No Mars, Venus: Men, women have same brain, argues neuroscientist

 

by FP Staff Mar 11, 2014

Men from Mars, Women from Venus, boys prefer blue while girls 'naturally' prefer the colour pink. Not really.

Neuroscientist Prof Gina Rippon, of Aston University, Birmingham has reminded the world that men and women's brains aren't really different and that most of the gender differences emerge only through environmental factors. In a report in Telegraph Rippon argues, "that any differences in brain circuitry only come about through the ‘drip, drip, drip’ of gender stereotyping."

Her work assumes importance in light of a recent study that was released by the researchers based at the University of Pennsylvania who had argued that men and women's brain have different wirings and thus it explains why women were intuitive thinkers and good at multi-tasking while men were good at sports and map-reading.

The earlier study had said that men’s brains had more connectivity within each brain hemisphere, whereas women’s brains had more connectivity across the two hemispheres. Based on these wiring differences, they inferred in their paper, that this explained behavioural differences between the sexes. You can view the study by University of Pennsylvania researchers here.

The study was led by Ragini Verma, among others. Representational Image. Reuters Representational Image. Reuters According to Rippon however, the difference in wiring is purely to environmental factors.

She told The Telegraph that “What often isn’t picked up on is how plastic and permeable the brain is. It is changing throughout out lifetime. The world is full of stereotypical attitudes and unconscious bias. It is full of the drip, drip, drip of the gendered environment.” She also points out that you can't say that one brain is male and one is female, since they tend to look the same.

As to women, being better at multi-tasking, she argues that the only reason a women’s brain may be ‘wired’ for multi-tasking is because society expects that of her and so she uses that part of her brain more often. “The bottom line is that saying there are differences in male and female brains is just not true. There is pretty compelling evidence that any differences are tiny and are the result of environment not biology,” Prof Rippon told the English daily. She also points out that children's toys tend to play an early role in separating boys and girls, as girls are often given toys which are dolls or tea sets or kitchen sets, while boys are normally given cars, soldiers etc.

As far as the other study goes, which had argued that male and female brains are differently wired and thus do better at some things, it has faced some serious criticisms for the manner in which it arrived at its conclusions.

According to this piece in Wired written by Christian Jarrett, a cognitive neuroscientist turned science writer, the study at University of Pennsylvania used reference inference when drawing their conclusions. While they see different wiring when came to male and female brains, they didn't actually look at behavioural differences in the course of their study and relied on older material to support conclusions for new data.

He argues, that "The way Verma and her colleagues have arrived at the idea that their results support gender stereotypes about map reading, and so on, is via a logical mistake known as “reverse inference”.

They looked at where in the brain they found wiring differences and then they’ve made assumptions about the functional meaning of those differences based on what other studies have suggested those brain regions are for." He points out that they used older studies to boost their findings that difference in brain wiring meant that one sex was better map-reading, while another at multi-tasking.

He writes," They dredged up old ideas about the left brain hemisphere being for analytical thought and the right hemisphere being intuitive. And the one brain region where men supposedly had more cross-hemisphere interconnectivity than women – the cerebellum – the researchers linked purely with motor function, which they said supports the idea that men are wired for action.

Maybe they don’t realise, but modern research has shown that the cerebellum is involved in lots of other functions too."
Read more at: http://www.firstpost.com/living/no-mars-venus-men-women-have-same-brain-argues-neuroscientist-1428775.html?utm_source=ref_article

Skull fragments reveal new ancient crocodile species

11 March 2014 Last updated at 08:13

The newly discovered crocodile species was similar to those living today

Two fossilised skull fragments from a 2ft (60cm) crocodile found on the Isle of Wight point to the discovery of a new ancient species, a study has found.

The pieces - a snout and back part of the skull - were found by different private collectors three months apart.

Experts at the Dinosaur Isle museum near Sandown found the 126 million-year-old fragments "fitted together perfectly to make a complete skull".

The species has been named Koumpiodontosuchus aprosdokiti.

The name - meaning "unexpected button-toothed crocodile" - was given by University of Portsmouth palaeontologist Dr Steve Sweetman, who has published a paper on the discovery in the journal Acta Palaeontologica Polonica.

The first piece, the skull, was found on a beach near Sandown in March 2011 by Diane Trevarthen who was on a fossil-hunting holiday with her family.

She took it to the museum where staff thought it might belong to a large Cretaceous crocodile baby.

Three months later, Austin and Finley Nathan found the snout while fossil-hunting on their holiday.

When museum staff saw their find, they recalled seeing the other piece and asked Ms Trevarthen to bring it back.

Both collectors donated their specimens to the museum.

The bone structure at the back of the palate of the skull is different to other ancient species

Dr Sweetman said: "Both parts of this wonderful little skull are in good condition, which is most unusual when you consider that crashing waves usually batter and blunt the edges of fossils like this within days or even hours of them being washed onto the beach.

"Both parts must therefore have been found very soon after they were released from the mud and debris originally laid down on a dinosaur-trampled river floodplain around 126 million years ago.

"The sheer serendipity of this discovery is quite bizarre.

"Finding the two parts is in itself remarkable. That they should be found three months apart by different collectors and taken to the museum where the same members of staff were on duty and therefore able to recall the first specimen defies belief."

Dr Steve Sweetman examined the fragments found on the beach near Sandown in 2011

When he first saw it Dr Sweetman thought the skull belonged to a Bernissartia fagesii crocodile, known from skeletons of a similar age discovered in Belgium and Spain.

"I was convinced it was a Bernissartia skull because of its small size - the fully grown animal was only a little over two feet long from nose to tail - but particularly because of its button-shaped teeth, which are unique among crocodyliforms.

