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How big science failed to unlock the mysteries of the human brain

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How big science failed to unlock the mysteries of the human brain


Even if it were possible to record all spikes from all neurons at once, he argued, a brain doesn’t exist in isolation: in order to properly connect the dots, you’d need to simultaneously record external stimuli that the brain is exposed to, as well as the behavior of the organism. And he reasoned that we need to understand the brain at a macroscopic level before trying to decode what the firings of individual neurons mean.  

Others had concerns about the impact of centralizing control over these fields. Cornelia Bargmann, a neuroscientist at Rockefeller University, worried that it would crowd out research spearheaded by individual investigators. (Bargmann was soon tapped to co-lead the BRAIN Initiative’s working group.)

There isn’t a single, agreed-upon theory of how the brain works, and not everyone in the field agreed that building a simulated brain was the best way to study it.

While the US initiative sought input from scientists to guide its direction, the EU project was decidedly more top-down, with Markram at the helm. But as Noah Hutton documents in his 2020 film In Silico, Markram’s grand plans soon unraveled. As an undergraduate studying neuroscience, Hutton had been assigned to read Markram’s papers and was impressed by his proposal to simulate the human brain; when he started making documentary films, he decided to chronicle the effort. He soon realized, however, that the billion-dollar enterprise was characterized more by infighting and shifting goals than by breakthrough science.

In Silico shows Markram as a charismatic leader who needed to make bold claims about the future of neuroscience to attract the funding to carry out his particular vision. But the project was troubled from the outset by a major issue: there isn’t a single, agreed-upon theory of how the brain works, and not everyone in the field agreed that building a simulated brain was the best way to study it. It didn’t take long for those differences to arise in the EU project. 

In 2014, hundreds of experts across Europe penned a letter citing concerns about oversight, funding mechanisms, and transparency in the Human Brain Project. The scientists felt Markram’s aim was premature and too narrow and would exclude funding for researchers who sought other ways to study the brain. 

“What struck me was, if he was successful and turned it on and the simulated brain worked, what have you learned?” Terry Sejnowski, a computational neuroscientist at the Salk Institute who served on the advisory committee for the BRAIN Initiative, told me. “The simulation is just as complicated as the brain.” 

The Human Brain Project’s board of directors voted to change its organization and leadership in early 2015, replacing a three-member executive committee led by Markram with a 22-member governing board. Christoph Ebell, a Swiss entrepreneur with a background in science diplomacy, was appointed executive director. “When I took over, the project was at a crisis point,” he says. “People were openly wondering if the project was going to go forward.”

But a few years later he was out too, after a “strategic disagreement” with the project’s host institution. The project is now focused on providing a new computational research infrastructure to help neuroscientists store, process, and analyze large amounts of data—unsystematic data collection has been an issue for the field—and develop 3D brain atlases and software for creating simulations.

The US BRAIN Initiative, meanwhile, underwent its own changes. Early on, in 2014, responding to the concerns of scientists and acknowledging the limits of what was possible, it evolved into something more pragmatic, focusing on developing technologies to probe the brain. 

New day

Those changes have finally started to produce results—even if they weren’t the ones that the founders of each of the large brain projects had originally envisaged. 

Last year, the Human Brain Project released a 3D digital map that integrates different aspects of human brain organization at the millimeter and micrometer level. It’s essentially a Google Earth for the brain. 

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Donald ’67, SM ’69, and Glenda Mattes

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Donald ’67, SM ’69, and Glenda Mattes


Don Mattes started giving to the Picower Institute for Learning and Memory at MIT before he himself was diagnosed with Alzheimer’s disease. Since his death in 2020, his wife, Glenda, has carried forward Don’s passion for its work. “My wish is that no one ever has to go through the horrors of Alzheimer’s disease ever again,” Glenda says. The Matteses have also supported the Koch Institute for Integrative Cancer Research at MIT.

Legacy sparks hope. An early key employee of Andover Controls who later ran the company’s European operations, Don visited six continents with Glenda during their 30-year marriage—often to ski or bicycle. “Don’s was a life well lived, just too short,” Glenda says. The couple made provisions in their estate plan to support the Picower Institute. After Don died, Glenda made a gift to MIT of real estate that established both endowed and current-use funds there to support research on Alzheimer’s, dementia, and other neurodegenerative diseases. Glenda is a cancer survivor, and the gift also endowed a fund in the couple’s name at the Koch Institute.

