The Broad Institute, a biomedical research juggernaut in Cambridge, has received the biggest gift worldwide for psychiatric research, a $650 million commitment that could help scientists unravel the genetic underpinnings of diseases such as schizophrenia and bipolar disorder and begin to develop better treatments.
The gift from philanthropist and businessman Ted Stanley, to be announced Tuesday, coincides with the publication of the largest genomic study of schizophrenia, which identified more than 100 spots in the genome that are associated with the disease. That study, done by a group that includes Broad researchers and published in the journal Nature Monday, is only a first step toward the ultimate goal of developing treatments that target the molecular causes of the disease, but it is the type of research the donation will help support.
Such information would allow scientists to finally understand what causes diseases that have remained some of medicine’s toughest puzzles, so difficult that they have been largely abandoned by many drug companies though hundreds of millions of people suffer from mental illness at a global cost of $2.5 trillion per year, according to the World Health Organization.
Already, Stanley has given the Broad $175 million, and the new commitment makes him the research center’s largest benefactor so far. The $650 million will be provided as an annual cash flow that will vary, but is in the ballpark of tens of millions each year. The remainder will be given after Stanley’s death.
Stanley, 83, made his fortune heading MBI, a Connecticut company that markets and sells collectibles. He and his late wife, Vada, became deeply invested in mental health issues when their son, Jonathan, suffered from bipolar disorder in college. Jonathan was successfully treated with lithium and now works as an attorney and advocate for people with mental illness, but the struggle to help their son was, Stanley said, “a revelation moment” that gave direction to their philanthropy.
“There was a pill that saved his life. Essentially, it gave him the ability to have a normal life with a normal functioning brain,” Stanley said in an interview. “If I had had the same downfall at the same age that he had, I would have had my life ruined . . . because in between when I was that age and he was that age, someone had discovered that lithium makes people well when they have that illness.”
Stanley had read everything he could get his hands on while his son was sick and had become acutely aware that many people with mental illness were not as fortunate, a situation that he hoped he and his wife could help solve.
His donation will provide long-term security for the research program at a critical moment, when US government funding for biomedical research has become uncertain and more competitive. It is the latest in a series of high-profile gifts from private donors to support mental health research.
The Simons Foundation Autism Research Initiative has given more than $200 million to support research on autism. Microsoft cofounder Paul G. Allen has given $500 million to support the Allen Institute for Brain Science in Seattle.
“The federal support for biomedical research broadly, from cancer to mental health, really has stalled out over the last decade,” said Dr. Thomas Insel, director of the National Institute of Mental Health. “We’re at a point where we have the tools to be able to answer these questions. . . . We have the samples. We have the tools. We just haven’t had the funds to be able to do the actual [gene] sequencing that we need to. These funds will certainly help the Broad Institute, which is already at the forefront of this field, to move faster and further.”
Studying mental illness is particularly challenging.
“Cancer biology is very hard, of course,” said Dr. Steven Hyman, director of the Stanley Center for Psychiatric Research at the Broad, founded by Stanley and his wife in 2007. “But in cancer, the surgeon literally hands the scientist the cells that are the disease, and then people can go to work on them.”
With mental illness, the cells are inaccessible. “Our brains are both sacrosanct and protected behind a bony skull,” Hyman said, leaving genetics as the only way to get “molecular clues . . . that could be exploited for therapy.”
Eric Lander, founding director of the Broad, said he hopes that better characterizing the molecular underpinnings of psychiatric diseases will finally give researchers the insights they need to start a revolution like the one that has occurred in cancer, where there are hundreds of drugs in development.
“It isn’t going to lead to any new cures next week or next year, but it will — as with cancer, I believe — lead to major therapies and in some cases, cures,” Lander said. He pointed to the new Nature paper as both an example of the scale of the problem and the promise of the approach.
Previously, roughly 30 spots in people’s DNA had been identified that were associated with schizophrenia. The new study, which drew on the efforts of hundreds of doctors and scientists from more than 20 countries, compared the genomes of 37,000 people with schizophrenia and 113,000 people without the disease.
The spots found to be associated with the disease confirm leading theories behind schizophrenia’s origins, for example, underscoring the importance of signaling between brain cells involving a chemical called dopamine.
The findings also point to new spots to be investigated further, including a region of the genome involved in how the body learns to recognize pathogens, suggesting that the immune system may play a role in the disease.
“The scale of this effort is amazing and has few precedents in human genetics,” said Steve McCarroll, director of genetics for the Stanley Center.
The study was done by an international consortium including researchers from the Broad and Massachusetts General Hospital.
Insel said that what was most exciting to him was a promising finding hinted at near the end of the paper. When researchers looked for particular genetic changes in several groups of people, they found signature genetic patterns that appeared to be signs of elevated risk of the disease.
“We’re pretty convinced in schizophrenia, we’re getting involved very late in the game,” Insel said. “It’s a little bit like for heart disease we only used to see patients when they had a heart attack. Wouldn’t it be great if we could figure out who was at risk for schizophrenia and give them all the support they need, so they don’t actually become psychotic?”
Already, researchers are planning their next project, including studying even greater numbers of people with disease and without. They also hope to use advances in stem cell biology and genome editing tools to begin to figure out what genetic changes do to alter cell function and cause disease.