Can The Human Brain Project Succeed?

Image: Getty Images

An ambitious effort to build human brain simulation capability is meeting with some very human resistance. On Monday, a group of researchers sent an open letter to the European Commission protesting the management of the Human Brain Project, one of two Flagship initiatives selected last year to receive as much as €1 billion over the course of 10 years (the other award went to a far less controversy-courting project devoted to graphene).

The letter, which now has more than 450 signatories, questions the direction of the project and calls for a careful, unbiased review. Although he’s not mentioned by name in the letter, news reports cited resistance to the path chosen by project leader Henry Markram of the Swiss Federal Institute of Technology in Lausanne. One particularly polarizing change was the recent elimination of a subproject, called Cognitive Architectures, as the project made its bid for the next round of funding.

According to Markram, the fuss all comes down to differences in scientific culture. He has described the project, which aims to build six different computing platforms for use by researchers, as an attempt to build a kind of CERN for brain research, a means by which disparate disciplines and vast amounts of data can be brought together. This is a "methodological paradigm shift" for neuroscientists accustomed to individual research grants, Markram told Science, and that's what he says the letter signers are having trouble with.

But some question the main goals of the project, and whether we're actually capable of achieving them at this point. The program's Brain Simulation Platform aims to build the technology needed to reconstruct the mouse brain and eventually the human brain in a supercomputer. Part of the challenge there is technological. Markram has said that an exascale-level machine (one capable of executing 1000 or more petaflops) would be needed to "get a first draft of the human brain", and the energy requirements of such machines are daunting.

Crucially, some experts say that even if we had the computational might to simulate the brain, we're not ready to. "The main apparent goal of building the capacity to construct a larger-scale simulation of the human brain is radically premature," signatory Peter Dayan, who directs a computational neuroscience department at University College London, told the Guardian. He called the project a "waste of money" that "can't but fail from a scientific perspective". To Science, he said "the notion that we know enough about the brain to know what we should simulate is crazy, quite frankly.”

This last comment resonated with me, as it reminded me of a feature that Steve Furber of the University of Manchester wrote for IEEE Spectrum a few years ago. Furber, one of the co-founders of the mobile chip design powerhouse ARM, is now in the process of stringing a million or so of the low-power processors together to build a massively parallel computer capable of simulating 1 billion neurons, about 1% as many as are contained in the human brain.

Furber and his collaborators designed their computing architecture quite carefully in order to take into account the fact that there are still a host of open questions when it comes to basic brain operation. General-purpose computers are power-hungry and slow when it comes to brain simulation. Analog circuitry, which is also on the Human Brain Project's list, might better mimic the way neurons actually operate, but, he wrote,

“as speedy and efficient as analog circuits are, they’re not very flexible; their basic behavior is pretty much baked right into them. And that’s unfortunate, because neuroscientists still don’t know for sure which biological details are crucial to the brain’s ability to process information and which can safely be abstracted away”

The Human Brain Project's website admits that exascale computing will be hard to reach: "even in 2020, we expect that supercomputers will have no more than 200 petabytes." To make up for the shortfall, it says, "what we plan to do is build fast storage random-access storage systems next to the supercomputer, store the complete detailed model there, and then allow our multi-scale simulation software to call in a mix of detailed or simplified models (models of neurons, synapses, circuits, and brain regions) that matches the needs of the research and the available computing power. This is a pragmatic strategy that allows us to keep build ever more detailed models, while keeping our simulations to the level of detail we can support with our current supercomputers."

This does sound like a flexible approach. But, as is par for the course with any ambitious research project, particularly one that involves a great amount of synthesis of disparate fields, it's not yet clear whether it will pay off.

And any big changes in direction may take a while. Although the proposal for the second round of funding will be reviewed this year, according to Science, which reached out to the European Commission, the first review of the project itself won't begin until January 2015.

Rachel Courtland can be found on Twitter at @rcourt.

ORIGINAL: Spectrum
By Rachel Courtland
Posted 9 Jul 2014 | 17:00 GMT

Developing neuroscience knowledge with the Human Brain Project

ORIGINAL: Science Omegaby Richard Walker
02 July 2013

Photo: Vesna Njagulj

What we don’t know today is how much detail is actually needed to reproduce brain function. The proof will come when we have a model with a certain level of detail that actually exhibits the function we are interested in.

