CAMBRIDGE, Mass. – What a way to celebrate World Brain Day, July 22, with a big bang.

Philanthropist Ted Stanley announced a $650 million donation to the Broad Institute, a collaborative research enterprise created in 2004 by MIT and Harvard, one of the largest gifts ever to fund biomedical research to study mental illness targeting genomic structure and translational medicine.

Dr. Thomas Insel, director of the National Institute of Mental Health, hailed the $650 million gift, saying that federal support for biomedical research had stalled out over the last decade.

“We’re at a point where we have the tools to be able to answer these questions,” he said, as reported in the Boston Globe. “We have the samples. We just haven’t had the funds to be able to do the actual [gene] sequencing that we need to.”

The large gift fits well into the research framework that Insel has been advocating at NIMH. In 2013, Insel launched the Research Domain Criteria in 2013 to transform diagnosis of mental illness by incorporating genetics, imaging and cognitive sciences to lay to foundation of a new classification system.

“For scientists, we want people to begin going beyond this classification by symptoms and get deeper into the biology at many different levels – genetics, imaging, and cognition,” he told ConvergenceRI in an interview on May 9, 2013, following his talk, “Rethinking Mental Illness,” at a Brown University Department of Psychiatry and Human Behavior’s research symposium at Butler Hospital.

The research, according to the Broad Institute, seeks to accomplish four major goals:
• Create a complete list of all genes that play roles in severe psychiatric disorders, including schizophrenia, bipolar disorder, and autism, putting together a comprehensive catalogue of the genetic variations that underlies mental illness.
• Reveal the biological pathways in which these genes act, working with new techniques that allow scientists to manipulate and measure the dynamic activity of cells, determining where, when and how these genes act in human brain cells – and how in psychiatric patients these processes may go awry.
• Develop cellular and animal models that faithfully mimic the genetic variation and biochemical processes seen in human disorders, using cutting-edge techniques such as genome editing.
• Develop chemicals to modulate biological pathways to serve as drug leads, building upon the Broad Institute’s Therapeutics Platform and its ability to create and screen hundreds of thousands of compounds, in order to identify molecules that can precisely influence specific biological pathways relevant to psychiatric disorders.

The announcement of the gift was timed to coincide with a large genomic study of schizophrenia in Nature by researchers, including many from the Broad Institute, that identified 108 chromosomal sites in the human genome that were associated with the disease – 83 of which had not been previously reported. “Schizophrenia’s genetic skyline is rising,” according to the National Institute of Mental Health news release. 

“I think this is an unprecedented commitment, with the potential to be transformative,” said Dr. Audrey Tyrka, director of research at Butler Hospital. “That amount of money -- $650 million – is remarkable,” noting that the entire budget of the NIMH is $1.5 billion a year.

More importantly, she continued, “this kind of commitment – and the excitement around the work that can be done, will hopefully spur greater investments by government, by foundations and by other philanthropists.”

To put the size of the gift in perspective, the size of the gift to establish the world-class Norman Prince Neurosciences Institute in August 2009 was $15 million, the largest single philanthropic gift in Rhode Island Hospital’s history. Similarly, in November 2013, Tom and Cathy Ryan’s $15 million donation to the University of Rhode Island established the George & Anne Ryan Institute for Neuroscience. Together, those two gifts are about 5 percent of the total of the Stanley gift.

The gift is not without some precedent. Microsoft's co-founder Paul G. Allen has given about $500 million to provide support for the Allen Institute for Brain Science in Seattle, Wash.

The Simons Foundation Autism Research Initiative has given more than $200 million to support research on autism, including a $1.2 million grant in 2013 to create a first-of-its-kind confidential registry of every individual diagnosed with autism in Rhode Island, undertaken by the R.I. Consortium for Autism Research and Treatment.

Moving from research to the marketplace
As promising as the new $650 million investment in biomedical research and translational genomics may be, the pathway to new clinical treatments developed for mental illness and brain disorders will take some time, according to Kollol Pal, the CEO of Mnemosyne Pharmaceuticals, a Providence-based drug R&D firm researching promising new opportunities for small molecule drugs to treat neuropsychiatric disorders.

Mnemosyne has raised $11.5 million in Series A financing, including most recently $6 million in July of 2013, with new investment support coming from Atlas Venture and continued support from Clal Biotechnology Industries. 



Their research platform – initially focused on schizophrenia – has now branched out to include drug development opportunities for depression and Rett Syndrome [a genetic neurodevelopmental disorder that occurs almost exclusively in girls]. There is a potential to enter into clinical partnerships as early as 2015, according to Pal.

“I think that understanding the molecular pathways of all these diseases is beneficial in the long run,” Pal told ConvergenceRI. “I would be surprised if schizophrenia and depression are linked to a single gene, but I don’t know that for a fact."

Pal was hesitant to say that the new research platform was going to immediately speed up the development of new drugs entering the marketplace. “In cancer, people have been working on the cancer genome for a long, long time,” he said. “We’re just seeing drugs hitting the marketplace.”

Pal agreed that a better understanding of the basic biology of these mental diseases was going to be important in finding more effective treatments. Another very significant benefit of the $650 million gift, he continued, is the ability of scientists to ask for and received increased funding. “There is a direct correlation between knowledge gained and the funding available,” he said.

