Mostrando entradas con la etiqueta BAM. Mostrar todas las entradas
Mostrando entradas con la etiqueta BAM. Mostrar todas las entradas

sábado, 30 de marzo de 2013

Is Brain Mapping Ready for Big Science?

ORIGINAL: GEN


The BAM project will be an expensive undertaking. Will it be worth the cost?

The Brain Activity Map Project is aimed at reconstructing the full record of neural activity across complete neural circuits, with the goal of understanding fundamental and pathological brain processes. [V. Yakobchuk/Fotolia.com]
President Barack Obama’s public-private initiative to create an activity map of the human brain will cost more than $3 billion, projections say, or $300 million annually for 10 years. The project has multiple private and public institutions lined up to participate, including the Defense Advanced Research Projects Agency (DARPA) and the National Science Foundation. All parties hope that the initiative will move brain science forward with the same kind of money and focused effort that drove the Genome Project.

Every dollar we invested to map the human genome returned $140 to our economy—every dollar,” the president commented. “Today our scientists are mapping the human brain to unlock the answers to Alzheimer’s. They’re developing drugs to regenerate damaged organs, devising new materials to make batteries 10 times more powerful. Now is not the time to gut these job-creating investments in science and innovation.

George M. Church, Ph.D., professor of genetics at Harvard Medical School and director of PersonalGenomes.org, said he was helping to plan the Brain Activity Map project.

If you look at the total spending in neuroscience and nanoscience that might be relative to this today, we are already spending more than that. We probably won’t spend less money, but we will probably get a lot more bang for the buck,” he commented in the New York Times.

BAM
The proposal for the project came from six scientists, among them Dr. Church, who said in the journal Neuron, “We propose launching a large-scale, international public effort, the Brain Activity Map project (BAM), aimed at reconstructing the full record of neural activity across complete neural circuits. This technological challenge could prove to be an invaluable step toward understanding fundamental and pathological brain processes.

The collective idea for the initiative was generated at a meeting of neuroscientists and nanoscientists convened in September 2011 at the Kavli Royal Society International, U.K., organized by Tom Kalil, deputy director for policy at the White House’s Office of Science and Technology Policy (OSTP), and Miyoung Chun, Ph.D., vice president of science programs at the Kavli Foundation in Oxnard, California.

The Kavli institute has founded institutes for brain science at UC San Diego, Yale, and the Norwegian University of Science and Technology.

Meeting attendees articulated the issues the BAM will address in its report, mentioning “our persistent ignorance of the brain’s micro-circuitry—the minute and multitudinous connections contained within,” and citing the great brain scientist Ramon y Cajal’s 1923 quote that refers to the interconnected, intermixed, and dynamical network of different cell types as “impenetrable jungles where many investigators have lost themselves.” “Another equally fundamental shortcoming,” they noted, “is our inability to monitor network interactions and coordinated brain activities densely, and to do so simultaneously across extended regions of the brain, and with sufficient temporal and spatial resolution.

And most scientists, whether proponents or opponents of the big science approach to brain mapping, agree that its biggest challenge is the need to develop novel tools to study the brain.

Revolutionary New Tools Needed
Partha Mitra, Ph.D., a theoretical physicist and currently Crick-Clay professor of biomathematics at Cold Spring Harbor Laboratory, says that current methods to visualize living or dead brains provide only glimpses of small portions of the full spatial extent of neurons in the human brain, or pictures of thin sections of brain, with pieces of the neurons in them. “No one has yet seen, under the microscope or in digital reconstruction, a complete human brain neuron that sends projections to distant parts of the brain. To do that at the whole-brain scale would be like seeing a new continent or planet.Dr. Mitra’s research currently combines experimental, theoretical, and informatics approaches to gain an understanding of how brains work.

Dr. Chun has been developing the project since the beginning and has described herself as the “glue” holding the diverse stakeholders together. She told Nature that “there’s clearly an issue with tool development—and not just amending current, existing tools, although that will be important in the initial stages. In the long run, one of the very important points would be to come up with revolutionary new tools that will measure brain activity in a completely different way than what we know now.

And project proponents say the only way to tackle some thus far tricky intractable human diseases, like Alzheimer’s and Parkinson’s disease, is with a huge program. “We are right on the edge of finding out really vital information about the brain,” says Brown University neuroscientist John Donoghue, Ph.D., who was part of the project team. “There are questions we can now answer that can only be tackled as a collaborative project,” not by individual labs.

In Dr. Donaghue's view, the problem is that the people developing novel technologies and the neuroscience community don’t communicate effectively. Biologists don't know enough about the tools already out there, and the materials scientists aren't getting feedback from them on ways to make their tools more useful.

