Mathematical Model Of Consciousness Proves Human Experience Cannot Be Modelled On A Computer

A new mathematical model of consciousness implies that your PC will never be conscious in the way you are

The Physics arXiv Blog in The Physics arXiv Blog

One of the most profound advances in science in recent years is the way researchers from a variety of fields are beginning to think about consciousness. Until now, the c-word was been taboo for most scientists. Any suggestion that a researchers was interested in this area would be tantamount to professional suicide.

That has begun to change thanks to a new theory of consciousness developed in the last ten years or so by Giulio Tononi, a neuroscientist at the University of Wisconsin in Madison, and others. Tononi’s key idea is that consciousness is phenomenon in which information is integrated in the brain in a way that cannot be broken down.

So each instant of consciousness integrates the smells, sounds and sights of that moment of experience. And consciousness is simply the feeling of this integrated information experience.

What makes Tononi’s ideas different from other theories of consciousness is that it can be modelled mathematically using ideas from physics and information theory. That doesn’t mean this theory is correct. But it does mean that, for the first time, neuroscientists, biologists physicists and anybody else can all reason about consciousness using the universal language of science: mathematics.

This has led to an extraordinary blossoming of ideas about consciousness. A few months ago, for example, we looked at how physicists are beginning to formulate the problem consciousness in terms of quantum mechanics and information theory.

Today, Phil Maguire at the National University of Ireland and a few pals take this mathematical description even further. These guys make some reasonable assumptions about the way information can leak out of a consciousness system and show that this implies that consciousness is not computable. In other words, consciousness cannot be modelled on a computer.

Maguire and co begin with a couple of thought experiments that demonstrate the nature of integrated information in Tononi’s theory. They start by imagining the process of identifying chocolate by its smell. For a human, the conscious experience of smelling chocolate is unified with everything else that a person has smelled (or indeed seen, touched, heard and so on).

This is entirely different from the process of automatically identifying chocolate using an electronic nose, which measures many different smells and senses chocolate when it picks out the ones that match some predefined signature.

A key point here is that it would be straightforward to access the memory in an electronic nose and edit the information about its chocolate experience. You could delete this with the press of a button.

But ask a neuroscientist to do the same for your own experience of the smell of chocolate—to somehow delete this—and he or she would be faced with an impossible task since the experience is correlated with many different parts of the brain.

Indeed, the experience will be integrated with all kinds of other experiences. “According to Tononi, the information generated by such [an electronic nose] differs from that generated by a human insofar as it is not integrated,” say Maguire and co.

This process of integration is then crucial and Maguire and co focus on the mathematical properties it must have. For instance, they point out that the process of integrating information, of combining it with many other aspects of experience, can be thought of as a kind of information compression.

This compression allows the original experience to be constructed but does not keep all of the information it originally contained.

To better understand this, they give as an analogy the sequence of numbers: 4, 6, 8, 12, 14, 18, 20, 24…. This is an infinite series defined as: odd primes plus 1. This definition does not contain all the infinite numbers but it does allow it be reproduced. It is clearly a compression of the information in the original series.

The brain, say Maguire and co, must work like this when integrating information from a conscious experience. It must allow the reconstruction of the original experience but without storing all the parts.

That leads to a problem. This kind of compression inevitably discards information. And as more information is compressed, the loss becomes greater.

But if our memories were like that cannot be like that, they would be continually haemorrhaging meaningful content. “Memory functions must be vastly non-lossy, otherwise retrieving them repeatedly would cause them to gradually decay,” say Maguire and co.

The central part of their new work is to describe the mathematical properties of a system that can store integrated information in this way but without it leaking away. And this leads them to their central proof. “The implications of this proof are that we have to abandon either the idea that people enjoy genuinely [integrated] consciousness or that brain processes can be modelled computationally,” say Maguire and co.

Since Tononi’s main assumption is that consciousness is the experience of integrated information, it is the second idea that must be abandoned: brain processes cannot be modelled computationally.

They go on to discuss this in more detail. If a person’s behaviour cannot be analysed independently from the rest of their conscious experience, it implies that something is going on in their brain that is so complex it cannot feasibly be reversed, they say.

In other words, the difference between cognition and computation is that computation is reversible whereas cognition is not. And they say that is reflected in the inability of a neuroscientist to operate and remove a particular memory of the small of chocolate.

That’s an interesting approach but it is one that is likely to be controversial. The laws of physics are computable, as far as we know. So critics might ask how the process of consciousness can take place at all if it is non-computable. Critics might even say this is akin to saying that consciousness is in some way supernatural, like magic.

But Maguire and go counter this by saying that their theory doesn’t imply that consciousness is objectively non-computable only subjectively so. In other words, a God-like observer with perfect knowledge of the brain would not consider it non-computable. But for humans, with their imperfect knowledge of the universe, it is effectively non-computable.

There is something of a card trick about this argument. In mathematics, the idea of non-computability is not observer-dependent so it seems something of a stretch to introduce it as an explanation.

What’s more, critics might point to other weaknesses in the formulation of this problem. For example, the proof that conscious experience is non-computable depends critically on the assumption that our memories are non-lossy.

But everyday experience is surely the opposite—our brains lose most of the information that we experience consciously. And the process of repeatedly accessing memories can cause them to change and degrade. Isn’t the experience of forgetting a face of a known person well documented?

Then again, critics of Maguire and co’s formulation of the problem of consciousness must not lose sight of the bigger picture—that the debate about consciousness can occur on a mathematical footing at all. That’s indicative of a sea change in this most controversial of fields.

Of course, there are important steps ahead. Perhaps the most critical is that the process of mathematical modelling must lead to hypotheses that can be experimentally tested. That’s the process by which science distinguishes between one theory and another. Without a testable hypothesis, a mathematical model is not very useful.

