EUREKA_NEUROss

NEUROSCIENCE

NEUROSCIENCE

Breakthrough in neuroscience could allow troops to use mind control WORDS: Ian Sample ILLUSTRATIONS: Tommings Soldiers could have their minds plugged directly into weapons systems, undergo brain scans during recruitment and take courses of neural stimulation to boost their learning, if the armed forces embrace the latest developments in neuroscience to hone the performance of their troops.

These scenarios are described in a report into the military and law enforcement uses of neuroscience, published on Tuesday, which also highlights a raft of legal and ethical concerns that innovations in the field may bring.

The report by the Royal Society, the UK's national academy of science, says that while the rapid advance of neuroscience is expected to benefit society and improve treatments for brain disease and mental illness, it also has substantial security applications that should be carefully analysed.

The report's authors also anticipate new designer drugs that boost performance, make captives more talkative and make enemy troops fall asleep.

"Neuroscience will have more of an impact in the future," said Rod Flower, chair of the report's working group. "People can see a lot of possibilities, but so far very few have made their way through to actual use.

"All leaps forward start out this way. You have a groundswell of ideas and suddenly you get a step change."

The authors argue that while hostile uses of neuroscience and related technologies are ever more likely, scientists remain almost oblivious to the dual uses of their research.

The report calls for a fresh effort to educate neuroscientists about such uses of the work early in their careers.

Some techniques used widely in neuroscience are on the brink of being adopted by the military to improve the training of soldiers, pilots and other personnel.

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A growing body of research suggests that passing weak electrical signals through the skull, using transcranial direct current stimulation (tDCS), can improve people's performance in some tasks.

One study cited by the report described how US neuroscientists employed tDCS to improve people's ability to spot roadside bombs, snipers and other hidden threats in a virtual reality training programme used by US troops bound for the Middle East.

"Those who had tDCS learned to spot the targets much quicker," said Vince Clark, a cognitive neuroscientist and lead author on the study at the University of New Mexico.

"Their accuracy increased twice as fast as those who had minimal brain stimulation. I was shocked that the effect was so large."

Clark, whose wider research on tDCS could lead to radical therapies for those with dementia, psychiatric disorders and learning difficulties, admits to a tension in knowing that neuroscience will be used by the military. "As a scientist I dislike that someone might be hurt by my work. I want to reduce suffering, to make the world a better place, but there are people in the world with different intentions, and I don't know how to deal with that.

"If I stop my work, the people who might be helped won't be helped. Almost any technology has a defence application."

Research with tDCS is in its infancy, but work so far suggests it might help people by boosting their attention and memory.

According to the Royal Society report, when used with brain imaging systems, tDCS "may prove to be the much sought-after tool to enhance learning in a military context".

One of the report's most striking scenarios involves the use of devices called brain-machine interfaces (BMIs) to connect people's brains directly to military technology, including drones and other weapons systems.

The work builds on research that has enabled people to control cursors and artificial limbs through BMIs that read their brain signals.

"Since the human brain can process images, such as targets, much faster than the subject is consciously aware of, a neurally interfaced weapons system could provide significant advantages over other system control methods in terms of speed and accuracy," the report states.

The authors go on to stress the ethical and legal concerns that surround the use of BMIs by the military. Flower, a professor

of pharmacology at the William Harvey Research Institute at Barts and the London hospital, said: "If you are controlling a drone and you shoot the wrong target or bomb a wedding party, who is responsible for that action? Is it you or the BMI? "There's a blurring of the line between individual responsibility and the functioning of the machine. Where do you stop and the machine begin?"

Another tool expected to enter military use is the EEG (electroencephalogram), which uses a hairnet of electrodes to record brainwaves through the skull. Used with a system called "neurofeedback", people can learn to control their brainwaves and improve their skills. According to the report, the technique has been shown to improve training in golfers and archers.

The US military research organisation, Darpa, has already used EEG to help spot targets in satellite images that were missed by the person screening them. The EEG traces revealed that the brain sometimes noticed targets but failed to make them conscious thoughts. Staff used the EEG traces to select a group of images for closer inspection and improved their target detection threefold, the report notes.

