by John H. Richardson

In an ordinary hospital room in Los Angeles, a young woman named Lauren Dickerson waits for her chance to make history.

She’s 25 years old, a teacher’s assistant in a middle school, with warm eyes and computer cables emerging like futuristic dreadlocks from the bandages wrapped around her head. Three days earlier, a neurosurgeon drilled 11 holes through her skull, slid 11 wires the size of spaghetti into her brain, and connected the wires to a bank of computers. Now she’s caged in by bed rails, with plastic tubes snaking up her arm and medical monitors tracking her vital signs. She tries not to move.

The room is packed. As a film crew prepares to document the day’s events, two separate teams of specialists get ready to work—medical experts from an elite neuroscience center at the University of Southern California and scientists from a technology company called Kernel. The medical team is looking for a way to treat Dickerson’s seizures, which an elaborate regimen of epilepsy drugs controlled well enough until last year, when their effects began to dull. They’re going to use the wires to search Dickerson’s brain for the source of her seizures. The scientists from Kernel are there for a different reason: They work for Bryan Johnson, a 40-year-old tech entrepreneur who sold his business for $800 million and decided to pursue an insanely ambitious dream—he wants to take control of evolution and create a better human. He intends to do this by building a “neuroprosthesis,” a device that will allow us to learn faster, remember more, “coevolve” with artificial intelligence, unlock the secrets of telepathy, and maybe even connect into group minds. He’d also like to find a way to download skills such as martial arts, Matrix-style. And he wants to sell this invention at mass-market prices so it’s not an elite product for the rich.

Right now all he has is an algorithm on a hard drive. When he describes the neuroprosthesis to reporters and conference audiences, he often uses the media-friendly expression “a chip in the brain,” but he knows he’ll never sell a mass-market product that depends on drilling holes in people’s skulls. Instead, the algorithm will eventually connect to the brain through some variation of noninvasive interfaces being developed by scientists around the world, from tiny sensors that could be injected into the brain to genetically engineered neurons that can exchange data wirelessly with a hatlike receiver. All of these proposed interfaces are either pipe dreams or years in the future, so in the meantime he’s using the wires attached to Dickerson’s hippo­campus to focus on an even bigger challenge: what you say to the brain once you’re connected to it.

That’s what the algorithm does. The wires embedded in Dickerson’s head will record the electrical signals that Dickerson’s neurons send to one another during a series of simple memory tests. The signals will then be uploaded onto a hard drive, where the algorithm will translate them into a digital code that can be analyzed and enhanced—or rewritten—with the goal of improving her memory. The algorithm will then translate the code back into electrical signals to be sent up into the brain. If it helps her spark a few images from the memories she was having when the data was gathered, the researchers will know the algorithm is working. Then they’ll try to do the same thing with memories that take place over a period of time, something nobody’s ever done before. If those two tests work, they’ll be on their way to deciphering the patterns and processes that create memories.

Although other scientists are using similar techniques on simpler problems, Johnson is the only person trying to make a commercial neurological product that would enhance memory. In a few minutes, he’s going to conduct his first human test. For a commercial memory prosthesis, it will be the first human test. “It’s a historic day,” Johnson says. “I’m insanely excited about it.”

For the record, just in case this improbable experiment actually works, the date is January 30, 2017.

At this point, you may be wondering if Johnson’s just another fool with too much money and an impossible dream. I wondered the same thing the first time I met him. He seemed like any other California dude, dressed in the usual jeans, sneakers, and T-shirt, full of the usual boyish enthusiasms. His wild pronouncements about “reprogramming the operating system of the world” seemed downright goofy.

But you soon realize this casual style is either camouflage or wishful thinking. Like many successful people, some brilliant and some barely in touch with reality, Johnson has endless energy and the distributed intelligence of an octopus—one tentacle reaches for the phone, another for his laptop, a third scouts for the best escape route. When he starts talking about his neuroprosthesis, they team up and squeeze till you turn blue.

And there is that $800 million that PayPal shelled out for Braintree, the online-­payment company Johnson started when he was 29 and sold when he was 36. And the $100 million he is investing into Kernel, the company he started to pursue this project. And the decades of animal tests to back up his sci-fi ambitions: Researchers have learned how to restore memories lost to brain damage, plant false memories, control the motions of animals through human thought, control appetite and aggression, induce sensations of pleasure and pain, even how to beam brain signals from one animal to another animal thousands of miles away.

And Johnson isn’t dreaming this dream alone—at this moment, Elon Musk and Mark Zuckerberg are weeks from announcing their own brain-hacking projects, the military research group known as Darpa already has 10 under way, and there’s no doubt that China and other countries are pursuing their own. But unlike Johnson, they’re not inviting reporters into any hospital rooms.

Here’s the gist of every public statement Musk has made about his project: (1) He wants to connect our brains to computers with a mysterious device called “neural lace.” (2) The name of the company he started to build it is Neuralink.

Thanks to a presentation at last spring’s F8 conference, we know a little more about what Zuckerberg is doing at Facebook: (1) The project was until recently overseen by Regina Dugan, a former director of Darpa and Google’s Advanced Technology group. (2) The team is working out of Building 8, Zuckerberg’s research lab for moon-shot projects. (3) They’re working on a noninvasive “brain–computer speech-to-text interface” that uses “optical imaging” to read the signals of neurons as they form words, find a way to translate those signals into code, and then send the code to a computer. (4) If it works, we’ll be able to “type” 100 words a minute just by thinking.

As for Darpa, we know that some of its projects are improvements on existing technology and some—such as an interface to make soldiers learn faster—sound just as futuristic as Johnson’s. But we don’t know much more than that. That leaves Johnson as our only guide, a job he says he’s taken on because he thinks the world needs to be prepared for what is coming.

All of these ambitious plans face the same obstacle, however: The brain has 86 billion neurons, and nobody understands how they all work. Scientists have made impressive progress uncovering, and even manipulating, the neural circuitry behind simple brain functions, but things such as imagination or creativity—and memory—are so complex that all the neuroscientists in the world may never solve them. That’s why a request for expert opinions on the viability of Johnson’s plans got this response from John Donoghue, the director of the Wyss Center for Bio and Neuroengineering in Geneva: “I’m cautious,” he said. “It’s as if I asked you to translate something from Swahili to Finnish. You’d be trying to go from one unknown language into another unknown language.” To make the challenge even more daunting, he added, all the tools used in brain research are as primitive as “a string between two paper cups.” So Johnson has no idea if 100 neurons or 100,000 or 10 billion control complex brain functions. On how most neurons work and what kind of codes they use to communicate, he’s closer to “Da-da” than “see Spot run.” And years or decades will pass before those mysteries are solved, if ever. To top it all off, he has no scientific background. Which puts his foot on the banana peel of a very old neuroscience joke: “If the brain was simple enough for us to understand, we’d be too stupid to understand it.”

I don’t need telepathy to know what you’re thinking now—there’s nothing more annoying than the big dreams of tech optimists. Their schemes for eternal life and floating libertarian nations are adolescent fantasies; their digital revolution seems to be destroying more jobs than it created, and the fruits of their scientific fathers aren’t exactly encouraging either. “Coming soon, from the people who brought you nuclear weapons!”

But Johnson’s motives go to a deep and surprisingly tender place. Born into a devout Mormon community in Utah, he learned an elaborate set of rules that are still so vivid in his mind that he brought them up in the first minutes of our first meeting: “If you get baptized at the age of 8, point. If you get into the priesthood at the age of 12, point. If you avoid pornography, point. Avoid masturbation? Point. Go to church every Sunday? Point.” The reward for a high point score was heaven, where a dutiful Mormon would be reunited with his loved ones and gifted with endless creativity.

