For years, Henry Markram has claimed that he can simulate the human brain in a computer within a decade. On 23 January 2013, the European Commission told him to prove it. His ambitious Human Brain Project (HBP) won one of two ceiling-shattering grants from the EC to the tune of a billion euros, ending a two-year contest against several other grandiose projects. Can he now deliver? Is it even possible to build a computer simulation of the most powerful computer in the world – the 1.4-kg (3 lb) cluster of 86 billion neurons that sits inside our skulls?
The very idea has many neuroscientists in an uproar, and the HBP’s substantial budget, awarded at a tumultuous time for research funding, is not helping. The common refrain is that the brain is just too complicated to simulate, and our understanding of it is at too primordial a stage.
Then, there’s Markram’s strategy. Neuroscientists have built computer simulations of neurons since the 1950s, but the vast majority treat these cells as single abstract points. Markram says he wants to build the cells as they are – gloriously detailed branching networks, full of active genes and electrical activity. He wants to simulate them down to their ion channels – the molecular gates that allow neurons to build up a voltage by shuttling charged particles in and out of their membrane borders. He wants to represent the genes that switch on and off inside them. He wants to simulate the 3,000 or so synapses that allow neurons to communicate with their neighbours.
Erin McKiernan, who builds computer models of single neurons, is a fan of this bottom-up approach. “Really understanding what’s happening at a fundamental level and building up – I generally agree with that,” she says. “But I tend to disagree with the time frame. [Markram] said that in 10 years, we could have a fully simulated brain, but I don’t think that’ll happen.”
Even building McKiernan’s single-neuron models is a fiendishly complicated task. “For many neurons, we don’t understand well the complement of ion channels within them, how they work together to produce electrical activity, how they change over development or injury,” she says. “At the next level, we have even less knowledge about how these cells connect, or how they’re constantly reaching out, retracting or changing their strength.” It’s ignorance all the way down.
“For sure, what we have is a tiny, tiny fraction of what we need,” says Markram. Worse still, experimentally mapping out every molecule, cell and connection is completely unfeasible in terms of cost, technical requirements and motivation. But he argues that building a unified model is the only way to unite our knowledge, and to start filling in the gaps in a focused way. By putting it all together, we can use what we know to predict what we don’t, and to refine everything on the fly as new insights come in.
The crucial piece of information, and the one Markram’s team is devoting the most time towards, is a complete inventory of which genes are active in which neurons. Neurons aren’t all the same – they come in a variety of types that perform different roles and deploy different genes. Once Markram has the full list – the so-called “single-cell transcriptome” – he is confident that he can use it to deduce the blend of different neurons in various parts of the brain, recreate the electrical behaviour of each type of cell, or even simulate how a neuron’s branches would grow from scratch. “We’re discovering biological principles that are putting the brain together,” he says.