"They were used to crush mollusc shells and other invertebrates with tough outer coatings."

But after the skull had been cleaned, Dr Sweetman could see it had significant differences in the arrangement of bones.

"The location of the hole in the mouth, where the airway from the nose opens, was surrounded by bones at the very back of the palate.

"This tells us that the discovery is not only a new species but also a new genus of ancient croc closely related to, but subtly different to, those alive today."

------------------------------

Cretaceous period

• The Cretaceous period began 142 million years ago
• With sea levels at their highest, much of what we now know as dry land - including southern England and the US Midwest - was under water
• Theropod dinosaurs such as Tyrannosaurus, Velociraptor and Spinosaurus were the top predators
• Ended with the Cretaceous-Tertiary mass extinction, famed for the death of the dinosaurs

------------------------------

Cretaceous period



The Cretaceous ended with the most famous mass extinction in history - the one that killed the dinosaurs. Prior to that, it was a warm period with no ice caps at the poles. Much of what we now know as dry land - such as southern England and the midwest of the USA - was underwater, since sea levels reached their highest ever during this time. The Atlantic Ocean grew much wider as North and South America drew apart from Europe and Africa. The Indian Ocean was formed at this time, and the island that was India began its journey north towards Asia.

Began: 142 million years ago

Ended: Cretaceous-Tertiary mass extinction
65 million years ago

http://www.bbc.com/news/uk-england-26519396

STEPHEN HAWKING: How to build a time machine

 

By STEPHEN HAWKING

Created 7:47 PM on 27th April 2010

 

All you need is a wormhole, the Large Hadron Collider or a rocket that goes really, really fast

'Through the wormhole, the scientist can see himself as he was one minute ago. But what if our scientist uses the wormhole to shoot his earlier self? He's now dead. So who fired the shot?'

Hello. My name is Stephen Hawking. Physicist, cosmologist and something of a dreamer. Although I cannot move and I have to speak through a computer, in my mind I am free. Free to explore the universe and ask the big questions, such as: is time travel possible? Can we open a portal to the past or find a shortcut to the future? Can we ultimately use the laws of nature to become masters of time itself?

Time travel was once considered scientific heresy. I used to avoid talking about it for fear of being labelled a crank. But these days I'm not so cautious. In fact, I'm more like the people who built Stonehenge. I'm obsessed by time. If I had a time machine I'd visit Marilyn Monroe in her prime or drop in on Galileo as he turned his telescope to the heavens. Perhaps I'd even travel to the end of the universe to find out how our whole cosmic story ends.

To see how this might be possible, we need to look at time as physicists do - at the fourth dimension. It's not as hard as it sounds. Every attentive schoolchild knows that all physical objects, even me in my chair, exist in three dimensions. Everything has a width and a height and a length.

But there is another kind of length, a length in time. While a human may survive for 80 years, the stones at Stonehenge, for instance, have stood around for thousands of years. And the solar system will last for billions of years. Everything has a length in time as well as space. Travelling in time means travelling through this fourth dimension.

To see what that means, let's imagine we're doing a bit of normal, everyday car travel. Drive in a straight line and you're travelling in one dimension. Turn right or left and you add the second dimension. Drive up or down a twisty mountain road and that adds height, so that's travelling in all three dimensions. But how on Earth do we travel in time? How do we find a path through the fourth dimension?

Let's indulge in a little science fiction for a moment. Time travel movies often feature a vast, energy-hungry machine. The machine creates a path through the fourth dimension, a tunnel through time. A time traveller, a brave, perhaps foolhardy individual, prepared for who knows what, steps into the time tunnel and emerges who knows when. The concept may be far-fetched, and the reality may be very different from this, but the idea itself is not so crazy.

Physicists have been thinking about tunnels in time too, but we come at it from a different angle. We wonder if portals to the past or the future could ever be possible within the laws of nature. As it turns out, we think they are. What's more, we've even given them a name: wormholes. The truth is that wormholes are all around us, only they're too small to see. Wormholes are very tiny. They occur in nooks and crannies in space and time. You might find it a tough concept, but stay with me.

Enlarge

A wormhole is a theoretical 'tunnel' or shortcut, predicted by Einstein's theory of relativity, that links two places in space-time - visualised above as the contours of a 3-D map, where negative energy pulls space and time into the mouth of a tunnel, emerging in another universe. They remain only hypothetical, as obviously nobody has ever seen one, but have been used in films as conduits for time travel - in Stargate (1994), for example, involving gated tunnels between universes, and in Time Bandits (1981), where their locations are shown on a celestial map

Nothing is flat or solid. If you look closely enough at anything you'll find holes and wrinkles in it. It's a basic physical principle, and it even applies to time. Even something as smooth as a pool ball has tiny crevices, wrinkles and voids. Now it's easy to show that this is true in the first three dimensions. But trust me, it's also true of the fourth dimension. There are tiny crevices, wrinkles and voids in time. Down at the smallest of scales, smaller even than molecules, smaller than atoms, we get to a place called the quantum foam. This is where wormholes exist. Tiny tunnels or shortcuts through space and time constantly form, disappear, and reform within this quantum world. And they actually link two separate places and two different times.

Unfortunately, these real-life time tunnels are just a billion-trillion-trillionths of a centimetre across. Way too small for a human to pass through - but here's where the notion of wormhole time machines is leading. Some scientists think it may be possible to capture a wormhole and enlarge it many trillions of times to make it big enough for a human or even a spaceship to enter.

Given enough power and advanced technology, perhaps a giant wormhole could even be constructed in space. I'm not saying it can be done, but if it could be, it would be a truly remarkable device. One end could be here near Earth, and the other far, far away, near some distant planet.