When he was 4, Johnson’s father left the church and divorced his mother. Johnson skips over the painful details, but his father told me his loss of faith led to a long stretch of drug and alcohol abuse, and his mother said she was so broke that she had to send Johnson to school in handmade clothes. His father remembers the letters Johnson started sending him when he was 11, a new one every week: “Always saying 100 different ways, ‘I love you, I need you.’ How he knew as a kid the one thing you don’t do with an addict or an alcoholic is tell them what a dirtbag they are, I’ll never know.”

Johnson was still a dutiful believer when he graduated from high school and went to Ecuador on his mission, the traditional Mormon rite of passage. He prayed constantly and gave hundreds of speeches about Joseph Smith, but he became more and more ashamed about trying to convert sick and hungry children with promises of a better life in heaven. Wouldn’t it be better to ease their suffering here on earth?

“Bryan came back a changed boy,” his father says.

Soon he had a new mission, self-assigned. His sister remembers his exact words: “He said he wanted to be a millionaire by the time he was 30 so he could use those resources to change the world.”

His first move was picking up a degree at Brigham Young University, selling cell phones to help pay the tuition and inhaling every book that seemed to promise a way forward. One that left a lasting impression was Endurance, the story of Ernest Shackleton’s botched journey to the South Pole—if sheer grit could get a man past so many hardships, he would put his faith in sheer grit. He married “a nice Mormon girl,” fathered three Mormon children, and took a job as a door-to-door salesman to support them. He won a prize for Salesman of the Year and started a series of businesses that went broke—which convinced him to get a business degree at the University of Chicago.

When he graduated in 2008, he stayed in Chicago and started Braintree, perfecting his image as a world-beating Mormon entrepreneur. By that time, his father was sober and openly sharing his struggles, and Johnson was the one hiding his dying faith behind a very well-protected wall. He couldn’t sleep, ate like a wolf, and suffered intense headaches, fighting back with a long series of futile cures: antidepressants, biofeedback, an energy healer, even blind obedience to the rules of his church.

In 2012, at the age of 35, Johnson hit bottom. In his misery, he remembered Shackleton and seized a final hope—maybe he could find an answer by putting himself through a painful ordeal. He planned a trip to Mount Kilimanjaro, and on the second day of the climb he got a stomach virus. On the third day he got altitude sickness. When he finally made it to the peak, he collapsed in tears and then had to be carried down on a stretcher. It was time to reprogram his operating system.

The way Johnson tells it, he started by dropping the world-beater pose that hid his weakness and doubt. And although this may all sound a bit like a dramatic motivational talk at a TED conference, especially since Johnson still projects the image of a world-beating entrepreneur, this much is certain: During the following 18 months, he divorced his wife, sold Braintree, and severed his last ties to the church. To cushion the impact on his children, he bought a house nearby and visited them almost daily. He knew he was repeating his father’s mistakes but saw no other option—he was either going to die inside or start living the life he always wanted.

He started with the pledge he made when he came back from Ecuador, experimenting first with a good-government initiative in Washington and pivoting, after its inevitable doom, to a venture fund for “quantum leap” companies inventing futuristic products such as human-­organ-­mimicking silicon chips. But even if all his quantum leaps landed, they wouldn’t change the operating system of the world.

Finally, the Big Idea hit: If the root problems of humanity begin in the human mind, let’s change our minds.

Fantastic things were happening in neuroscience. Some of them sounded just like miracles from the Bible—with prosthetic legs controlled by thought and microchips connected to the visual cortex, scientists were learning to help the lame walk and the blind see. At the University of Toronto, a neurosurgeon named Andres Lozano slowed, and in some cases reversed, the cognitive declines of Alzheimer’s patients using deep brain stimulation. At a hospital in upstate New York, a neuro­technologist named Gerwin Schalk asked computer engineers to record the firing patterns of the auditory neurons of people listening to Pink Floyd. When the engineers turned those patterns back into sound waves, they produced a single that sounded almost exactly like “Another Brick in the Wall.” At the University of Washington, two professors in different buildings played a videogame together with the help of electroencephalography caps that fired off electrical pulses—when one professor thought about firing digital bullets, the other one felt an impulse to push the Fire button.

Johnson also heard about a biomedical engineer named Theodore Berger. During nearly 20 years of research, Berger and his collaborators at USC and Wake Forest University developed a neuroprosthesis to improve memory in rats. It didn’t look like much when he started testing it in 2002—just a slice of rat brain and a computer chip. But the chip held an algorithm that could translate the firing patterns of neurons into a kind of Morse code that corresponded with actual memories. Nobody had ever done that before, and some people found the very idea offensive—it’s so deflating to think of our most precious thoughts reduced to ones and zeros. Prominent medical ethicists accused Berger of tampering with the essence of identity. But the implications were huge: If Berger could turn the language of the brain into code, perhaps he could figure out how to fix the part of the code associated with neurological diseases.

In rats, as in humans, firing patterns in the hippocampus generate a signal or code that, somehow, the brain recognizes as a long-term memory. Berger trained a group of rats to perform a task and studied the codes that formed. He learned that rats remembered a task better when their neurons sent “strong code,” a term he explains by comparing it to a radio signal: At low volume you don’t hear all of the words, but at high volume everything comes through clear. He then studied the difference in the codes generated by the rats when they remembered to do something correctly and when they forgot. In 2011, through a breakthrough experiment conducted on rats trained to push a lever, he demonstrated he could record the initial memory codes, feed them into an algorithm, and then send stronger codes back into the rats’ brains. When he finished, the rats that had forgotten how to push the lever suddenly remembered.

Five years later, Berger was still looking for the support he needed for human trials. That’s when Johnson showed up. In August 2016, he announced he would pledge $100 million of his fortune to create Kernel and that Berger would join the company as chief science officer. After learning about USC’s plans to implant wires in Dickerson’s brain to battle her epilepsy, Johnson approached Charles Liu, the head of the prestigious neurorestoration division at the USC School of Medicine and the lead doctor on Dickerson’s trial. Johnson asked him for permission to test the algorithm on Dickerson while she had Liu’s wires in her hippocampus—in between Liu’s own work sessions, of course. As it happened, Liu had dreamed about expanding human powers with technology ever since he got obsessed with The Six Million Dollar Man as a kid. He helped Johnson get Dickerson’s consent and convinced USC’s institutional research board to approve the experiment. At the end of 2016, Johnson got the green light. He was ready to start his first human trial.

In the hospital room, Dickerson is waiting for the experiments to begin, and I ask her how she feels about being a human lab rat.

“If I’m going to be here,” she says, “I might as well do something useful.”

Useful? This starry-eyed dream of cyborg supermen? “You know he’s trying to make humans smarter, right?”

“Isn’t that cool?” she answers.

Over by the computers, I ask one of the scientists about the multi­colored grid on the screen. “Each one of these squares is an electrode that’s in her brain,” one says. Every time a neuron close to one of the wires in Dickerson’s brain fires, he explains, a pink line will jump in the relevant box.

Johnson’s team is going to start with simple memory tests. “You’re going to be shown words,” the scientist explains to her. “Then there will be some math problems to make sure you’re not rehearsing the words in your mind. Try to remember as many words as you can.”

One of the scientists hands Dickerson a computer tablet, and everyone goes quiet. Dickerson stares at the screen to take in the words. A few minutes later, after the math problem scrambles her mind, she tries to remember what she’d read. “Smoke … egg … mud … pearl.”

Next, they try something much harder, a group of memories in a sequence. As one of Kernel’s scientists explains to me, they can only gather so much data from wires connected to 30 or 40 neurons. A single face shouldn’t be too hard, but getting enough data to reproduce memories that stretch out like a scene in a movie is probably impossible.

Sitting by the side of Dickerson’s bed, a Kernel scientist takes on the challenge. “Could you tell me the last time you went to a restaurant?”

“It was probably five or six days ago,” Dickerson says. “I went to a Mexican restaurant in Mission Hills. We had a bunch of chips and salsa.”

He presses for more. As she dredges up other memories, another Kernel scientist hands me a pair of headphones connected to the computer bank. All I hear at first is a hissing sound. After 20 or 30 seconds go by I hear a pop.

