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

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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.