Posts
http://www.fellowgeek.com/a-Researchers-Teach-Things-Subliminally-Matrix-Learning-not-Far-Away.html
For the first time ever, scientists from Boston University and ATR Computational Neuroscience Laboratories in Kyoto, Japan have managed to use functional Magnetic Resonance Imaging, or fMRI to decode the process of learning.
Here’s the basic procedure:
* Find someone capable of performing a task, for example juggling. Then stick them into an fMRI machine and have them imagine juggling. As they mentally go through how they do it, the scientists decode the brain patterns into something they can use later
* Find another person. Stick them in an MRI machine and have them try and imagine juggling. Decode as before, then compare.
* Use neurofeedback by rewarding people for increasing the similarity in brain patterns.
* Nothing else. By mimicking the state of the professional juggler, you are learning how to juggle.
Not Here Yet, but Soon
As the research stands to date, it isn’t capable of much. Rather than working with skills like juggling, the researchers relied on images so they could tie into the vision part of the brain, the part that they have managed to partially decode.
Nevertheless, they demonstrated that information could be taught using neurofeedback techniques. And it was effective even when people didn’t know they were learning.
The researchers are cautiously optimistic on the ability to automatically teach information. As said Mitsudo Kawato of ATR Computational Neuroscience Laboratories, "In theory, hypnosis or a type of automated learning is a potential outcome. However, in this study we confirmed the validity of our method only in visual perceptual learning. So we have to test if the method works in other types of learning in the future. At the same time, we have to be careful so that this method is not used in an unethical way."
Monday, December 12, 2011
Sunday, December 11, 2011
The condescending UI
http://www.theverge.com/2011/12/9/2616204/the-condescending-ui
(see graphics on the original post)
By Paul Miller
I have a kneejerk reaction to most modern computer user interfaces (also, all microwave user interfaces). I've used plenty of excuses over the years: my "eye for design," my love of minimalism, a sense of utility. Today, I finally put my finger on it, and it's not just a desire for the-computer-as-pure-machine, or a spartan aesthetic. It's quite simple, really: I don't like the condescending tone.
Growing up I was always very small for my age. I didn't mind the size ("the bigger they are, the harder they fall!" was my rallying cry), but I hated being thought of as younger than I was, be it in physical or intellectual capabilities. When you're a knowledge sponge as a kid, the first time someone tells you something, it feels amazing, and you love that person. The second time someone tells you the same fact, it's pure torture. "I know this already, I'm not an idiot! Sheesh."
My problem with many modern UIs is that they never get past the telling phase. They're always dressing up their various functions with glows and bevels and curves, and in the process they somehow become overbearing to my senses. "Did you know you can click this? Don't forget there's a save button over here! Let me walk you to your control panel." Imagine a car that verbally explains all of its various knobs and levers the first time you get into the car. Wonderful, right? Now imagine that car explaining all of these various functions every single time you get in the car for the next five years, until you finally snap and drive it off a cliff.
Swoosih-final-loop-new
An example of this is the dramatic, quasi-utilitarian animated transition. The first few times, it's conveying important information: click that button? That launches this action! Swoosh. The next 10,000 times, it's mainly just slowing me down. A "wizard" is supposed to ask a pertinent question that eventually leads me to a specific control panel, but once I know the actual control panel I want, the friendly "wizard" is more like a guard at the gates. The Ribbon in Microsoft Office products (which is making its way to the file manager in Windows 8) is constantly talking down to me, assuming I don't know how to use a menu, a key command, or a honest-to-goodness toolbar.
But it's not just functionality, there's something deeper that bugs me, about the decorations themselves. Like the ubiquitous drop shadow. "Did you know that this window is on top of this window?" it whispers to me, endlessly. Apple's love of reflections and faux 3D subtly imply to me that I might be lost, needing landmarks and a sense of place to find my way. Microsoft's oddly-sized minimize / maximize / close buttons in Windows 7 are only there to help, but they also hint at some lack of eye-hand coordination on my part. Soft edges, endless gradients, and rounded corners seem designed to keep me from hurting myself on an acute angle, as if the desktop is a choke-proof toy for babies, instead of a sharpened pencil. A huge graphical icon representing an app might look incredible and enticing, but after a while it's sort of oversharing. It's constantly reintroducing itself, in case I didn't catch its name the first time.
And of course, there is the transgression of the century: Apple's downward spiral into overt 1:1 metaphors. The physical bookshelf, the leather desk calendar (complete with a torn page), the false-paginated address book, whatever Game Center is trying to pull off. At least Cover Flow's LP-flipping simulation was cute and emergent, if quickly tiresome, but these new tricks are horrible and offensive. They're not only condescending and overwrought, they're actually counter-functional. For some true analysis of Apple's recent sins in this department, check out John Siracusa's in-depth look over at Ars Technica.
Of course, seeking out an aesthetically pleasing interface seems a nice goal. The muted chrome of Lion is really (relatively) wonderful, and I like the vibrant color palette of Windows 7. These are truly great efforts, by great designers, but I still can't help but feel like they're taking the operating systems I knew, in all their "ugly" 1990s glory, and dressing them up in Little Lord Fauntleroy suits. Perhaps without the limitations of a finite number of colors and pixels to force simplicity, UI designers just don't know what to do with themselves. I'd argue they do too much. Luckily, OS X has improved some over recent years, reining in the horrible early 2000s excesses of Aqua (minus the aforementioned iCal and Address Book), but Microsoft's traditional, windowed desktop experience seems to be trending in the opposite direction.
Ultimately, an OS is much more than its chrome, it's about what it can do, and how efficiently it can do it. I know plenty of people who, like me, pine for BeOS. Many of us never even used BeOS, or at least not seriously. And yet we check up on the Haiku blog (Haiku is an open source project to rebuild BeOS from the ground up) every month or so, hoping against hope that BeOS will return to save us from overwrought UI, and the overwrought kernels underneath. BeOS is purely digital, with a sort of 8-bit charm, complete with pixel-perfect isometric icons. It's much like the appeal of "retro" indie games, which deal in our native, shared gaming language and metaphors, not something borrowed from action movies or an overblown sense of virtual reality. But it's all a fantasy, really: I'll probably never be able to do even a fraction of my daily work on Haiku. Just like how my SNES will never run Skyrim.
Maybe Microsoft's excellent "Metro" design language, which is on Windows Phone, and is headed to the Xbox and the Windows 8 Start screen, is the answer. Microsoft itself describes Metro as "authentically digital," which seems like a great place to start. Still, even Metro seems to be a little over-designed at times, with its oversized fonts bleeding off the screen, low information density, and an abundance of swoops and swipes. It's saying "look how minimal I am," but in the loudest way possible. I'm still waiting for my UI knight in shining armor.
