"Nothing quite like it exists yet, but we have begun building it," Henry Markram wrote in the June 2012 issue of Scientific American. He was referring to a "fantastic new scientific instrument"—a biologically realistic and detailed model of a working human brain hosted on supercomputers. Markram, who directs the Brain Mind Institute at the École Polytechnique Fédérale de Lausanne in Switzerland, has been working on the Blue Brain Project, more recently known as the Human Brain Project, since 2005. "A digital brain will be a resource for the entire scientific community: researchers will reserve time on it, as they do on the biggest telescopes, to conduct their experiments," Markram wrote in SA. "They will use it to test theories of how the human brain works in health and in disease. They will recruit it to help them develop not only new diagnostic tests for autism or schizophrenia but also new therapies for depression and Alzheimer's disease. The wiring plan for tens of trillions of neural circuits will inspire the design of brainlike computers and intelligent robots. In short, it will transform neuroscience, medicine and information technology."
This is a segment from Year 3 of Bluebrain, Noah Hutton's 10-Year documentary on the Blue Brain Project. Hutton's first documentary feature was Crude Independence, a portrait of small-town life during the present-day oil boom in North Dakota. The film premiered at SXSW in 2009. Hutton has since directed music videos (including one for neuroscientist Joe LeDoux's band The Amygdaloids), the concert documentary King for Two Days, and freelance work that helps finance ongoing personal projects, such as Bluebrain.
Markram has claimed, at various times, that he can complete this ambitious project within 10 years. His critics argue that his ultimate goal is unachievable because the human brain is too complex to simultaneously simulate at every level, from the molecule to the cortex. Say one wanted to build an exact replica of a large and intricate circuit board. One would first need to map every wire linking every component and then re-create these links. In the same way, making a model of the human brain requires knowing the trillions of connections between its neurons. A map of all the connections between neurons in a brain is called a connectome, and no such map exists for the human brain. In fact, the only organism with a complete connectome is the tiny nematode C. elegans, which has 302 neurons total. The human brain has more than 80 billion neurons and 100 trillion connections between those cells.
Markram counters that one can build a realistic virtual brain without understanding the function of every last molecule or pinpointing every single connection in a living brain. In December 2006 Markram and his team simulated a rat's neocortical column, a small functional unit of brain tissue containing about 10,000 neurons. A rat's brain has perhaps 100,000 of these columns, whereas the human brain likely has more than two million of them, each of which comprises 100,000 neurons. Markram did not create a connectome for the rat's cortical column. Instead, he gathered all the available information about how the many different types of neurons in a single column connect and programmed his virtual cells to link up in the same way. Instead of manually connecting his virtual neurons one by one, he's hoping to get his supercomputers to do the linking on their own, following the same rules—genetic, geometric or otherwise—that govern neural connections in a fleshy brain.
Mapping connections is just one of the many hurdles Markram will have to overcome or circumvent to make his project a success. Another barrier is funding: Right now Markram is competing with five other teams for a one-billion-euro grant from the European Commission. Debate about how that money is best spent—and whether Markram should even be in the running—is heated.
To capture the controversy, the science and the evolution of this scientific enterprise, independent filmmaker Noah Hutton flies from New York City to Lausanne each year. Hutton has been working on this 10-year documentary since 2009, when he first learned of the Blue Brain project by listening to Markram's TED talk. Above, you can watch a segment from the third year of this ongoing documentary and, below, you can read a Q&A with Hutton.
Tell us a little about your documentary. Why are you making this film?
This is a 10-year documentary film that I began making in 2009, focusing on The Blue Brain Project in Lausanne, Switzerland. It's going to continue to focus on Blue Brain at its center, but starting this year I'm expanding its scope to explore the work of some other ambitious projects and labs that are trying to understand the brain. I'm hoping that the film can provide a platform over the rest of this decade for a conversation about the relative accomplishments, advantages and potential weaknesses of the paths taken by each project towards that understanding—be it mapping the brain, poking and prodding it or building it with supercomputers—and can become sort of a state-of-the-union documentary that tracks the evolution of our understanding of the brain over the rest of this decade.
So I am making the film first from a place of personal interest in these pursuits. We've seen some strong cases presented by some prominent figures in recent years, and I am very interested to see how these projects unfold over the next decade. I also think that a documentary film, like some long-form written journalism, allows for a certain kind of independent conversation and exploration to take place that might not otherwise appear in the public forum. And I've been interested to see how that exploration might unfold over the course of a decade—with short-length, edited updates to the film released publicly each year the film is getting made and these projects are releasing the results of their work. It also makes for an interesting relationship with the subjects of the film, in terms of the normal sequence of events of shooting footage for a documentary, editing it and then presenting the completed version. Here the subjects see a glimpse each year of where this film about them is heading, even as it's still being made.
Are you working alone?