Richard Walker 

The Human Brain Project Spokesman Richard Walker tells Editor Lauren Smith why he believes the initiative is capable of producing important new basic science, enabling medical discoveries and allowing new technologies...

In January, the European Commission announced two EU Future and Emerging Technologies (FET) flagship programmes, which would each be allocated €1bn in funding to drive forward radical scientific research across the continent and enable greater understanding of key elements in our society. One focus area was the wonder material graphene; the other the vast Human Brain Project (HBP), which hopes to gain profound insight into the nature of humanity, to develop new treatments for brain diseases and progress revolutionary computing technologies.

In the first of a two-part special on the latter, Richard Walker, of the HBP, explains to Editor Lauren Smith the vast scope, expec­tations and hopes that are being placed on this initiative, looking this time particularly at the elements of developing neuroscience understanding and brain disease treatments.

The HBP will build on, and subsume, what has been learnt already from the Blue Brain Project, both being led by Henry Markram at École polytechnique fédérale de Lausanne (EFPL) in Switzerland, and other neuroscience related models.

"The original idea did come through the Blue Brain Project," Walker begins. "And the Blue Brain did in turn come from a wealth of experience in electrophysiology. Markram started specifically looking at this area in the 1990s and made many important discoveries. It became fairly obvious at that point that the quantity of experimental work that was necessary to really understand the brain was just enormous. There were different routes being taken by people working in different parts of the world, addressing different measures, looking at various problems and using various species. So, putting all of this together to try and get a coherent picture was not possible.

"Markram considered the idea of using brain modelling simulation as an integration tool – to put everything that is known into a model that represents the brain at different levels of detail, whereby each new piece of knowledge is a new constraint on our modelling so that even the unknown parts of the model become even more tightly constrained as things go on."

The flagship concept
This fledgling idea was developed through the specifically Swiss initiative from 2005 to 2011, with the goal to provide a proof of concept and to illustrate the feasibility of this approach. The researchers involved built the basic tools necessary to integrate data into multiple level biologically detailed models.

"In parallel," Walker explains, "Europe was looking for new approaches to funding research. It came up with the flagship concept, to provide a very large amount of money for long-term visionary research. Markram was part of developing the concept of these flagships and so we saw the programme as a way of making a real leap in the scale of what we are doing."

The bigger international undertaking that would become the HBP looks to expand beyond the rat brain that was the focus of the earlier initiative, to the scope of the human brain. "Whereas Blue Brain looked exclusively at neurons," he says, "we wanted to get down to the molecular level, which is fundamental as this is where, for instance, disease happens. In doing that, we were also able to look at the applications of brain research. In the HBP, brain simulation is only one-third of it. The other two-thirds cover medical research – actually using our models to get new insight into brain disease and how to treat them – and information technology – using our knowledge of the brain to build new computing technologies."

The power of ICT
The first stage of the overall plan is to consolidate the massive volume of data that already exists in the relevant fields. Walker explains that the best way to do this is through exploiting the power of information communication technologies (ICT). The first step is to introduce six ICT platforms – 

• for neuroinformatics, 
• brain simulation, 
• high performance computing, 
• medical informatics, 
• neuromorphic computing, and 
• neurorobotics.

"These will be tools that we can use, on the one hand to collect the data and the other to put it into models, to provide the necessary computing power, to provide medical data (about the healthy brain) and add in developing technologies and to add in our brain models to robotics," Walker says.

"Our plan is to build these platforms and then make them available to the scientific community. The first version of these platforms is due to be ready in month 30, and from then on scientists will be able to apply to use our platforms just like you can apply for observation time at a telescope. Proposals will be peer reviewed and checked to make sure that they are feasible with the platform and be cost-effective; then the successful groups will be able to use our platforms to do experiments. We will not tell scientists what research they should do with the instruments, but we will help them to do their research using our instruments."

Once in place, it is anticipated that the brain modelling will have a wide-reaching impact on the research arena for pharmaceuticals and in turn support the development of new treatments for brain conditions over the decades to come.