For example, Maguire and co could use their model to make predictions about the limits in the way information can leak from a conscious system. These limits might be testable in experiments focusing on the nature of working memory or long-term memory in humans.

That’s the next challenge for this brave new field of consciousness.

Ref: arxiv.org/abs/1405.0126 : Is Consciousness Computable? Quantifying Integrated Information Using Algorithmic Information Theory

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ORIGINAL: Medium

Decodificaron el genoma de una bacteria canina

Poco se sabe de la Brucella canis, una bacteria patógena que afecta a perros y humanos.  

Investigadores de la Alma Mater lograron la secuenciación genómica de una cepa local, un paso adelante en la investigación internacional para lograr desarrollos más efectivos de diagnóstico y tratamiento.

Esta bacteria puede ocasionar problemas reproductivos en las hembras caninas, mortalidad neonatal e infertilidad en los machos.

Desde el 2005 un grupo de investigadores de la Alma Mater viene investigando sobre la bacteria Brucella canis. Gracias al trabajo conjunto entre el Grupo de investigación Vericel-Biogénesis, y el Centro Nacional de Secuenciación Genómica de la Universidad de Antioquia —CNSG—, lograron secuenciar y analizar completamente el genoma de esta bacteria patógena.

A través de muestras de sangre de los animales, que habían sido recogidas en varios criaderos de Medellín, los investigadores adelantaron un proceso de diagnóstico que permitió obtener la bacteria aislada y así posteriormente obtener el ADN genómico purificado.

Las pruebas iniciales hicieron que se enfocaran en los factores de riesgo. En un trabajo previo de una estudiante de maestría del grupo, se detectó una seroprevalencia de 15% en caninos de criaderos. Sin embargo, esta prueba no permitía descubrir la bacteria en aquellos animales que recién se habían contagiado.

Brucella canis puede ocasionar problemas reproductivos en las hembras caninas, mortalidad neonatal e infertilidad en los machos. Mientras que en las personas, si bien en algunos casos el sistema inmunológico puede defenderse, en otros puede acarrear cuadros sistémicos o problemas para las articulaciones. Esta bacteria se contagia a los humanos, en especial a veterinarios o cuidadores, cuando éstos atienden partos o les hacen limpieza a los lugares donde habitan los caninos.

El trabajo de los investigadores esta permitiendo mejorar y estandarizar las pruebas serológicas y moleculares con blancos mucho más precisos, que se comparan con los método tradicionales de hemocultivo. “Así vigilamos si hay signos de la presencia de la bacteria. En este caso hacemos pruebas moleculares para decir 'sí', la bacteria está en el animal”, explicó Miryan Sánchez Jiménez, estudiante de doctorado e investigadora de Vericel-Biogénesis.

En un estudio realizado en varios criaderos del Área Metropolitana, encontraron que en un total de 220 perros muestreados, el 17,2 por ciento tenía la bacteria. Y de 92 personas que analizaron, 9 dieron positivas por serología. “No hay una prueba diagnóstica buena para humanos. Por eso es que se han venido desarrollando estas investigaciones, para poder establecer un mejor diagnóstico”, explicó la profesora Martha Olivera, investigadora del Grupo Biogénesis y Vericel, grupos que hacen parte de la Facultad de Ciencias Agrarias de la Alma Mater.

La reglamentación de Estados Unidos determina que todos los animales que dan positivos con esta bacteria, deben ser sacrificados. En Colombia, en cambio, solo se manda a sacrificar a los animales de abasto, es decir a los bovinos, donde la bacteria corresponde a otra especie del género Brucella, la Brucella abortus.

“Pero la infección de los perros los reglamenta el Ministerio de Salud y aún no los ha reglamentado. Por eso lo que estamos haciendo es tratar de mejorar el diagnóstico y, con esas mejoras, lograr una vacuna a mediano plazo”, dijo Olivera.

Miryan Sánchez Jiménez y Martha Olivera hacen parte del Grupo de investigación Biogénesis y Vericel. Juan Fernando Alzate es el director del Centro de Secuenciación Genómica de la Universidad de Antioquia. Su trabajo y el de otros profesionales, como Juan Pablo Isaza, dio como resultado la secuenciación de la bacteria.

Genómica se une a la búsqueda Hay pocas investigaciones sobre la composición genómica de Brucella canis. Tras varios años dedicados a este tema, la profesora Martha y sus pupilos decidieron estudiar al maximo detalle esta bacteria. A ese propósito se les unió el Centro Nacional de Secuenciación Genómica, también de la Universidad de Antioquia, laboratorio de referencia en Colombia para estos analisis.

Los investigadores, inicialmente durante dos meses, analizaron reiteradamente los hemocultivos. Cuando consiguieron una cepa pura de la bacteria, empezó el trabajo de secuenciación. “Para este proyecto leímos 280 mil fragmentos de ADN de esa cepa, luego los analizamos computacionalmente para reconstruir toda la información genética contenida en los 2 cromosomas de este microorganismo”, explicó Juan Fernardo Alzate, director del CNSG.

Ese proceso arroja unos resultados computacionales que hay que decodificar, para hacer un inventario de los genes que componen la bacteria y las funciones que tiene cada uno, así determinan sus propiedades biológicas. Esa información se publica en una base de datos mundial, que es rigurosamente revisada.

“A este trabajo le damos mucho valor porque es la única cepa de campo americana secuenciada, además de que hicimos todo el análisis de la bacteria sin salir de nuestro país. Reportamos cada uno de los genes, algo que se ha hecho con pocas cepas en el mundo. De Brucella canis sólo se ha hecho con tres”, precisó Alzate.

