Merging Humans and Robots--More Coffee, Please

With the help of a tiny chip implanted in the brain, human beings who cannot move their own limbs are able to move a robotic arm, in one case taking a drink of coffee on one’s own for the first time in fifteen years.

"The smile on her face was a remarkable thing to see. For all of us involved, we were encouraged that the research is making the kind of progress that we had all hoped," said the trial's lead investigator, Leigh Hochberg, M.D., Ph.D., in a press release issued by the National Institutes of Health, which provided some of the funding. Hochberg is an associate professor of engineering at Brown University and a critical care neurologist at Massachusetts General Hospital (MGH)/Harvard Medical School.

The field of brain-computer interface research is not new, but this is the first peer-reviewed report of people using brain signals to control a robotic arm, making it perform in three-dimensional space much as their natural arms once did. By imagining they were controlling their paralyzed limb, they were able to move the robotic arm. Brain activity is detected as electrical activity by the BrainGate chip, processed by an external computer, and fed into a robot that translates the signals into movement.

More research is underway, and in fact this clinical trial is recruiting more volunteers.

Caption: The BrainGate array, which is implanted on the motor cortex, comprises nearly 100 electrodes on a chip the size of a baby aspirin. Credit: www.braingate2.org Usage Restrictions: With Credit.

With future advances, researchers hope to be able to improve the quality of movement in prosthetic limbs or to restore in part the function of paralyzed limbs, perhaps by creating an electronic by-pass to normal nerves.

"This is another big jump forward to control the movements of a robotic arm in three-dimensional space. We're getting closer to restoring some level of everyday function to people with limb paralysis," said John Donoghue, Ph.D., who leads the development of BrainGate technology and is the director of the Institute for Brain Science at Brown University.

Beyond therapy, it is possible to imagine other uses as we humans and our machines co-evolve and increasingly converge, probably to do more than drink coffee.

This report is published in the May 17, 2012 issue of Nature.

How Old Is Art?

Confirmed dates for the world’s oldest art just got older, according to the report of an international research team published in the May 14 issue of the Proceedings of the National Academy of Sciences.

Dating back about 37,000 years, the art consists of engravings made in stone that has since fallen from the ceiling of a cave at Abri Castanet in southwestern France. While not as visually arresting as the more famous cave art found at Chauvet, the Castanet engravings are both older and represent what is very likely an earlier stage in the history of the Aurignacian culture, which spanned 40,000 to about 28,000 years ago. Some of the Chauvet paintings are now confirmed at between 30,000 and 32,000 years ago.

Credit: HTO. A replica of a painting, now in the public domain.

The Castanet engravings are both simpler artistically and were located in the general living area of the cave. The Aurignacian culture that created both the paintings and the engravings is known for is many forms of art. According to New York University anthropology professor Randall White, one of the study's co-authors, the Aurignacians "had relatively complex social identities communicated through personal ornamentation, and they practiced sculpture and graphic arts."

"But unlike the Chauvet paintings and engravings, which are deep underground and away from living areas, the engravings and paintings at Castanet are directly associated with everyday life, given their proximity to tools, fireplaces, bone and antler tool production, and ornament workshops," White said in press release issued by NYU.

With more refined archeological techniques, the story of the rise of human symbolic culture is likely to become more complex and more ancient. While there may well have been bursts of cultural creativity in which symbolic advance occurred rapidly, additional findings may also suggest a more steady rise in the story of human art. The study, entitled “Context and dating of Aurignacian vulvar representations from Abri Castanet, France,” appears in the May 14, 2012 edition of PNAS.

Human Intelligence: Does It Depend on a Genetic Error?

What makes humans different from the great apes? What makes our brains larger and more complex? We know that our DNA is remarkable similar to other mammals. What subtle genetic changes can explain such huge behavioral differences? One surprising possibility is that our brains are bigger and more complex not so much because of new genes but because of gene duplication.

One gene in particular—SRGAP2—plays a role in how brain cells migrate. It is found widely in mammals of all sorts, from mice to humans. In the great apes, the more archaic form of SRGAP2 results in a relatively slow spread of neurons throughout the brain. Twice in the ancient past, however, SRGAP2 was duplicated, first about 3.4 million years ago and then again around 2.4 million years ago. The second duplication occurred right around the time when the genus Homo separated from Australopithecus. It appears that as a result of these duplications, brains in the Homo lineage—including our own as Homo sapiens—are both large and complex in their number of neuronal connections and in their ability to process information.