"In our medical research, the first thing we want to do is federate data from hospitals that are participating in our study," Walker outlines. "Today, if you have a brain scan the doctor will look at it, diagnose you, and the scan will then go into the hospital archive for 10 or 15 years before it is destroyed. No research is going to use that data, which is immensely valuable. This is a very bad use of taxpayers’ money.

"What we would like to do is anonymise data from each brain scan so that it cannot be traced back to the individual, and then mine the data for biological signatures of disease. So, if you have a particular form of Alzheimer’s, we could look at how your brain is different, in respect to someone who has a different form of Alzheimer’s, or in respect to someone who is healthy. That is very valuable in itself, as today it is very hard to objectively diagnose people with any brain disease."

Towards objective testing
As he explains, current diagnosis is usually done in terms of symptoms, but very often people with the same symptoms may have very different problems in their brains and, conversely, people with the same problem may present to a doctor with very different symptoms. It is hoped that, within two or three years of the project commencing, there should be sufficient data to start being able to distinguish between patients with objectively different diseases.

"This has a very practical implication for pharmaceutical companies," Walker comments. "Today, clinical trials compare the impact of drugs in control subjects and in people who are sick. But you will actually find that a large number of the controls are sick but no one knows it, and a large proportion of the people who are sick are not sick with the disease that the pharmaceutical company thinks they have. Once we have objective tests, we can select the people to participate in clinical trials much better, making it more likely that we will have positive results from the trials and find more effective treatments. We might be able to re-purpose drugs that already exist, which is a very cheap solution because they are already known to be safe, or we can find new ones."

Once these differences are better understood, the next step would be to model those variations and make comparisons with the model of the healthy brain. This should vastly enhance mechanistic understanding of the causes of brain disease – from environmental influences, to secondary effects, illness and drug use, for example.

"Untangling all of the potential causes is incredibly complicated," he suggests. "If we’ve got a brain model, we can do experiments that we can’t do with real patients. You may suspect it’s a particular thing that’s had an effect, so if we take it out of the model, we can see if the disease goes away or if a secondary affect has been found that doesn’t matter so much. We can also use them to get a handle on treatments. For treatment of an individual with a particular disease and symptoms, there are a huge number of treatment combinations available. Unless we have an indication that a certain option may work, it would be completely unethical to try this regime on patients, as it may be too dangerous. For many brain diseases we can’t do tests on animals, since we don’t have animals who suffer from delusions, for example. On the model, we can do it free of risk, so we will have a tool for the industry to test new treatments."

No miracle cures
Walker is insistent that they are not promising miracle cures, highlighting that even if a new drug is found that appears to cure a major condition, such as Alzheimer’s, it would still take a decade or more for it to be used in a clinical setting, given the extensive amount of animal and human testing required before it is authorised for use. HBP is not looking to create a system to replace all of the existing processes, but to make them more effective, using simulation to drastically reduce the time and money that is wasted testing things that are never going to work.

The substantial funding that the project has been awarded, to the tune of €1bn over 10 years, reflects the economical and social expectations placed on the outcomes, but Walker feels it is reasonable proportional to what they are trying to achieve.

"Although certainly considerable, if you think of how much it costs to design a new car, which is somewhat simpler than designing a brain, our budget is not so huge," he says. "A manufacturer can put a billion dollars simply into the design of a new engine. So, we do need to have things in perspective, but of course in terms of science funding this is extraordinarily large.

"We believe that we are going to produce very important new basic science, enable medical discoveries and allow new technologies. So the impact is going to be very large, but we also want to warn people against excessive expectations. This will take a very long time – that is the nature of real scientific research. If you know that you’re going to have an impact in one or two years’ time, it’s not research, it is development!"

Risking failure
There are an immense number of variables involved in understanding brain function and translating this into computational models meaning that, as with any major project, there always remains a risk that the lofty aims of the project could fundamentally fail.

