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Human Brain Project: Henry Markram Plans to Spend €1Bn Building a Perfect Model of the Human Brain | Science | the Observer 08/11/13 14:39

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Human Brain Project: Henry Markram Plans to Spend €1Bn Building a Perfect Model of the Human Brain | Science | the Observer 08/11/13 14:39 Human Brain Project: Henry Markram plans to spend €1bn building a perfect model of the human brain | Science | The Observer 08/11/13 14:39 Human Brain Project: Henry Markram plans to spend €1bn building a perfect model of the human brain Henry Markram, co-director of the Human Brain Project, based in Lausanne, Switzerland, has been awarded €1bn by the EU. Photograph: Jean-Christophe Bott/EPA In a spartan office looking across Lake Geneva to the French Alps, Henry Markram is searching for a suitably big metaphor to describe his latest project. "It's going to be the Higgs boson of the brain, a Noah's archive of the mind," he says. "No, it's like a telescope that can span all the way across the universe of the brain from the micro the macro level." We are talking about the Human Brain Project, Markram's audacious plan to build a working model of the human brain – from neuron to hemisphere level – and simulate it on a supercomputer within the next 10 years. When Markram first unveiled his idea at a TEDGlobal conference in Oxford four years ago, few of his peers took him seriously. The brain was too complex, they said, and in any case there was no computer fast enough. Even last year when he presented a more detailed plan at a scientific meeting in Bern, showing how the requisite computer power would be available by 2020, many neuroscientists continued to insist it could not be done and dismissed his http://www.theguardian.com/science/2013/oct/15/human-brain-project-henry-markram Pagina 1 di 13 Human Brain Project: Henry Markram plans to spend €1bn building a perfect model of the human brain | Science | The Observer 08/11/13 14:39 claims as hype. The Blue Gene Q Supercomputer. Photograph: Jean- Christophe Bott/EPA Today, thanks to the largesse of the European Union, which awarded Markram €1bn last year to make his dream a reality, many of those naysayers are being forced to take him seriously. The gift, which comes on top of a state-of-the-art IBM Blue Gene computer from the Swiss government, makes Markram's unit at the Swiss Federal Institute of Technology in Lausanne the biggest dog on the neuro block. It also gives Markram a headstart on brain-mapping projects in Japan and the US, where Barack Obama is hoping to persuade Congress to award $3bn to a similar initiative called Brain (so far Obama has pledged $100m). The timing of Obama's initiative and the EU's award, the largest in its history, has led to talk of an international "brain race". But Markram argues that a better parallel is the Human Genome Project. Just as the decade-long effort to map the 3.3 billion base pairs that make up the 23 chromosomes in the human genome required close co- ordination between scientists worldwide, so Markram argues mapping the human brain in all its neural complexity will take a similarly co-operative international research effort. The problem, as he sees it, is that neuroscience has become hopelessly fragmented. Each year sees the publication of about 100,000 papers, but neuroscientists are so specialised they have trouble understanding each other. We know a lot about the organisation and interaction of individual neurons and there have been countless studies, using functional magnetic resonance imaging (fMRI), of brain regions at the scale of tens of millions of neurons, but we have little information about the scales in between. Nor do we have an integrated understanding of how events at the level of http://www.theguardian.com/science/2013/oct/15/human-brain-project-henry-markram Pagina 2 di 13 Human Brain Project: Henry Markram plans to spend €1bn building a perfect model of the human brain | Science | The Observer 08/11/13 14:39 genes, proteins and synapses cascade through the brain to produce behaviour and cognition. Markram points out that, using conventional approaches, it takes 20,000 experiments to map a neural circuit. Yet, in all, the brain contains 86 billion neurons. On top of that, to fully understand the operation of every synapse and how they interact with neurons in other parts of the neo-cortex, scientists would need to trace all of the 100 trillion connections between them – something that is impossible to do experimentally. But what if, instead of trying to map these neural structures piece by piece, we could tease out some underlying principles governing their morphology and architecture? What if we could use a supercomputer to run thousands of statistical simulations so as to predict the way that those neurons are likely to combine and then check the resulting models against