NEUROSCIENCE Building a vast digital simulation of the brain could transform neuroscience and medicine and reveal new ways of making more powerful computers By Henry Markram IT’S TIME TO CHANGE THE WAY WE STUDY THE BRAIN. Reductionist biology—examining to investigate the parts and then reas- individual brain parts, neural circuits semble them to re-create the whole. and molecules—has brought us a long Putting things together to devise a way, but it alone cannot explain the complete simulation of the human workings of the human brain, an in- brain is the goal of an undertaking formation processor within our skull that intends to construct a fantastic that is perhaps unparalleled any- new scientific instrument. Nothing ) where in the universe. We must con- quite like it exists yet, but we have be- struct as well as reduce and build as gun building it. One way to think of well as dissect. To do that, we need a this instrument is as the most power- new paradigm that combines both ful flight simulator ever built—only analysis and synthesis. The father of rather than simulating flight through AND www.humanconnectomeproject.org reductionism, French philosopher open air, it will simulate a voyage ( René Descartes, wrote about the need through the brain. This “virtual brain” IN BRIEF Imaging Neuro of Laboratory Computer simulation will intro­ By the year 2020 digital brains A sim brain can act as a stand­in duce ever greater verisimilitude in­ may be able to represent the inner for the genuine article, thus foster­ Imaging Biomedical for Center Martinos to digital depictions of the work­ workings of a single brain cell or ing a new understanding of autism ings of the human brain. even the whole brain. or per mitting virtual drug trials. COURTESY OF ARTHUR W. TOGA TOGA W. ARTHUR OF COURTESY BUCKNER RANDY 50 Scientific American, June 2012 © 2012 Scientific American June 2012, ScientificAmerican.com 51 © 2012 Scientific American will run on supercomputers and incorpo­ Henry Markram directs the Blue Brain Project at the Swiss Federal rate all the data that neuroscience has Institute of Technology in Lausanne. He has done extensive work on how neurons interconnect, communicate and learn. He also discovered generated to date. fundamental principles of brain plasticity and is co-discoverer of the A digital brain will be a resource for the intense world theory of autism and the theory of how the brain entire scientific community: researchers computes as a liquid that is constantly perturbed. will reserve time on it, as they do on the biggest telescopes, to conduct their experi­ ments. They will use it to test theories of at them simply as sets of symptoms. The ing to—at least, not all of it. We intend to how the human brain works in health and breadth of this perspective would allow reproduce the myriad connections among in disease. They will recruit it to help them us to move forward to develop a genera­ brain cells by different means. develop not only new diagnostic tests for tion of treatments that selectively target The key to our approach is to craft the autism or schizophrenia but also new ther­ the underlying abnormalities. basic blueprint according to which the apies for depression and Alzheimer’s dis­ The second reason is that computing is brain is built: the set of rules that has guid­ ease. The wiring plan for tens of trillions of fast approaching barriers to further devel­ ed its construction over evolution and neural circuits will inspire the design of opment. Computers cannot do many tasks does so anew in each developing fetus. In brainlike computers and intelligent robots. that animal brains do effortlessly, despite theory, those rules are all the information In short, it will transform neuroscience, the inexorable increase in processing pow­ we need to start building a brain. The medicine and information technology. er. For instance, although computer scien­ skeptics are right: the complexity they tists have made huge progress in visual generate is daunting—hence our need for BRAIN IN A BOX recognition, the machines still struggle to supercomputers to capture it. But unravel­ scientists could be running the first simu­ make use of context in a scene or to use ar­ ing the rules themselves is a far more trac­ lations of the human brain by the end of bitrary scraps of information to predict fu­ table problem. If we pull it off, there is no this decade, when supercomputers will be ture events in the way the brain can. logical reason why we cannot apply the powerful enough to support the massive Moreover, because more powerful com­ blueprint in the same way that biology number of calculations needed. The in­ puters require more energy, supplying their does and build an “in silico” brain. strument will not require that all myster­ needs will one day no longer be feasible. The kind of rules we are talking about ies of the brain be unraveled first. Instead The performance of today’s supercomput­ are ones that govern the genes that lead to it will furnish a framework to accommo­ ers is measured in petaflops—quadrillions the types of cells there are in the brain and date what we do know, while enabling us of logic operations per second. The next the underlying plan for the way those cells to make predictions about what we do not. generation, due around 2020, will be 1,000 are distributed and how they are connect­ Those predictions will show us where to times faster and will be measured in exa­ ed. We know that such rules exist because target our future experiments to prevent flops—quintillions of operations per sec­ we discovered some of them while laying wasted effort. The knowledge we generate ond. By itself, the first exa­scale machine the groundwork for the HBP. We started will be integrated with existing knowl­ will probably consume around 20 mega­ doing that almost 20 years ago by measur­ edge, and the “holes” in the framework watts, roughly the energy requirement of a ing the characteristics of individual neu­ will be filled in with increasingly realistic small town in winter. To create increasing­ rons. We collected vast amounts of data detail until, eventually, we will have a uni­ ly powerful computers that perform some about the geometric properties of different fied working model of the brain—one that of the simple but useful things that hu­ neuronal types and digitally reconstructed reproduces it accurately from the whole mans are capable of in an energy­efficient hundreds of them in three dimensions. brain down to the level of molecules. way, we need a radically new strategy. Using a painstaking method called patch Building this instrument is the goal of We could do worse than take inspira­ clamping, which involves placing the tip the Human Brain Project (HBP), an initia­ tion from the human brain, which per­ of a microscopic glass pipette up against tive involving about 130 universities forms a range of intelligent functions on a a cell membrane to measure the voltage around the world. The HBP is one of six mere 20 or so watts—a million times fewer across its ion channels, we also recorded projects competing for a glittering prize, than an exa­scale machine and equivalent the neurons’ electrical properties. up to €1 billion to be provided over 10 to a weak lightbulb. For that, we need to In 2005 modeling a single neuron took years by the European Union to each of understand the multilevel organization of a powerful computer and a three­year two winners, who will be announced in the brain, from genes to behavior. The Ph.D. project. It was clear that more ambi­ February 2013. knowledge is out there, but we need to tious goals would soon become achiev­ We need the simulator for at least two bring it together—and our instrument will able, however, and that we could model reasons. In Europe alone, brain diseases provide the platform on which to do that. larger elements of brain circuitry even if affect 180 million people, or roughly one Critics say that the goal of modeling our knowledge of those elements was in­ in three—a number that is set to grow as the human brain is unachievable. One of complete. At the Brain Mind Institute at the population ages. At the same time, their principal objections is that it is im­ the Swiss Federal Institute of Technology pharm aceutical companies are not invest­ possible to reproduce the connectivity in Lausanne, we launched one of the ing in new treatments for the ailing ner­ among the brain’s 100 trillion synapses be­ HBP’s predecessors, the Blue Brain Proj­ vous system. A holistic view of the brain cause we cannot measure it. They are cor­ ect. We would build what we call “unifying would enable us to reclassify such diseas­ rect that we cannot measure the web of computer models”—models that integrate es in biological terms rather than looking connections, which is why we are not go­ all existing data and hypotheses about a 52 Scientific American, June 2012 © 2012 Scientific American given brain circuit, while reconciling con­ watched, the neurons began to speak to equations on supercomputers. We also flicts in that information and highlighting one another. “Spikes,” or action poten­ need to create software that will construct where knowledge is lacking. tials—the language of the brain—spread a brain that conforms to the inherent biol­ through the column as it began to work as ogy. We call it the “brain builder.” SYNTHESIS BIOLOGY an integrated circuit.