Según el National Institutes of Health, de Estados Unidos, hay 27 proyectos de investigación sobre el genoma de Brucella canis, de esos solo hay tres culminados: uno coreano, otro norteamericano y el realizado en la Universidad de Antioquia, que además fue aceptado y se puede consultar publicamente en la base de datos europea del EBI. Los investigadores de la Alma Mater nombraron esta bacteria Brucella canis str. Oliveri, en honor a la profesora Martha, pionera de esta investigación en Colombia.

Este logro investigativo permite pensar en el desarrollo de vacunas futuras, así como procedimientos mucho más precisos y rápidos para detectar la infección por la bacteria en animales y humanos. “Todo el trabajo que estamos realizando, lo estamos basando en esa secuencia genómica”, dijo Sánchez.


ORIGINAL: Universidad de Antioquia
por Pedro Correa Ochoa - UdeA Noticias
24 de Feberero de 2014

What Is the Resolution of the Human Eye?

The new iPhone camera is 8-megapixels. Meanwhile, Canon is reportedly testing a new DSLR with 75-megapixels. But how many megapixels is the human eye? That is, how many megapixels would an image the size of your field of vision need to be to look normal?

Well, as Vsauce explains in its latest video, the better question is actually:
What is the resolution of the human eye? 

It's a complicated question, one that must take into account the peculiar anatomy of the eye which is different than the less peculiar engineering of a digital camera. As such, it's worth watching all ten minutes of the video, explaining not only how we see but also how well. Spoiler: the human eye is 576 megapixels—but really only about 7 megapixels matter. [YouTube]

ORIGINAL: Gizmodo

By Adam Clark Estes

Two Mutations Found to Have Triggered Evolutionary Leap 500 Million Years Ago In Humans

ORIGINAL: 33rdSquare
June 24, 2013

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A research team led by a University of Chicago scientist has discovered two key mutations that sparked a hormonal revolution 500 million years ago.

Evolution, it seems, sometimes jumps instead of crawls.

A research team led by a University of Chicago scientist has discovered two key mutations that sparked a hormonal revolution 500 million years ago.

In a feat of "molecular time travel," the researchers resurrected and analyzed the functions of the ancestors of genes that play key roles in modern human reproduction, development, immunity and cancer. By re-creating the same DNA changes that occurred during those genes' ancient history, the team showed that two mutations set the stage for hormones like estrogen, testosterone and cortisol to take on their crucial present-day roles.

"Changes in just two letters of the genetic code in our deep evolutionary past caused a massive shift in the function of one protein and set in motion the evolution of our present-day hormonal and reproductive systems," said Joe Thornton, PhD, professor of human genetics and ecology & evolution at the University of Chicago, who led the study.

"If those two mutations had not happened, our bodies today would have to use different mechanisms to regulate pregnancy, libido, the response to stress, kidney function, inflammation, and the development of male and female characteristics at puberty," Thornton said.

The findings were published online in the Proceedings of the National Academy of Sciences.

Laura Deming: “Mi meta es extender la esperanza de vida”

ORIGINAL: Prensa Libre

POR ROBERTO VILLALOBOS VIATOD REVISTA D

07/04/13

Es una chica sonriente y espontánea. Delgada y alta. Conversadora. Muy inteligente. Laura Deming nació hace 18 años en Nueva Zelanda, un país insular de Oceanía localizado en el suroeste del océano Pacífico, formado por dos grandes islas y muchas otras más pequeñas.

Laura Deming. Una fundación le dio US$100 mil para que abandonara sus estudios y se dedicara a la investigación. La joven lo hizo y le va bastante bien. Esta es su historia.

Laura, aún bastante joven, ya es una destacada bióloga. Apenas tenía 12 años cuando, con su familia, se mudó a San Francisco, Estados Unidos, para trabajar con Cynthia Kenyon, una prestigiosa bióloga molecular que estudia el proceso del envejecimiento. A los 14 se mudó a Boston para ingresar en el Instituto Tecnológico de Massachusetts (MIT, en inglés), una auténtica “fábrica de cerebros”.

A los 17, la Fundación Thiel puso en sus manos US$100 mil a cambio de que abandonara sus estudios —eso fue en el 2011—. Claro, el trato no era “así por así”. La brillante Laura, además, debía implementar tecnologías de punta con teorías innovadoras en el campo en el que se desenvolvía. En su caso, se enfoca en crear una terapia para incrementar la esperanza de vida del ser humano; es decir, obtener una fórmula para detener el envejecimiento. Fue así que cofundó la compañía Floreat Capital, con la cual lucha para alcanzar esa meta.

La joven Deming estuvo hace unos días en Guatemala, invitada por la Universidad Francisco Marroquín, donde impartió varias conferencias, todas en inglés, donde expuso las investigaciones y resultados que ha efectuado en su ya vasta y fructífera carrera científica.

¿Cómo te vino la idea de que el envejecimiento puede ser tratado?

Sucedió cuando tenía 8 años. Mi mamá me habló acerca de la muerte y no podía parar de llorar. Eso me parecía una tragedia. La vida es increíble, pero la muerte es inevitable. Para entonces ya me había gustado la biología. Desde entonces, mi concepción de ciencia cambió, pues la empecé a ver como un factor que puede salvar vidas.

Pese a esa corta edad, decidiste ponerte manos a la obra.

(Ríe). Sí. Cuando tenía 12 años —vivía en Nueva Zelanda— le escribí un correo electrónico a Cinthia Kenyon —biogerontóloga y bióloga molecular—, quien para mí es la mejor científica que estudia el envejecimiento en Estados Unidos. No tenía nada qué perder. Ella, sorprendentemente, me contestó y me invitó a trabajar en su laboratorio en la Universidad de California, en San Francisco (UCSF). Tomó el riesgo de permitir que yo, entonces una niña, empezara a investigar sobre ese tema. Fue así que Kenyon se convirtió en mi mentora.