Work on brain connectivity has already raised the prospect of using scans to select fast learners during recruitment drives.

Research last year by Scott Grafton at the University of California, Santa Barbara, drew on functional magnetic resonance imaging (fMRI) scans to measure the flexibility of brain networks. They found that a person's flexibility helped predict how quickly they would learn a new task.

Other studies suggest neuroscience could help distinguish risk-takers from more conservative decision-makers, and so help with assessments of whether they are better suited to peacekeeping missions or special forces, the report states. "Informal assessment occurs routinely throughout the military community. The issue is whether adopting more formal techniques based on the results of research in neuroeconomics, neuropsychology and other neuroscience disciplines confers an advantage in decisionmaking." www.pnas.org/content/108/18/7641.full March 2012 | Eureka | THE TIMES | 30

LUCA: Part 1

LUCA: Part 2

LUCA: The lowdown on primary genetics Bacterial Viruses

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Bacteria are present in most habitats on Earth, growing in soil, acidic hot springs, radioactive waste, water, and deep in the Earth's crust, as well as in organic matter and the live bodies of plants and animals, providing outstanding examples of mutualism in the digestive tracts of humans, termites and cockroaches. There are typically 40 million bacterial cells in a gram of soil and a million bacterial cells in a millilitre of fresh water; in all, there are approximately five nonillion (5Ă—1030) bacteria on Earth, forming a biomass that exceeds that of all plants and animals. Bacteria are vital in recycling nutrients, with many steps in nutrient cycles depending on these organisms, such as the fixation of nitrogen from the atmosphere and putrefaction. In the biological communities surrounding hydrothermal vents and cold seeps, bacteria provide the nutrients needed to sustain life by converting dissolved compounds such as hydrogen sulphide and methane. Most bacteria have not been characterised, and only about half of the phyla of bacteria have species that can be grown in the laboratory.

Initially, archaea were seen as extremophiles that lived in harsh environments, such as hot springs and salt lakes, but they have since been found in a broad range of habitats, including soils, oceans, marshlands and the human colon. Archaea are particularly numerous in the oceans, and the archaea in plankton may be one of the most abundant groups of organisms on the planet. Archaea are now recognized as a major part of Earth’s life and may play roles in both the carbon cycle and the nitrogen cycle. No clear examples of archaeal pathogens or parasites are known, but they are often mutualists or commensals. One example is the methanogens that inhabit the gut of humans and ruminants, where their vast numbers aid digestion. Methanogens are used in biogas production and sewage treatment, and enzymes from extremophile archaea that can endure high temperatures and organic solvents are exploited in biotechnology.

Cell division in eukaryotes is different from that in organisms without a nucleus (Prokaryote). It involves separating the duplicated chromosomes, through movements directed by microtubules.

There are two types of division processes.

In mitosis, one cell divides to produce two genetically identical cells. In meiosis, which is required in sexual reproduction, one diploid cell (having two instances of each chromosome, one from each parent) undergoes recombination of each pair of parental chromosomes, and then two stages of cell division, resulting in four haploid cells (gametes). Each gamete has just one complement of chromosomes, each a unique mix of the corresponding pair of parental chromosomes.

March 2012 | Eureka | THE TIMES | 30

LUCA: Part 3

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LUCA: the global mega-organism WORDS: Ian Sample ILLUSTRATIONS: Tommings ONCE upon a time, 3 billion years ago, there lived a single organism called LUCA. It was enormous: a mega-organism like none seen since, it filled the planet's oceans before splitting into three and giving birth to the ancestors of all living things on Earth today.

This strange picture is emerging from efforts to pin down the last universal common ancestor - not the first life that emerged on Earth but the life form that gave rise to all others.

The latest results suggest LUCA was the result of early life's fight to survive, attempts at which turned the ocean into a

global genetic swap shop for hundreds of millions of years. Cells struggling to survive on their own exchanged useful parts with each other without competition - effectively creating a global mega-organism.