Economic Incentives
And there’s no denying the economic incentives the project provides. “What motivates people to pursue these big projects is not the belief that they will solve problems,” says Michael Eisen, Ph.D., a biologist at the University of California, Berkeley. “It’s the belief that this is the way to get money.”

John Mazziotta, M.D., Ph.D., UCLA’s department of neurology chair and director of its Brain Mapping Center, says, “This initiative is more comprehensive than anything I’ve ever seen medicine and neuroscience. This effort will be both the stimulus and the challenge to work and collaborate in ways we haven’t done before, but always have wanted to.

UCLA will likely benefit handsomely from the initiative as it says it is “well-positioned” to play a significant role in the effort and to capture funding that will support such an initiative, owing to the existence Ahmanson-Lovelace Brain Mapping Center and its “excellence” in nanoscience and nanotechnology.

Dr. Church is also in favor of spreading the funding for the project around. In an interview with Harvard Medical School News last month, he said, “The Genome Project didn’t adequately embrace small science. I think enabling small labs to do amazing things might be more powerful than having a juggernaut of a large lab, or worse yet, a race among a few large labs.

A report from the Battelle Technology Partnership says that, between 1988 and 2010, federal investment in genomic research generated an economic impact of $796 billion, “impressive” considering that Human Genome Project (HGP) spending between 1990–2003 amounted to $3.8 billion and an ROI of 141:1.

Apart from job creation and ROI, if this massive initiative provides new treatment targets for intractable human neurological and psychiatric disorders, it will have been worth the investment.

Patricia Fitzpatrick Dimond, Ph.D. (pdimond@genengnews.com), is technical editor at Genetic Engineering & Biotechnology News.

lunes, 25 de marzo de 2013

Proposed Brain Activity Map may also advance nanotechnology

ORIGINAL: Foresight


(credit: Comp. Cog. Neurosci Lab
/ Olaf Sporns, Indiana Univ.)
A proposal alluded to by President Obama in his State of the Union address to construct a dynamic “functional connectomeBrain Activity Map (BAM) would leverage current progress in neuroscience, synthetic biology, and nanotechnology to develop a map of each firing of every neuron in the human brain—a hundred billion neurons sampled on millisecond time scales. Although not the intended goal of this effort, a project on this scale, if it is funded, should also indirectly advance efforts to develop artificial intelligence and atomically precise manufacturing. In his blog, Robert L. Blum provides an excellent overview and brief introduction. From “BAM: Brain Activity Map: Every Spike from Every Neuron“:


A recent research proposal called BAM for Brain Activity Map Project generated much excitement. (The BAM proposal, published in Neuron in June 2012 is online, and an earlier draft with far greater detail is also online.)

(Addendum: 18 Feb 2013: I started drafting this story in Nov, 2012. Today it was headline news when it was made public that THIS is the very proposal that President Obama alluded to in his recent State of the Union address. See John Markoff’s NY Times piece. NIH is drafting a 3 billion dollar, 10 year proposal to fund this project. Also see this 25 Feb 2013 NY Times follow-up by Markoff.) …

The essence of the BAM proposal is to create the technology over the coming decade to be able to record every spike from every neuron in the brain of a behaving organism. While this notion seems insanely ambitious, coming from a group of top investigators, the paper deserves scrutiny. At minimum it shows what might be achieved in the future by the combination of nanotechnology and neuroscience. …

The Neuron article cited by Blum argues that in addition to breakthroughs in basic science with large medical and economic benefits, the BAM project will advance technology in terms of important general capabilities.

Many technological breakthroughs are bound to arise from the BAM Project, as it is positioned at the convergence of biotechnology and nanotechnology. These new technologies could include optical techniques to image in 3D; sensitive, miniature, and intelligent nanosystems for fundamental investigations in the life sciences, medicine, engineering, and environmental applications; capabilities for storage and manipulation of massive data sets; and development of biologically inspired, computational devices.

I think the emphasis on nanosystems of nanodevices integrated to provide complex functions is very important, even if many or most of those devices will, in the beginning, not be atomically precise. The more detailed description of the BAM proposal cited by Blum above hints at how nanoparticle-based sensors could be developed to noninvasively provide micrometer-scale spatial resolution and millisecond-scale temporal resolution to groups of millions of neurons deep inside the brain of a living, active animal (or human). The mention combining semiconductor quantum dots and nanodiamonds with organic nanostructures to functionalize them, so that they may be directed to and embedded in neural membranes to monitor synapses. In addition, nanotubes or nanowires could be developed to deliver photons to specific locations, or collect or release specific chemicals. Further, they suggest developing graphene into membrane patches for detailed monitoring of neurons. Taken together, the requirements for this ambitious project entail the need to develop a variety of nanoparticles for specific applications, and then integrating multifunctional nanoprobes, nanoparticles, and nanodevices into large functional systems, and producing such nanosystems en masse.