“That’s a neuron firing,” he says.

As Dickerson continues, I listen to the mysterious language of the brain, the little pops that move our legs and trigger our dreams. She remembers a trip to Costco and the last time it rained, and I hear the sounds of Costco and rain.

When Dickerson’s eyelids start sinking, the medical team says she’s had enough and Johnson’s people start packing up. Over the next few days, their algorithm will turn Dickerson’s synaptic activity into code. If the codes they send back into Dickerson’s brain make her think of dipping a few chips in salsa, Johnson might be one step closer to reprogramming the operating system of the world.

But look, there’s another banana peel­—after two days of frantic coding, Johnson’s team returns to the hospital to send the new code into Dickerson’s brain. Just when he gets word that they can get an early start, a message arrives: It’s over. The experiment has been placed on “administrative hold.” The only reason USC would give in the aftermath was an issue between Johnson and Berger. Berger would later tell me he had no idea the experiment was under way and that Johnson rushed into it without his permission. Johnson said he is mystified by Berger’s accusations. “I don’t know how he could not have known about it. We were working with his whole lab, with his whole team.” The one thing they both agree on is that their relationship fell apart shortly afterward, with Berger leaving the company and taking his algorithm with him. He blames the break entirely on Johnson. “Like most investors, he wanted a high rate of return as soon as possible. He didn’t realize he’d have to wait seven or eight years to get FDA approval—I would have thought he would have looked that up.” But Johnson didn’t want to slow down. He had bigger plans, and he was in a hurry.

Eight months later, I go back to California to see where Johnson has ended up. He seems a little more relaxed. On the whiteboard behind his desk at Kernel’s new offices in Los Angeles, someone’s scrawled a playlist of songs in big letters. “That was my son,” he says. “He interned here this summer.” Johnson is a year into a romance with Taryn Southern, a charismatic 31-year-old performer and film producer. And since his break with Berger, Johnson has tripled Kernel’s staff—he’s up to 36 employees now—adding experts in fields like chip design and computational neuroscience. His new science adviser is Ed Boyden, the director of MIT’s Synthetic Neurobiology Group and a superstar in the neuroscience world. Down in the basement of the new office building, there’s a Dr. Frankenstein lab where scientists build prototypes and try them out on glass heads.

When the moment seems right, I bring up the purpose of my visit. “You said you had something to show me?”

Johnson hesitates. I’ve already promised not to reveal certain sensitive details, but now I have to promise again. Then he hands me two small plastic display cases. Inside, two pairs of delicate twisty wires rest on beds of foam rubber. They look scientific but also weirdly biological, like the antennae of some futuristic bug-bot.

I’m looking at the prototypes for Johnson’s brand-new neuromodulator. On one level, it’s just a much smaller version of the deep brain stimulators and other neuromodulators currently on the market. But unlike a typical stimulator, which just fires pulses of electricity, Johnson’s is designed to read the signals that neurons send to other neurons—and not just the 100 neurons the best of the current tools can harvest, but perhaps many more. That would be a huge advance in itself, but the implications are even bigger: With Johnson’s neuromodulator, scientists could collect brain data from thousands of patients, with the goal of writing precise codes to treat a variety of neurological diseases.

In the short term, Johnson hopes his neuromodulator will help him “optimize the gold rush” in neurotechnology—financial analysts are forecasting a $27 billion market for neural devices within six years, and countries around the world are committing billions to the escalating race to decode the brain. In the long term, Johnson believes his signal-reading neuromodulator will advance his bigger plans in two ways: (1) by giving neuroscientists a vast new trove of data they can use to decode the workings of the brain and (2) by generating the huge profits Kernel needs to launch a steady stream of innovative and profitable neural tools, keeping the company both solvent and plugged into every new neuroscience breakthrough. With those two achievements in place, Johnson can watch and wait until neuroscience reaches the level of sophistication he needs to jump-start human evolution with a mind-enhancing neuroprosthesis.

Liu, the neurologist with the Six Million Dollar Man dreams, compares Johnson’s ambition to flying. “Going back to Icarus, human beings have always wanted to fly. We don’t grow wings, so we build a plane. And very often these solutions will have even greater capabilities than the ones nature created—no bird ever flew to Mars.” But now that humanity is learning how to reengineer its own capabilities, we really can choose how we evolve. “We have to wrap our minds around that. It’s the most revolutionary thing in the world.”

The crucial ingredient is the profit motive, which always drives rapid innovation in science. That’s why Liu thinks Johnson could be the one to give us wings. “I’ve never met anyone with his urgency to take this to market,” he says.

When will this revolution arrive? “Sooner than you think,” Liu says.

Now we’re back where we began. Is Johnson a fool? Is he just wasting his time and fortune on a crazy dream? One thing is certain: Johnson will never stop trying to optimize the world. At the pristine modern house he rents in Venice Beach, he pours out idea after idea. He even took skepticism as helpful information—when I tell him his magic neuroprosthesis sounds like another version of the Mormon heaven, he’s delighted.

“Good point! I love it!”

He never has enough data. He even tries to suck up mine. What are my goals? My regrets? My pleasures? My doubts?

Every so often, he pauses to examine my “constraint program.”

“One, you have this biological disposition of curiosity. You want data. And when you consume that data, you apply boundaries of meaning-making.”

“Are you trying to hack me?” I ask.

Not at all, he says. He just wants us to share our algorithms. “That’s the fun in life,” he says, “this endless unraveling of the puzzle. And I think, ‘What if we could make the data transfer rate a thousand times faster? What if my consciousness is only seeing a fraction of reality? What kind of stories would we tell?’ ”

In his free time, Johnson is writing a book about taking control of human evolution and looking on the bright side of our mutant humanoid future. He brings this up every time I talk to him. For a long time I lumped this in with his dreamy ideas about reprogramming the operating system of the world: The future is coming faster than anyone thinks, our glorious digital future is calling, the singularity is so damn near that we should be cheering already—a spiel that always makes me want to hit him with a copy of the Unabomber Manifesto.

But his urgency today sounds different, so I press him on it: “How would you respond to Ted Kaczynski’s fears? The argument that technology is a cancerlike development that’s going to eat itself?”

“I would say he’s potentially on the wrong side of history.”

“Yeah? What about climate change?”

“That’s why I feel so driven,” he answered. “We’re in a race against time.”

He asks me for my opinion. I tell him I think he’ll still be working on cyborg brainiacs when the starving hordes of a ravaged planet destroy his lab looking for food—and for the first time, he reveals the distress behind his hope. The truth is, he has the same fear. The world has gotten way too complex, he says. The financial system is shaky, the population is aging, robots want our jobs, artificial intelligence is catching up, and climate change is coming fast. “It just feels out of control,” he says.

He’s invoked these dystopian ideas before, but only as a prelude to his sales pitch. This time he’s closer to pleading. “Why wouldn’t we embrace our own self-directed evolution? Why wouldn’t we just do everything we can to adapt faster?”

I turn to a more cheerful topic. If he ever does make a neuroprosthesis to revolutionize how we use our brain, which superpower would he give us first? Telepathy? Group minds? Instant kung fu?

He answers without hesitation. Because our thinking is so constrained by the familiar, he says, we can’t imagine a new world that isn’t just another version of the world we know. But we have to imagine something far better than that. So he’d try to make us more creative—that would put a new frame on everything.

Ambition like that can take you a long way. It can drive you to try to reach the South Pole when everyone says it’s impossible. It can take you up Mount Kilimanjaro when you’re close to dying and help you build an $800 million company by the time you’re 36. And Johnson’s ambitions drive straight for the heart of humanity’s most ancient dream: For operating system, substitute enlightenment.

By hacking our brains, he wants to make us one with everything.

https://www.wired.com/story/inside-the-race-to-build-a-brain-machine-interface/?mbid=nl_111717_editorsnote_list1_p1

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In June 14, 2014, the State Council of China published an ominous-sounding document called “Planning Outline for the Construction of a Social Credit System”. In the way of Chinese policy documents, it was a lengthy and rather dry affair, but it contained a radical idea. What if there was a national trust score that rated the kind of citizen you were?