In my personal quest to escape the condescension, I recently switched my Windows 7 install over to the "Classic Theme," which is basically Windows 95 incarnate, just with all the under-the-hood improvements I've come to rely on. I really like it. It feels right, and if it isn't beautiful, at least it's honest. I wish there was a similar OS 9 mode for OS X. Sometimes I like to dink around in Terminal, accomplishing nothing, but at least knowing that I'm engaging the computer on my own terms, with no buffer. Maybe someday someone can port over the old NeXT UI to OS X, or perhaps Mac OS X Server 1.0's approximation of OS 9's chrome. The retro affectations are silly and quixotic, but at least now I know why I put myself through these contortions. I'm a grown up! Sheesh.
(see graphics on the original post)
By Paul Miller
I have a kneejerk reaction to most modern computer user interfaces (also, all microwave user interfaces). I've used plenty of excuses over the years: my "eye for design," my love of minimalism, a sense of utility. Today, I finally put my finger on it, and it's not just a desire for the-computer-as-pure-machine, or a spartan aesthetic. It's quite simple, really: I don't like the condescending tone.
Growing up I was always very small for my age. I didn't mind the size ("the bigger they are, the harder they fall!" was my rallying cry), but I hated being thought of as younger than I was, be it in physical or intellectual capabilities. When you're a knowledge sponge as a kid, the first time someone tells you something, it feels amazing, and you love that person. The second time someone tells you the same fact, it's pure torture. "I know this already, I'm not an idiot! Sheesh."
My problem with many modern UIs is that they never get past the telling phase. They're always dressing up their various functions with glows and bevels and curves, and in the process they somehow become overbearing to my senses. "Did you know you can click this? Don't forget there's a save button over here! Let me walk you to your control panel." Imagine a car that verbally explains all of its various knobs and levers the first time you get into the car. Wonderful, right? Now imagine that car explaining all of these various functions every single time you get in the car for the next five years, until you finally snap and drive it off a cliff.
Swoosih-final-loop-new
An example of this is the dramatic, quasi-utilitarian animated transition. The first few times, it's conveying important information: click that button? That launches this action! Swoosh. The next 10,000 times, it's mainly just slowing me down. A "wizard" is supposed to ask a pertinent question that eventually leads me to a specific control panel, but once I know the actual control panel I want, the friendly "wizard" is more like a guard at the gates. The Ribbon in Microsoft Office products (which is making its way to the file manager in Windows 8) is constantly talking down to me, assuming I don't know how to use a menu, a key command, or a honest-to-goodness toolbar.
But it's not just functionality, there's something deeper that bugs me, about the decorations themselves. Like the ubiquitous drop shadow. "Did you know that this window is on top of this window?" it whispers to me, endlessly. Apple's love of reflections and faux 3D subtly imply to me that I might be lost, needing landmarks and a sense of place to find my way. Microsoft's oddly-sized minimize / maximize / close buttons in Windows 7 are only there to help, but they also hint at some lack of eye-hand coordination on my part. Soft edges, endless gradients, and rounded corners seem designed to keep me from hurting myself on an acute angle, as if the desktop is a choke-proof toy for babies, instead of a sharpened pencil. A huge graphical icon representing an app might look incredible and enticing, but after a while it's sort of oversharing. It's constantly reintroducing itself, in case I didn't catch its name the first time.
And of course, there is the transgression of the century: Apple's downward spiral into overt 1:1 metaphors. The physical bookshelf, the leather desk calendar (complete with a torn page), the false-paginated address book, whatever Game Center is trying to pull off. At least Cover Flow's LP-flipping simulation was cute and emergent, if quickly tiresome, but these new tricks are horrible and offensive. They're not only condescending and overwrought, they're actually counter-functional. For some true analysis of Apple's recent sins in this department, check out John Siracusa's in-depth look over at Ars Technica.
Of course, seeking out an aesthetically pleasing interface seems a nice goal. The muted chrome of Lion is really (relatively) wonderful, and I like the vibrant color palette of Windows 7. These are truly great efforts, by great designers, but I still can't help but feel like they're taking the operating systems I knew, in all their "ugly" 1990s glory, and dressing them up in Little Lord Fauntleroy suits. Perhaps without the limitations of a finite number of colors and pixels to force simplicity, UI designers just don't know what to do with themselves. I'd argue they do too much. Luckily, OS X has improved some over recent years, reining in the horrible early 2000s excesses of Aqua (minus the aforementioned iCal and Address Book), but Microsoft's traditional, windowed desktop experience seems to be trending in the opposite direction.
Ultimately, an OS is much more than its chrome, it's about what it can do, and how efficiently it can do it. I know plenty of people who, like me, pine for BeOS. Many of us never even used BeOS, or at least not seriously. And yet we check up on the Haiku blog (Haiku is an open source project to rebuild BeOS from the ground up) every month or so, hoping against hope that BeOS will return to save us from overwrought UI, and the overwrought kernels underneath. BeOS is purely digital, with a sort of 8-bit charm, complete with pixel-perfect isometric icons. It's much like the appeal of "retro" indie games, which deal in our native, shared gaming language and metaphors, not something borrowed from action movies or an overblown sense of virtual reality. But it's all a fantasy, really: I'll probably never be able to do even a fraction of my daily work on Haiku. Just like how my SNES will never run Skyrim.
Maybe Microsoft's excellent "Metro" design language, which is on Windows Phone, and is headed to the Xbox and the Windows 8 Start screen, is the answer. Microsoft itself describes Metro as "authentically digital," which seems like a great place to start. Still, even Metro seems to be a little over-designed at times, with its oversized fonts bleeding off the screen, low information density, and an abundance of swoops and swipes. It's saying "look how minimal I am," but in the loudest way possible. I'm still waiting for my UI knight in shining armor.
In my personal quest to escape the condescension, I recently switched my Windows 7 install over to the "Classic Theme," which is basically Windows 95 incarnate, just with all the under-the-hood improvements I've come to rely on. I really like it. It feels right, and if it isn't beautiful, at least it's honest. I wish there was a similar OS 9 mode for OS X. Sometimes I like to dink around in Terminal, accomplishing nothing, but at least knowing that I'm engaging the computer on my own terms, with no buffer. Maybe someday someone can port over the old NeXT UI to OS X, or perhaps Mac OS X Server 1.0's approximation of OS 9's chrome. The retro affectations are silly and quixotic, but at least now I know why I put myself through these contortions. I'm a grown up! Sheesh.
Friday, December 9, 2011
quantum physics in photosynthesis
http://arstechnica.com/science/news/2011/12/more-evidence-found-for-quantum-physics-in-photosynthesis.ars
More evidence found for quantum physics in photosynthesis
By Brandon Keim, wired.com
Physicists have found the strongest evidence yet of quantum effects fueling photosynthesis.
