New spark for a stagnant search

One day in 1988,  a college dropout named Jonathan Stanley was visiting New York City when he became convinced that government agents were closing in on him. He bolted, and for three days and nights raced through the city streets and subway tunnels.

His flight ended in a deli, where he climbed a plastic crate and stripped off his clothes. The police took him to a hospital, and he finally received effective treatment two years after getting a diagnosis of bipolar disorder.

“My son’s life was saved,” his father, Ted Stanley, said recently. When he himself was in college, he added, “those drugs didn’t exist; I would have had a nonfunctioning brain all the rest of my life.” The older Stanley, 84, who earned a fortune selling collectibles, created a foundation to support psychiatric research. “I would like to purchase that happy ending for other people,” he said.

Late on Monday, the Broad Institute, a biomedical research center, announced a $650 million donation for psychiatric research from the Stanley Family Foundation — one of the largest private gifts ever for scientific research.

It comes at a time when basic research into mental illness is sputtering, and many drug makers have all but abandoned the search for new treatments. Despite decades of costly research, experts have learned virtually nothing about the causes of psychiatric disorders and have developed no truly novel drug treatments.

Clear pathforward

Broad Institute officials hope that Stanley’s donation will change that, and they timed their announcement to coincide with the publication of the largest analysis to date on the genetics of schizophrenia.
 The analysis, reported by the journal Nature on Monday, identified more than 100 regions of DNA associated with the disease.  “For the first time, there’s a clear path forward,” said Eric Lander, the president of the Broad Institute.

Experts not affiliated with the institute or the new paper agreed that the news on both fronts was good, but characterized the research as a first step in a long process. “The signals they found are real signals, period, and that is encouraging,” said David B.Goldstein, a Duke University geneticist who has been critical of previous large-scale projects.

“But at the same time, they give us no mechanistic insight, no targets for drug development. That will take a lot more work.”

Jonathan Stanley, now 48, cannot explain why he suddenly developed bipolar disorder at 19. All he knows is that his brain responded well to lithium. He was eventually able to return to college, complete law school and become a lawyer. “You’re talking to a guy who went from psychotic to normal with some pills,” he said.

When scientists began to discover psychiatric drugs like lithium in the mid-20th century, they did so mostly by accident, not out of an understanding of the biology of the diseases they hoped to cure. For many years, they worked backward, hoping that by figuring out the action of the drugs, they could understand the causes of the diseases. But they came up empty.

Some researchers argued that a better strategy would be to find the genes involved in psychiatric disorders. This approach would give them new molecular targets for drugs they could test. Yet the staggering complexity of the brain has yielded few secrets. More than 80 per cent of the roughly 20,000 genes in human DNA are active in the brain.

Soon, the Broad Institute joined forces with scores of other research groups to form a consortium that could pool tens of thousands of subjects for analysis. In 2011, the consortium reported five genetic markers associated with schizophrenia. The group added more people to its studies and found even more genetic links.

Dr. Lander cautioned that each variant accounts for only a tiny portion of the risk of developing schizophrenia. “It shouldn’t be used for a risk predictor,” he said. Still, Dr Samuel Barondes, a professor of neurobiology and psychiatry at the University of California, San Francisco, who was not involved in the study, called the findings encouraging.

Even though schizophrenia is a “diverse disorder, with a horribly complicated genetic basis,” he said, “it is possible to pick up a reliable genetic signal if you have enough people.”

Other research teams are making progress on other conditions, such as bipolar disorder and autism, and finding that some mutations are rare while others are common variants.