Imagine a world where many of your daily activities were constantly monitored and evaluated: what you buy at the shops and online; where you are at any given time; who your friends are and how you interact with them; how many hours you spend watching content or playing video games; and what bills and taxes you pay (or not). It’s not hard to picture, because most of that already happens, thanks to all those data-collecting behemoths like Google, Facebook and Instagram or health-tracking apps such as Fitbit. But now imagine a system where all these behaviours are rated as either positive or negative and distilled into a single number, according to rules set by the government. That would create your Citizen Score and it would tell everyone whether or not you were trustworthy. Plus, your rating would be publicly ranked against that of the entire population and used to determine your eligibility for a mortgage or a job, where your children can go to school – or even just your chances of getting a date.

A futuristic vision of Big Brother out of control? No, it’s already getting underway in China, where the government is developing the Social Credit System (SCS) to rate the trustworthiness of its 1.3 billion citizens. The Chinese government is pitching the system as a desirable way to measure and enhance “trust” nationwide and to build a culture of “sincerity”. As the policy states, “It will forge a public opinion environment where keeping trust is glorious. It will strengthen sincerity in government affairs, commercial sincerity, social sincerity and the construction of judicial credibility.”

Others are less sanguine about its wider purpose. “It is very ambitious in both depth and scope, including scrutinising individual behaviour and what books people are reading. It’s Amazon’s consumer tracking with an Orwellian political twist,” is how Johan Lagerkvist, a Chinese internet specialist at the Swedish Institute of International Affairs, described the social credit system. Rogier Creemers, a post-doctoral scholar specialising in Chinese law and governance at the Van Vollenhoven Institute at Leiden University, who published a comprehensive translation of the plan, compared it to “Yelp reviews with the nanny state watching over your shoulder”.

For now, technically, participating in China’s Citizen Scores is voluntary. But by 2020 it will be mandatory. The behaviour of every single citizen and legal person (which includes every company or other entity)in China will be rated and ranked, whether they like it or not.

Prior to its national roll-out in 2020, the Chinese government is taking a watch-and-learn approach. In this marriage between communist oversight and capitalist can-do, the government has given a licence to eight private companies to come up with systems and algorithms for social credit scores. Predictably, data giants currently run two of the best-known projects.

The first is with China Rapid Finance, a partner of the social-network behemoth Tencent and developer of the messaging app WeChat with more than 850 million active users. The other, Sesame Credit, is run by the Ant Financial Services Group (AFSG), an affiliate company of Alibaba. Ant Financial sells insurance products and provides loans to small- to medium-sized businesses. However, the real star of Ant is AliPay, its payments arm that people use not only to buy things online, but also for restaurants, taxis, school fees, cinema tickets and even to transfer money to each other.

Sesame Credit has also teamed up with other data-generating platforms, such as Didi Chuxing, the ride-hailing company that was Uber’s main competitor in China before it acquired the American company’s Chinese operations in 2016, and Baihe, the country’s largest online matchmaking service. It’s not hard to see how that all adds up to gargantuan amounts of big data that Sesame Credit can tap into to assess how people behave and rate them accordingly.

So just how are people rated? Individuals on Sesame Credit are measured by a score ranging between 350 and 950 points. Alibaba does not divulge the “complex algorithm” it uses to calculate the number but they do reveal the five factors taken into account. The first is credit history. For example, does the citizen pay their electricity or phone bill on time? Next is fulfilment capacity, which it defines in its guidelines as “a user’s ability to fulfil his/her contract obligations”. The third factor is personal characteristics, verifying personal information such as someone’s mobile phone number and address. But the fourth category, behaviour and preference, is where it gets interesting.

Under this system, something as innocuous as a person’s shopping habits become a measure of character. Alibaba admits it judges people by the types of products they buy. “Someone who plays video games for ten hours a day, for example, would be considered an idle person,” says Li Yingyun, Sesame’s Technology Director. “Someone who frequently buys diapers would be considered as probably a parent, who on balance is more likely to have a sense of responsibility.” So the system not only investigates behaviour – it shapes it. It “nudges” citizens away from purchases and behaviours the government does not like.

Friends matter, too. The fifth category is interpersonal relationships. What does their choice of online friends and their interactions say about the person being assessed? Sharing what Sesame Credit refers to as “positive energy” online, nice messages about the government or how well the country’s economy is doing, will make your score go up.

Alibaba is adamant that, currently, anything negative posted on social media does not affect scores (we don’t know if this is true or not because the algorithm is secret). But you can see how this might play out when the government’s own citizen score system officially launches in 2020. Even though there is no suggestion yet that any of the eight private companies involved in the ongoing pilot scheme will be ultimately responsible for running the government’s own system, it’s hard to believe that the government will not want to extract the maximum amount of data for its SCS, from the pilots. If that happens, and continues as the new normal under the government’s own SCS it will result in private platforms acting essentially as spy agencies for the government. They may have no choice.

Posting dissenting political opinions or links mentioning Tiananmen Square has never been wise in China, but now it could directly hurt a citizen’s rating. But here’s the real kicker: a person’s own score will also be affected by what their online friends say and do, beyond their own contact with them. If someone they are connected to online posts a negative comment, their own score will also be dragged down.

So why have millions of people already signed up to what amounts to a trial run for a publicly endorsed government surveillance system? There may be darker, unstated reasons – fear of reprisals, for instance, for those who don’t put their hand up – but there is also a lure, in the form of rewards and “special privileges” for those citizens who prove themselves to be “trustworthy” on Sesame Credit.

If their score reaches 600, they can take out a Just Spend loan of up to 5,000 yuan (around £565) to use to shop online, as long as it’s on an Alibaba site. Reach 650 points, they may rent a car without leaving a deposit. They are also entitled to faster check-in at hotels and use of the VIP check-in at Beijing Capital International Airport. Those with more than 666 points can get a cash loan of up to 50,000 yuan (£5,700), obviously from Ant Financial Services. Get above 700 and they can apply for Singapore travel without supporting documents such as an employee letter. And at 750, they get fast-tracked application to a coveted pan-European Schengen visa. “I think the best way to understand the system is as a sort of bastard love child of a loyalty scheme,” says Creemers.

Higher scores have already become a status symbol, with almost 100,000 people bragging about their scores on Weibo (the Chinese equivalent of Twitter) within months of launch. A citizen’s score can even affect their odds of getting a date, or a marriage partner, because the higher their Sesame rating, the more prominent their dating profile is on Baihe.

Sesame Credit already offers tips to help individuals improve their ranking, including warning about the downsides of friending someone who has a low score. This might lead to the rise of score advisers, who will share tips on how to gain points, or reputation consultants willing to offer expert advice on how to strategically improve a ranking or get off the trust-breaking blacklist.

Indeed, Sesame Credit is basically a big data gamified version of the Communist Party’s surveillance methods; the disquieting dang’an. The regime kept a dossier on every individual that tracked political and personal transgressions. A citizen’s dang’an followed them for life, from schools to jobs. People started reporting on friends and even family members, raising suspicion and lowering social trust in China. The same thing will happen with digital dossiers. People will have an incentive to say to their friends and family, “Don’t post that. I don’t want you to hurt your score but I also don’t want you to hurt mine.”

We’re also bound to see the birth of reputation black markets selling under-the-counter ways to boost trustworthiness. In the same way that Facebook Likes and Twitter followers can be bought, individuals will pay to manipulate their score. What about keeping the system secure? Hackers (some even state-backed) could change or steal the digitally stored information.

The new system reflects a cunning paradigm shift. As we’ve noted, instead of trying to enforce stability or conformity with a big stick and a good dose of top-down fear, the government is attempting to make obedience feel like gaming. It is a method of social control dressed up in some points-reward system. It’s gamified obedience.