Multiple experiments in recent years have suggested as much, but it's been hard to be sure. Quantum effects were clearly present in the light-harvesting antenna proteins of plant cells, but their precise role in processing incoming photons remained unclear.
In an experiment published Dec. 6 in Proceedings of the National Academy of Sciences, a connection between coherence—far-flung molecules interacting as one, separated by space but not time—and energy flow is established.
"There was a smoking gun before," said study co-author Greg Engel of the University of Chicago. "Here we can watch the relationship between coherence and energy transfer. This is the first paper showing that coherence affects the probability of transport. It really does change the chemical dynamics."
The new findings are the latest in a series that have, piece by piece, promised to expand scientific understanding of photosynthesis, one of life's fundamental processes. Until a few years ago, it seemed a straightforward piece of chemistry.
Then came observations of coherence in antenna-protein chlorophylls from green sulfur bacteria. They lasted far longer than anyone expected, long enough to hint at a functional role. Those observations were, however, made at unrealistically ultracold temperatures; then they were made at room temperatures, and in antenna proteins found in plants everywhere.
Confronted with this unexpected coherence, researchers hypothesized a role in enabling ultra-efficient energy transfer. Energy from incoming photons could simultaneously explore every possible chlorophyll route from a protein's surface to the reaction center at its core, then settle on the shortest path.
An antenna protein complex. The protein scaffolding is grey and chlorophyll molecules are green
An antenna protein complex. The protein scaffolding is grey and chlorophyll molecules are green
Greg Engels
To see if that happened, a team led by Engel and Shaul Mukamel of the University of California, Irvine analyzed the fluctuation of lasers as they passed through antenna proteins. Depending on how they shifted, the researchers could track what happened inside.
They found a clear mathematical link between energy flows and fluctuations in chlorophyll coherence. The link was so clear it could be described in derivative sines and cosines, mathematical concepts taught in college trigonometry.
"The mounting evidence that quantum effects can be seen in natural systems when excited by lasers is compelling," said Greg Scholes, a University of Toronto biophysicist who first found quantum effects in room temperature photosynthesis.
Further research is needed to understand the full role of quantum physics, said Scholes. "How much do they change our understanding? How much are they needed?" he said.
Engel sees a lesson in the importance of the antenna proteins in which chlorophyll molecules are embedded. "The protein does a lot more for this system than we thought," he said. "It's not just a simple structural element."
Molecular biologists "are trained to look at the molecule," Engel said. "We don't usually design systems. We design molecules. The question becomes: Which aspects of this do we strive to recreate? We are very interested in the design principles. How could you design one of these?"
More evidence found for quantum physics in photosynthesis
By Brandon Keim, wired.com
Physicists have found the strongest evidence yet of quantum effects fueling photosynthesis.
Multiple experiments in recent years have suggested as much, but it's been hard to be sure. Quantum effects were clearly present in the light-harvesting antenna proteins of plant cells, but their precise role in processing incoming photons remained unclear.
In an experiment published Dec. 6 in Proceedings of the National Academy of Sciences, a connection between coherence—far-flung molecules interacting as one, separated by space but not time—and energy flow is established.
"There was a smoking gun before," said study co-author Greg Engel of the University of Chicago. "Here we can watch the relationship between coherence and energy transfer. This is the first paper showing that coherence affects the probability of transport. It really does change the chemical dynamics."
The new findings are the latest in a series that have, piece by piece, promised to expand scientific understanding of photosynthesis, one of life's fundamental processes. Until a few years ago, it seemed a straightforward piece of chemistry.
Then came observations of coherence in antenna-protein chlorophylls from green sulfur bacteria. They lasted far longer than anyone expected, long enough to hint at a functional role. Those observations were, however, made at unrealistically ultracold temperatures; then they were made at room temperatures, and in antenna proteins found in plants everywhere.
Confronted with this unexpected coherence, researchers hypothesized a role in enabling ultra-efficient energy transfer. Energy from incoming photons could simultaneously explore every possible chlorophyll route from a protein's surface to the reaction center at its core, then settle on the shortest path.
An antenna protein complex. The protein scaffolding is grey and chlorophyll molecules are green
An antenna protein complex. The protein scaffolding is grey and chlorophyll molecules are green
Greg Engels
To see if that happened, a team led by Engel and Shaul Mukamel of the University of California, Irvine analyzed the fluctuation of lasers as they passed through antenna proteins. Depending on how they shifted, the researchers could track what happened inside.
They found a clear mathematical link between energy flows and fluctuations in chlorophyll coherence. The link was so clear it could be described in derivative sines and cosines, mathematical concepts taught in college trigonometry.
"The mounting evidence that quantum effects can be seen in natural systems when excited by lasers is compelling," said Greg Scholes, a University of Toronto biophysicist who first found quantum effects in room temperature photosynthesis.
Further research is needed to understand the full role of quantum physics, said Scholes. "How much do they change our understanding? How much are they needed?" he said.
Engel sees a lesson in the importance of the antenna proteins in which chlorophyll molecules are embedded. "The protein does a lot more for this system than we thought," he said. "It's not just a simple structural element."
Molecular biologists "are trained to look at the molecule," Engel said. "We don't usually design systems. We design molecules. The question becomes: Which aspects of this do we strive to recreate? We are very interested in the design principles. How could you design one of these?"
17-year-old wins 100k for creating cancer-killing nanoparticle
http://www.geek.com/articles/geek-cetera/17-year-old-wins-100k-for-creating-cancer-killing-nanoparticle-2011128/
At the age of 17 I was paying attention in college, but still enjoying the student life as much as studying towards my career goals. What I wasn’t doing was working at the cutting edge of cancer treatment and developing a potential cure.
Angela Zhang is, and she’s just been awarded the $100,000 Grand Prize in the Individual category of the Siemens Competition in Math, Science & Technology. Her project was entitled “Design of Image-guided, Photo-thermal Controlled Drug Releasing Multifunctional Nanosystem for the Treatment of Cancer Stem Cells.”
Her creation is being heralded as a “Swiss army knife of cancer treatment.” Zhang managed to develop a nanoparticle that can be delivered to the site of a tumor through the drug salinomycin. Once there it kills the cancer stem cells. However, Zhang went further and included both gold and iron-oxide components, which allow for non-invasive imaging of the site through MRI and Photoacoustics.
As to why she chose this as her project, Zhang explains that she was surprised when looking at the survival rates of patients receiving cancer treatment. As cancer stem cells are resistant to many forms of cancer treatment, it seemed like an area worth focusing on. Her nanoparticle is award-winning due to the fact it has the potential to overcome cancer resistance while offering up the ability to monitor the effects of the treatment in real-time using existing imaging techniques.