"If there is no risk of failure, it is not research," Walker states. "In our research we are making a lot of hypotheses about how things function and we cannot guarantee that those hypotheses are right. We have to test them. Today, we have quite a good comprehension of some of the basic mechanics of the brain. We know a lot about how neurons and synapses function, how they change and some of the basic mechanisms of learning. Cognitive neuroscientists know an awful lot about which areas of the brain light up when you do certain things, such as talking, moving and making decisions.

"But there is a gap. We have very little understanding of the low-level functioning neurons. Imagine it like the transistors on a smartphone and how that links to the high-level activity, like an app running on the device. We don’t understand that link and we want to resolve that through modelling and simulation. We are going to model the brain circuitry and the neurons one by one, with each having an individual behaviour and so on. What we don’t know today is how much detail is actually needed to reproduce brain function. The proof will come when we have a model with a certain level of detail that actually exhibits the function we are interested in. Until we reach that point, there is a risk that our hypotheses could indeed be wrong."

As Walker concludes, people have been trying to understand how humans think and how the brain works for millennia. "We can’t promise that we’re going to succeed in all of this but we do have a handle on how to do it. It is really amazing that this is no longer an unapproachable problem – it is a difficult problem, but we do begin to see how we could resolve it."

In the next edition of Science Omega Review, we discuss this issue further, exploring the potential the project offers for supercomputing.


Richard Walker
Project Spokesman
Human Brain Project
www.humanbrainproject.eu


[This article was originally published on 1st July 2013 as part of Science Omega Review Europe 02]
Read more: http://www.scienceomega.com/article/1154/developing-neuroscience-knowledge-human-brain-project#ixzz2Y0HNyd6Y

Europa y EEUU lanzan una colosal carrera para apoderarse de los secretos del cerebro

ORIGINAL: Es Materia

Javier Salas

07/03/2013 

Dos proyectos en competición se gastarán más de 3.000 millones de euros en la próxima década para entender, controlar y reproducir los mecanismos del cerebro humano. Ambas iniciativas están dirigidas por neurocientíficos españoles

Recreación de un entramado neuronal. / Wellcome Images

Esta es la década de la neurociencia, ya no cabe ninguna duda. Hasta hace unos meses se podía suponer, porque el conocimiento del cerebro se ha convertido en esa “última frontera” de la que se suele hablar a menudo en las noticias científicas. Pero de pronto, la materia gris se ha colocado a comienzos de 2013 en el eje principal de la política científica mundial. EEUU y la Unión Europea quieren poner su bandera en el primer mapa del cerebro, ser los primeros en desentrañar sus secretos, ganar el dinero y el prestigio de los grandes descubrimientos. La carrera está lanzada, durará más de una década y los dos competidores cuentan con carísimos bólidos: 2.300 millones de euros invertirá Washington y más de 1.000 se pondrán en Bruselas.

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Más: #neurociencia

“Ahora es el momento de alcanzar un nivel de investigación y desarrollo sin precedentes desde la carrera espacial”, dijo el presidente de EEUU, Barack Obama, el pasado 12 de febrero, nada menos que en su Discurso del Estado de la Unión. Se refería a realizar una inversión descomunal para descifrar las claves del cerebro que ayude a poner coto a enfermedades mentales. Inmediatamente después, Rafael Yuste, tuiteaba: “Obama menciona la necesidad de hacer un mapa del cerebro en su discurso!!”. Solo recibió ocho retuits, pero su trascendencia es fundamental. Yuste, neurocientífico madrileño, lidera este proyecto, denominado The Brain Activity Map (BAM), y que hoy describe junto a sus colegas en un artículo de la revista Science.

«¿Dónde estamos después de décadas de investigación y miles de científicos? Hemos avanzado muy poco, sabemos poquísimo»JAVIER DE FELIPE

Neurobiólogo del Instituto Cajal (CSIC)

“Es imparable”, asegura Yuste a Materia, “pero el tamaño del proyecto y su organización no está decidido todavía. Ya no depende de nosotros. El grupo de científicos que lo propusimos hemos pasado el testigo a la administración pública de la ciencia y a las fundaciones privadas para que lo dirijan”. Este neurocientífico, que lleva 16 años en la universidad neoyorquina de Columbia, cuenta que llevan algo más de un año lidiando con la Casa Blanca para que amparen el proyecto. Una especie de artículo fundacional en la revista Neuron dio el pistoletazo de salida a su proyecto, que se ha marcado metas de 15 años pero “durará más seguro”, augura Yuste, considerado uno de los cinco científicos a seguir en 2013 por Nature.