In a trendy neighbourhood in downtown Beijing, the BBC news services hit the streets in October 2015 to ask people about their Sesame Credit ratings. Most spoke about the upsides. But then, who would publicly criticise the system? Ding, your score might go down. Alarmingly, few people understood that a bad score could hurt them in the future. Even more concerning was how many people had no idea that they were being rated.

Currently, Sesame Credit does not directly penalise people for being “untrustworthy” – it’s more effective to lock people in with treats for good behaviour. But Hu Tao, Sesame Credit’s chief manager, warns people that the system is designed so that “untrustworthy people can’t rent a car, can’t borrow money or even can’t find a job”. She has even disclosed that Sesame Credit has approached China’s Education Bureau about sharing a list of its students who cheated on national examinations, in order to make them pay into the future for their dishonesty.

Penalties are set to change dramatically when the government system becomes mandatory in 2020. Indeed, on September 25, 2016, the State Council General Office updated its policy entitled “Warning and Punishment Mechanisms for Persons Subject to Enforcement for Trust-Breaking”. The overriding principle is simple: “If trust is broken in one place, restrictions are imposed everywhere,” the policy document states.

For instance, people with low ratings will have slower internet speeds; restricted access to restaurants, nightclubs or golf courses; and the removal of the right to travel freely abroad with, I quote, “restrictive control on consumption within holiday areas or travel businesses”. Scores will influence a person’s rental applications, their ability to get insurance or a loan and even social-security benefits. Citizens with low scores will not be hired by certain employers and will be forbidden from obtaining some jobs, including in the civil service, journalism and legal fields, where of course you must be deemed trustworthy. Low-rating citizens will also be restricted when it comes to enrolling themselves or their children in high-paying private schools. I am not fabricating this list of punishments. It’s the reality Chinese citizens will face. As the government document states, the social credit system will “allow the trustworthy to roam everywhere under heaven while making it hard for the discredited to take a single step”.

According to Luciano Floridi, a professor of philosophy and ethics of information at the University of Oxford and the director of research at the Oxford Internet Institute, there have been three critical “de-centering shifts” that have altered our view in self-understanding: Copernicus’s model of the Earth orbiting the Sun; Darwin’s theory of natural selection; and Freud’s claim that our daily actions are controlled by the unconscious mind.

Floridi believes we are now entering the fourth shift, as what we do online and offline merge into an onlife. He asserts that, as our society increasingly becomes an infosphere, a mixture of physical and virtual experiences, we are acquiring an onlife personality – different from who we innately are in the “real world” alone. We see this writ large on Facebook, where people present an edited or idealised portrait of their lives. Think about your Uber experiences. Are you just a little bit nicer to the driver because you know you will be rated? But Uber ratings are nothing compared to Peeple, an app launched in March 2016, which is like a Yelp for humans. It allows you to assign ratings and reviews to everyone you know – your spouse, neighbour, boss and even your ex. A profile displays a “Peeple Number”, a score based on all the feedback and recommendations you receive. Worryingly, once your name is in the Peeple system, it’s there for good. You can’t opt out.

Peeple has forbidden certain bad behaviours including mentioning private health conditions, making profanities or being sexist (however you objectively assess that). But there are few rules on how people are graded or standards about transparency.

China’s trust system might be voluntary as yet, but it’s already having consequences. In February 2017, the country’s Supreme People’s Court announced that 6.15 million of its citizens had been banned from taking flights over the past four years for social misdeeds. The ban is being pointed to as a step toward blacklisting in the SCS. “We have signed a memorandum… [with over] 44 government departments in order to limit ‘discredited’ people on multiple levels,” says Meng Xiang, head of the executive department of the Supreme Court. Another 1.65 million blacklisted people cannot take trains.

Where these systems really descend into nightmarish territory is that the trust algorithms used are unfairly reductive. They don’t take into account context. For instance, one person might miss paying a bill or a fine because they were in hospital; another may simply be a freeloader. And therein lies the challenge facing all of us in the digital world, and not just the Chinese. If life-determining algorithms are here to stay, we need to figure out how they can embrace the nuances, inconsistencies and contradictions inherent in human beings and how they can reflect real life.

You could see China’s so-called trust plan as Orwell’s 1984 meets Pavlov’s dogs. Act like a good citizen, be rewarded and be made to think you’re having fun. It’s worth remembering, however, that personal scoring systems have been present in the west for decades.

More than 70 years ago, two men called Bill Fair and Earl Isaac invented credit scores. Today, companies use FICO scores to determine many financial decisions, including the interest rate on our mortgage or whether we should be given a loan.

For the majority of Chinese people, they have never had credit scores and so they can’t get credit. “Many people don’t own houses, cars or credit cards in China, so that kind of information isn’t available to measure,” explains Wen Quan, an influential blogger who writes about technology and finance. “The central bank has the financial data from 800 million people, but only 320 million have a traditional credit history.” According to the Chinese Ministry of Commerce, the annual economic loss caused by lack of credit information is more than 600 billion yuan (£68bn).

China’s lack of a national credit system is why the government is adamant that Citizen Scores are long overdue and badly needed to fix what they refer to as a “trust deficit”. In a poorly regulated market, the sale of counterfeit and substandard products is a massive problem. According to the Organization for Economic Co-operation and Development (OECD), 63 per cent of all fake goods, from watches to handbags to baby food, originate from China. “The level of micro corruption is enormous,” Creemers says. “So if this particular scheme results in more effective oversight and accountability, it will likely be warmly welcomed.”

The government also argues that the system is a way to bring in those people left out of traditional credit systems, such as students and low-income households. Professor Wang Shuqin from the Office of Philosophy and Social Science at Capital Normal University in China recently won the bid to help the government develop the system that she refers to as “China’s Social Faithful System”. Without such a mechanism, doing business in China is risky, she stresses, as about half of the signed contracts are not kept. “Given the speed of the digital economy it’s crucial that people can quickly verify each other’s credit worthiness,” she says. “The behaviour of the majority is determined by their world of thoughts. A person who believes in socialist core values is behaving more decently.” She regards the “moral standards” the system assesses, as well as financial data, as a bonus.

Indeed, the State Council’s aim is to raise the “honest mentality and credit levels of the entire society” in order to improve “the overall competitiveness of the country”. Is it possible that the SCS is in fact a more desirably transparent approach to surveillance in a country that has a long history of watching its citizens? “As a Chinese person, knowing that everything I do online is being tracked, would I rather be aware of the details of what is being monitored and use this information to teach myself how to abide by the rules?” says Rasul Majid, a Chinese blogger based in Shanghai who writes about behavioural design and gaming psychology. “Or would I rather live in ignorance and hope/wish/dream that personal privacy still exists and that our ruling bodies respect us enough not to take advantage?” Put simply, Majid thinks the system gives him a tiny bit more control over his data.

When I tell westerners about the Social Credit System in China, their responses are fervent and visceral. Yet we already rate restaurants, movies, books and even doctors. Facebook, meanwhile, is now capable of identifying you in pictures without seeing your face; it only needs your clothes, hair and body type to tag you in an image with 83 per cent accuracy.

In 2015, the OECD published a study revealing that in the US there are at least 24.9 connected devices per 100 inhabitants. All kinds of companies scrutinise the “big data” emitted from these devices to understand our lives and desires, and to predict our actions in ways that we couldn’t even predict ourselves.

Governments around the world are already in the business of monitoring and rating. In the US, the National Security Agency (NSA) is not the only official digital eye following the movements of its citizens. In 2015, the US Transportation Security Administration proposed the idea of expanding the PreCheck background checks to include social-media records, location data and purchase history. The idea was scrapped after heavy criticism, but that doesn’t mean it’s dead. We already live in a world of predictive algorithms that determine if we are a threat, a risk, a good citizen and even if we are trustworthy. We’re getting closer to the Chinese system – the expansion of credit scoring into life scoring – even if we don’t know we are.