Siendo tan pequeña, ¿entendías lo que ella te enseñaba?

Kenyon tenía una manera adecuada para describir las cosas. Por ejemplo, me decía que los científicos son como detectives, que tratan de resolver misterios y descubrir a los “culpables” genéticos del envejecimiento.

¿Qué fue lo que hiciste en la UCSF?

Juguetear con pequeños gusanos —C. elegans— en el laboratorio de biología, tratando de que estos vivieran más de lo esperado, lo cual logré. También tomé clases de genética y bioquímica, entre otras materias.

Luego vinieron tus estudios en el prestigioso Instituto Tecnológico de Massachusetts (MIT, en inglés).

Sí. Ingresé cuando tenía 14 años.

***

En el laboratorio Guarente, del MIT, Deming investigó el potencial terapéutico de la enzima SIRT1 en la osteoporosis y en el envejecimiento de mamíferos. Efectuó, asimismo, ensayos bioquímicos para estudiar la función proteica y trabajó con factores mutantes en ratones para establecer ensayos sobre osteoporosis. También efectuó estudios en el iGEM (International Genetically Engineered Machine Competition) y el Laboratorio Weiss, ambos del MIT.

***

Luego te ofrecieron US$100 mil para que dejaras tus estudios.

(Ríe). Así es. Es la Beca 20 under 20 proporcionada por la Fundación Thiel.

***

Dicha beca es facilitada por el magnate Peter Thiel, cofundador de la empresa de pagos en línea PayPal y uno de los primeros que apostó por Facebook.

Thiel incentiva con US$100 mil a jóvenes con mentes brillantes por debajo de los 20 años para que abandonen sus estudios y pasen los próximos dos años en Silicon Valley, San Francisco, para desarrollar proyectos innovadores.

Este empresario, quien tiene dos títulos por la Universidad de Stanford, considera que la educación superior actual está en una “burbuja loca”, como la ha denominado, pues hay miles de estudiantes que se endeudan para pagar una cuantiosa matrícula, la cual deben pagar al graduarse, consiguiendo, además, un trabajo que solo produce un pequeño retorno a la inversión.

Jim O’Neill, director de la Fundación Thiel, expresó en una entrevista con la BBC de Londres: “Hay obsesión por los títulos y las credenciales y no se presta suficiente atención a las habilidades y el talento (...) Hay muchos ejemplos de empresarios exitosos que crean un negocio rentable y no vuelven a la universidad, tales como Bill Gates, de Microsoft, o Steve Jobs, de Apple”.

Jim Danielson, otro de los becarios, también expresó en esa ocasión: “A veces el sistema universitario frena la innovación”. De momento, Danielson desarrolla un motor eléctrico para un automóvil Porsche 924S con energía electrónica que él mismo inventó.

Para Deming, el objetivo es diferente.

***

¿Cuál es tu meta con esa beca?

Conseguir la primera terapia que permita incrementar la esperanza de vida del ser humano. Hasta ahora hemos tenido resultados alentadores. Con ratones de laboratorio, con la misma edad y características, pero algunos con modificaciones respecto de otros, se ha logrado incrementar su esperanza de vida. ¿Funcionará en humanos? Es posible, pero se necesitan más estudios. Para eso, quizás hagan falta otros 20 años.

¿Qué causa el envejecimiento?

Es causado por una complicada mezcla de factores genéticos y estocásticos.

¿Por qué para ti es tan importante vivir más?

Porque si no se encuentra algo para vivir más, el ser humano seguirá muriendo en torno a los cien años. Además, en el camino, es posible que se encuentren formas para detener o curar enfermedades propias del envejecimiento, como el alzhéimer, párkinson o Huntington.

Aparte de las enfermedades que me mencionaste, ¿crees posible curar el cáncer?

Quizás en unos 20 años se pueda conseguir una cura para el alzhéimer, pero el cáncer es muy complicado, ya que es muy diferente a otras enfermedades.

¿Temes envejecer?

No, no le temo a ese proceso, pero sí creo que es necesario encontrar una terapia que lo retrase.

Me has hablado de crear una terapia antienvejecimiento. ¿Consideras que tal proceso es una enfermedad?

La Administración de Alimentos y Medicamentos (FDA, en inglés) no lo cataloga como tal.

Entonces, ¿cómo es que has podido crear un negocio alrededor de eso?

No es una hazaña. Mi compañía —Floreat Capital, de la cual es cofundadora y en la que trabaja con Corey Goodman, una destacada biotecnóloga—, procuramos crear una estructura rentable y autosostenible que permita tener varios proyectos antienvejecimiento, y luego comercializar las investigaciones. Es importante, además, que los científicos tengan fuentes estables para financiar proyectos de este tipo.

La Iglesia Católica no tiene una postura oficial en cuanto a la investigación genética. Ahora se ha elegido a un nuevo papa —Francisco—. ¿Esperas que esa institución se pronuncie al respecto?

Ese es un punto interesante. En realidad no sé qué decir. No soy católica, pero lo que esperaría es que la Iglesia esté abierta a la ciencia, pues las investigaciones que se llevan a cabo son para mejorar la salud y la calidad de vida en general. Sería terrible si hubiera algo que detuviera el desarrollo de este tipo de estudios.

¿Cuando termine tu beca —al final de este año—, planeas regresar a la Universidad?

Extraño estudiar para los exámenes, pero creo que podría aprender mucho más acerca de biotecnología —tanto en el aspecto científico como en lo empresarial— sumergiéndome en ella.

Al hablarte se nota tu entusiasmo por lo que haces. ¿Cómo pueden los jóvenes encontrar su aptitud?

Es una pregunta bastante difícil, pero creo que todo se dirige a encontrar aquello que a cada quien le apasiona. ¿Cómo se halla? Pues hay que hacer muchas cosas; experimentar. En ese proceso, esa persona se dará cuenta de cuáles son las cosas que le gustan hacer.

