University of Chicago molecular geneticist decides which mice to create based on his own research on neurological disorders. But last year, he got a hot tip.
A scientist who ordinarily wouldn't have breathed a word of his discovery to outsiders told Prof. Popko about a gene that seems to play a role in "re-myelination." Myelin is the fatty sheath that insulates neurons. Its loss causes multiple sclerosis, and its restoration might cure it. Using genetic engineering, Prof. Popko will create mice in which he can turn on and off that gene and others to test their effect on re-myelination. The mice should be ready a year sooner than they would have been, thanks to a unique collaboration that is slaying some of the most sacred cows in biomedicine.
From Alzheimer's and diabetes to cancer, schizophrenia and even baldness, the list of ailments that elude cure marches on. The crisis in "translational science," or turning basic discoveries into therapies, has been brewing for years, but it hit a depressing nadir in 2005, when just 20 new drugs won approval from the Food and Drug Administration.
"Basic scientists and clinical investigators haven't had enough to do with each other," says endocrinologist William Crowley, director of clinical research at Massachusetts General Hospital. The resulting "bench-to-bedside block has been of great concern throughout academic medicine. But now we're starting to see things that hopefully will overcome it."
Mass General, for instance, will hold a meeting this month to craft ways to increase interactions between basic and clinical investigators. The 80 general clinical research centers funded by the National Institutes of Health will close by 2010 as NIH revamps its translational research program, a recognition that the centers have failed to wring something helpful to patients from biomedical research. This fall, Stanford University will launch a master's of science in medicine program, training Ph.D. students in bench-to-bedside research.
"There are so many biomedical discoveries, but we're not converting enough of them into treatments," says Stanford neurologist Ben Barres, who will serve as the program's director. "We haven't taught researchers enough about human diseases. They know about mice and worms, but not about people."
Like Chicago's Prof. Popko, he is funded by the three-year-old Myelin Repair Foundation, which requires that the five biologists it supports share results in real time. Because they don't keep discoveries under wraps until publication, they can build on each other's work sooner. Last year, for instance, Prof. Barres's lab identified genes active in cells that develop into oligodendrocytes, which are cells that myelinate neurons. At the same time, David Colman of McGill University, Montreal, and his team found proteins that are active in the same pathway.
"At the top of both lists is the same gene and protein, which may play a crucial role in re-myelination," says Prof. Barres. If so, then "the failure of re-myelination and the death of neurons in MS may be caused by the loss of this protein. It raises the question, would delivering this protein into the spinal fluid of MS patients promote re-myelination?"
To find out, he passed the gene/protein discovery on to Prof. Popko, who will make mice that lack the gene and hence the protein. "We'll use these mice to study whether you get myelination if oligodendrocytes do not make this protein, and whether re-myelination is enhanced when it's available," says Prof. Barres. "The collaboration has gotten 'pure' researchers out of their ivory towers and truly engaged in working on human disease."
The foundation's insistence that its scientists exchange results every two months is a sea change from the standard every-two-to-five-years progress report. "This has been one of the most difficult transitions, getting scientists to understand accountability in the short term," says Robert Miller of Case Western Reserve University.
It isn't only scrappy new foundations that are scrapping the old research model. Since its founding in 1970, the Juvenile Diabetes Research Foundation has spent some $900 million on research. It has a pile of discoveries to show for it -- but no cure.
"We've funded basic research, but the job of academics isn't to develop drugs," says Paul Burn, senior vice president for research. "What's missing is taking discoveries forward." To do that, the foundation is siphoning money into something once left to industry: turning promising discoveries (such as an antibody against immune cells that destroy insulin-making beta cells) into therapies.
"We're moving an increasing share of our budget to this, derisking discoveries by taking them through animal testing and even Phase I and II clinical trials," says Richard Insel, executive vice president for research. Discoveries, after all, are supposed to be good for something besides filling science journals.