It was around 2.9 billion years ago that LUCA split into the three domains of life: the single-celled bacteria and archaea, and the more complex eukaryotes that gave rise to animals and plants (see timeline). It's hard to know what happened before the split. Hardly any fossil evidence remains from this time, and any genes that date that far back are likely to have mutated beyond recognition.

That isn't an insuperable obstacle to painting LUCA's portrait, says Gustavo Caetano-Anollés of the University of Illinois at Urbana-Champaign. While the sequence of genes changes quickly, the three-dimensional structure of the proteins they code for is more resistant to the test of time. So if all organisms today make a protein with the same overall structure, he says, it's a good bet that the structure was

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present in LUCA. He calls such structures living fossils, and points out that since the function of a protein is highly dependent on its structure, they could tell us what LUCA could do. "Structure is known to be conserved when sequences aren't," agrees Anthony Poole of the University of Canterbury in Christchurch, New Zealand, though he cautions that two very similar structures could conceivably have evolved independently after LUCA. To reconstruct the set of proteins LUCA could make, Caetano-Anollés searched a database of proteins from 420 modern organisms, looking for structures that were common to all. Of the structures he found, just 5 to 11 per cent were universal, meaning they were conserved enough to have originated in LUCA. By looking at their function, he concludes that LUCA had enzymes to break down and extract energy from nutrients, and some protein-making equipment, but it lacked the enzymes for making and reading DNA molecules.

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This is in line with unpublished work by Wolfgang Nitschke of the Mediterranean Institute of Microbiology in Marseille, France. He reconstructed the history of enzymes crucial to metabolism and found that LUCA could use both nitrate and carbon as energy sources. Nitschke presented his work at the UCL Symposium on the Origin of Life in London on 11 November.

If LUCA was made of cells it must have had membranes, and Armen Mulkidjanian of the University of Osnabrück in Germany thinks he knows what kind. He traced the history of membrane proteins and concluded that LUCA could only make simple isoprenoid membranes, which were leaky compared with more modern designs (Proceedings of the International Moscow

Conference on Computational Molecular Biology, 2011, p 92).

LUCA probably also had an organelle, a cell compartment with a specific function.

Organelles were thought to be the preserve of eukaryotes, but in 2003 researchers found an organelle called the acidocalcisome in bacteria. Caetano-Anollés has now found that tiny granules in some archaea are also acidocalcisomes, or at least their precursors.

That means acidocalcisomes are found in all three domains of life, and date back to LUCA. So LUCA had a rich metabolism that used different food sources, and it had internal organelles. So far, so familiar. But its genetics are a different story altogether.

For starters, LUCA may not have used DNA. Poole has studied the history of enzymes called ribonucleotide reductases, which create the building blocks of DNA, and found no evidence that LUCA had them.

Instead, it may have used RNA: many biologists think RNA came first because it can store information and control chemical reactions (New Scientist, 13 August, p 32).

The crucial point is that LUCA was a "progenote", with poor control over the proteins that it made, says Massimo Di Giulio of the Institute of Genetics and Biophysics in Naples, Italy. Progenotes can make proteins using genes as a template, but the process is so error-prone that the

proteins can be quite unlike what the gene specified. Both Di Giulio and CaetanoAnollés have found evidence that systems that make protein synthesis accurate appear long after LUCA. "LUCA was a clumsy guy trying to solve the complexities of living on primitive Earth," says Caetano-Anollés.

He thinks that in order to cope, the early cells must have shared their genes and proteins with each other. New and useful molecules would have been passed from cell to cell without competition, and eventually gone global. Any cells that dropped out of the swap shop were doomed. “It was more important to keep the living system in place than to compete with other systems,” says Caetano-Anollés. He says the free exchange and lack of competition mean this living primordial ocean essentially functioned as a single mega-organism.

“There is a solid argument in favour of sharing genes, enzymes and metabolites,” says Mulkidjanian. Remnants of this geneswapping system are seen in communities of microorganisms that can only survive in mixed communities. And LUCA’s leaky membranes would have made it easier for cells to share. “It’s a plausible idea,” agrees Eric Alm of the Massachusetts Institute of Technology. But he says he “honestly can’t tell” if it is true.