¿Es posible que todos logremos nuestros sueños?

Es posible que no sea posible lograr todo lo que quieras, pero si no lo intentas nunca lo sabrás. Los sueños grandes, lógicamente, son los más difíciles de alcanzar. Son realmente duros. Pero vale la pena intentarlo. No importa la edad. El solo hecho de estar vivo quiere decir que tienes la oportunidad de luchar por eso que quieres.

PERFIL

Laura Deming, neozelandesa de 18 años, estudió con la bióloga molecular Cinthia Kenyon, de junio del 2006 a mayo del 2009.

Del 2009 al 2011 ingresó en el Instituto Tecnológico de Massachusetts (MIT, en inglés), para estudiar Física y Biología.

En el 2011 fue seleccionada para la Beca Thiel, que proporciona US$100 mil como incentivo para dejar los estudios, a cambio de desarrollar negocios y tecnologíasinnovadoras. Laura Deming se enfoca en crear una terapia efectiva para incrementar la esperanza de vida del ser humano.

Crucial Step in Human DNA Replication Observed Using Fluorescent Tags

ORIGINAL: Penn State

Stephen J. Benkovic, Mark Hedglin, and other members of Professor Benkovic's research team have studied the importance of "clamp loader" enzymes and their activities during DNA replication. In this image, the clamp loader is represented, for illustrative purposes, by a hand, which is loading the sliding clamp ring onto DNA. Credit: Benkovic lab, Penn State University

1 April 2013 — For the first time, an elusive step in the process of human DNA replication has been demystified by scientists at Penn State University. According to senior author Stephen J. Benkovic, an Evan Pugh Professor of Chemistry and Holder of the Eberly Family Chair in Chemistry at Penn State, the scientists "discovered how a key step in human DNA replication is performed." The results of the research will be published in the journal eLife on 2 April 2013.

Part of the DNA replication process -- in humans and in other life forms -- involves loading of molecular structures called sliding clamps onto DNA. This crucial step in DNA replication had remained somewhat mysterious and had not been well studied in human DNA replication. Mark Hedglin, a post-doctoral researcher in Penn State's Department of Chemistry and a member of Benkovic's team, explained that the sliding clamp is a ring-shaped protein that acts to encircle the DNA strand, latching around it like a watch band. The sliding clamp then serves to anchor special enzymes called polymerases to the DNA, ensuring efficient copying of the genetic material. "Without a sliding clamp, polymerases can copy very few bases -- the molecular 'letters' that make up the code of DNA -- at a time. But the clamp helps the polymerase to stay in place, allowing it to copy thousands of bases before being removed from the strand of DNA," Hedglin said.

Hedglin explained that, due to the closed circular structure of sliding clamps, another necessary step in DNA replication is the presence of a "clamp loader," which acts to latch and unlatch the sliding clamps at key stages during the process. "The big unknown has always been how the sliding clamp and the clamp loader interact and the timing of latching and unlatching of the clamp from the DNA," said Hedglin. "We know that polymerases and clamp loaders can't bind the sliding clamp at the same time, so the hypothesis was that clamp loaders latched sliding clamps onto DNA, then left for some time during DNA replication, returning only to unlatch the clamps after the polymerase left so they could be recycled for further use."

To test this hypothesis, the team of researchers used a method called Förster resonance energy transfer (FRET), a technique of attaching fluorescent "tags" to human proteins and sections of DNA in order to monitor the interactions between them. "With these tags in place, we then observed the formation of holoenzymes -- the active form of the polymerase involved in DNA replication, which consists of the polymerase itself along with any accessory factors that optimize its activity," Hedglin said. "We found that whenever a sliding clamp is loaded onto a DNA template in the absence of polymerase, the clamp loader quickly removed the clamp so that free clamps did not build up on the DNA. However, whenever a polymerase was present, it captured the sliding clamp and the clamp loader then dissociated from the DNA strand."

The team members also found that, during the moments when both the clamp loader and the clamp were bound to the DNA, they were not intimately engaged with each other. Rather, the clamp loader released the closed clamp onto the DNA, allowing an opportunity for the polymerase to capture the clamp, completing the assembly of the holoenzyme. Subsequently, the clamp loader dissociated from DNA. "Our research demonstrates that the DNA polymerase holoenzyme in humans consists of only a clamp and a DNA polymerase. The clamp loader is not part of it. It disengages from the DNA after the polymerase binds the clamp," Hedglin added.

Benkovic noted that this mechanism provides a means for the cell to recycle scarce clamps when they are not in use for productive replication.

In addition to Benkovic and Hedglin, other Penn State researchers who contributed to the paper include Senthil K Perumal and Zhenxin Hu.

The research was funded by the National Institutes of Health.

Most popular human cell in science gets sequenced

ORIGINAL: Nature

Ewen Callaway

15 March 2013

The HeLa cell genome is riddled with errors, raising questions about its continued use.

HeLa cells have contributed to work in thousands
of research papers but sequencing shows their genome
to be full of errors.
 THOMAS DEERINCK,
NCMIR/SCIENCE PHOTO LIBRARY

The research world’s most famous human cell has had its genome decoded, and it’s a mess. German researchers this week report the genome sequence of the HeLa cell line, which originates from a deadly cervical tumour taken from a patient named Henrietta Lacks.

Established after Lacks died in 1951, HeLa cells were the first human cells to grow well in the laboratory. The cells have contributed to more than 60,000 research papers, the development of a polio vaccine in the 1950s and, most recently, an international effort to characterize the genome, known as ENCODE.