A key piece of supporting evidence comes from recent discoveries of the role of SRGAP2 in the development of the human neocortex. When the distinctly human SRGAP2 variants are missing, normal human brain development is impaired. This research appears in two papers appearing May 3, 2012 in the journal Cell. According to one of the papers, “It is intriguing that the general timing of the potentially functional copies…corresponds to the emergence of the genus Homo from Australopithecus (2-3 mya). This period of human evolution has been associated with the expansion of the neocortex and the use of stone tools, as well as dramatic changes in behavior and culture.”

Caption: A team led by Scripps Research Institute scientists has found evidence that, as humans evolved, an extra copy of a brain-development gene allowed neurons to migrate farther and develop more connections. Credit: Photo courtesy of The Scripps Research Institute Usage Restrictions: None

The uniquely human duplications work in a surprising ways, especially the second duplication. The original SRGAP2 remains present in humans today, along with the duplicated versions. The second duplication—SRGAP2C—has the effect of interfering with the original SRGAP2. The reason why SRGAP2C interferes with SRGAP2 rather than boosts it is because the duplicated version is incomplete—in other words, an advantageous copying error.

According to one of the studies, once SRGAP2C appeared about 2.4 million years ago, it created a “dominant negative interaction equivalent to a knockdown of the ancestral copy…The incomplete nature of the segmental duplication was, therefore, ideal to establish the new function by virtue of its structure,” acting in a way that was “instantaneous” in terms of evolution.

"This innovation couldn't have happened without that incomplete duplication," according to Evan Eichler, another leader in the research team. "Our data suggest a mechanism where incomplete duplication of this gene created a novel function 'at birth'."

Even though SRGAP2 duplications seem to play a significant role in distinguishing human beings from the apes, other duplications and mutations are very likely to be involved in the story of human evolution. "There are approximately 30 genes that were selectively duplicated in humans," said Franck Polleux, one of the lead researchers involved in the study, in a press release from the journal. "These are some of our most recent genomic innovations."

Rather than standard mutations, "episodic and large duplication events could have allowed for radical – potentially earth-shattering – changes in brain development and brain function," according to Eichler. For these reasons, this is one of the most intriguing areas for research into the origins of human intelligence.

Whether other duplications—including “incomplete duplications or erroneous copies—also explain our complex brains is something that will be discovered in the next few years.

But what is surprising and somewhat sobering, just based on this SRGAP2 discovery, is how our much-vaunted human uniqueness seems to hang on such a fine thread. If the SGGAP2 duplication is even partly responsible for our complex brains, should we think that our intelligence arose because of a copying error or an incomplete duplication? Is the rise of intelligence and consciousness—truly one of the great events in the story of cosmic evolution—really just based in part on a fluke of nature? Religious or not, hardly anyone is likely to think that thinking is sheer accident.

The papers, Charrier et al.: "Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation" and Dennis et al.: "Human-specific evolution of novel SRGAP2 genes by incomplete segmental duplication," appear in the journal Cell.

Extending Healthy Lifespans? A Pill on the Horizon?

Resveratrol, the much-hyped ingredient found in red wine and sold widely as a nutritional supplement, is known to improve the health and extend the lifespan of mice. Can it do the same for humans? Without nasty side effects? And at what dose?

A study published today in Cell Metabolism helps unravel a few more of resveratrol’s mysteries. In particular, researchers have shed new light on how resveratrol works. Key to its effectiveness is a gene known as SIRT1, found in slightly different forms in species as different as yeast and humans. SIRT1 plays many roles, some tied to core metabolic processes. The new study shows that in mice, even a low dose of resveratrol interacts with SIRT1 to improve metabolism.

What makes this study especially interesting is that researchers had to create a special strain of mice in order to test whether SIRT1 is necessary for resveratrol to work. If mice have no SIRT1, they do not develop properly. So two graduate students, Nathan Price and Ana Gomes, developed a novel strain of mice with an unusual copy of the SIRT1 gene, one that could be switched off at adulthood.

By administering a drug (tamoxifen), researchers can “induce” or switch the SIRT1 gene on and off, a strategy that will likely be used in other studies. "This is a drug inducible, whole body deletion of a gene," David Sinclair, the study's senior author, said in a press release from Harvard Medical School. "This is something that's rarely been done so efficiently. Moving forward, this mouse model will be valuable to many different labs for other areas of research."