real data from biology? Then in theory we could predict those structures and use them to reverse-engineer the human brain. That, in a nutshell, is the principle behind the Human Brain Project and the vision that drives Markram. "The fact is we are never going to experimentally map the human brain and people who think otherwise are deluding themselves," he says. "Instead, we have to search for the fundamental principles and then use those principles to construct a hypothesis of the bits of the brain no human has ever seen and no human will ever see. Then we have to test those hypotheses and refine the principles until our model gets better. Otherwise, we are just stabbing in the dark." When Markram speaks this way, it is easy to see how he raises other scientists' hackles. Markram's belief in the ability of computing technology to solve the big questions of neuroscience is messianic. It is a messianism he combines with the tousled good looks of an ageing matinée idol and an undeniable charisma that at TED in Oxford four years ago had some members of the audience spellbound. In a field dominated by big brains and even bigger egos, each mining their own esoteric field, Markram's big data approach to experimental neuroscience represents a cultural revolution. "We're saying look, if you think you're going to understand the brain on your own forget about it. We're going to have to work very differently. We're http://www.theguardian.com/science/2013/oct/15/human-brain-project-henry-markram Pagina 3 di 13 Human Brain Project: Henry Markram plans to spend €1bn building a perfect model of the human brain | Science | The Observer 08/11/13 14:39 going to have to work in teams, in swarms. To someone who is used to deciding what experiment they should do I can see how that might come across as antagonistic." Virtual brain. Illustration: Alexander Wells Markram's belief in the need for teamwork is rooted in his own experience as a brain researcher and his conviction that only neuroscience is capable of solving the deeper mysteries of how the electrical signals zinging between neurons produce consciousness and how interferences or malfunctions in those electrical channels produce disordered or "diseased" thinking. Markram credits the awakening of his interest in these subjects to a Latin teacher at the boarding school in Durban where, at the age of 13, he was sent from the rural South African farm where he was raised. Within a term, he had changed from a rugby playing jock with little interest in schooling to being obsessed with biology and trying to understand how a slight alteration in the biochemistry of the brain could lead to conditions such as depression and schizophrenia. This interest in biology led him to an undergraduate degree in medicine at the University of Cape Town where he hoped to specialise in psychiatry. But he quickly became disillusioned with what he saw as the discipline's lack of scientific rigour. "Psychiatry completely shocked me. The idea that you could write a computer programme to classify mental diseases and on that basis prescribe a medicine struck me as crazy." Instead, Markram switched to experimental neuroscience and in 1985 joined a Cape http://www.theguardian.com/science/2013/oct/15/human-brain-project-henry-markram Pagina 4 di 13 Human Brain Project: Henry Markram plans to spend €1bn building a perfect model of the human brain | Science | The Observer 08/11/13 14:39 Town laboratory directed by a young researcher named Rodney Douglas. It was Douglas, now an emeritus professor at the Swiss Federal Institute of Technology in Zurich, who first fired Markram's enthusiasm for lab work and, with his exceptionally steady hands – useful when stitching together neurons smaller than a pinhead, Markram was soon enjoying a meteoric rise. A PhD at the Weizmann Institute of Science, one of the leading research universities in Israel, was followed by postdoctorates at the National Institutes of Health in Bethesda, Maryland, and the Max Planck Institute for Medical Research in Heidelberg, Germany. Then, in 1995, Markram was lured back to the Weizmann as an associate professor. There he earned a formidable reputation as an experimenter, becoming the first researcher to patch two connected neurons simultaneously. This put him in a position to see how they interacted in response to differently timed electrical signals. A fundamental postulate of neuroscience is Hebb's rule – that neurons that fire together wire together. However, Markram discovered that the strength of these connections varies according to when impulses arrive and leave. If an input spike of electrical current occurs before an output spike and within a certain time window, on average the input connection was strengthened. However, if the input occurred after the output spike within the same time window, then the connection was weakened.
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