Previous work showed that HeLa cells, like many tumours, have bizarre, error-filled genomes, with one or more extra copies of many chromosomes. To get a closer look at these alterations, a team led by Lars Steinmetz, a geneticist at the European Molecular Biology Laboratory in Heidelberg, Germany, sequenced the popular 'Kyoto' version of the cell line and compared the sequence with that of a reference human genome. The team's results are published in G31.

Steinmetz’s team confirmed that HeLa cells contain one extra version of most chromosomes, with up to five copies of some. Many genes were duplicated even more extensively, with four, five or six copies sometimes present, instead of the usual two. Furthermore, large segments of chromosome 11 and several other chromosomes were reshuffled like a deck of cards, drastically altering the arrangement of the genes.

Without the genome sequence of Lacks’ healthy cells or that of her original tumour, it is difficult to trace the origin of these alterations. Steinmetz points out that other cervical tumours have massive rearrangements on chromosome 11, so the changes in the HeLa cell may have contributed to Lacks’ tumour.

Henrietta Lacks, whose cancer
gave rise to HeLa cells. 
OBSTETRICS & GYNAECOLOGY/SCIENCE
PHOTO LIBRARY

Potential uses

Having been replicating in labs around the world for six decades, HeLa cells have also accrued errors not present in the original tumour DNA. Moreover, not all HeLa cells are identical, and Steinmetz says that it would be interesting to chart the cell’s evolution.

Whatever their origin, the genetic changes raise questions over the widespread use of HeLa cells as models for human cell biology, Steinmetz says. For instance, his team found that around 2000 genes are expressed at levels higher than those of normal human tissues because of the duplications. Alternative cell lines, such as induced pluripotent stem cells generated from patient skin cells, offer a more accurate window on human biology, he says.

Mathew Garnett, a cancer biologist at the Wellcome Trust Sanger Institute near Cambridge, UK, says that HeLa cells could prove useful for studying aspects of the biology of cervical tumours, such as their response to cancer drugs.In recent years, the genomes of many cervical tumours have been sequenced, and so it should be possible to see how these compare with the HeLa genome.

Steinmetz also points out that thousands of research papers based on HeLa cells, along with HeLa resources such as genetically manipulated lines and now a genome, means that labs will continue to stock the cells, even if they are not a perfect model of human biology. “These are not going to go out of fashion over the next 10 years,” he says. "I’m not sure where we’re going to be 20 years from now."Nature doi:10.1038/nature.2013.12609

References

Landry, J. et al. G3 http://dx.doi.org/10.1534/g3.113.005777 (2013).

Harvard's Wyss Institute and Sony DADC Announce Collaboration on Organs-on-Chips

ORIGINAL: Wyss Institute

Date: Mar 18, 2013

Boston, MA -- Today the Wyss Institute for Biologically Inspired Engineering at Harvard University and Sony DADC announced a collaboration that will harness Sony DADC's global manufacturing expertise to further advance the Institute's Organs-on-Chips technologies. 

Human Organs-on-Chips are composed of a clear, flexible polymer about the size of a computer memory stick, and contain hollow microfluidic channels lined by living human cells -- allowing researchers to recapitulate the physiological and mechanical functions of the organs, and to observe what happens in real time. The goal is to provide more predictive and useful measures of the efficacy and safety of new drugs in humans -- and at a fraction of the time and costs associated with traditional animal testing.

"We are excited to apply Sony DADC's deep manufacturing expertise to confront one of the major challenges in the life sciences by helping to accelerate the translation of the Wyss Institute's Organ-on-Chips from the benchtop to the marketplace," said Christoph Mauracher, Senior Vice President of the BioSciences division of Sony DADC. "The Organs-on-Chips have the potential to revolutionize testing of drugs, chemicals, toxins and cosmetics."

Organs on a Chip from Wyss Institute on Vimeo.

This collaboration builds on the momentum the Wyss Institute team has gained recently on its Organs-on-Chips research program. With support from Defense Advanced Research Projects Agency (DARPA)*, National Institutes of Health (NIH), Food and Drug Administration (FDA), and pharmaceutical partners, more than ten Organs-on-Chips are currently under development at the Wyss Institute, including a lung, heart, liver, kidney, bone marrow, and gut-on-a-chip; there is also a major effort to integrate these organ chips into "human body on-chips" that mimic whole body physiology.

In February, Wyss Founding Director Don Ingber, M.D., Ph.D., who leads the Organs-on-Chips research program, received the prestigious 3Rs Prize from the UK's National Centre for the Replacement, Refinement and Reduction of Animals in Research for the lung-on-a-chip. This month, the Society of Toxicology awarded him the Leading Edge in Basic Science Award for his "seminal scientific contributions and advances to understanding fundamental mechanisms of toxicity."

"Our work with Sony is a wonderful example of the Wyss Institute model in action," said Ingber. "We collaborate with industry to help de-risk the technologies we develop, both technically and commercially, and therefore expedite their translation into real world applications."

###

*Part of this research was sponsored by the U.S. Army Research Office (ARO) and DARPA; the views and conclusions contained in this document are those of the authors and should not be interpreted as representing the official policies, either expressed or implied, of ARO, DARPA or the U.S. Government.

Contacts

Wyss Institute for Biologically Inspired Engineering 

Kristen M. Kusek

+1 617-432-8266

Kristen.kusek@wyss.harvard.edu 

Sony DADC

Manfred Koranda

+43 6246 880 8143

manfred.koranda@sonydadc.com

Tiny mutation may have shaped modern humans, scientists say

ORIGINAL: LATimes

By Eryn Brown, Los Angeles Times

February 14, 2013

Add caption

A genetic variant could have helped people survive crippling heat by giving them extra sweat glands, says a report from a team that sought to replicate the effect in mice.

About 30,000 years ago, a tiny mutation arose in a gene known as EDAR and began to spread rapidly in central China, eventually becoming common in the region.

