NEUROENHANCEMENT

Google Trends for “nootropics”

DESIGNER BRAINS
http://www.reddit.com/r/nootropics/wiki/beginners
http://gizmodo.com/nootropics-and-the-lab-rats-of-reddit-1692737550
https://www.minds.com/blog/view/388404529630023680/the-planet039s-2nd-smartest-human-reveals-50-mind-drugs-and-supplements-he-takes-every-day
http://www.thedailybeast.com/articles/2015/05/27/silicon-valley-s-eating-up-super-ritalin-i-got-the-best-of-it.html
http://www.theatlantic.com/magazine/archive/2015/06/brain-hacking/392084/
Hacking the Brain : How we might make ourselves smarter in the future
by Maria Konnikova  /  June 2015

The perfectibility of the human mind is a theme that has captured our imagination for centuries—the notion that, with the right tools, the right approach, the right attitude, we might become better, smarter versions of ourselves. We cling to myths like “the 10 percent brain”—which holds that the vast majority of our thinking power remains untapped—in part because we hope the minds of the future will be stronger than those of today. It’s as much a personal hope as a hope for civilization: If we’re already running at full capacity, we’re stuck, but what if we’re using only a small fraction of our potential? Well, then the sky’s the limit. But this dream has a dark side: The possibility of a dystopia where an individual’s fate is determined wholly by his or her access to cognition-enhancing technology. Where some ultra-elites are allowed to push the limits of human intelligence, while the less fortunate lose any chance of upward mobility. Where some Big Brother–like figure could gain control of our minds and decide how well we function. What’s possible now, and what may one day be? In a series of conversations with neuroscientists and futurists, I glimpsed a vision of a world where cognitive enhancement is the norm. Here’s what that might look like, and how we can begin thinking about the implications.

Personalized Smart Pills
In many ways, we’re already living in a world of constant neuroenhancement. There’s methylphenidate (a k a Ritalin), intended to treat ADHD and narcolepsy and now used by test takers and paper-writers the world over. In controlled trials, the drug has been shown to improve memory, concentration, and motivation in individuals who have no cognitive impairment. There’s modafinil, developed to treat narcolepsy and other sleep disorders. In people who have gotten a full night’s rest, it has been shown to increase executive function, memory, and attention—and in those who have gone without much sleep, it has helped stave off symptoms of sleep deprivation. There’s also donepezil, developed to treat Alzheimer’s. Like other anti-dementia drugs, it has been shown in clinical trials to improve both verbal and procedural memory (the memory we use to perform a complex set of actions, like driving a car) in healthy individuals. None of these, of course, is the mythical “smart pill,” a supplement we could take to instantly boost our IQ by 10 points. Instead, each targets specific components of intellectual output: memory, concentration, motivation. And sometimes those functions come at the expense of others. Increase concentration with Ritalin, for instance, and your creativity could suffer. But the day may come, says Guoping Feng, a neuroscientist at MIT, when we understand neural mechanisms well enough to design personalized pills that can bolster your particular strengths and minimize your weaknesses. Several biotech companies are looking to do just that.

Give Yourself a Jolt
The idea of using electric currents to change brain function is not new—the electroconvulsive therapies of yore were based on the concept—but in recent years we’ve gotten much better at controlling where that current goes and how much of it is administered. Today’s electric stimulation is the fine watercolor to electroshock therapy’s finger painting. The most common approach, transcranial direct-current stimulation, or tDCS, involves applying a small current to the scalp in order to modulate brain activity. It has gotten a lot of attention lately, and with good reason: In several recent studies, tDCS appears to improve concentration, problem-solving ability, and working memory (which enables us to hold in our minds the information we need to carry out a complicated task). The effects can last anywhere from 30 minutes to two hours. Jamie Tyler, an Arizona State University neuroscientist, co‑founded a company called Thync because he was inspired by the potential benefits of brain modulation. Thync has developed a prototype device, tested on more than 3,000 people to date, that can either calm us down or give us a boost of energy—providing an avenue toward concentration or creative association, respectively. “It’s just another tool to be able to navigate your daily life,” says Tyler—akin to a cup of coffee during a late-night cram session or a few minutes of meditation before a big presentation. (Some kinks remain, though: When I tested a beta prototype in Thync’s Boston office, I received a mild electric shock to the head instead of the promised calming vibe. A failure of a software update and not the device itself, I was told.)