Zhang’s achievement is impressive considering she is only 17 years old, but also due to the level of understanding required to create such a nanoparticle in the first place. She has spent over 1,000 hours since 2009 researching and developing the particle, and wants to go on to study chemical engineering, biomedical engineering, or physics. Her dream job is to be a research professor.
The Siemens Competition is in its 13th year and aims to highlight talent at the high school level for those interested in science research. Last year 15-year-old Benjamin Clark won the Individual category for his work into how stars are born. In 2009 Ruoyi Jiang won for his research into chemotherapy drug resistance.
I think we can all agree this is a very worthwhile competition, and long may it continue if it pushes young minds to create solutions to some of our biggest problems.
Read more at the Siemens Foundation and The George Washington University
At the age of 17 I was paying attention in college, but still enjoying the student life as much as studying towards my career goals. What I wasn’t doing was working at the cutting edge of cancer treatment and developing a potential cure.
Angela Zhang is, and she’s just been awarded the $100,000 Grand Prize in the Individual category of the Siemens Competition in Math, Science & Technology. Her project was entitled “Design of Image-guided, Photo-thermal Controlled Drug Releasing Multifunctional Nanosystem for the Treatment of Cancer Stem Cells.”
Her creation is being heralded as a “Swiss army knife of cancer treatment.” Zhang managed to develop a nanoparticle that can be delivered to the site of a tumor through the drug salinomycin. Once there it kills the cancer stem cells. However, Zhang went further and included both gold and iron-oxide components, which allow for non-invasive imaging of the site through MRI and Photoacoustics.
As to why she chose this as her project, Zhang explains that she was surprised when looking at the survival rates of patients receiving cancer treatment. As cancer stem cells are resistant to many forms of cancer treatment, it seemed like an area worth focusing on. Her nanoparticle is award-winning due to the fact it has the potential to overcome cancer resistance while offering up the ability to monitor the effects of the treatment in real-time using existing imaging techniques.
Zhang’s achievement is impressive considering she is only 17 years old, but also due to the level of understanding required to create such a nanoparticle in the first place. She has spent over 1,000 hours since 2009 researching and developing the particle, and wants to go on to study chemical engineering, biomedical engineering, or physics. Her dream job is to be a research professor.
The Siemens Competition is in its 13th year and aims to highlight talent at the high school level for those interested in science research. Last year 15-year-old Benjamin Clark won the Individual category for his work into how stars are born. In 2009 Ruoyi Jiang won for his research into chemotherapy drug resistance.
I think we can all agree this is a very worthwhile competition, and long may it continue if it pushes young minds to create solutions to some of our biggest problems.
Read more at the Siemens Foundation and The George Washington University
Saturday, December 3, 2011
How a Computer Game is Reinventing the Science of Expertise
http://blogs.scientificamerican.com/observations/2011/12/01/how-a-computer-game-is-reinventing-the-science-of-expertise-video/
By Sandra Upson
If there is one general rule about the limitations of the human mind, it is that we are terrible at multitasking. The old phrase “united we stand, divided we fall” applies equally well to the mechanisms of attention as it does to a patriotic cause. When devoted to a single task, the brain excels; when several goals splinter its focus, errors become unavoidable.
But clear exceptions challenge that general rule. Two weeks ago, thousands of computer game enthusiasts descended on a convention center in downtown Providence, Rhode Island, to observe some of these exceptions in action. They were attending the championships of one of the world’s hottest computer games, StarCraft 2. Hands fluttered over keyboards like hummingbirds mid-hover at about fifty computers set up in a dimly lit open hall. Players, many of whom flew in from South Korea to compete, vied to advance through their brackets to the finals. This game is no joke, with the prize money to prove it—$50,000 went to the winner, a 16-year-old Korean who goes by the name Leenock. The agility on display in Providence —as seen in the players’ multitasking, their nonstop decision-making, and the stunning speed of their fingers—has not gone unnoticed by cognitive scientists.
For decades, a different game, chess, has held the exalted position of “the drosophila of cognitive science”—the model organism that scientists could poke and prod to learn what makes experts better than the rest of us. StarCraft 2, however, might be emerging as the rhesus macaque: its added complexity may confound researchers initially, but the answers could ultimately be more telling.
This real-time strategy game demands the frenetic pursuit of numerous simultaneous goals, any of which can change in the blink of an eye. Players play a god-like role over a cluster of creatures, leading them to develop their economy and prepare them for skirmishes with a neighboring society. Wildly popular among gamers—StarCraft 2 was the top-selling computer game in 2010, the year it was released—for researchers the appeal lies in the data each game generates. When two players face off, their computers each produce a record of the actions taken during the game. Called replay files, those logs reflect what a gamer was thinking at every stage of play. “I can’t think of a cognitive process that’s not involved in StarCraft,” says Mark Blair, a cognitive scientist at Simon Fraser University. “It’s working memory. It’s decision making. It involves very precise motor skills. Everything is important and everything needs to work together.”
That intellectual rigor and the corresponding data trail, multiplied across hundreds of thousands of players worldwide, makes StarCraft an unparalleled resource that scientists are only now tapping for the study of attention, multitasking, and learning. (As a rough estimate, at the time of writing about 11,000 games are being played on the servers of Blizzard Entertainment, the company that created StarCraft.) Recent experiments on computer games are beginning to suggest that players develop skills that could be useful in other contexts—skills that might allow those individuals to cope better with certain types of information overload. Thousands of these gamers are now contributing to a project under Blair’s watch, called SkillCraft, to learn what separates experts from novices and everyone in between. By all appearances this study of StarCraft players is the world’s biggest experiment on how expertise develops and, ultimately, on how we learn.
Video game research has reached a turning point: psychologists are no longer asking only whether the violence in some games corrupts young minds, or whether games are dangerously addictive, thus corrupting young minds. At least in some cases, gamers are being recognized for the specific forms of learning they cultivate, with the data trail that could finally unravel some of the major mysteries of the human brain.
Why StarCraft
To really appreciate why scientists are turning to StarCraft 2, you need to know a few basics of the game. Two players, connected over the internet, fight for control of a territory of which they have an aerial view. Each player begins with a small base of one of three species—terran (humans), zerg (insectoid creatures), or protoss (photosynthetic aliens). To win, one species’ army must defeat the other, a simple enough goal. But the number of variables that can shift during the game is enormous, demanding constant slight adjustments to strategy. Unlike in a board game, StarCraft players don’t take turns—they simply do as much as they possibly can and hope their opponent is not as fast.
The species’ first task is to start extracting minerals and a fictitious vespene gas, which form the foundation of a StarCraft economy. Each player must balance building up his or her economic production with developing fighters, defenses, and eventually more bases. A player must also try to discern the economic and military strategy of the opponent, whose base is initially hidden from view. As mineral and gas production ramps up, the gamer gains capital to spend on developing more advanced technology, a larger economy, or more fighters. StarCraft 2’s overarching strategic challenge is to decide how much time and money to devote to building up either an economy or an army.