Only when some of the cells evolved ways of producing everything they needed could the mega-organism have broken apart. We don’t know why this happened, but it appears to have coincided with the appearance of oxygen in the atmosphere, around 2.9 billion years ago. Regardless of the cause, life on Earth was never the same again

March 2012 | LUCA Feature | Eureka | THE TIMES | 30

Animals demonstrate a much higher level of cognitive ability than previous studies, but does it make them intelligent?

By now, the intelligence of birds is well known. Alex the African gray parrot had great verbal skills. Scrub jays, which hide caches of seeds and other food, have remarkable memories. And New Caledonian crows make and use tools in ways that would put the average home plumber to shame.

Pigeons, it turns out, are no slouches either. It was known that they could count. But all sorts of animals, including bees, can count. Pigeons have now shown that they can learn abstract rules about numbers, an ability that until now had been demonstrated only in primates. In the 1990s scientists trained rhesus monkeys to look at groups of items on a screen and to rank them from the lowest number of items to the highest.

They learned to rank groups of one, two and three items in various sizes and shapes.

When tested, they were able to do the task even when unfamiliar numbers of things were introduced. In other words, having learned that two was more than one and three more than two, they could also figure out that five was more than two, or eight more than six.

Damian Scarf, a postdoctoral fellow at the University of Otago, in New Zealand, tried the same experiment with pigeons, and he and two colleagues report in the current issue of the journal Science that the pigeons did just as well as the monkeys.

Elizabeth Brannon, a professor of psychology and neuroscience at Duke University, and one of the scientists who did the original experiments with monkeys, was impressed by the new results. “Their performance looks just like the monkeys’,” she said.

Score one for the birds. The pigeons had learned an abstract rule: peck images on a screen in order, lower numbers to higher.

It may have taken a year of training, with different shapes, sizes and colors of items, always in groups of one, two or three, but all that work paid off when it was time for higher math.

pick, or peck, the images in the right order.

This is one more bit of evidence of how smart birds really are, and it is intriguing because the pigeons’ performance was so similar to the monkeys’. “I was surprised,” Dr. Scarf said.

He and his colleagues wrote that the common ability to learn rules about numbers is an example either of different groups — birds and primates, in this case — evolving these abilities separately, or of both pigeons and primates using an ability that was already present in their last common ancestor.

That would really be something, because the common ancestor of pigeons and primates would have been alive around 300 million years ago, before dinosaurs and mammals. It may be that counting was already important, but Dr. Scarf said that if he had to guess, he would lean toward the idea that the numerical ability he tested evolved separately. “I can definitely see why both monkeys and pigeons could profit from this ability,” he said.

No testing has been done with numbers greater than nine, so whether a pigeon can count large numbers of bread crumbs or popcorn kernels is a question still open to investigation.

Given groups of six and nine, they could

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March 2012 | Eureka | THE TIMES | 30

ANIMAL MAGIC

With a few liberating swipes of their paws, a group of research rats freed trapped labmates and raised anew the possibility that empathy isn’t unique to humans and a few extra-smart animals, but is widespread in the animal world. Though more studies are needed on the rats’ motivations, it’s at least plausible they demonstrated “empathically motivated pro-social behavior.”

People would generally call that helpfulness, or even kindness.

“Rats help other rats in distress. That means it’s a biological inheritance,” said neurobiologist Peggy Mason of the University of Chicago. “That’s the biological program we have.”

In a study published Dec. 7 in Science, Mason and University of Chicago psychologists Jean Decety and Inbal Ben-Ami Bartal describe their rat empathy-testing apparatus: An enclosure into which pairs of rats were placed, with one roaming free and the other restrained inside a plastic tube.

It could only be opened from the outside, which is exactly what the free rats did — again and again and again, seemingly in response to their trapped companions’ distress.

The experiment built on research conducted several years ago by geneticist Jeff Mogil at McGill University, where mice were shown capable of “emotional contagion” — a slightly scary-sounding term denoting a tendency to become upset when cagemates were in pain. This might not seem surprising, but anecdotes from wild animal observations don’t pass academic scrutiny, and it hadn’t before been shown in captive mice. It hinted at unexpectedly sophisticated cognition: Mice were supposed to feel pain, but not each other’s, at least not outside children’s stories.