This week, scientists at Harvard University offered some explanations for why the EDAR mutation may have been so successful — by observing how it affects mice, animals long used in disease research but never before pressed into service for the study of human evolution.

The small change, substituting one chemical letter of DNA for another, may have helped humans in Asia survive crippling heat and humidity by endowing them with extra sweat glands, the scientists reported Thursday in the journal Cell. It may also have made people with the mutation more attractive to the opposite sex by allowing them to grow thicker hair or fuller breasts.

The research showed how scientists are getting better at zeroing in on the key DNA changes that shaped who we are today. The analysis also revealed that mutations in genes involved in bone density, skin color and immune system function were likely pivotal in helping humans adapt to new environments as they spread throughout the world.

"You can let the genome tell you what's been important in human evolution," said Harvard computational geneticist Pardis Sabeti, senior author of the two studies published in Cell.

Living beings evolve through a process known as selection. Organisms with advantageous traits thrive, passing their DNA to another generation. Harmful traits die off when their hosts can't live long enough to reproduce.

Scientists can recognize patterns in DNA that indicate a particular version of a gene has spread through a population because it boosts survival. But those beneficial mutations are usually passed down along with thousands of other variants that happen to live in their chromosomal neighborhood.

That has made it hard for researchers to determine exactly which genetic tweaks conferred the competitive advantage.

"It's like you walk around a ghost town and you see the clues that something happened, but you don't know exactly what or how," said UC Santa Cruz biomolecular engineer Ed Green, who was not involved in the new studies.

Sabeti and an international group of colleagues are using multiple techniques to dig out the key drivers of human evolution in the avalanche of genetic data made possible by faster, cheaper sequencing technology. A single human genome contains 3 billion pairs of the chemical letters A, C, G and T.

To sort through all that, the researchers used powerful computers to identify genetic changes that seemed to be linked to evolutionary change. They examined the DNA of 179 people from Utah, East Asia and West Africa and revealed hundreds of potentially key variants, including mutations that made bones stronger and helped people absorb more vitamin D from the sun as they moved to northern latitudes.

Sabeti wanted to understand more about how these mutations influenced human traits. Such work requires experimentation — and that is where the mice entered the picture.

The EDAR gene was already known to influence hair thickness and to alter tooth shape in humans. But Sabeti wasn't sure whether the mutation her team turned up was a key change that drove human evolution.

To arrive at an answer, she and her collaborators genetically engineered mice that had the Asian version of EDAR.

They found that, as with humans, the mice had thicker hair than their counterparts without the variant. They also displayed traits the researchers hadn't expected to see, including more sweat glands and changes in their mammary glands. (The variant had no discernible effect on the animals' teeth.)

Next, the team examined the fingertips and EDAR genes of 623 people in Taizhou, China, to see if those who had the mutation also had a larger number of active sweat glands. They did.

The results present a fuller picture of how the EDAR mutation may have helped drive evolution.

People who inherited the variant may have reproduced more successfully because having more sweat glands helped their bodies cool off in hot, humid weather.

Or it might have spread through sexual selection. Thicker hair may have been more appealing in a mate. In addition, the mutation could have changed breast size or shape, making people who had it more attractive to the opposite sex.

That scientists could study a mouse and reveal such insights into human evolution was "amazing," said Green, who co-wrote an essay about the work that was also published in Cell on Thursday.

The story was similar for the TLR-5 gene, which is involved in protecting the body from certain bacteria. Instead of testing in mice, the scientists used cell cultures in lab dishes to demonstrate that the mutation reduced the immune system's inflammatory response to a key protein in the bacterial pathogens.

The team's analysis suggested that many of the key genetic changes weren't in genes themselves, but in regions of the chromosome that scientists think contain instructions for how those genes should be turned on and off, or tuned up or down, Sabeti said.

The work offers a long-awaited view into the key mutations that billions of us share and that made us who we are, said David Kingsley, an evolutionary geneticist at Stanford University who was not involved in the new studies.

"We're reading a book of information about our past that has never been available before," he said.

eryn.brown@latimes.com

"Extinción del tigre de Tasmania, recae exclusivamente en el ser humano", aclara estudio

ORIGINAL: Más Verde

by masverde

febrero 14th, 2013

Los seres humanos son los únicos responsables de la desaparición del tigre de Tasmania (Thylacine cynocephalus), un marsupial carnívoro que habitó Australia hasta extinguirse en 1936, según un estudio divulgado en Australia.

La investigación de la Universidad de Adelaida contradice la creencia generalizada que vincula la desaparición del tigre de Tasmania con una enfermedad, según un comunicado de esa institución académica.

El tigre de Tasmania era un marsupial que poblaba gran parte del territorio de la isla de Tasmania, en el sur de Australia, antes de la colonización europea en 1803.

La población de este carnívoro menguó cuando, entre 1886 y 1909, el gobierno de Tasmania alentó su caza con recompensas por cada 2.000 ejemplares capturados hasta que en 1933 fue capturado el último de estos animales.

“Muchas personas creen que esa recompensa por la caza de estos animales no causó su extinción y se culpa de ello a una enfermedad epidémica desconocida”, dijo Thomas Prowse, investigador de la Escuela de Ciencias de la Tierra y el Ambiente.

Para probar su teoría, los investigadores utilizaron un modelo matemático para evaluar si la presencia de los colonos europeos había provocado la extinción del marsupial, sin la influencia de alguna enfermedad.

“(El modelo) simuló los efectos directos de la recompensa por la caza, la pérdida del hábitat y los efectos indirectos de la reducción de las presas del tigre (canguros y wallabies) debido a los cultivos y a la competición por los alimentos con millones de ovejas que fueron introducidas al territorio”, dijo Prowse.