Great discoveries being made at MIT: “Don always said the best thing he got from MIT was being taught how to think,” Glenda says. “MIT is an amazing place. Picower Institute director Li-Huei Tsai and her team are doing more than looking for a treatment for Alzheimer’s. They’re looking for the root cause of the disease. I am also fascinated with the Koch’s melding of engineering and biology. The chances they are going to solve the cancer issue someday are very high.” 

Help MIT build a better world.
For more information, contact Amy Goldman: (617) 253-4082;  goldmana@mit.edu. Or visit giving.mit.edu/planned-giving.

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Investing in women pays off

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Investing in women pays off


“Starting a business is a privilege,” says Burton O’Toole, who worked at various startups before launching and later selling AdMass, her own marketing technology company. The company gave her access to the HearstLab program in 2016, but she soon discovered that she preferred the investment aspect and became a vice president at HearstLab a year later. “To empower some of the smartest women to do what they love is great,” she says. But in addition to rooting for women, Burton O’Toole loves the work because it’s a great market opportunity. 

“Research shows female-led teams see two and a half times higher returns compared to male-led teams,” she says, adding that women and people of color tend to build more diverse teams and therefore benefit from varied viewpoints and perspectives. She also explains that companies with women on their founding teams are likely to get acquired or go public sooner. “Despite results like this, just 2.3% of venture capital funding goes to teams founded by women. It’s still amazing to me that more investors aren’t taking this data more seriously,” she says. 

Burton O’Toole—who earned a BS from Duke in 2007 before getting an MS and PhD from MIT, all in mechanical engineering—has been a “data nerd” since she can remember. In high school she wanted to become an actuary. “Ten years ago, I never could have imagined this work; I like the idea of doing something in 10 more years I couldn’t imagine now,” she says. 

When starting a business, Burton O’Toole says, “women tend to want all their ducks in a row before they act. They say, ‘I’ll do it when I get this promotion, have enough money, finish this project.’ But there’s only one good way. Make the jump.”

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Preparing for disasters, before it’s too late

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Preparing for disasters, before it’s too late


All too often, the work of developing global disaster and climate resiliency happens when disaster—such as a hurricane, earthquake, or tsunami—has already ravaged entire cities and torn communities apart. But Elizabeth Petheo, MBA ’14, says that recently her work has been focused on preparedness. 

It’s hard to get attention for preparedness efforts, explains Petheo, a principal at Miyamoto International, an engineering and disaster risk reduction consulting firm. “You can always get a lot of attention when there’s a disaster event, but at that point it’s too late,” she adds. 

Petheo leads the firm’s projects and partnerships in the Asia-Pacific region and advises globally on international development and humanitarian assistance. She also works on preparedness in the Asia-Pacific region with the United States Agency for International Development. 

“We’re doing programming on the engagement of the private sector in disaster risk management in Indonesia, which is a very disaster-prone country,” she says. “Smaller and medium-sized businesses are important contributors to job creation and economic development. When they go down, the impact on lives, livelihoods, and the community’s ability to respond and recover effectively is extreme. We work to strengthen their own understanding of their risk and that of their surrounding community, lead them through an action-planning process to build resilience, and link that with larger policy initiatives at the national level.”

Petheo came to MIT with international leadership experience, having managed high-profile global development and risk mitigation initiatives at the World Bank in Washington, DC, as well as with US government agencies and international organizations leading major global humanitarian responses and teams in Sri Lanka and Haiti. But she says her time at Sloan helped her become prepared for this next phase in her career. “Sloan was the experience that put all the pieces together,” she says.

Petheo has maintained strong connections with MIT. In 2018, she received the Margaret L.A. MacVicar ’65, ScD ’67, Award in recognition of her role starting and leading the MIT Sloan Club in Washington, DC, and her work as an inaugural member of the Graduate Alumni Council (GAC). She is also a member of the Friends of the MIT Priscilla King Gray Public Service Center.

“I believe deeply in the power and impact of the Institute’s work and people,” she says. “The moment I graduated, my thought process was, ‘How can I give back, and how can I continue to strengthen the experience of those who will come after me?’”

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