So are we heading for a future where we will all be branded online and data-mined? It’s certainly trending that way. Barring some kind of mass citizen revolt to wrench back privacy, we are entering an age where an individual’s actions will be judged by standards they can’t control and where that judgement can’t be erased. The consequences are not only troubling; they’re permanent. Forget the right to delete or to be forgotten, to be young and foolish.

While it might be too late to stop this new era, we do have choices and rights we can exert now. For one thing, we need to be able rate the raters. In his book The Inevitable, Kevin Kelly describes a future where the watchers and the watched will transparently track each other. “Our central choice now is whether this surveillance is a secret, one-way panopticon – or a mutual, transparent kind of ‘coveillance’ that involves watching the watchers,” he writes.

Our trust should start with individuals within government (or whoever is controlling the system). We need trustworthy mechanisms to make sure ratings and data are used responsibly and with our permission. To trust the system, we need to reduce the unknowns. That means taking steps to reduce the opacity of the algorithms. The argument against mandatory disclosures is that if you know what happens under the hood, the system could become rigged or hacked. But if humans are being reduced to a rating that could significantly impact their lives, there must be transparency in how the scoring works.

In China, certain citizens, such as government officials, will likely be deemed above the system. What will be the public reaction when their unfavourable actions don’t affect their score? We could see a Panama Papers 3.0 for reputation fraud.

It is still too early to know how a culture of constant monitoring plus rating will turn out. What will happen when these systems, charting the social, moral and financial history of an entire population, come into full force? How much further will privacy and freedom of speech (long under siege in China) be eroded? Who will decide which way the system goes? These are questions we all need to consider, and soon. Today China, tomorrow a place near you. The real questions about the future of trust are not technological or economic; they are ethical.

If we are not vigilant, distributed trust could become networked shame. Life will become an endless popularity contest, with us all vying for the highest rating that only a few can attain.

https://www.wired.co.uk/article/chinese-government-social-credit-score-privacy-invasion

Last year, doctors of optometry detected more than 320,000 cases of diabetes. Imagine if they could make the same impact when it comes to exposing early signs of Alzheimer’s disease.

November is National Alzheimer’s Disease Awareness Month. An estimated 5.4 million Americans are affected by Alzheimer’s disease, according to the Centers for Disease Control and Prevention (CDC). Projections put the number at 13.8 million by 2050.

Maryke Nijhuis Neiberg, O.D., associate professor in the School of Optometry at Massachusetts College of Pharmacy and Heath Sciences, in Worcester, Massachusetts, considers this an unrealized patient education opportunity for doctors of optometry.

“The earlier diagnoses give doctors and patients a better chance at managing the progressive brain disease and preserving the patient’s quality of life,” Dr. Neiberg says. “There has been some increase in Alzheimer’s awareness over the years, particularly in the eye community, but not enough yet.

“Alzheimer’s is a significant future public health issue,” she adds. “It is still a terminal disease.”

Early intervention

Much of the research on Alzheimer’s disease seeks to slow the disease’s progression. For instance, a study in Biological Psychiatry on Nov. 6 by researchers at the University of Iowa and the University of Texas Southwestern Medical Center in Dallas reports that there may be a new treatment that can slow the depression and cognitive decline associated with Alzheimer’s disease, without affecting amyloid plaque deposits or reactive glia in rats.

Among the early signs of Alzheimer’s, the researchers say, are anxiety, depression and irritability-long before the devastating effects of memory loss.

“Thus, P7C3 compounds may form the basis for a new class of neuroprotective drugs for mitigating the symptoms in patients with Alzheimer’s disease by preserving neuronal cell survival, irrespective of other pathological events,” researchers say. “P7C3 compounds represent a novel route to treating depression, and new-onset depression in elderly patients may herald the development of Alzheimer’s disease with later cognitive impairments to follow.”

Another study in JAMA Ophthalmology in September by researchers at Stanford University and Veterans Affairs Palo Alto Health Care System linked visual impairment and cognition in older adults and also stressed the “potential importance” of vision screening in identifying these patients’ eye disease and cognitive deficits. The AOA strongly recommends comprehensive eye examinations and stresses the limitations of screenings.

Optometry’s role

According to the CDC:

The rate of Alzheimer’s jumped 50 percent between 1999 and 2014.

Americans fear losing their mental capacity more than losing their physical abilities.

More than $230 billion is estimated to be spent in 2017 on providing health care, long-term care, hospice plus unpaid care for relatives with Alzheimer’s and other dementias.

More large-scale research on Alzheimer’s needs to be done, but progress is being made. Dr. Neiberg pointed to research linking optical coherence tomography (OCT) of the macula to Alzheimer’s and Parkinson’s diseases.

“With the advent of OCT, we now know that the retinal ganglion cell layer thins and that the optic nerve cup-to-disc ratio increases in size, not unlike glaucoma,” Dr. Neiberg says. “Alzheimer’s produces visual field defects that are easily confused with glaucoma. What we need is large-scale research to determine how much of the normal tension glaucoma we diagnose and treat is ultimately related to Alzheimer’s disease.”

She adds, “The early perceptual changes that occur in early Alzheimer’s are startling and measurable. One of the earliest signs is a decline in the Benton Visual Retention Test, a test of visual memory. This test requires the duplication of shapes on paper with a pencil, and is scored.

“Research has shown that this test is able to predict high risk for Alzheimer’s 15 years before diagnosis,” she says. “It’s a simple test many developmental and pediatric optometrists already have on their shelves. If we combine that test and the ocular findings we see, we have a very strong indication that something is indeed amiss. Armed with this information, the patient can then consult with their primary care physician, initiate lifestyle modification and request a referral if necessary.”

There is no cure for Alzheimer’s disease. But doctors of optometry can engage patients in conversation about Alzheimer’s disease and how they can manage their own risk factors, including:

Smoking
Mid-life obesity
Sedentary lifestyle
High-cholesterol diet|
Vascular disease (i.e., diabetes and hypertension)

“Lifestyle modification and early access to medication, which can delay the progression of dementia, might be enough to keep the disease at bay for longer,” Dr. Neiberg says. “We should include the Alzheimer’s disease connection when we educate our patients about lifestyle diseases.”

https://finchannel.com/society/health-beauty/69483-doctors-of-optometry-can-spot-early-signs-of-alzheimer-s-disease


A one-time intravenous infusion of the high dose of gene therapy at Nationwide Children’s Hospital in Ohio extended the survival of patients with spinal muscular atrophy type 1 (SMA1) in a Phase 1 clinical trial, according to a study.

A one-time intravenous infusion of the high dose of gene therapy extended the survival of patients with spinal muscular atrophy type 1 (SMA1) in a Phase 1 clinical trial, according to a study published in the New England Journal of Medicine. The study was conducted by Researchers from Nationwide Children’s Hospital in collaboration with AveXis, Inc. and The Ohio State University College of Medicine.

“My team at Nationwide Children’s has worked with commitment and dedication to develop a therapy that may subsequently be shown through future clinical trials to potentially alter the course of this unforgiving condition and provide a therapeutic option for the families and infants with SMA1,” says Jerry Mendell, MD, principal investigator in the Center for Gene Therapy at Nationwide Children’s.

SMA1 is a progressive, childhood, neuromuscular disease caused by a mutation in a single gene. Children with SMA1 fail to meet motor milestones and typically die or require permanent mechanical ventilation by 2 years of age. The phase 1 clinical trial is the first to test the functional replacement of the mutated gene responsible for SMA1.

A one-time intravenous injection of modified adeno-associated virus serotype 9 (AAV9) delivered the SMN gene to 15 patients. Three patients received a low dose, while 12 patients received a high dose. In the Phase 1 trial, patients in the high dose group demonstrated improvement in motor function and they had a decreased need for supportive care compared to the natural history of the disease.