El equipo europeo lleva más de un año de ventaja al estadounidense en los preparativos. Pero, casualmente, ha recibido el cheque a la vez. El 21 de enero, Materia adelantaba que la Comisión Europea decidía respaldar el Human Brain Project (HBP), una iniciativa muy similar a la de Yuste: poner la viga maestra para alzar el edificio de la neurociencia del futuro. Al frente del proyecto está el controvertido Henry Markram, que ya lo intentó con el Blue Brain Project. Y el responsable de una de sus patas principales, la de la neurociencia molecular y celular, es el español Javier De Felipe, del Instituto Cajal (CSIC).

Yuste, en su laboratorio. / Universidad de Columbia

“La ventaja de este tipo de apuesta es que es de largo recorrido, eso asegura la consecución de éxitos”, asegura De Felipe al recordar que cuentan con 100 millones anuales durante una década. Tanto a un lado como al otro del Atlántico han surgido críticas por la financiación de plataformas tan colosales con cifras de inversión astronómicas. El neurobiólogo del Instituto Cajal las despacha asegurando que “vienen de quienes no están” y pone el acento en la importancia de que se haga “ciencia a lo grande” para avanzar en este campo. “Conocer el cerebro es esencial para la humanidad. Es el único órgano que desconocemos casi por completo y eso que es el que nos da nuestra esencia. Sin embargo, ¿dónde estamos después de décadas de investigación y miles de científicos? Hemos avanzado muy poco, sabemos poquísimo”, lamenta De Felipe.

Roma frente a la guerra de guerrillas

Entonces recurre a la metáfora bélica: “La guerra de guerrillas no funciona. Es mejor organizar un ejército sólido, legiones como las de Roma, para empezar a conquistar nuevos territorios”. Según explica, la importancia de esta iniciativa es la de hacer de catalizador de la investigación de cientos de científicos en toda Europa, y otros de fuera que se suman al HBP, incluso desde EEUU y Japón. “Somos miles estudiando el cerebro, hay que poner orden, crean estándares, compartir hallazgos, provocar sinergias. Solo por el trabajo que llevo compartiendo con mis colegas en el diseño de nuestra división habría merecido la pena”, explica.

“En estos tiempos de austeridad, hace falta galvanizar al público sobre la importancia de la ciencia”, dice Yuste

Los ejércitos que se enfrentarán en esta batalla para mapear, reproducir y controlar el cerebro contarán con legiones de científicos punteros de todas las áreas: matemáticos que sepan cómo expresar los descubrimientos, expertos en el análisis geométrico, estadísticos, genetistas, fisiólogos. Y los mejores ingenieros de computación: no es fácil abarcar las cantidades de información con las que trabajarán. El equipo americano mantuvo una reunión de trabajo (PDF) con responsablesde Google, Microsoft, DARPA, Amazon, Caltech y otras instituciones punteras para preguntarles, sencillamente, si era posible procesar la ingente suma de información que requiere leer un cerebro. La primera estimación es de tres petabytes anuales (tres millones de gigas), bastante menos que el LHC. Pero la necesidad de procesar información puede crecer exponencialmente.

Como explica Yuste, tendrán que usar máquinas que todavía no existen. Habrá que crear herramientas capaces de fotografiar simultáneamente la actividad de cada neurona, de la mayoría o incluso la totalidad de un cerebro. Será necesario diseñar mecanismos que permitan controlar la actividad de cada neurona, “porque examinar requiere intervenir”. Y, por último, se desarrollarán métodos para almacenar, administrar y compartir imágenes y datos fisiológicos a gran escala. Máquinas capaces de analizar todos esos datos y de recrear modelos de circuitos neuronales que les lleven a revelar, finalmente, los principios que rigen al cerebro.