But that’s just one level of play. When you attack, you do not simply dispatch fighters—you manually control them by using your mouse to click on them and set them in motion. A skilled player will monitor the health of individual fighters in the frontlines of a battle and pull them back to the rear as they lose strength, giving them time to recover while fresher troops bear the brunt of the attack. At any given time, you can have several dozen fighters with different abilities pottering around a map, numerous laborers busily mining minerals and gas, and various facilities producing new tools and resources that should be deployed immediately. With so many moving parts, even a top-level player can succumb to paralysis.
A screenshot from a StarCraft 2 game.
Translating those goals into cognitive load, the brain’s executive functions manage most of the game’s demands. Several types of memory may be engaged to keep track of the weapons at one’s disposal and the locations of multiple objects on a map; attentional systems allow a player to plan future moves, switch focus to different activities around the map, and evaluate the enemy’s strategy. Motor skills are needed to rapidly click around the map to move and implement actions.
In short, the game is a relentless exercise in multitasking and constant decision-making. The winner, often, is the person who can make the most moves—an elite player can perform about 5 or 6 actions a second, which translates into a flurry of key presses and mouse maneuvers (see video, above).
Commentators react to events in a game. Credit: Major League Gaming
But you don’t have to be elite to be intriguing from a psychological perspective. According to the Entertainment Software Association, 72 percent of American households play computer or video games. With people engaging with games at all ages, scientists have become increasingly curious about how visually arresting—and in the case of StarCraft and similar games, cognitively demanding—software might be interacting with the brain. “From the perspective of the cognitive motor system, StarCraft is the most interesting thing you could do online,” Blair says.
The Trouble with Brain Training
The question now tantalizing psychologists is whether the rest of us can learn anything from these hyper-specialized multitasking gamers. Perhaps we, too, can accomplish some 300 things each minute—such productivity! Maybe we can learn to pick up new skills faster or use such games to stave off aging.
Given appropriate practice, humans seem to improve on almost any task they tackle. Ask us to sculpt a cake in the shape of Pinocchio, and with sufficient time and motivation we probably will. But multitasking abilities tend to resist practice. Perhaps Starcraft, somehow, possesses the elixir that can morph us into successful multitaskers.
Part of the problem is that once developed, human skills generally stay specific to the original task. Expert chess players, for example, have significantly superior recall of the positions of chess pieces on a board after a brief exposure than non-experts. That is as you might expect: years and years of practice have produced deep familiarity with the arrangements of pawns, rooks, and knights and what strategic opportunities they represent. But chess players turn out to be no better than others when asked to remember the arrangements of chess pieces placed at random, in configurations that could not appear in a game. Experiments in numerous other domains have demonstrated a similar lack of transfer.
In the last decade, however, some experiments have begun to suggest that video games might indeed teach transferable skills. Cognitive scientist Daphne Bavelier at the University of Rochester and her colleagues have used video games to investigate what kinds of learning humans are good at, and along the way they’ve turned up some promising, if modest, examples of brain training. (When scientists search for newly acquired abilities that transfer from one domain to another, they boil them down to skills so basic that you could be forgiven for responding with the raise of a single eyebrow.)
Early results suggest that gamers may have faster visual reaction times, enhanced visuomotor coordination, and heightened ability to visualize spatial arrangements. They may also be better at rotating an object in their minds and may distinguish more deftly between the trajectories of moving objects. Players might also have an edge when paying attention to several objects at once.
Because the tests did not mimic exactly the characteristics of the games participants played, the researchers are optimistic that more general skills were heightened. “There are few obvious links between chasing monsters across a star-spotted “spacescape” and determining the orientation of a single black ‘T’ on a uniform gray background, or between driving a car through a crowded cityscape while shooting at rival vehicles and counting the number of white squares that are quickly flashed against a black background,” Bavelier and colleagues wrote in support of the transfer effects in a 2008 article in Psychology and Aging.
The literature, however, is no Greek chorus of collective ascent. Some studies have failed to replicate the benefits of gaming, as a recent review article points out, and most experiments in the field have struggled to prove that they’ve lopped off all of the placebo effect’s nefarious tentacles.
The vast majority of these studies focused on first-person-shooter games, which may share only a few characteristics with real-time strategy games. Nonetheless, small hints from the StarCraft 2 community also suggest that players might be developing some generalizable expertise. Most current top players initially participated in the original StarCraft, an obviously related but nonetheless distinct game, or Warcraft, another variation on the real-time-strategy theme. Of course, a selection bias may be muddying the waters: the elite players who are drawn to these types of games may already have stronger-than-average multitasking skills. Even so, the fact that long-time players entered the new game at a substantial advantage suggests that they had honed some sort of Starcraftian skill.
In a paper published this year, cognitive scientist Joshua Lewis and colleagues at the University of California – San Diego analyzed what actions players took in 2000 games to see if certain capabilities stood out as hallmarks of success. Unlike previous studies, which tested participants before and after they played games to see if their behaviors changed, the approach taken by Lewis and colleagues allowed them to look for specific differences in what players are doing and perceiving.
They tracked several measures, including how many actions players took per minute and the distances between the locations where actions occurred across the map. Not surprisingly, they found that players who made the most moves tended to win. Of more interest was the second calculation. Distributing actions more widely across a map, which the authors argue reflects a player’s ability to distribute attention, also correlated highly with winning.
Now the question is whether people can learn to divide their attention more effectively. Professional Starcraft players belong to teams, with coaches and practice schedules, and they devote the majority of their time to developing their abilities. “If there is some methodology for building up multitasking skills, we might be able to figure out a way to train people to better distribute their attention,” Lewis says. “Maybe these teams have learned that implicitly.”
A New Model Organism?
In a traditional experiment on expertise, investigators corral about ten highly ranked professionals into a study and compare them with a similar number of novices. With StarCraft 2, scientists can mine the replay files of players at all stages, from chumps up to champions.
Blair, the Simon Fraser University scientist running the SkillCraft project, asked gamers at all ability levels to submit their replay files. He and his colleagues collected more than 4500 files, of which at least 3500 turned out to usable. “What we’ve got is a satellite view of expertise that no one was able to get before,” he says. “We have hundreds of players at the basic levels, then hundreds more at level slightly better, and so on, in 8 different categories of players.” By comparing the techniques and attributes of low-level players with other gamers up the chain of ability, they can start to discern how skills develop—and perhaps, over the long run, identify the most efficient training regimen.