Theoretically, a time tunnel or wormhole could do even more than take us to other planets. If both ends were in the same place, and separated by time instead of distance, a ship could fly in and come out still near Earth, but in the distant past. Maybe dinosaurs would witness the ship coming in for a landing.

The fastest manned vehicle in history was Apollo 10. It reached 25,000mph. But to travel in time we'll have to go more than 2,000 times faster

Now, I realise that thinking in four dimensions is not easy, and that wormholes are a tricky concept to wrap your head around, but hang in there. I've thought up a simple experiment that could reveal if human time travel through a wormhole is possible now, or even in the future. I like simple experiments, and champagne.

So I've combined two of my favourite things to see if time travel from the future to the past is possible.

Let's imagine I'm throwing a party, a welcome reception for future time travellers. But there's a twist. I'm not letting anyone know about it until after the party has happened. I've drawn up an invitation giving the exact coordinates in time and space. I am hoping copies of it, in one form or another, will be around for many thousands of years. Maybe one day someone living in the future will find the information on the invitation and use a wormhole time machine to come back to my party, proving that time travel will, one day, be possible.

In the meantime, my time traveller guests should be arriving any moment now. Five, four, three, two, one. But as I say this, no one has arrived. What a shame. I was hoping at least a future Miss Universe was going to step through the door. So why didn't the experiment work? One of the reasons might be because of a well-known problem with time travel to the past, the problem of what we call paradoxes.

Paradoxes are fun to think about. The most famous one is usually called the Grandfather paradox. I have a new, simpler version I call the Mad Scientist paradox.

I don't like the way scientists in movies are often described as mad, but in this case, it's true. This chap is determined to create a paradox, even if it costs him his life. Imagine, somehow, he's built a wormhole, a time tunnel that stretches just one minute into the past.

Hawking in a scene from Star Trek with dinner guests from the past, and future: (from left) Albert Einstein, Data and Isaac Newton

Through the wormhole, the scientist can see himself as he was one minute ago. But what if our scientist uses the wormhole to shoot his earlier self? He's now dead. So who fired the shot? It's a paradox. It just doesn't make sense. It's the sort of situation that gives cosmologists nightmares.

This kind of time machine would violate a fundamental rule that governs the entire universe - that causes happen before effects, and never the other way around. I believe things can't make themselves impossible. If they could then there'd be nothing to stop the whole universe from descending into chaos. So I think something will always happen that prevents the paradox. Somehow there must be a reason why our scientist will never find himself in a situation where he could shoot himself. And in this case, I'm sorry to say, the wormhole itself is the problem.

In the end, I think a wormhole like this one can't exist. And the reason for that is feedback. If you've ever been to a rock gig, you'll probably recognise this screeching noise. It's feedback. What causes it is simple. Sound enters the microphone. It's transmitted along the wires, made louder by the amplifier, and comes out at the speakers. But if too much of the sound from the speakers goes back into the mic it goes around and around in a loop getting louder each time. If no one stops it, feedback can destroy the sound system.

The same thing will happen with a wormhole, only with radiation instead of sound. As soon as the wormhole expands, natural radiation will enter it, and end up in a loop. The feedback will become so strong it destroys the wormhole. So although tiny wormholes do exist, and it may be possible to inflate one some day, it won't last long enough to be of use as a time machine. That's the real reason no one could come back in time to my party.

Any kind of time travel to the past through wormholes or any other method is probably impossible, otherwise paradoxes would occur. So sadly, it looks like time travel to the past is never going to happen. A disappointment for dinosaur hunters and a relief for historians.

But the story's not over yet. This doesn't make all time travel impossible. I do believe in time travel. Time travel to the future. Time flows like a river and it seems as if each of us is carried relentlessly along by time's current. But time is like a river in another way. It flows at different speeds in different places and that is the key to travelling into the future. This idea was first proposed by Albert Einstein over 100 years ago. He realised that there should be places where time slows down, and others where time speeds up. He was absolutely right. And the proof is right above our heads. Up in space.

This is the Global Positioning System, or GPS. A network of satellites is in orbit around Earth. The satellites make satellite navigation possible. But they also reveal that time runs faster in space than it does down on Earth. Inside each spacecraft is a very precise clock. But despite being so accurate, they all gain around a third of a billionth of a second every day. The system has to correct for the drift, otherwise that tiny difference would upset the whole system, causing every GPS device on Earth to go out by about six miles a day. You can just imagine the mayhem that that would cause.

The problem doesn't lie with the clocks. They run fast because time itself runs faster in space than it does down below. And the reason for this extraordinary effect is the mass of the Earth. Einstein realised that matter drags on time and slows it down like the slow part of a river. The heavier the object, the more it drags on time. And this startling reality is what opens the door to the possibility of time travel to the future.

Right in the centre of the Milky Way, 26,000 light years from us, lies the heaviest object in the galaxy. It is a supermassive black hole containing the mass of four million suns crushed down into a single point by its own gravity. The closer you get to the black hole, the stronger the gravity. Get really close and not even light can escape. A black hole like this one has a dramatic effect on time, slowing it down far more than anything else in the galaxy. That makes it a natural time machine.

I like to imagine how a spaceship might be able to take advantage of this phenomenon, by orbiting it. If a space agency were controlling the mission from Earth they'd observe that each full orbit took 16 minutes. But for the brave people on board, close to this massive object, time would be slowed down. And here the effect would be far more extreme than the gravitational pull of Earth. The crew's time would be slowed down by half. For every 16-minute orbit, they'd only experience eight minutes of time.