I've worked with a small crew on some of the interviews in the U.S. so far, but I've made the yearly trips to Blue Brain in Switzerland on my own, because I've been self-funding this project through my production company here in New York City, as I have wanted to stay independent. I'm actively looking to secure outside funding from a source not tied to any of the subjects or projects in the film so that I can make more trips, stay longer in places and work with a crew. I'm trying to find a funder who is open to the timeline and is interested in seeing this film get made.
What are your main sources of inspiration in making this documentary? Are there particular movies or directors that have guided your own thinking?
My main source of inspiration in making the film is the thing that is at the heart of all of the scientists' pursuits in the film: the human quest to explore and understand the brain, to try to use the most advanced machines of science to reveal this great unknown within us. And the fact that some believe it to be an impossible quest in their lifetimes, while others believe it will be achieved in theirs—maybe even in 10 years—to me, this makes for an inspiring subject. Certainly the work of other filmmakers who have done longitudinal projects—I think first of Seven Up! and there are several other interesting ones—the ambitions and structures of these longitudinal films have inspired me.
What has Henry Markram achieved so far?
What I understand on a general level is that Blue Brain has begun to create the infrastructure for how they see the future of 21st-century neuroscience. They talk about it in terms of building new facilities. That means building a biologically realistic simulation of a scalable, functional unit of cortex—the column—which can be used to do experiments, and also building more efficient data-mining tools that they will use to continue to feed in biological data to their simulations. They also speak of some interesting insights gleaned thus far from the behavior of the network they're simulating, which they've presented in papers and at some conferences.
It's also worth noting that Markram's earlier biological work at the cellular level, beginning with his work with Bert Sakmann, is widely regarded now as part of the bedrock of the field. I first heard about Markram about a year before I saw his TED talk, when I was assigned as an undergrad studying neuroscience in 2008 to read and write a summary of one of his widely cited papers from the '90s.
Do you think Markram will achieve his ultimate goal of reverse engineering the human brain as a biologically realistic computer model? Do you think that reaching that goal matters?
I don't have a prediction. I don't feel I know enough yet to make one. Some do seem to make predictions with their tone of coverage of Blue Brain, and I'm somewhat skeptical of anyone in the press or elsewhere dooming it to fail or painting an excessively grim portrait at this stage without getting specific and staying open. Because Blue Brain is not off in the woods, impervious somehow to legitimate feedback—what I have learned is that they are periodically reviewed by their funders, by an outside panel of experts—they continue to do well and be funded, and continue to move forward. And from spending time there, I can say from my own perspective that the project is made up of very sharp scientists from around the world, and they are very detailed in their thinking—most of all, Henry Markram.
On the question of whether Blue Brain reaching its goal matters, I would say I'm not really in it to be rooting for one thing or another, and I'm not even sure how one would predict whether reaching their goal will eventually matter or not at this early stage. Though if evidence mounts that understanding the brain through Blue Brain's methods will lead to medical advances in treating diseases or damage to the brain, I am rooting. From a more philosophical point of view, I can say for myself that in making this film, I'm equally interested in success as I am in failure. Because if we have mapped the brain, fully simulated it or otherwise grappled with it comprehensively, and if we're still not yet understanding it or watching it come alive, what are we missing?
Markram is competing with five other research groups for a mega-grant from the European Commission of one billion Euros ($1.4 billion) over 10 years. Many scientists have argued that Markram's project is so daunting and, perhaps, impossible that the money is better spent elsewhere. Do you have an opinion on the matter?
I trust that with so much money at stake, the European Commission has vetted the proposals at a pretty high level, so I don't see what I would know that they don't towards this question of where the money is best spent. But I am of course aware of the criticism you're referencing. I wonder if it's helpful to look at this as more of a positive-sum thing for neuroscience on the whole—this is what Rafael Yuste of Columbia [University] told me this year when I interviewed him for the film. He said, in talking about the relationship of structural connectomics to functional brain simulation, that we too often view this as a zero-sum game, with clear winners and losers, when, in reality, the very fact that governments are carving out new pockets of funding for brain research of any kind, and that data is being gathered and analyzed at all—it's all a positive-sum affair in an age of longer life spans and increased rates of neurodegenerative conditions. So whether you agree with him or not, Markram has been very successful in raising the profile of a line of brain research and securing government funding for it. The fact that he is perhaps in the position to do so again, on a larger scale, and at the expense of any of those other projects that would not be funded, will inevitably charge the passions of supporters and critics alike.
I think this also has something to do with the nature of how the commission has structured this grant-awarding process—a call for flagship proposals, then a group of finalists battling it out for two mega-grants, thereby creating winners and losers, like any competition would. Another interesting question to ask is whether another brain-related project could have even made it into the final group, had Markram's not been there. I'm not sure about the answer to that, but this is where the positive-sum perspective comes into play for me.