LosirA, a 19-year-old multitasking phenom, merely thinks for a moment. Credit: Major League Gaming
Both Blair and Lewis see parallels between the game and emergency management systems. In a high-stress crisis situation, the people in charge of coordinating a response may find themselves facing competing demands. Alarms might be alerting them to a fire burning in one part of town, a riot breaking out a few streets over, and the contamination of drinking water elsewhere. The mental task of keeping cool and distributing attention among equally urgent activities might closely resemble the core challenge of Starcraft 2. “For emergencies, you don’t get to train eight hours a day. You get two emergencies in your life but you better be good because lives are at stake,” Blair says. “Training in something like Starcraft could be really useful.”
Indeed. But they know what we really want. Even more useful would be stumbling on the secrets of multitasking hidden in the replay files, then distilling them into helpful hints for the rest of us.
By Sandra Upson
If there is one general rule about the limitations of the human mind, it is that we are terrible at multitasking. The old phrase “united we stand, divided we fall” applies equally well to the mechanisms of attention as it does to a patriotic cause. When devoted to a single task, the brain excels; when several goals splinter its focus, errors become unavoidable.
But clear exceptions challenge that general rule. Two weeks ago, thousands of computer game enthusiasts descended on a convention center in downtown Providence, Rhode Island, to observe some of these exceptions in action. They were attending the championships of one of the world’s hottest computer games, StarCraft 2. Hands fluttered over keyboards like hummingbirds mid-hover at about fifty computers set up in a dimly lit open hall. Players, many of whom flew in from South Korea to compete, vied to advance through their brackets to the finals. This game is no joke, with the prize money to prove it—$50,000 went to the winner, a 16-year-old Korean who goes by the name Leenock. The agility on display in Providence —as seen in the players’ multitasking, their nonstop decision-making, and the stunning speed of their fingers—has not gone unnoticed by cognitive scientists.
For decades, a different game, chess, has held the exalted position of “the drosophila of cognitive science”—the model organism that scientists could poke and prod to learn what makes experts better than the rest of us. StarCraft 2, however, might be emerging as the rhesus macaque: its added complexity may confound researchers initially, but the answers could ultimately be more telling.
This real-time strategy game demands the frenetic pursuit of numerous simultaneous goals, any of which can change in the blink of an eye. Players play a god-like role over a cluster of creatures, leading them to develop their economy and prepare them for skirmishes with a neighboring society. Wildly popular among gamers—StarCraft 2 was the top-selling computer game in 2010, the year it was released—for researchers the appeal lies in the data each game generates. When two players face off, their computers each produce a record of the actions taken during the game. Called replay files, those logs reflect what a gamer was thinking at every stage of play. “I can’t think of a cognitive process that’s not involved in StarCraft,” says Mark Blair, a cognitive scientist at Simon Fraser University. “It’s working memory. It’s decision making. It involves very precise motor skills. Everything is important and everything needs to work together.”
That intellectual rigor and the corresponding data trail, multiplied across hundreds of thousands of players worldwide, makes StarCraft an unparalleled resource that scientists are only now tapping for the study of attention, multitasking, and learning. (As a rough estimate, at the time of writing about 11,000 games are being played on the servers of Blizzard Entertainment, the company that created StarCraft.) Recent experiments on computer games are beginning to suggest that players develop skills that could be useful in other contexts—skills that might allow those individuals to cope better with certain types of information overload. Thousands of these gamers are now contributing to a project under Blair’s watch, called SkillCraft, to learn what separates experts from novices and everyone in between. By all appearances this study of StarCraft players is the world’s biggest experiment on how expertise develops and, ultimately, on how we learn.
Video game research has reached a turning point: psychologists are no longer asking only whether the violence in some games corrupts young minds, or whether games are dangerously addictive, thus corrupting young minds. At least in some cases, gamers are being recognized for the specific forms of learning they cultivate, with the data trail that could finally unravel some of the major mysteries of the human brain.
Why StarCraft
To really appreciate why scientists are turning to StarCraft 2, you need to know a few basics of the game. Two players, connected over the internet, fight for control of a territory of which they have an aerial view. Each player begins with a small base of one of three species—terran (humans), zerg (insectoid creatures), or protoss (photosynthetic aliens). To win, one species’ army must defeat the other, a simple enough goal. But the number of variables that can shift during the game is enormous, demanding constant slight adjustments to strategy. Unlike in a board game, StarCraft players don’t take turns—they simply do as much as they possibly can and hope their opponent is not as fast.
The species’ first task is to start extracting minerals and a fictitious vespene gas, which form the foundation of a StarCraft economy. Each player must balance building up his or her economic production with developing fighters, defenses, and eventually more bases. A player must also try to discern the economic and military strategy of the opponent, whose base is initially hidden from view. As mineral and gas production ramps up, the gamer gains capital to spend on developing more advanced technology, a larger economy, or more fighters. StarCraft 2’s overarching strategic challenge is to decide how much time and money to devote to building up either an economy or an army.
But that’s just one level of play. When you attack, you do not simply dispatch fighters—you manually control them by using your mouse to click on them and set them in motion. A skilled player will monitor the health of individual fighters in the frontlines of a battle and pull them back to the rear as they lose strength, giving them time to recover while fresher troops bear the brunt of the attack. At any given time, you can have several dozen fighters with different abilities pottering around a map, numerous laborers busily mining minerals and gas, and various facilities producing new tools and resources that should be deployed immediately. With so many moving parts, even a top-level player can succumb to paralysis.
A screenshot from a StarCraft 2 game.
Translating those goals into cognitive load, the brain’s executive functions manage most of the game’s demands. Several types of memory may be engaged to keep track of the weapons at one’s disposal and the locations of multiple objects on a map; attentional systems allow a player to plan future moves, switch focus to different activities around the map, and evaluate the enemy’s strategy. Motor skills are needed to rapidly click around the map to move and implement actions.
In short, the game is a relentless exercise in multitasking and constant decision-making. The winner, often, is the person who can make the most moves—an elite player can perform about 5 or 6 actions a second, which translates into a flurry of key presses and mouse maneuvers (see video, above).
Commentators react to events in a game. Credit: Major League Gaming
But you don’t have to be elite to be intriguing from a psychological perspective. According to the Entertainment Software Association, 72 percent of American households play computer or video games. With people engaging with games at all ages, scientists have become increasingly curious about how visually arresting—and in the case of StarCraft and similar games, cognitively demanding—software might be interacting with the brain. “From the perspective of the cognitive motor system, StarCraft is the most interesting thing you could do online,” Blair says.
The Trouble with Brain Training
The question now tantalizing psychologists is whether the rest of us can learn anything from these hyper-specialized multitasking gamers. Perhaps we, too, can accomplish some 300 things each minute—such productivity! Maybe we can learn to pick up new skills faster or use such games to stave off aging.