In his NY Times report John Markoff notes the possible effect of this project on the development of artificial intelligence: “Moreover, the project holds the potential of paving the way for advances in artificial intelligence.” Indeed, the information to be provided by BAM about how circuits of thousands or millions of neurons work should advance Ray Kurzweil’s program of reverse engineering the human brain to develop artificial general intelligence, as described in his new book How to Create a Mind: The Secret of Human Thought Revealed.

The next best thing to large program to develop molecular manufacturing is a large program aimed at other worthy and useful goals that also makes heavy use of nanotechnology and may promote some of the same or similar enabling technologies that will lead toward productive nanosystems.
—James Lewis, PhD

This entry was posted on Friday, March 1st, 2013 

jueves, 21 de marzo de 2013

Flashing fish brains filmed in action

ORIGINAL: Nature
18 March 2013 

Fast imaging in larval zebrafish produces first neuron-level vertebrate brain-activity map.

It looks like an oddly shaped campfire, but it is activity of individual neurons across a larval fish brain. It is the first time that researchers have been able to image an entire vertebrate brain at the level of single cells.

At first glance, it looks like an oddly shaped campfire: smoky grey shapes light up with red sparks and flashes. But the video actually represents a different sort of crackle — the activity of individual neurons across a larval fish brain. It is the first time that researchers have been able to image an entire vertebrate brain at the level of single cells. 

We see the big picture without losing resolution,” says Phillipp Keller, a microscopist at the Howard Hughes Medical Institute's Janelia Farm Research Campus in Ashburn, Virginia, who developed the system with Janelia neurobiologist Misha Ahrens. The researchers are able to record activity across the whole fish brain almost every second, detecting 80% of its 100,000 neurons. (The rest lie in hard-to-access areas, such as between the eyes; their activity is visible but cannot be pinned down to single cells.) The work is published today in Nature Methods1

It’s phenomenal,” says Rafael Yuste, a neuroscientist at Columbia University in New York. “It is a bright star now in the literature, suggesting that it is not crazy to map every neuron in the brain of an animal.” Yuste has been leading the call for a big biology project2 that would do just that in the human brain, which contains about 85,000 times more neurons than the zebrafish brain

Related stories


The resolution offered by the zebrafish study will enable researchers to understand how different regions of the brain work together, says Ahrens. With conventional techniques, imaging even 2,000 neurons at once is difficult, so researchers must pick and choose which to look at, and extrapolate. Now, he says, “you don't need to guess what is happening — you can see it”. 

The increased imaging power could, for example, help to explain how the brain coordinates movement, consolidates learning or processes sights and smells. “It allows a much better view of the dynamics throughout the brain during different behaviours and during learning paradigms,” says Joseph Fetcho, a neurobiologist at Cornell University in Ithaca, New York. 

Light, camera, activity 
The imaging system relies on a genetically engineered zebrafish (Danio rerio). The fish's neurons make a protein that fluoresces in response to fluctuations in the concentration of calcium ions, which occur when nerve cells fire. A microscope sends sheets of light rather than a conventional beam through the fish's brain, and a detector captures the signals like a viewer watching a cinema screen. The system records activity from the full brain every 1.3 seconds
Ahrens, Keller and others have previously used light-sheet microscopy to image developing embryos over days3; for the latest study, they modified light detectors and other aspects of the system to increase the rate of imaging tenfold. In a series of hour-long experiments, each of which generated 1 terabyte (1 million megabytes) of data, the researchers were able to see populations of neurons in distinct regions that correlated to their activity (see video above). 

The technique does have its limitations. For one thing, it works best in zebrafish embryos, which are transparent. Ahrens and Keller think that it could work in intact mammal brains, but it would require surgery and would cover only a small fraction of the brain. 

Another limitation is that neither the protein sensor nor the imaging system yet works fast enough to distinguish whether a neuron has fired once or several times in quick succession. But Fetcho says that it is fast enough to start to understand how activity flows through the brain. “No one is anywhere in the ball park of this for any other animal model.” 

Nature doi:10.1038/nature.2013.12621 
Ahrens, M. B. & Keller, P. J. Nature Meth. http://dx.doi.org/10.1038/NMETH.2434 (2013). Show context

Alivasatos, A. P. et al. Science 339, 1284–1285 (2013). 


Tomer, R., Khairy, K., Amat, F. & Keller, P. J. Nature Meth. 9, 755–763 (2012). 


From nature.com 


06 March 2013


23 January 2013


23 January 2013


29 November 2011






martes, 19 de marzo de 2013

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

ORIGINAL: Es Materia
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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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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