Photo by R. Cole-Turner

In this case, the switchable SIRT1 mouse provided proof that SIRT1 is key to resveratrol’s effectiveness. Why is that important? Because resveratrol is a complex molecule that interacts with the body in many unknown ways. While it may be beneficial, it may have unwanted side effects. So researchers are trying to design a more simple molecule that provides the benefits of resveratrol without all the risks. One strategy is to boost SIRT1 activity. By proving that SIRT1 is involved, this study provides support for that strategy, which is already being pursued by pharmaceutical firms.

"The results were surprisingly clear," said. "Without the mitochondria-boosting gene SIRT1, resveratrol does not work."

Are we any nearer a magic pill that slows aging or promotes longevity? Perhaps. The headline of the press release from the publisher, Cell Press, claims that this work “restores hope for anti-aging pill.” Remember, of course, that the work reported here is entirely with mice.

Even so, the paper itself concludes with this statement: “This model supports the enticing possibility of designing and developing potent small molecules that provide the health benefits of resveratrol by activating SIRT1 and downstream pathways to treat metabolic and other age-related diseases.”

The treatment of age-related diseases, including diabetes, is a huge target for pharmaceutical firms. But beyond that lies that even bigger market for human enhancement, specifically for enhancing the span of healthy decades.

The study, "SIRT1 Is Required for AMPK Activation and the Beneficial Effects of Resveratrol on Mitochondrial Function," appears in the May 1, 2012 issue of Cell Metabolism.

Spreading Farming, Spreading Genes

Agriculture probably originated in the Middle East about 11,000 years ago. Over the next six thousand years, it spread to other parts of the globe, including northern Europe, gradually replacing hunting and gathering as the primary means of human survival.

How did it spread? Were hunter-gatherers converted to the efficiencies of agriculture? Or did farmers from the south spread north, bringing their agriculture with them?

A new study suggests that farming spread because farmers moved. The movement was slow, taking five to six thousand years to reach Scandinavia. Early in the process, farmers of southern ancestry lived side by side with their more northerly human cousins, who still lived by hunting and gathering. Eventually, after a thousand years or so, farmers interbred with hunter-gatherers and farming became the dominant way of life.

The new study, which appears in the April 27 issue of Science, is based on an analysis of four skeletons, all found in Sweden and dating from about 5,000 years ago. Three were hunter-gatherers and one was a farmer. All of them lived their entire lives close to where they were buried, the hunter-gatherers in a flat grave and the farmer a stone megalith like the one pictured below.

Caption: Several hundred megalith tombs are known from the Falbygden area, including Gökhem and Valle parishes in Östergötland,Sweden.Credit: Göran Burenhult

"We know that the hunter-gatherer remains were buried in flat-bed grave sites, in stark contrast to the megalithic sites that the farmers built," said Mattias Jakobsson, a senior author from Uppsala University. "The farmer we analyzed was buried under such a megalith, and that's just one difference that helps distinguish the two cultures," Jakobsson said in a press release issued by the journal.

What is most significant in this study comes from an analysis of the human DNA extracted from the four skeletons. By studying their DNA, researchers found that the farmer belonged to a community with ancestral roots in the eastern Mediterranean, most closely resembling today's Greeks and Cypriots. The hunter-gatherers, on the other hand, were more like today’s northern Europeans, most closely resembling today's Finns. "What is interesting and surprising is that Stone Age farmers and hunter-gatherers from the same time had entirely different genetic backgrounds and lived side by side for more than a thousand years, to finally interbreed," Jakobsson said.

Caption: The skeleton belongs to a young female in her 20s, and can be dated to around 4,700 years ago. Credit: Göran Burenhult

"The results suggest that agriculture spread across Europe in concert with a migration of people," added Pontus Skoglund, also of Uppsala University. "If farming had spread solely as a cultural process, we would not expect to see a farmer in the north with such genetic affinity to southern populations."

The article, entitled "Origins and Genetic Legacy of Neolithic Farmers and Hunter-Gatherers in Europe," appears in the April 27 issue of Science, published by the American Association for the Advancement of Science.

Synthetic Biology: Is There Life beyond DNA?

Life as we know it is based on DNA and RNA. Could it have been otherwise? Might other worlds have life based on a different “genetic” system? We may never know for sure.

But we do know that synthetic biology is moving briskly toward the goal of engineered life beyond DNA and RNA.