Specifically, at the end of the study period, all 15 patients appeared to have a favorable safety profile and to be generally well tolerated. Of the 12 patients treated with the high dose, 92 percent of patients have achieved head control, 75 percent of patients can roll over and 92 percent of patients can sit with assistance. Seventy-five percent of these patients are now sitting for 30 seconds or longer. Two patients can crawl, pull to stand and stand and walk independently.

According to natural history of the disease, patients require nutritional and respiratory support by 12 months of age, and are not able to swallow or speak effectively. Of the patients who received the high dose in study, 11 patients are able to speak, 11 patients are fed orally and seven do not require bi-level positive airway pressure as of the data cut-off (August 7, 2017).

“In this first phase of clinical trials, we have observed preliminary results that appear to be promising compared to the natural history of SMA Type 1,” says Dr. Mendell, also a faculty member at The Ohio State University College of Medicine.

This study builds on nearly three decades of foundational research led by teams at Nationwide Children’s and Ohio State’s Wexner Medical Center and exemplifies the strong basic science and clinical bonds between the two institutions. Arthur Burghes, PhD, of Ohio State created a ground-breaking SMA mouse model that remains the standard by which all therapies, including AVXS-101, are initially tested. Senior author of the study, Brian Kaspar, PhD, during his appointment at Nationwide Children’s discovered that the AAV9 vector was capable of crossing the blood brain barrier when injected into the vascular system to deliver genes directly to motor neurons. The two laboratories then collaborated to show that scAAV9-SMN, when delivered to SMA mice shortly after birth, completely prevented their neuromuscular disorder. The laboratories also collaborated to successfully prove that reversing a protein deficiency through gene therapy is effective in improving and stabilizing SMA in a large animal model. “In neurological disease, it is rare to go from gene defect to therapy so directly, and the fact that this has happened here in one place is perhaps even rarer,” said John Kissel, MD, chair of Neurology at Ohio State and director of the SMA Clinic at Nationwide Children’s.

AveXis, Inc., a clinical-stage gene therapy company developing treatments for patients suffering from rare and life-threatening neurological genetic diseases, announced in July 2016 that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for the treatment based on preliminary clinical results from the trial of AVXS-101.

“At AveXis, we are enormously pleased to see that all children who received AVXS-101 are alive and free of permanent ventilatory support at 20 months of age and older — an age where, sadly, only eight percent of untreated children with SMA Type 1 are expected to survive without permanent breathing support,” said Dr. Kaspar, now serving as Chief Scientific Officer at AveXis. “The New England Journal of Medicine publication marks an exciting milestone in the development of AVXS-101.”

Journal Reference:

Jerry R. Mendell, Samiah Al-Zaidy, Richard Shell, W. Dave Arnold, Louise R. Rodino-Klapac, Thomas W. Prior, Linda Lowes, Lindsay Alfano, Katherine Berry, Kathleen Church, John T. Kissel, Sukumar Nagendran, James L’Italien, Douglas M. Sproule, Courtney Wells, Jessica A. Cardenas, Marjet D. Heitzer, Allan Kaspar, Sarah Corcoran, Lyndsey Braun, Shibi Likhite, Carlos Miranda, Kathrin Meyer, K.D. Foust, Arthur H.M. Burghes, Brian K. Kaspar. Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy. New England Journal of Medicine, 2017; 377 (18): 1713 DOI: 10.1056/NEJMoa1706198


The image shows brain tissue from Alzheimer’s rats that were untreated (left) or treated (right) with the neuroprotective compound. The white “holes” indicated by the arrows are areas of brain cell death, and are more numerous in the untreated rats. Although the treatment protects the animals from neuronal cell death and Alzheimer’s-type symptoms, it does not alter the buildup of amyloid plaques and neurofibrillary tangles in the rat brains. The research from the Iowa Neuroscience Institute at the University of Iowa was published online in the journal Biological Psychiatry. Credit: Pieper Lab, University of Iowa.

Treatment with a neuroprotective compound that saves brain cells from dying also prevents the development of depression-like behavior and the later onset of memory and learning problems in a rat model of Alzheimer’s disease. Although the treatment protects the animals from Alzheimer’s-type symptoms, it does not alter the buildup of amyloid plaques and neurofibrillary tangles in the rat brains.

“We have known for a long time that the brains of people with Alzheimer’s disease have amyloid plaques and neurofibrillary tangles of abnormal tau protein, but it isn’t completely understood what is cause or effect in the disease process,” say senior study author Andrew Pieper, MD, PhD, professor of psychiatry in the University of Iowa Carver College of Medicine and associate director of the Iowa Neuroscience Institute at the University of Iowa. “Our study shows that keeping neurons alive in the brain helps animals maintain normal neurologic function, regardless of earlier pathological events in the disease, such as accumulation of amyloid plaque and tau tangles.

Alzheimer’s disease is a devastating neurodegenerative condition that gradually erodes a person’s memory and cognitive abilities. Estimates suggest that more than 5 million Americans are living with Alzheimer’s disease and it is the sixth leading cause of death in the United States, according the National Institute on Aging. In addition to the impact on cognition and memory, Alzheimer’s disease can also affect mood, with many people experiencing depression and anxiety before the cognitive decline is apparent. In fact, people who develop depression for the first time late in life are at a significantly increased risk of developing Alzheimer’s disease.

“Traditional therapies have targeted the characteristic lesions in Alzheimer’s disease, amyloid deposition and tau pathologies. The findings of this study show that simply protecting neurons in Alzheimer’s disease without addressing the earlier pathological events may have potential as a new and exciting therapy,” says Jaymie Voorhees, PhD, first author of the study, which is an article-in-press in Biological Psychiatry.

Saving brain cells protects brain function

Pieper and Voorhees used an experimental compound called P7C3-S243 to prevent brain cells from dying in a rat model of Alzheimer’s disease. The original P7C3 compound was discovered by Pieper and colleagues almost a decade ago, and P7C3-based compounds have since been shown to protect newborn neurons and mature neurons from cell death in animal models of many neurodegenerative diseases, including Parkinson’s disease, amyotrophic lateral sclerosis (ALS), stroke, and traumatic brain injury. P7C3 compounds have also been shown to protect animals from developing depression-like behavior in response to stress-induced killing of nerve cells in the hippocampus, a brain region critical to mood regulation and cognition.

The researchers tested the P7C3 compound in a well-established rat model of Alzheimer’s disease. As these rats age, they develop learning and memory problems that resemble the cognitive impairment seen in people with Alzheimer’s disease. However, the new study revealed another similarity with Alzheimer’s patients. By 15 months of age, before the onset of memory problems, the rats developed depression-like symptoms. Developing depression for the first time late in life is associated with a significantly increased risk for developing Alzheimer’s disease, but this symptom has not been previously seen in animal models of the disease.

Over a three-year period, Voorhees tested a large number of male and female Alzheimer’s and wild type rats that were divided into two groups. One group received the P7C3 compound on a daily basis starting at six months of age, and the other group received a placebo. The rats were tested at 15 months and 24 months of age for depressive-type behavior and learning and memory abilities.

At 15-months of age, all the rats – both Alzheimer’s model and wild type, treated and untreated – had normal learning and memory abilities. However, the untreated Alzheimer’s rats exhibited pronounced depression-type behavior, while the Alzheimer’s rats that had been treated with the neuroprotective P7C3 compound behaved like the control rats and did not show depressive-type behavior.
At 24 months of age (very old for rats), untreated Alzheimer’s rats had learning and memory deficits compared to control rats. In contrast, the P7C3-treated Alzheimer’s rats were protected and had similar cognitive abilities to the control rats.

The team also examined the brains of the rats at the two time points. They found that the traditional hallmarks of Alzheimer’s disease, amyloid plaques, tau tangles, and neuroinflammation, were dramatically increased in the Alzheimer’s rats regardless of whether they were treated with P7C3 or not. However, significantly more neurons survived in the brains of Alzheimer’s rats that had received the P7C3 treatment.