Given appropriate practice, humans seem to improve on almost any task they tackle. Ask us to sculpt a cake in the shape of Pinocchio, and with sufficient time and motivation we probably will. But multitasking abilities tend to resist practice. Perhaps Starcraft, somehow, possesses the elixir that can morph us into successful multitaskers.
Part of the problem is that once developed, human skills generally stay specific to the original task. Expert chess players, for example, have significantly superior recall of the positions of chess pieces on a board after a brief exposure than non-experts. That is as you might expect: years and years of practice have produced deep familiarity with the arrangements of pawns, rooks, and knights and what strategic opportunities they represent. But chess players turn out to be no better than others when asked to remember the arrangements of chess pieces placed at random, in configurations that could not appear in a game. Experiments in numerous other domains have demonstrated a similar lack of transfer.
In the last decade, however, some experiments have begun to suggest that video games might indeed teach transferable skills. Cognitive scientist Daphne Bavelier at the University of Rochester and her colleagues have used video games to investigate what kinds of learning humans are good at, and along the way they’ve turned up some promising, if modest, examples of brain training. (When scientists search for newly acquired abilities that transfer from one domain to another, they boil them down to skills so basic that you could be forgiven for responding with the raise of a single eyebrow.)
Early results suggest that gamers may have faster visual reaction times, enhanced visuomotor coordination, and heightened ability to visualize spatial arrangements. They may also be better at rotating an object in their minds and may distinguish more deftly between the trajectories of moving objects. Players might also have an edge when paying attention to several objects at once.
Because the tests did not mimic exactly the characteristics of the games participants played, the researchers are optimistic that more general skills were heightened. “There are few obvious links between chasing monsters across a star-spotted “spacescape” and determining the orientation of a single black ‘T’ on a uniform gray background, or between driving a car through a crowded cityscape while shooting at rival vehicles and counting the number of white squares that are quickly flashed against a black background,” Bavelier and colleagues wrote in support of the transfer effects in a 2008 article in Psychology and Aging.
The literature, however, is no Greek chorus of collective ascent. Some studies have failed to replicate the benefits of gaming, as a recent review article points out, and most experiments in the field have struggled to prove that they’ve lopped off all of the placebo effect’s nefarious tentacles.
The vast majority of these studies focused on first-person-shooter games, which may share only a few characteristics with real-time strategy games. Nonetheless, small hints from the StarCraft 2 community also suggest that players might be developing some generalizable expertise. Most current top players initially participated in the original StarCraft, an obviously related but nonetheless distinct game, or Warcraft, another variation on the real-time-strategy theme. Of course, a selection bias may be muddying the waters: the elite players who are drawn to these types of games may already have stronger-than-average multitasking skills. Even so, the fact that long-time players entered the new game at a substantial advantage suggests that they had honed some sort of Starcraftian skill.
In a paper published this year, cognitive scientist Joshua Lewis and colleagues at the University of California – San Diego analyzed what actions players took in 2000 games to see if certain capabilities stood out as hallmarks of success. Unlike previous studies, which tested participants before and after they played games to see if their behaviors changed, the approach taken by Lewis and colleagues allowed them to look for specific differences in what players are doing and perceiving.
They tracked several measures, including how many actions players took per minute and the distances between the locations where actions occurred across the map. Not surprisingly, they found that players who made the most moves tended to win. Of more interest was the second calculation. Distributing actions more widely across a map, which the authors argue reflects a player’s ability to distribute attention, also correlated highly with winning.
Now the question is whether people can learn to divide their attention more effectively. Professional Starcraft players belong to teams, with coaches and practice schedules, and they devote the majority of their time to developing their abilities. “If there is some methodology for building up multitasking skills, we might be able to figure out a way to train people to better distribute their attention,” Lewis says. “Maybe these teams have learned that implicitly.”
A New Model Organism?
In a traditional experiment on expertise, investigators corral about ten highly ranked professionals into a study and compare them with a similar number of novices. With StarCraft 2, scientists can mine the replay files of players at all stages, from chumps up to champions.
Blair, the Simon Fraser University scientist running the SkillCraft project, asked gamers at all ability levels to submit their replay files. He and his colleagues collected more than 4500 files, of which at least 3500 turned out to usable. “What we’ve got is a satellite view of expertise that no one was able to get before,” he says. “We have hundreds of players at the basic levels, then hundreds more at level slightly better, and so on, in 8 different categories of players.” By comparing the techniques and attributes of low-level players with other gamers up the chain of ability, they can start to discern how skills develop—and perhaps, over the long run, identify the most efficient training regimen.
LosirA, a 19-year-old multitasking phenom, merely thinks for a moment. Credit: Major League Gaming
Both Blair and Lewis see parallels between the game and emergency management systems. In a high-stress crisis situation, the people in charge of coordinating a response may find themselves facing competing demands. Alarms might be alerting them to a fire burning in one part of town, a riot breaking out a few streets over, and the contamination of drinking water elsewhere. The mental task of keeping cool and distributing attention among equally urgent activities might closely resemble the core challenge of Starcraft 2. “For emergencies, you don’t get to train eight hours a day. You get two emergencies in your life but you better be good because lives are at stake,” Blair says. “Training in something like Starcraft could be really useful.”
Indeed. But they know what we really want. Even more useful would be stumbling on the secrets of multitasking hidden in the replay files, then distilling them into helpful hints for the rest of us.
Friday, December 2, 2011
Gene therapy can protect against HIV
http://www.nature.com/news/gene-therapy-can-protect-against-hiv-1.9516
An introduced gene conveys long-lived resistance to HIV infection in mice.
by Lauren Gravitz
Gene therapy, an approach most commonly explored for curing chronic genetic diseases such as cystic fibrosis, may also prove practical for disease prevention. In research published today in Nature1, scientists in California show that a single injection — which inserted the DNA for an HIV-neutralizing antibody into the muscle cells of live mice — completely protected the animals against HIV transmission.
The road to a vaccine against HIV has proved to be far longer than originally anticipated. More than 2 million adults are newly infected with HIV every year and, nearly three decades after the virus was first identified, researchers haven’t found a reliable way to prevent infection. The classic vaccine approach, which uses all or part of an inactivated virus to induce immunity, has yielded little success because HIV has managed to disguise most of the easily-recognised external structures that antibodies would target. Researchers have thus had a tough time finding a molecule that can induce even moderately broad responses against the virus in all its different mutations. So although it might sound extreme to use gene therapy as a preventative treatment for HIV/AIDS, the method could provide a much-needed alternative.
Researchers hope to prevent the spread of HIV (virus particle pictured) by using gene therapy to get cells to produce antibodies.