Recall that in “DNA” and “RNA,” the “NA” part stands for “nucleic acids.” It’s the four nucleic acids that carry the genetic information in a chemical code. The “D” and the “R,” however, stand for sugars that hold the nucleic acids in place, allowing them to form pairs and to copy themselves. Can other sugars work as well?

Recent work in synthetic biology has led beyond DNA and RNA to xeno-nucleic acids or “XNAs.” Now, using six different forms of XNAs, an international team of researchers led by Vitor Pinheiro reports success in getting XNAs to store and propagate information. One of their XNAs actually “evolved” by responding to imposed selective constraints. Their work is published in the April 20, 2012 issue of the journal Science.

Caption: Courtesy--National Human Genome Research Institute

In a commentary on the research, Gerald F. Joyce writes in Science that this work has implications for the “understanding of life itself.” In addition, it opens new insight into the possible origins of life on our planet or else where in the cosmos.

At the same time, far more work lies ahead before synthetic biologists create XNA-based life. Pinheiro’s team was able to get their synthetic XNA “genes” to interact with DNA, but “they have not yet realized a synthetic genetic system.” One big challenge is in getting XNA sequences to copy themselves the way DNA does. Some XNAs can copy themselves to DNA and back again to XNA, but XNA-to-XNA copying is not reliable.

According to Joyce, however, “future studies are likely to yield improvements of the the various XNA-to-XNA copying reaction.” If that happens, synthetic biology will take yet another step toward “synthetic genetics.”

All this prompts a warning from Joyce: “Synthetic biologists are beginning to frolic on the worlds of alternative genetics but must not tread into areas that have the potential to harm our biology.” As ever, greater knowledge brings greater risks. More than ever, public awareness and careful thought are needed.

The research article, "Synthetic Genetic Polymers Capable of Heredity and Evolution" and the commentary, "Toward an Alternative Biology," are both published in the April 20, 2012 issue of Science, the journal of the American Association for the Advancement of Science.

A Million Years of Fire

One of our newest technologies has just shed new light on one of our oldest.

When did our human ancestors learn to control and use fire? Armed with the latest high tech tools, an international team of researchers has pushed the date back to 1 million years. That’s 300,000 years earlier than previous unambiguous dates.

The massive Wonderwerk Cave is in northern South Africa on the edge of the Kalahari. Previous excavations have shown extensive human occupation. Using the new techniques of micromorphological analysis and Fourier transform infrared microspectroscopy (mFTIR), researchers analyzed cave sediments at a far more detailed level than possible before.

Caption: This is a panoramic view of the entrance to Wonderwerk Cave, South Africa. Credit: H. Ruther. Usage Restrictions: None

In the cave sediments researchers found bits of ash from plants along with fragments of burned bone. Did the wind blow burning debris into the cave? The evidence—collected about 100 feet from the current opening of the cave—supports the conclusion that the fire burned in the cave. Also part of the proof: the surrounding surfaces are discolored.

”The analysis pushes the timing for the human use of fire back by 300,000 years, suggesting that human ancestors as early as Homo erectus may have begun using fire as part of their way of life," anthropologist Michael Chazan said in a press release from the University of Toronto.

According to the paper, "Through the application of micromorphological analysis and Fourier transform infrared microspectroscopy (mFTIR) of intact sediments and examination of associated archaeological finds— fauna, lithics, and macrobotanical remains—we provide unambiguous evidence in the form of burned bone and ashed plant remains that burning events took place in Wonderwerk Cave during the early Acheulean occupation, approximately 1.0 Ma. To date, to the best of our knowledge, this is the earliest secure evidence for burning in an archaeological context."

Caption: Interior of Wonderwerk Cave. Images courtesy of M. Chazan.

"The control of fire would have been a major turning point in human evolution," says Chazan. "The impact of cooking food is well documented, but the impact of control over fire would have touched all elements of human society. Socializing around a camp fire might actually be an essential aspect of what makes us human."

How important are fire and cooking for human evolution. A recent book, Catching Fire: How Cooking Made Us Human by Richard Wrangham, argues that cooking is essential to our humanity. Now in the paper published on April 2, the team concludes that its study “is the most compelling evidence to date offering some support for the cooking hypothesis of Wrangham.”

Their work is published as “Microstratigraphic evidence of in situ fire in the Acheulean strata of Wonderwerk Cave, Northern Cape Province, South Africa,” in the April 2, 2012 issue of the Proceedings of the National Academy of Sciences.