Inside the Large Hadron Collider

Around and around they'd go, experiencing just half the time of everyone far away from the black hole. The ship and its crew would be travelling through time. Imagine they circled the black hole for five of their years. Ten years would pass elsewhere. When they got home, everyone on Earth would have aged five years more than they had.

So a supermassive black hole is a time machine. But of course, it's not exactly practical. It has advantages over wormholes in that it doesn't provoke paradoxes. Plus it won't destroy itself in a flash of feedback. But it's pretty dangerous. It's a long way away and it doesn't even take us very far into the future. Fortunately there is another way to travel in time. And this represents our last and best hope of building a real time machine.

You just have to travel very, very fast. Much faster even than the speed required to avoid being sucked into a black hole. This is due to another strange fact about the universe. There's a cosmic speed limit, 186,000 miles per second, also known as the speed of light. Nothing can exceed that speed. It's one of the best established principles in science. Believe it or not, travelling at near the speed of light transports you to the future.

To explain why, let's dream up a science-fiction transportation system. Imagine a track that goes right around Earth, a track for a superfast train. We're going to use this imaginary train to get as close as possible to the speed of light and see how it becomes a time machine. On board are passengers with a one-way ticket to the future. The train begins to accelerate, faster and faster. Soon it's circling the Earth over and over again.

To approach the speed of light means circling the Earth pretty fast. Seven times a second. But no matter how much power the train has, it can never quite reach the speed of light, since the laws of physics forbid it. Instead, let's say it gets close, just shy of that ultimate speed. Now something extraordinary happens. Time starts flowing slowly on board relative to the rest of the world, just like near the black hole, only more so. Everything on the train is in slow motion.

This happens to protect the speed limit, and it's not hard to see why. Imagine a child running forwards up the train. Her forward speed is added to the speed of the train, so couldn't she break the speed limit simply by accident? The answer is no. The laws of nature prevent the possibility by slowing down time onboard.

Now she can't run fast enough to break the limit. Time will always slow down just enough to protect the speed limit. And from that fact comes the possibility of travelling many years into the future.

Imagine that the train left the station on January 1, 2050. It circles Earth over and over again for 100 years before finally coming to a halt on New Year's Day, 2150. The passengers will have only lived one week because time is slowed down that much inside the train. When they got out they'd find a very different world from the one they'd left. In one week they'd have travelled 100 years into the future. Of course, building a train that could reach such a speed is quite impossible. But we have built something very like the train at the world's largest particle accelerator at CERN in Geneva, Switzerland.

Deep underground, in a circular tunnel 16 miles long, is a stream of trillions of tiny particles. When the power is turned on they accelerate from zero to 60,000mph in a fraction of a second. Increase the power and the particles go faster and faster, until they're whizzing around the tunnel 11,000 times a second, which is almost the speed of light. But just like the train, they never quite reach that ultimate speed. They can only get to 99.99 per cent of the limit. When that happens, they too start to travel in time. We know this because of some extremely short-lived particles, called pi-mesons. Ordinarily, they disintegrate after just 25 billionths of a second. But when they are accelerated to near-light speed they last 30 times longer.

It really is that simple. If we want to travel into the future, we just need to go fast. Really fast. And I think the only way we're ever likely to do that is by going into space. The fastest manned vehicle in history was Apollo 10. It reached 25,000mph. But to travel in time we'll have to go more than 2,000 times faster. And to do that we'd need a much bigger ship, a truly enormous machine. The ship would have to be big enough to carry a huge amount of fuel, enough to accelerate it to nearly the speed of light. Getting to just beneath the cosmic speed limit would require six whole years at full power.

The initial acceleration would be gentle because the ship would be so big and heavy. But gradually it would pick up speed and soon would be covering massive distances. In one week it would have reached the outer planets. After two years it would reach half-light speed and be far outside our solar system. Two years later it would be travelling at 90 per cent of the speed of light. Around 30 trillion miles away from Earth, and four years after launch, the ship would begin to travel in time. For every hour of time on the ship, two would pass on Earth. A similar situation to the spaceship that orbited the massive black hole.

After another two years of full thrust the ship would reach its top speed, 99 per cent of the speed of light. At this speed, a single day on board is a whole year of Earth time. Our ship would be truly flying into the future.

The slowing of time has another benefit. It means we could, in theory, travel extraordinary distances within one lifetime. A trip to the edge of the galaxy would take just 80 years. But the real wonder of our journey is that it reveals just how strange the universe is. It's a universe where time runs at different rates in different places. Where tiny wormholes exist all around us. And where, ultimately, we might use our understanding of physics to become true voyagers through the fourth dimension. 

'Stephen Hawking's Universe' begins on May 9 on Discovery Channel (HD) at 9pm

Read more: http://www.dailymail.co.uk/home/moslive/article-1269288/STEPHEN-HAWKING-How-build-time-machine.html#ixzz2vaGzZcwp
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Giant virus resurrected from 30,000-year-old ice

March 8, 2014

Updated: March 8, 2014 16:28 IST

Larger than some bacteria, this virus - seen in a cross-section under a transmission electron microscope - was still able to infect amoebae despite having spent 30 millennia in a frozen state.

In what seems like a plot straight out of a low-budget science-fiction film, scientists have revived a giant virus that was buried in Siberian ice for 30,000 years - and it is still infectious. Its targets, fortunately, are amoebae, but the researchers suggest that as Earth’s ice melts, this could trigger the return of other ancient viruses, with potential risks for human health.