At the time, ethologist Frans de Waal of Emory University, whose work has helped redefine what’s known scientifically about thoughts and feelings in chimpanzees and dolphins and elephants, said Mogil’s experiment “justifies speaking of ‘empathy’” — the ability to both put oneself in the shoes, or paws, of another, and to become emotionally involved in their situation.

Sure, mice almost certainly weren’t so empathic as humans, but maybe they had the seeds of it. Maybe empathy wasn’t the result of some high-powered cognitive process, as most biologists and psychologists preferred to think, but a relatively simple phenomenon.

Wrote de Waal in Scientific American, “This mouse experiment suggests that the emotional component of this process is at least as old as the mammals and runs deep within us.”

Still, it was hard to know what to think, and emotional contagion didn’t equal empathy. Maybe the mice were simply fearful for themselves. But the possibility was open for investigation. And around the same time as the McGill studies, Bartal — then researching cancer in Israel — noticed rats at her lab becoming distressed when surgeries were performed on other rats.

She couldn’t shake the feeling that empathy was involved. When she read about a rat bringing food to a trapped rat, she again thought about empathy.

Bartal went to the University of Chicago, where she joined with Decety, a leading scholar on empathy and prosocial behavior, and Mason, who’d been intrigued by Mogil’s work. Together they designed the new study — and not only did they find what might be empathy, but the rats acted on it.

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ANIMAL MAGIC

Rats display empathy as they recognise when when of their fellow labmates are trapped, but is this solid evidence of advanced cognitive ability?

WORDS: Ian Sample ILLUSTRATIONS: Tommings

Once rats learned to free their trapped and agitated partners, they did so almost immediately in trial after trial. The behavior was clearly deliberate. When the restrainer was empty, rats ignored it. When stuffed rats were restrained, the rats ignored them.

“It’s compelling evidence that it’s the distress of the trapped cagemate motivating this helping behavior,” said Mason. “It is a huge leap up to use emotional contagion to actually do something, to actually help another individual.”

To make sure the rats weren’t responding to some immediate social reward — a rat version of a thank-you hug — the researchers tweaked the apparatus so that trapped rats were released into a separate cage. Again, the rats freed each other. When given the opportunity to eat chocolate treats first, rats were as likely to release their companions first, and even

shared the chocolate with them.

“Empathy is a truly powerful motivator, on a par with the desire for chocolate!” said de Waal, who was not involved in the new study.

According to de Waal, the results “show for the first time that rodents are not just affected by the emotions of others, but that empathy motivates altruism.” He believes the rats responded to an instinctive urge to make their compatriots feel better, just as humans and chimpanzees and some cetaceans do.

“The mechanism must ancient,” said de Waal.

However, the researchers stopped short of ascribing the results to a conclusive display of empathy. It’s possible the rats were less concerned with alleviating the suffering of brethren than soothing their own upset feelings. Perhaps the trapped rats’ distress calls were simply loud and annoying, and the free rats wanted to quiet them. One

potentially important experimental condition — the opportunity for free rats to simply leave — wasn’t tested.

“The reservation I have is that it’s very difficult to demonstrate empathy.

You have to show that the animal is putting itself in another’s shoes, and I’m not sure that’s demonstrated here,” said Joshua Plotnik, an Emory University psychologist and collaborator with de Waal. But Plotnik still called the observations “very exciting.”

‘Nature made it rewarding for us to end the suffering of another.’According to Mason, further tests are planned in which rats’ stress responses will be damped by drugs. If a rat feels no distress itself but still frees a trapped companion, or if a trapped rat expresses no distress but is still rescued, empathy will seem more likely. “We can figure this question out. It’s completely tractable,” said Mason. “And this experimental model is unbelievably easy to set up. It’s our fervent hope this model will be used by many people to look at helping behavior.”

Cognitive mechanisms thought to underlie empathy and helpfulness could be tested, Mason said. So could the effects of personality traits, sex differences — females rats seemed more helpful, which tracks with studies of chimps and humans — or genetic and environmental variables. Indeed, the tests needn’t be restricted to rats, but could involve any species amenable to captivity.