MEDICAL RF.COM/SPL
David Baltimore, a virologist and HIV researcher at the California Institute of Technology in Pasadena, and his colleagues used a genetically altered adenovirus to infect muscle cells and deliver DNA that codes for antibodies isolated from the blood of people infected with HIV. The DNA is incorporated into the muscle cells’ genome and programs the cells to manufacture the antibody, which is then secreted into the bloodstream. The tactic builds on earlier work by scientists at the Children’s Hospital of Philadelphia in Pennsylvania, who in 2009 first described the effectiveness of this technique in preventing transmission of simian immunodeficiency virus, which is similar to HIV but infects monkeys2.
As for the rationale for using gene therapy for HIV: “This is something way out of the ordinary, and it’s perfectly reasonable to say that there’s no reason to do it if there’s an alternative," says Baltimore. "But if there’s no alternative — and that’s where we’re at today — then we should be thinking of new ways to protect people.”
Dennis Burton, an immunologist at the Scripps Research Institute in La Jolla, California, who has developed a number of antibodies against HIV, agrees. “Obviously, the best thing of all is a vaccine. That’s a tried-and-tested method that carries very few risks. But if that doesn’t work, what’s our fall-back position?” he asks. “We have these antibodies, and we have them available now. If this works in humans, and that’s a reasonable supposition, you’d have something you can do now.”
Prolonged protection
Baltimore and his colleagues tested five different broadly neutralizing antibodies, one at a time, in mice with humanized immune systems. Two of the antibodies, called b12 and VRC01, proved completely protective — even when the mice received doses of HIV that were 100 times higher than a natural infection. After 52 weeks, the levels of antibody expression remained high, suggesting that a single dose would result in long-lasting protection. “We showed that you can express protective levels of antibodies in a mammal and have that expression last for a long period of time,” Baltimore says. “It sets the stage for human trials.”
Providing patients with periodic doses of these antibodies throughout their lifetime would be safer than coaxing antibody production from muscle cells, but it would be far from cost-effective. The gene-therapy approach, by contrast, recruits muscle cells to act as antibody factories and could be administered using a single intramuscular shot.
Experts in the field are cautiously optimistic. “Mice and monkeys don’t always tell the truth. It’s a really interesting idea, and it should be assessed in clinical trials,” says Wayne Koff, senior vice-president for research and development at the International AIDS Vaccine Initiative in New York. “Until someone shows that we can make these broadly neutralizing antibodies with a [classic] vaccine, I think this is an important concept that should be supported.”
But both Burton and Koff caution that gene therapy comes with its own set of problems. Because the antibody DNA is permanently inserted into the genome, there’s no way to turn it off if someone has an immune reaction against the antibodies. But it won't be known whether such side effects exist until the method is tested in people, something that Baltimore aims to do in the next few years. The researchers at the Children’s Hospital of Philadelphia, meanwhile, hope to get the first round of human trials of their technique started before the end of 2012.
An introduced gene conveys long-lived resistance to HIV infection in mice.
by Lauren Gravitz
Gene therapy, an approach most commonly explored for curing chronic genetic diseases such as cystic fibrosis, may also prove practical for disease prevention. In research published today in Nature1, scientists in California show that a single injection — which inserted the DNA for an HIV-neutralizing antibody into the muscle cells of live mice — completely protected the animals against HIV transmission.
The road to a vaccine against HIV has proved to be far longer than originally anticipated. More than 2 million adults are newly infected with HIV every year and, nearly three decades after the virus was first identified, researchers haven’t found a reliable way to prevent infection. The classic vaccine approach, which uses all or part of an inactivated virus to induce immunity, has yielded little success because HIV has managed to disguise most of the easily-recognised external structures that antibodies would target. Researchers have thus had a tough time finding a molecule that can induce even moderately broad responses against the virus in all its different mutations. So although it might sound extreme to use gene therapy as a preventative treatment for HIV/AIDS, the method could provide a much-needed alternative.
Researchers hope to prevent the spread of HIV (virus particle pictured) by using gene therapy to get cells to produce antibodies.
MEDICAL RF.COM/SPL
David Baltimore, a virologist and HIV researcher at the California Institute of Technology in Pasadena, and his colleagues used a genetically altered adenovirus to infect muscle cells and deliver DNA that codes for antibodies isolated from the blood of people infected with HIV. The DNA is incorporated into the muscle cells’ genome and programs the cells to manufacture the antibody, which is then secreted into the bloodstream. The tactic builds on earlier work by scientists at the Children’s Hospital of Philadelphia in Pennsylvania, who in 2009 first described the effectiveness of this technique in preventing transmission of simian immunodeficiency virus, which is similar to HIV but infects monkeys2.
As for the rationale for using gene therapy for HIV: “This is something way out of the ordinary, and it’s perfectly reasonable to say that there’s no reason to do it if there’s an alternative," says Baltimore. "But if there’s no alternative — and that’s where we’re at today — then we should be thinking of new ways to protect people.”
Dennis Burton, an immunologist at the Scripps Research Institute in La Jolla, California, who has developed a number of antibodies against HIV, agrees. “Obviously, the best thing of all is a vaccine. That’s a tried-and-tested method that carries very few risks. But if that doesn’t work, what’s our fall-back position?” he asks. “We have these antibodies, and we have them available now. If this works in humans, and that’s a reasonable supposition, you’d have something you can do now.”
Prolonged protection
Baltimore and his colleagues tested five different broadly neutralizing antibodies, one at a time, in mice with humanized immune systems. Two of the antibodies, called b12 and VRC01, proved completely protective — even when the mice received doses of HIV that were 100 times higher than a natural infection. After 52 weeks, the levels of antibody expression remained high, suggesting that a single dose would result in long-lasting protection. “We showed that you can express protective levels of antibodies in a mammal and have that expression last for a long period of time,” Baltimore says. “It sets the stage for human trials.”
Providing patients with periodic doses of these antibodies throughout their lifetime would be safer than coaxing antibody production from muscle cells, but it would be far from cost-effective. The gene-therapy approach, by contrast, recruits muscle cells to act as antibody factories and could be administered using a single intramuscular shot.
Experts in the field are cautiously optimistic. “Mice and monkeys don’t always tell the truth. It’s a really interesting idea, and it should be assessed in clinical trials,” says Wayne Koff, senior vice-president for research and development at the International AIDS Vaccine Initiative in New York. “Until someone shows that we can make these broadly neutralizing antibodies with a [classic] vaccine, I think this is an important concept that should be supported.”
But both Burton and Koff caution that gene therapy comes with its own set of problems. Because the antibody DNA is permanently inserted into the genome, there’s no way to turn it off if someone has an immune reaction against the antibodies. But it won't be known whether such side effects exist until the method is tested in people, something that Baltimore aims to do in the next few years. The researchers at the Children’s Hospital of Philadelphia, meanwhile, hope to get the first round of human trials of their technique started before the end of 2012.
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