The newly thawed virus is the biggest one ever found. At 1.5 micrometers long, it is comparable in size to a small bacterium. Evolutionary biologists Jean-Michel Claverie and Chantal Abergel, the husband-and-wife team at Aix-Marseille University in France who led the work, named it Pithovirus sibericum, inspired by the Greek word “pithos” for the large container used by the ancient Greeks to store wine and food. “We’re French, so we had to put wine in the story,” says Claverie. The results are published in Proceedings of the National Academy of Sciences.

Claverie and Abergel have helped to discover other so-called giant viruses - including the first, called Mimivirus, in 2003, and two others, known as Pandoraviruses, last year. “Once again, this group has opened our eyes to the enormous diversity that exists in giant viruses,” says Curtis Suttle, a virologist at the University of British Columbia in Vancouver, Canada, who was not involved in the work.

Two years ago, Claverie and Abergel’s team learned that scientists in Russia had resurrected an ancient plant from fruits buried in 30,000-year-old Siberian permafrost. “If it was possible to revive a plant, I wondered if it was possible to revive a virus,” says Claverie. Using permafrost samples provided by the Russian team, they fished for giant viruses by using amoebae - the typical targets of these pathogens - as bait. The amoebae started dying, and the team found giant-virus particles inside them.

Under a microscope, Pithovirus appears as a thick-walled oval with an opening at one end, much like the Pandoraviruses. But despite their similar shapes, Abergel notes that “they are totally different viruses.”

Surprising properties

Pithovirus has a “cork” with a honeycomb structure capping its opening (see electron-microscope image). It copies itself by building replication 'factories’ in its host’s cytoplasm, rather than by taking over the nucleus, as most viruses do. Only one-third of its proteins bear any similarity to those of other viruses. And, to the team’s surprise, its genome is much smaller than those of the Pandoraviruses, despite its larger size.

“That huge particle is basically empty,” says Claverie. “We thought it was a property of viruses that they pack DNA extremely tightly into the smallest particle possible, but this guy is 150 times less compacted than any bacteriophage [viruses that infect bacteria]. We don’t understand anything anymore!”

Although giant viruses almost always target amoebae, Christelle Desnues, a virologist at the French National Centre for Scientific Research in Marseilles, last year discovered signs that another giant virus, Marseillevirus, had infected an 11-month-old boy. He had been hospitalized with inflamed lymph nodes, and Desnues’s team discovered traces of Marseillevirus DNA in his blood, and the virus itself in the a node. “It is clear that giant viruses cannot be seen as stand-alone freaks of nature,” she says. “They constitute an integral part of the virosphere with implications in diversity, evolution and even human health.”

Claverie and Abergel are concerned that rising global temperatures, along with mining and drilling operations in the Arctic, could thaw out many more ancient viruses that are still infectious and that could conceivably pose a threat to human health.

But Suttle points out that people already inhale thousands of viruses every day, and swallow billions whenever they swim in the sea. The idea that melting ice would release harmful viruses, and that those viruses would circulate extensively enough to affect human health, “stretches scientific rationality to the breaking point,” he says. “I would be much more concerned about the hundreds of millions of people who will be displaced by rising sea levels.”

Copyright© 2014, The Hindu

Turning genes on and off can be fate-changing, says researcher

CHENNAI, February 23, 2014

Updated: February 23, 2014 03:53 IST

Ramya Kannan

Special Arrangement Ganesh N. Pandian (centre) with his team in his lab in Japan.

A Chennai-based researcher is part of team that has provided proof of the concept that turning on and turning off genes — a process if validated in therapeutics — will be “fate-changing.”

Ganesh N. Pandian lived nearly all his life in Chennai, and went to D.G. Vaishnav college and IIT, Madras, before he went to the Institute for Integrated Cell-Material Sciences (iCeMS), Kyoto University, Japan, for his PhD. But he stayed on to do more than that, landing himself in the middle of a game-changer project.

“We are trying to give silent genes a voice by turning them on. We are working on the premise that by re-programming or resetting cells, it might be possible to cure disease,” he says.

“Human beings are essentially shaped by their genetic coding. When a genetic programme gets corrupted, disease ensues. We then try to re-programme some of the genes using our approach.”

While the actual research methodology is couched in complex scientific terminology, Dr. Ganesh tries to whittle it down to the basics: “In our research, we activated a gene that is usually silent, but (when) expressed, inhibits the growth of HIV. This sort of gene can be called a therapeutic gene, and its mutation or non expression results in disease.”

What his team has done is to make an artificial switch, a policing process that controls gene expression, to turn genes on or off, in order to cure certain conditions. It is also able to tweak certain genes in such a manner as to reset the cell function: for instance, turn skin cells to nerve cells, or change skin cells to pluriporent stem cells.

Just consider the implications of this: If someone is able to over express a certain gene, it would be theoretically possible to reset the body condition from a cancer state to a normal state. “Of course it really is early stages, yet. But we have proof of concept that this is possible,” Dr. Ganesh says. The response to the research findings, globally, has been pretty good. One of the papers from the project was also published in the January 2014 edition of Nature.

Dr. Ganesh, who is now Premium Assistant Professor at the Institute, wants to share credit with his team that includes four other Indians, Vaijayanthi Thangavel, Abhijit Sahal, Anandhakumar Chandran, Syed Junetha, with graphics support from Sekar Latha, and a Japanese student Junichi Taniguchi. The team is hoping to establish collaborations with Indian research institutions, he adds.

Copyright© 2014, The Hindu

An Artificial Hand with Real Feeling

 

A new nerve interface gives a sense of touch to a prosthetic limb.

• By David Talbot | Photographs by Ryan Donnell on February 18, 2014

http://www.technologyreview.com/photoessay/524676/an-artificial-hand-with-real-feeling/

Igor Spetic’s hand was in a fist when it was severed by a forging hammer three years ago as he made an aluminum jet part at his job. For months afterward, he felt a phantom limb still clenched and throbbing with pain. “Some days it felt just like it did when it got injured,” he recalls.