The largesse of the gift may also spur venture capital investments in companies developing new compounds to treat mental illnesses such as depression, Pal continued, citing recent IPO activity. “The VCs are taking notice, the public markets are taking notice.”

For Rhode Island, the lessons to be gleaned from the $650 million research investment is the importance of collaborative research as a platform for attracting new investments, according to Pal. And, to pay better attention to what is happening in Cambridge.

“What I’m hearing is that lab space in Cambridge is very hard to get,” he said. “I think the opportunity for Rhode Island to tap into what is going on in Cambridge is very significant.”

Pal cited the recent conversation with Dr. Anne S. De Groot in Convergence. [See link to article below.]

“She talks about a skills gap in Rhode Island; I completely agree with that. I think the way that Rhode Island has to approach it is to attract the people, the talent, the companies from Boston and Cambridge, and from Connecticut, in a model very similar to what Mnemosyne has done.”

Pal added: “I’ve had no push back from [VC firms], asking why are we in Providence. There are no problems with what we do or how we operate.”

At the end of the day, Pal continued, “Part of the incentive to move to Providence has to be financial,” citing the initial support his firm received from the Slater Technology Fund. “There has to be other seeding opportunities to attract [talent] and other companies out of Eastern Connecticut and Cambridge to come into Rhode Island.”

Nature, nurture, genes and changing behavior
For Butler’s Tyrka, the new investment in translational biological research at the Broad Institute is an important focus, but she cautioned that there were other factors that can influence mental illness, such as environment, social supports and education.

“There is a lot of research showing how interactions and environmental experiences can change your psychological [situation],” Tyrka told ConvergenceRI in a recent interview. “Social support and education – and how society responds – can influence [a patient’s condition].

Beyond the emphasis on biology, Tyrka said that there is emerging evidence that psycho-social treatments can influence the biology. “Butler Hospital has some ongoing work to study changes that may occur in the biology of these conditions in response to treatments,” she said.

Using a medical model, she explained, using diabetes as an example, is one way of looking at the problem. “If a person has diabetes, they need to take insulin, check their blood sugar. But they also need to change what’s in their refrigerator, and their exercise patterns, so that it requires a whole change in lifestyle.”

Elements of behavior, mood and affective responses to your environment, Tyrka continued, “These are areas that need attention to help unravel the causes and [create effective] treatments.”

She cited that a person can take a pill to reduce cravings for alcohol. “But what if your partner is drinking heavily in your presence?” she asked.

Some early research findings at Butler has indicated that pyscho-social treatments and therapy, she continued, can change the biology. 

Tyrka said that further identifying the genetic associations with mental illnesses would have great value. “Using that information to really unfold the biology, to identify those targets and those genetic molecular pathways in mental illnesses, first seeing those targets and then manipulating those genes, can have a major and lasting impact on these devastating conditions,” she said.

Further, she hoped that such research might also focus on the disease of addiction. “Without question, it’s a real scourge, with the epidemic of overdoses as well as the morbidity – the pain and suffering and costs to individuals and families and to society – is enormous,” she said. “We don’t know very much about the underlying biology. Such a [similar] investment – or anything close to it – would have a major impact on this devastating illness.”

At the other end of the spectrum
For Robert Crossley, the president and CEO of East Bay Center, a community mental health center, the largesse of a $650 million gift to study the genomics of mental illness is light years away from the dire situation his agency is confronting: the aggressive dismantling and under funding of the community safety net for Rhode Islanders with mental health disorders.

“In Rhode Island, we are really being cut to the bone,” Crossley said, citing the loss of state contracts to treat the uninsured and the underinsured.

The assumption is that the new Medicaid expansion will pick up these folks, but Crossley expressed doubts that the transition would work. “Many still remain uninsured, they may not fit into the income guidelines to get on Medicaid, and even if they could afford a private [health insurance] plan, they many not be able to afford the co-pays and the deductible that go with that.”

According to Crossly, there are about 1,000 people statewide with serious and persistent mental illness that are affected by the R.I. General Assembly’s $10 million budget cut in services in the FY 2015 budget, with about 100 such clients at East Bay.

Unless these patients say that they are ready to kill themselves, Crossley continued, “We can’t afford to provide them services.”

In the last eight years, there has been a 30 percent increase in demand for services at East Bay, according to Crossley.

The ongoing epidemic in accidental overdoses and addiction in Rhode Island is a case in point, Crossley continued. “We live in a quick fix society,” he said. “My [problems] will be addressed by a pill, give me a pill,” he said. “There are many situational factors; when the economy tanks, when people lose their jobs, when parents fight. These are the root causes of these issues. Unless people get the support, the educational help, the peer groups, unless they can talk about their issues, [recovery will be difficult], no matter how many pills you give them.”

More than an acute medical condition, addiction is a chronic illness that requires a continuum of care.

For Crossley, the future financial viability of the community mental health center is the larger, overarching issue. He said that he has begun conversations with the two major hospital systems in Rhode Island about possible partnerships.

“We’re grappling with the financial realities right now,” he said. “The co-location and integration of primary care and behavioral health makes a lot of sense. We can help them in case management, counseling, medication adherence, smoking and drinking cessation.”

No one knows who will get the money in the future, Crossley continued. But, he added, “I don’t see our [legislative] leadership changing anything anytime soon. They don’t [want to] fund mental health services for children and adults.”