“El impacto negativo de la colonización europea fue lo suficientemente poderosa, incluso sin la ayuda de una enfermedad epidémica, para acabar con la especie”, añadió el responsable de la investigación en la que también participó la Universidad de Tasmania y la Sociedad Zoológica de Chicago.

Fuente: EFE, Agencias

Cloning Neanderthal May Be Possible Soon

ORIGINAL: 33rdSquare

By 33rd Square
January 18, 2013

Image: Nikola Solic/Reuters

With the help of synthetic biology,it may be possible to create a Neanderthal clone, American geneticist George Church told der SPIEGEL. Church suggests the surrogate mother would need to be "an adventurous female person." 

Previously we outlined how researchers in Korea are planning on cloning and bringing back to the earth, the woolly mammoth. —Now, perhaps in a projected need to control the potentially rampant future mammoth population, there are calls to also bring back one of the giant ice-age creature's main predators, Neanderthal man.

George Church, a Harvard geneticist recently told Der Spiegel he's close to developing the necessary technology to clone a Neanderthal, at which point all he'd need is an "adventurous human woman" — einen abenteuerlustigen weiblichen Menschen — to act as a surrogate mother.

At the time the initial Neanderthal genome was sequenced, it was suggested that the species did not die out from competition with Homo sapiens, rather the two species inter-bred and the Neanderthal line was absorbed by modern humans. Genetic testing revealed that European decedents, particularly from those around the Tuscany area, shared as much as 4% genetic material with Neanderthals, while modern Africans have virtually none. 

These results are once again up for debate, as new research causes doubt for the inter-breeding hypothesis. At any rate, as has been shown with other cross-species surrogate births, the ability for a human mother to carry a Neanderthal baby to term is not entirely out of the question. 

According to a 2008 study of a Neanderthal infant skeleton, "the head of the Neanderthal newborn was somewhat longer than that of a human newborn because of its relatively robust face," and Neanderthal women generally had a wider birth canal than human women. Neanderthal birth was simpler than human birth, because Neanderthal infants didn't have to rotate to get to the birth canal, but otherwise the processes were very similar, however it would most probably entail a C-section delivery.

For some reason, Church seems to think that there'll be a Neanderthal craze, as he told Bloomberg Businessweek last year:

"We have lots of Neanderthal parts around the lab. We are creating Neanderthal cells. Let's say someone has a healthy, normal Neanderthal baby. Well, then, everyone will want to have a Neanderthal kid. Were they superstrong or supersmart? Who knows? But there's one way to find out."

SOURCE Source: Gawker, MIT Technology Review Top Image: Nikola Solic/Reuters

Water purifier chemical 'increases food allergy risk'

ORIGINAL: Daily Telegraph

By Stephen Adams, Medical Correspondent

03 Dec 2012

A byproduct of chemicals used to help purify water could be to blame for a surge in food allergies, according to a study.

Researchers believe high levels of dichlorophenols, byproducts of chlorination, could lead to food allergies. Photo: ALAMY

Researchers have found that people exposed to high levels of dichlorophenols, produced when chlorine is added to water to ensure it is free of bugs, tend to be more prone to food allergies too.

Elina Jerschow, assistant professor of allergy and immunology at the Albert Einstein College of Medicine in New York, said: “Our research shows that high levels of dichlorophenol-containing pesticides can possibly weaken food tolerance in some people, causing food allergy.

“This chemical is commonly found in pesticides used by farmers and consumer insect and weed control products, as well as tap water.”

Together with colleagues, she looked at the incidence of food allergies among 2,211 people who were participants in the US National Health and Nutrition Examination Survey.

Of those, the quarter with the highest level of dichlorophenols in their urine were looked at in detail.

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The academics found their chance of having a food allergy - for example to eggs, peanuts, milk or shrimp - was 80 per cent higher than those with lower levels of dichlorophenols.

Writing in the journal Annals of Allergy, Asthma and Immunology, they concluded: "In this population, we found consistent associations between high levels of dichlorophenol exposure and a higher prevalence of food allergies.”

Among this group 550 or so people with the highest levels of the chemicals, their chance of having both a food allergy and an ‘environmental’ allergy - for example to pollen - was 61 per cent higher.

Dr Jerschow said: "Previous studies have shown that both food allergies and environmental pollution are increasing in the United States.

"The results of our study suggest these two trends might be linked, and that increased use of pesticides and other chemicals is associated with a higher prevalence of food allergies."

However, she said that further studies were necessary “to confirm this link”.

If firm evidence emerged that dichlorophenols triggered allergies, Dr Jerschow cautioned that avoiding tap water was unlikely to solve the problem.

Other dichlorophenol sources, such as pesticide-treated fruits and vegetables, may play a greater role in causing food allergy, she said.

Chlorophenols are a byproduct of chlorinating water. When the chlorinating agent is added, it reacts for phenols - organic compounds found in plants - which creates a range of chlorophenols.

According to the World Health Organisation, there are no guidelines for concentrations of dichlorophenols because data on toxicity “are limited”.

According to the Centres for Disease Control and Prevention, an increase in food allergy of 18 per cent was seen between 1997 and 2007. The most common food allergens are milk, eggs, peanuts, wheat, tree nuts, soy, fish, and shellfish.

Allergy experts agree that food allergies are also on the increase in Britain, and that this increase is not solely the result of people being more likely to report potential problems to their doctors.

A recent study conducted on the Isle of Wight found one in 20 children had a clinically confirmed allergy.

However, it is thought many people believe they suffer from a food allergy but actually do not.

In 2010 the National Institute for Health and Clinical Excellence (Nice) estimated that while more than a third of people believed they were allergic to some form of food, only a tenth actually were when properly tested.

A spokesman for Thames Water said: "We chlorinate water once it has been fully processed, so there is no organic matter in it."