Igor Spetic lost his hand in a workplace accident. Now he’s one of the first people ever to regain realistic finger sensations thanks to nerve interfaces (below) implanted in the arm.

He soon got a prosthesis. But for amputees like Spetic, these are more tools than limbs. Because the prosthetics can’t convey sensations, people wearing them can’t feel when they have dropped or crushed something.Now Spetic, 48, is getting some of his sensation back through electrodes that have been wired to residual nerves in his arm. Spetic is one of two people in an early trial that takes him from his home in Madison, Ohio, to the Cleveland Veterans Affairs Medical Center. In a basement lab, his prosthetic hand is rigged with force sensors that are plugged into 20 wires protruding from his upper right arm. These lead to three surgically implanted interfaces, seven millimeters long, with as many as eight electrodes apiece encased in a polymer, that surround three major nerves in Spetic’s forearm.

On a table, a nondescript white box of custom electronics does a crucial job: translating information from the sensors on Spetic’s prosthesis into a series of electrical pulses that the interfaces can translate into sensations. This technology “is 20 years in the making,” says the trial’s leader, Dustin Tyler, a professor of biomedical engineering at Case Western Reserve University and an expert in neural interfaces.

Left: To evaluate his sensory feedback, he picks up blocks held to the table with magnets.

Right: With sensation restored, he can pick up cherries and remove stems 93 percent of the time without crushing, even blindfolded.

As of February, the implants had been in place and performing well in tests for more than a year and a half. Tyler’s group, drawing on years of neuroscience research on the signaling mechanisms that underlie sensation, has developed a library of patterns of electrical pulses to send to the arm nerves, varied in strength and timing. Spetic says that these different stimulus patterns produce distinct and realistic feelings in 20 spots on his prosthetic hand and fingers. The sensations include pressing on a ball bearing, pressing on the tip of a pen, brushing against a cotton ball, and touching sandpaper, he says. A surprising side effect: on the first day of tests, Spetic says, his phantom fist felt open, and after several months the phantom pain was “95 percent gone.”

On this day, Spetic faces a simple challenge: seeing whether he can feel a foam block. He dons a blindfold and noise-­canceling headphones (to make sure he’s relying only on his sense of touch), and then a postdoc holds the block inside his wide-open prosthetic hand and taps him on the shoulder. Spetic closes his prosthesis—a task made possible by existing commercial interfaces to residual arm muscles—and reports the moment he touches the block: success.

While the results are promising, research that involves surgical implants is time-consuming. Completing the pilot study, refining stimulation methods, and launching full clinical trials is likely to take 10 years. Tyler is also finishing development of an implantable electronic device to deliver stimuli “so this is not just on a bench in a lab, but gets into the home eventually,” he says. And he is working with manufacturers of prostheses to integrate force sensors and force processing technology directly into future versions of the devices.

versions of the devices.

Left: Control boxes deliver signals to electrodes surrounding nerves in Spetic’s arm, producing sensations of touch.

Right: This device might eventually be implanted in his arm, replacing lab equipment to deliver signals. Force sensors and processing technology could be integrated into future prosthetic devices.

Nerve interfaces are implanted in the arm.

When the tests are over and the equipment is disconnected, Spetic’s sensory visitation with his lost hand abruptly ends. He says he’s “blessed to know these people and be a part of this.” But he can’t help thinking wistfully about what the future might bring. “It would be nice to know I can pick up an object without having to look at it, or I can hold my wife’s hand and walk down the street, knowing I have a hold of her,” he says, as he puts on his coat and starts back home. “Maybe all of this will help the next person.”

Watch video: Restoring a Sense of Touch in Amputees

http://www.technologyreview.com/photoessay/524676/an-artificial-hand-with-real-feeling/

Genome Surgery

Precise and easy ways to rewrite human genes could finally provide the tools that researchers need to understand and cure some of our most deadly genetic diseases.

 

• by Susan Young

MIT Technology Review Magazine

Researchers’ new ability to edit the genome will likely have profound consequences for disease treatments.

A sketch made by Francis Crick in 1953 shows his first impression of the DNA molecule.

Over the last decade, as DNA-sequencing technology has grown ever faster and cheaper, our understanding of the human genome has increased accordingly. Yet scientists have until recently remained largely ham-fisted when they’ve tried to directly modify genes in a living cell. Take sickle-cell anemia, for example. A debilitating and often deadly disease, it is caused by a mutation in just one of a patient’s three billion DNA base pairs. Even though this genetic error is simple and well studied, researchers are helpless to correct it and halt its devastating effects.

Now there is hope in the form of new genome-engineering tools, particularly one called CRISPR. This technology could allow researchers to perform microsurgery on genes, precisely and easily changing a DNA sequence at exact locations on a chromosome. Along with a technique called TALENs, invented several years ago, and a slightly older predecessor based on molecules called zinc finger nucleases, CRISPR could make gene therapies more broadly applicable, providing remedies for simple genetic disorders like sickle-cell anemia and eventually even leading to cures for more complex diseases involving multiple genes. Most conventional gene therapies crudely place new genetic material at a random location in the cell and can only add a gene. In contrast, CRISPR and the other new tools also give scientists a precise way to delete and edit specific bits of DNA—even by changing a single base pair. This means they can rewrite the human genome at will.