De ratones y hombres… muertos

Una de las principales apuestas del grupo europeo es la de aprovechar el conocimiento del cerebro humano para proporcionar un salto espectacular en el desarrollo de la informática. “Si se pudiera entender cómo hace el cerebro para procesar tanta información en tanto tiempo con tan poco consumo de energía… Un humano tarda milisegundos en reconocer una cara y un ordenador no sabe cómo. Si revelamos el mecanismo, se podría conseguir que una máquina reconociera a toda la gente de un aeropuerto en un segundo”, aventura De Felipe.

El grupo de Yuste anuncia que empezarán por estudiar el cerebro de bichos, como moscas, gusanos y sanguijuelas; y de ahí pasarán a analizar ratas, ratones y pececillos. “En 15 años, seremos capaces de controlar un millón de neuronas, el equivalente al cerebro de un pez cebra”. ¿Y el cerebro humano? “En mucho más tiempo, pero en ese caso hay también cuestiones éticas que se tienen que dirimir antes”, justifica Yuste. Eso sí, en paralelo se harán modelos e investigaciones del cerebro humano, pero no se atacará la posibilidad de intervenir directamente. En Europa, solo se trabajará con ratones y hombres, señala De Felipe. “El cerebro de cada animal tiene características únicas y conviene centrarse: yo llevo mucho tiempo trabajando en cerebros post mórtem con buenísimos resultados”, asegura.

El investigador Javier De Felipe, en su despacho. / HBP

El objetivo más desinteresado de ambos proyectos, en el fondo, es el mismo: resolver los problemas mentales de las personas. Yuste asegura que es eso lo que motiva a la Casa Blanca: “Nuestro trabajo con ellos ha sido una experiencia increíble, completamente limpia y sin intereses ni agendas ocultas. Solo se pretende conseguir el progreso de la neurociencia para ayudar a la humanidad. Un ejemplo a seguir en todos los países”, recalca. Ambos neurocientíficos sueñan con los males que se podrían curar si se supiera qué falla en el cerebro de los enfermos de alzhéimer, esquizofrenia, autismo, depresión…

Pero también está el dinero. Todos ponen como ejemplo el retorno que generó la inversión del Proyecto Genoma Humano: se gastaron 3.000 millones de euros y según Yuste se han obtenido unos 800.000 millones de vuelta, entre patentes, curas, tecnologías, etc. Obama se limitó a decir que se recibieron 140 dólares por cada dólar invertido. Al margen de la exactitud del cálculo, lo cierto es que los recursos que proporcionarán estas dos plataformas se multiplicarán casi desde el primer día. Más aún si se logra curar las enfermedades mentales de los humanos.

Se espera un retorno similar al que dicen que tuvo el Proyecto Genoma: unos 140 dólares por cada uno invertido

“Precisamente ahora, en estos tiempos de austeridad, hace falta galvanizar al público sobre la importancia de la ciencia, y la neurociencia en concreto, para el futuro de la humanidad. Y la necesidad de apoyar proyectos que puedan suponer un cambio de rumbo con repercusiones económicas”, defiende Yuste, que niega que se trate de una carrera entre EEUU y Europa. ”Solo son proyectos independientes. Les deseo lo mejor a mis colegas del proyecto europeo… yo también soy europeo”, recuerda.

De Felipe, en cambio, habla espontáneamente de carrera, un concepto que le parece beneficioso para la consecución de los objetivos. “Es una carrera que ya está lanzada y eso es muy bueno, porque nos obligará a dar lo mejor. En menos de un año, estaremos sujetos a una crítica feroz, mirarán con lupa cada cosa que publiquemos para ver si estamos fallando”, aventura. Lo más peculiar es que De Felipe y Yuste llevan más de una docena de años trabajando juntos, cuando el de Columbia regresa a España cada verano: la competencia no será tan feroz como entre legiones romanas. Aunque a pesar de tratarse de la apuesta científica de la década, les surgen pequeños enemigos: “En medio de la cobertura de prensa del BAM, tenemos una fuga de agua en el techo del laboratorio, para devolvernos a la Tierra”, tuiteó Yuste esta mañana. Solo tiene 270 seguidores.

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'The Brain Activity Map' DOI: 10.1126/science.1236939

MÁS INFO

» Human Brain Project (HBP)

» The Brain Activity Map (BAM)