“This suggests a potential clinical benefit from keeping the brain cells alive even in the presence of earlier pathological events in Alzheimer’s disease, such as amyloid accumulation, tau tangles and neuroinflammation,” Pieper says. “In cases of new-onset late life depression, a treatment like P7C3 might be particularly useful as it could help stabilize mood and also protect from later memory problems in patients with Alzheimer’s disease.”

https://medicalxpress.com/news/2017-11-neurons-approach-alzheimer-disease.html

Low-current electrical pulses delivered to a specific brain area during learning improved recollection of distinct memories, according to a study published online in eLife.

Researchers at the University of California, Los Angeles (UCLA) believe electrical stimulation offers hope for the treatment of memory disorders, such as Alzheimer’s disease.

The study involved 13 patients with epilepsy who had ultrafine wires implanted in their brains to pinpoint the origin of seizures. During a person-recognition task, researchers monitored the wires to record neuronal activity as memories were formed, and then sent a specific pattern of quick pulses to the entorhinal area of the brain, an area critical to learning and memory.
In 8 of 9 patients who received electrical pulses to the right side of the entorhinal area, the ability to recognize specific faces and disregard similar-looking ones improved significantly. However, the 4 patients who received electrical stimulation on the left side of the brain area showed no improvement in recall.

By using the ultrafine wires, researchers were able to precisely target the stimulation while using a voltage that was one-tenth to one-fifth of the strength used in previous studies.

“These results suggest that microstimulation with physiologic level currents—a radical departure from commonly used deep brain stimulation protocols—is sufficient to modulate human behavior,” researchers wrote.

The findings also point to the importance of stimulating the right entorhinal region to promote improved memory recollection.

—Jolynn Tumolo

References

Titiz AS, Hill MRH, Mankin EA, et al. Theta-burst microstimulation in the human entorhinal area improves memory specificity. eLife. 2017 October 24.

By Carolyn Gregoire

Long before microdosing was being touted as the Silicon Valley life hack du jour, Dr. James Fadiman was investigating the potential mind-enhancing effects of ingesting psychedelic drugs like LSD and psilocybin, more commonly known as magic mushrooms.

In the 1960s, Fadiman conducted pioneering psychedelic research, including one study in which he gave LSD and another hallucinogen, Mescaline, to scientists, mathematicians and architects to see how it affected creative problem-solving. (His research was one of the last investigations into LSD due to the Food and Drug Administration’s mid-1960s research ban of the substance.)

More recently, Fadiman authored “The Psychedelic Explorer’s Guide,” a how-to manual for safe and therapeutic psychedelic drug experiences.

Now, his research has taken a new turn.

Fadiman is examining the effects of administering psychedelic drugs like LSD and psilocybin in amounts so small that they are below the perceptual threshold. As part of an ongoing research project, Fadiman is collecting the self-reported testimonies of hundreds of people from around the globe who have experimented with psychedelic “microdosing” to treat ailments from anxiety to attention deficit hyperactivity disorder, or simply to improve productivity or break through writer’s block.

How does one microdose? You take a very small dose of either LSD or psilocybin (roughly one-tenth to one-fifth of a normal dose), on a regular schedule. Fadiman recommends dosing in the morning, once every three days. The dose isn’t enough to “trip,” but for some users, it can lead to subtle yet profound internal shifts. Many microdosers report experiencing improvements in mood; enhanced focus, productivity or creativity; less reactivity; and in some cases, even relief from depression or cluster headaches.

“What it seems to do is rebalance people,” Fadiman told The Huffington Post.

HuffPost Science recently sat down with Fadiman to learn more about how microdosing works, and its potential for enhancing well-being and treating a range of health problems.

Where did this idea of microdosing come from?

Dr. Albert Hofmann (the Swiss chemist who discovered LSD) had been microdosing for at least the last couple decades of his life. He lived to be 102 and at age 100 he was still giving two-hour lectures. Hoffman said that he would mainly use it when he was walking in trees, and it would clarify his thinking. So he was the person who first introduced this to many people, and he also said that this was a very under-researched area.

And of course, for thousands of years, indigenous people have been using low doses of mind-altering substances as well.

What types of people are microdosing, and who do you think can benefit most from the practice?

Microdosing seems to improve a vast range of conditions. I’ve explored microdosing as a safer way of doing psychedelics than the high doses that have been used before. Roughly 95 percent of the people who write me have considerable psychedelic experience. I’ll basically tell them, this isn’t going to harm you, let me know what happens.

The general response is that they feel better. There is an actual movement towards increased health or wellness. What that means, for instance, is that people who write in for anxiety seem to get help with their anxiety. People who use it for learning, improve their learning. One Ivy League student said he was using microdosing to get through the hardest math class in the undergraduate curriculum, and he did wonderfully in the class. Another young man used it for severe stuttering, and others have used it for social anxiety. One young woman, an art historian, even found that it regulated her periods and made them painless.

What does your microdosing protocol look like?

On day one, you dose. Day two, you’re still having the effects. Day three, you should be noticeably not having the effects, and on day four you dose again. For self-study, that’s ideal because it gives you a chance to see what’s going on. After a month — which is all I ask of people — most people say that they’re still microdosing, but not as often.

You’ve worked with hundreds of people on a self-reported microdosing study. How did that get started and what have you been finding?

Over the past number of years, people have written to me and said, “I’m interested in microdosing” for this or that reason, “can you help me?” They ask me to tell them what I’ve been suggesting to people, and they ask to be in the study. I then send them a protocol I’ve developed for a self-study and ask them to get back to me. I’ve probably sent out 200 or 300 of these, and I’ve gotten about half as many back as reports. A number are in process right now.

The range of interest goes from “Hey man, new drug, cool” to “I have post-traumatic stress, I’m recovering from cancer, and I hate my meds.” It’s a very wide range. I get a lot of people who say “I have anxiety or depression and I’ve either gotten off my meds or I hate my meds. Could microdosing help?” And my response is, “It’s helped a lot of other people and I hope it helps you. Here’s the protocol.”

I’ve heard there’s potential for enhancing focus and improving symptoms of ADHD, too.

What people basically say is that they’re better. They focus more in class. A number of people have told me that it’s like Adderall but without the side effects. Now these people are coming off Adderall and have used microdosing to help them taper off pharmaceuticals, or at least to take their pharmaceutical use way, way down.

In your study, are you seeing a lot of people turning to microdosing as a way to come off pharmaceuticals?

For some people, it can take a year or two to come off of a pharmaceutical. A number of people have simply said that with microdosing it was much easier. They said they could do it without incredible suffering. A woman who was coming off of some anti-psychotics that she probably should never have been put on said that it wasn’t that she didn’t have the same symptoms, but she didn’t identify with them as much. She said that she could think of her mood swings as her brain chemistry rebalancing.

What’s going on beneath the surface to create these changes?

What microdosing seems to do is rebalance people. Here’s a generalization, which is how I’ve come to this conclusion: A number of people, by the time they’ve finished a month, say, “I’m sleeping better, I’m eating more healthy food, I’ve returned to yoga and I’m doing meditation.” They’ve improved their relationship to their body ― or their body has improved their relationship to them.

One man quit smoking. He said that he knew smoking wasn’t good, and it was as if his body could actually help him make the decision. What seems to happen with microdosing is that you’re more attuned to your own real needs.

Why has there been so little research into microdosing?

There are two main problems. One is that nobody was interested in microdosing, even a couple of years ago. The early research was always high-dose, and the fact that you could take psychedelics as a microdose didn’t occur to people. The only person we knew of who microdosed seriously was Hofmann … It was basically invisible during the time when research was legal and most of the time when it wasn’t.

On the other side of it, I talked with a major researcher who’s done a number of psychedelic studies and who said that he would love to do a microdosing study. I asked him what was stopping him. He said that the Institutional Review Board is not going to say, “Oh you want to give a Schedule I drug to people every few days and have them just go run around?” It’s going to be really hard.

Now, there are two groups, one in Australia and one in Europe, who are starting microdosing studies. I’m working with both of those groups on designing the studies.

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