It is likely to be at least several years before such efforts can be developed into human therapeutics, but a growing number of academic researchers have seen some preliminary success with experiments involving sickle-cell anemia, HIV, and cystic fibrosis (see table below). One is Gang Bao, a bioengineering researcher at the Georgia Institute of Technology, who has already used CRISPR to correct the sickle-cell mutation in human cells grown in a dish. Bao and his team started the work in 2008 using zinc finger nucleases. When TALENs came out, his group switched quickly, says Bao, and then it began using CRISPR when that tool became available. While he has ambitions to eventually work on a variety of diseases, Bao says it makes sense to start with sickle-cell anemia. “If we pick a disease to treat using genome editing, we should start with something relatively simple,” he says. “A disease caused by a single mutation, in a single gene, that involves only a single cell type.”

In little more than a year, CRISPR has begun reinventing genetic research.

Bao has an idea of how such a treatment would work. Currently, physicians are able to cure a small percentage of sickle-cell patients by finding a human donor whose bone marrow is an immunological match; surgeons can then replace some of the patient’s bone marrow stem cells with donated ones. But such donors must be precisely matched with the patient, and even then, immune rejection—a potentially deadly problem—is a serious risk. Bao’s cure would avoid all this. After harvesting blood cell precursors called hematopoietic stem cells from the bone marrow of a sickle-cell patient, scientists would use CRISPR to correct the defective gene. Then the gene-­corrected stem cells would be returned to the patient, producing healthy red blood cells to replace the sickle cells. “Even if we can replace 50 percent, a patient will feel much better,” says Bao. “If we replace 70 percent, the patient will be cured.”

Though genome editing with CRISPR is just a little over a year old, it is already reinventing genetic research. In particular, it gives scientists the ability to quickly and simultaneously make multiple genetic changes to a cell. Many human illnesses, including heart disease, diabetes, and assorted neurological conditions, are affected by numerous variants in both disease genes and normal genes. Teasing out this complexity with animal models has been a slow and tedious process. “For many questions in biology, we want to know how different genes interact, and for this we need to introduce mutations into multiple genes,” says Rudolf ­Jaenisch, a biologist at the Whitehead Institute in Cambridge Massachusetts. But, says ­Jaenisch, using conventional tools to create a mouse with a single mutation can take up to a year. If a scientist wants an animal with multiple mutations, the genetic changes must be made sequentially, and the timeline for one experiment can extend into years. In contrast, ­Jaenisch and his colleagues, including MIT researcher Feng Zhang (a 2013 member of our list of 35 innovators under 35), reported last spring that CRISPR had allowed them to create a strain of mice with multiple mutations in three weeks.

Because a CRISPR system can easily be designed to target any specific gene, the technology is allowing researchers to do experiments that probe a large number of them. In December, teams led by Zhang and MIT researcher Eric Lander created libraries of CRISPRs, each of which targets a different human gene. These vast collections, which account for nearly all the human genes, have been made available to other researchers. The libraries promise to speed genome-wide studies on the genetics of cancer and many other human diseases.

Genome GPS

The biotechnology industry was born in 1973, when Herbert Boyer and Stanley Cohen inserted foreign DNA that they had manipulated in the lab into bacteria. Within a few years, Boyer had cofounded Genentech, and the company had begun using E. coli modified with a human gene to manufacture insulin for diabetics. In 1974, Jaenisch, then at the Salk Institute for Biological Studies in San Diego, created the first transgenic mouse by using viruses to spike the animal’s genome with a bit of DNA from another species. In these and other early examples of genetic engineering, however, researchers were limited to techniques that inserted the foreign DNA into the cell at random. All they could do was hope for the best.

It took more than two decades before molecular biologists became adept at efficiently changing specific genes in animal genomes. Dana Carroll of the University of Utah recognized that zinc finger nucleases, engineered proteins reported by colleagues at Johns Hopkins University in 1996, could be used as a programmable gene-­targeting tool. One end of the protein can be designed to recognize a particular DNA sequence; the other end cuts DNA. When a cell then naturally repairs those cuts, it can patch its genome by copying from supplied foreign DNA. While the technology finally enabled scientists to confidently make changes where they want to on a chromosome, it’s difficult to use. Every modification requires the researcher to engineer a new protein tailored to the targeted sequence—a difficult, time-consuming task that, because the proteins are finicky, doesn’t always work.

TALENs, another significant advance in gene editing, came along in 2010. TALENs are also proteins that find and cut a desired DNA sequence—but tailoring them to new gene targets is much easier. While they represented a great improvement over zinc fingers, however, TALENs are large proteins that are cumbersome to work with and deliver into cells.

CRISPR changed everything. It replaces the DNA-targeting proteins with a short bit of RNA that homes in on desired genes. Unlike the complex proteins, RNA—which has nearly the same simple structure as DNA—can be made routinely in the lab; a technician can quickly synthesize the roughly 20-letter-long sequences the method requires. The system makes it easy for medical researchers to modify a genome by replacing, deleting, or adding DNA.

CRISPR stands for “clustered regularly interspaced short palindromic repeats”—clusters of brief DNA sequences that read similarly forward and backward, which are found in many types of bacteria. Scientists first observed the puzzling DNA segments in the 1980s but didn’t understand for almost two decades that they are part of a bacterial defense system. When a virus attacks, bacteria can incorporate sequences of viral DNA into their own genetic material, sandwiching them between the repetitive segments. The next time the bacteria encounter that virus, they use the DNA in these clusters to make RNAs that recognize the matching viral sequences. A protein attached to one of these RNAs then cuts up the viral DNA.