For Bartal, whether rats were motivated by their companions’ distress or their own is less interesting than the simple fact they responded at all. “The bottom line here is that nature is very smart. Nature made it rewarding for us to end the suffering of another,” she said.

While the researchers didn’t discuss mechanisms underlying the possible empathy, Bartal and de Waal suspect it’s linked to the lengthy care and nursing provided, as in all mammals, by mother rats. “Mammals that need nurture and care after they’re born would require some form of empathic connection between mother and offspring,” Bartal said. Sociality could be another important factor. Rats live in large family groups with complex hierarchies, and empathy is especially important in social settings.

Rats also share basic neurological features, such as a highly developed limbic system and various hormones and neurotransmitters, with all other mammals. These could provide a common ancestral origin for empathy, said Bartal, or evolution could have shaped them independently in converging ways. All roads could lead to empathy.

Of course, mammals don’t have a monopoly on intelligence or sociality or maternal care. Octopi are extraordinarily smart. So are many birds, which also care for their young and can live in large colonies. The seeds of empathy, if that’s what the rats have, could be scattered widely. “Nature has an interesting way of using different structures for similar functions,” said Bartal.

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ANIMAL MAGIC

ANIMAL MAGIC

Animals demonstrate a much higher level of cognitive ability than previous studies, but does it make them intelligent?

A

sian elephants have passed a test of cooperation with flying colors, one that cognitive psychologists say demonstrates an ape-level awareness and sense of teamwork.

Their collaboration isn’t just the product of rote learning, but the result of careful thought. In the wild, of course, elephants routinely work together. But that doesn’t pass laboratory muster, said University of Cambridge psychologist Joshua Plotkin.

“It’s anecdotal evidence. These animals are empathetic, they’re cooperative,” he said.

“But how empathetic? How cooperative?

The best we can do is institute controls, do experiments like this, and figure out how what they do is unique from learning.”

Plotnik’s experiment, published March 8 in the Proceedings of the National Academy of Sciences, was conducted when he was a student of famed Emory University ethologist Frans de Waal. In 2006, they showed that elephants could recognize themselves in a mirror, a benchmark feat believed to indicate an especially sophisticated level of self-awareness, on par with that of young humans.

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recognition is just one test, and doesn’t address the sort of cooperative behavior for which elephants are famed in the wild. They’re known to help individuals in distress, cooperate in rearing children and may even mourn their dead. From a behavioral perspective, they clearly demonstrate empathy.

But behavioral records from the wild are not the currency of cognitive psychology. After all, bees display incredible coordination, but few people would compare an individual bee’s consciousness to that of a person. According to Plotnik, one could argue that elephants and other cooperative animals are acting reflexively rather than thoughtfully. So he and de Waal turned to a test originally developed to measure cooperation in chimpanzees.

In the original test, two chimps pulled on ropes attached to an otherwise inaccessible, food-containing box too heavy for one alone to move. In the version updated for elephantine strength — a too-heavy box would have been “as big as a 747,” said Plotnik — the rope was arranged so that if one elephant pulled alone, its partner

couldn’t reach the rope. To get a banana treat, both had to pull simultaneously.

Plotniks’ elephants pick the trick up quickly. Then, in the study’s key step, they demonstrated patience. If only one elephant was present, it would wait for a partner to arrive. Until then, it wouldn’t try to pull the rope, and often wouldn’t pick it up.

If the elephants pulled automatically, it would be evidence of reflexive behavior, said Plotnik. Waiting indicated something more. They understood that their own effort wasn’t enough. They understood their partner’s role.

Plotnik’s now working on other, more sophisticated tests of elephant cooperation.

He hopes to measure how they see other species, process information in the wild, find food and water, and care for one another. But he acknowledges that Asian elephants are unique among social, cooperative animals in their amenability to study. Other animals — say, lions — may be just as smart, but not so easy to test.

“Just because something hasn’t been tested doesn’t mean you reject it as not being possible,” he said.

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Animals demonstrate a much higher level of cognitive ability than previous studies, but does it make them intelligent?