In 2012, Emmanuelle Charpentier, a medical microbiologist who studies pathogens at the Helmholtz Centre for Infection Research, and Jennifer Doudna, a collaborator at the University of California, Berkeley, showed they could use a single RNA in conjunction with the cutting protein, an enzyme called Cas9, to slice any desired sequence of DNA in test tubes. It was still uncertain whether the method would work in animal cells, but in January 2013 came a dramatic breakthrough. Zhang and George Church, a Harvard Medical School geneticist, separately reported that the CRISPR/Cas9 system could be used for gene editing in the cells of animals, including humans.

Now a researcher who wants to go after a new gene need only synthesize the Cas9 protein and a bit of RNA that matches the sequences of the targeted region. The RNA then guides the enzyme to the DNA the researcher wants to cut. And because the same cutting protein is used regardless of the target, researchers can design experiments in which they change multiple genes in an organism simultaneously using Cas9 and multiple RNA guides. “It offers the potential to do experiments that in the past were very difficult or essentially not possible,” says Doudna.

Complex Mysteries

MIT’s Zhang, who is a member of the Broad Institute and the McGovern Institute for Brain Research, is interested in the genetics behind mental illness. To try to understand these complex conditions, Zhang has helped develop multiple gene- and neuron-modifying tools, including TALENs and optogenetics, a technique that involves controlling neuron activity with laser light. When he first heard about CRISPR, in 2011, he began to engineer it for use in human cells. Now he’s using CRISPR to help reveal the genetic secrets behind such devastating and poorly understood conditions as schizophrenia and autism.

The tool allows Zhang to begin systematically testing some of the DNA variants that have been linked to the illnesses. While much progress has been made over the last decade toward identifying genes that are common in people with these conditions, understanding how these genes relate to the symptoms is a daunting challenge. “What you learn from sequencing is only an observation,” says Zhang: in order to understand whether a suspected gene is actually causing the condition, you have to introduce the specific mutation into healthy cells or organisms and see what goes wrong. If the mutated cell or organism has features that mimic the human disease, that’s evidence implicating the gene.

Zhang can re-create, in both lab mice and cultured human cells, genetic variants found in people with autism and schizophrenia. “You can put a human mutation into the corresponding gene in a lab animal and then see: does that animal become less social or have a learning deficit?” he says. Then, he adds, you can study differences in the behavior and physiology of lab-cultured neurons grown from stem cells that have been modified with the same mutation. “With single-gene mutations, we will start to see aspects of the biological function that are involved in autism,” he says.

Perhaps scientists could rewrite normal genes so that humans could better fight infections.

Zhang is also using CRISPR to make multiple genetic changes at once. That becomes particularly important with complex diseases like autism and schizophrenia, which for the most part are not caused by the type of single DNA change behind sickle-cell anemia. Different patients are affected by different collections of mutations. Solving a puzzle of such immense complexity will require large, systematic studies on the effects of various genes and the way they interact. CRISPR makes such studies possible, says Zhang, and will be important in finding treatments for a variety of complex diseases. “We will understand more about pathways and disease mechanisms,” he says. “This knowledge will inform all kinds of drug development.”

Designer Babies

Late last year, Doudna, Zhang, Church, and two other pioneers of genome editing founded a startup that will develop novel treatments for human genetic diseases. In November the company, Editas Medicine, announced that it had raised $43 million in venture capital and said it plans to use genome-editing technologies against a broad range of illnesses.

The launch of Editas should benefit from a resurgence of interest in gene therapy thanks to years of technological improvements, including safer mechanisms for delivering treatment. “The landscape has changed for gene therapy,” says Church. (There are still no gene therapies approved in the United States, though a number are in human ­trials.) But he says the therapies that Editas will develop will be fundamentally different from the older approaches that use a virus to insert a gene into cells.

“Making a change or a deletion is out of range for most of those simple viral methods,” Church says. And deleting a bit of DNA, rather than adding a gene, may indeed be the key to treating many illnesses. Take Huntington’s disease. The fatal brain condition arises from a buildup of a toxic protein in neurons. Adding a healthy copy of the gene to the cell would not affect that protein’s poisonous activity: the original dysfunctional version must be rewritten. With the new genome-editing tools, says Church, rewriting the defective DNA may be possible: “You aren’t limited to adding back something that is missing.” And, he adds, “when you start realizing that the most common versions of genes are not necessarily the ideal versions, then you realize this is a much bigger field.” Perhaps scientists could rewrite normal genes so that humans can better fight infectious diseases. They might even be able to shake up the molecular pathways involved in aging.

Church also predicts that if genome editing is used to cure childhood diseases, some scientists will be tempted to use it to engineer embryos during in vitro fertilization. Researchers have already shown that genome editing can rewrite DNA sequences in rat and mouse embryos, and in late January, researchers in China reported that they had created genetically modified monkeys using CRISPR. With such techniques, a person’s genome might be edited before birth—or, if changes were made to the eggs or sperm-­producing cells of a prospective parent, even before conception.

These possibilities raise ethical questions. But if researchers prove they can safely correct diseases by editing the genome, it’s inevitable that some parents will also want to alter the genomes of healthy embryos. “If you can prevent mental retardation with gene therapy, presuming that that’s permissible, then there’s a whole spectrum of intellectual challenges that will be discussed,” says Church.

Such discussions are likely to heat up as CRISPR becomes more widely used. For now, though, the technology is still evolving: while researchers like Bao, Church, and Zhang ultimately hope to cure some of our most intractable diseases, much of their time is still spent simply fine-tuning the tool and exploring its possibilities. But even in these early days, CRISPR has already transformed how these researchers think about manipulating the genome. They are ham-fisted no longer.

Credit: Illustration courtesy of Wellcome Library, London

Tagged: Biomedicine, DNA, genetics, RNA, genes

http://www.technologyreview.com/review/524451/genome-surgery/