A Pacemaker for Your Head
Another option is to install electrodes deep inside your brain, to stimulate areas that tDCS cannot reliably reach. Deep-brain stimulation is already used to treat Parkinson’s disease as well as some severe cases of depression. A surgeon inserts electrodes directly into the brain—the location depends on the intent—and connects them to a device in the chest that resembles a pacemaker. That device can then regulate the brain’s electrical impulses and chemical levels via the electrodes. Applications of deep-brain stimulation may someday be more enhancing than therapeutic: in 2013, a team from UCLA showed that the procedure could buttress memory and improve the ability to process and store information, and this spring, a study using rats determined that it could potentially stave off memory loss and dementia-like symptoms. In other words, in addition to making us smarter, deep-brain stimulation could also ensure that we remain smart for longer.

Direct Connections
Electrodes aren’t the only things we may someday start implanting in our brains. Consider what you could do with a chip in your head that linked directly to the Internet: Within milliseconds, you could retrieve just about any piece of information. And with the collective knowledge of the Web at your disposal, you could quickly fill in your brain’s normal memory gaps—no one would ever guess you slept through that economics seminar. That’s the (distant) future envisioned by people like Anders Sandberg, a computational neuroscientist and self-described transhumanist at Oxford’s Future of Humanity Institute. Sandberg believes in the possibility of the extended mind, a way of transcending our cognitive limits through brain implants. And why stop at the Internet? A future mind could potentially connect directly to other future minds. Whether such connections would make us smarter or just overwhelm and confuse us—we’ll have to wait and see.

Designer Brains
Down the road, the most controversial approach to neuroenhancement could be a way not of stimulating the brain but of reengineering it. Until a few years ago, such a possibility was purely theoretical, the realm of philosophical debates and ethical quandaries. Now, however, researchers have developed a genome-editing technology called crispr (or, more technically, Cas9), which scientists could use to change any part of an embryo’s genome, one nucleotide at a time. It was developed to fight disease by correcting mutations before a baby is born. But one can imagine a day when we are able to identify genes associated with cognitive ability and manipulate them for higher output. Granted, that day is a long way off. “There’s no single gene for intelligence. We can’t just go in and change one gene and become cognitively enhanced,” Feng says. What we can do now is gain a deeper knowledge of the relationship between the genome and brain function—and perhaps in a few decades, we’ll be in a position to evaluate whether such tinkering is a good idea. When that day comes, health concerns may overshadow the ethical considerations around engineering supersmart babies. The truth is that we have no idea what the long-term effects of any artificial enhancement may be. Will our brains be able to withstand running at artificially heightened capacity? “There’s a discussion going on that our brains have evolved over millions of years and might already be at optimal neurochemical equilibrium, and any attempt to change something there can only do harm and can’t strongly enhance brain function,” Martin Dresler, a German neuroscientist who studies cognitive enhancement, told me. If that’s the case, ethics could be the least of our worries.

Simple technology makes CRISPR gene editing cheaper
Some DNA sequences appear multiple times in the genome. Here, an RNA guide probe labels repetitive regions in the nucleus of a Xenopus laevis sperm. [Credit: Andrew Lane, UC Berkeley]

GENE EDITING
http://www.wired.com/2015/07/crispr-dna-editing-2

http://phys.org/news/2015-02-crispr-cas9-controversy.html
http://phys.org/news/2015-07-simple-technology-crispr-gene-cheaper.html
Simple technology makes CRISPR gene editing cheaper / July 23, 2015

University of California, Berkeley, researchers have discovered a much cheaper and easier way to target a hot new gene editing tool, CRISPR-Cas9, to cut or label DNA. The CRISPR-Cas9 technique, invented three years ago at UC Berkeley, has taken genomics by storm, with its ability to latch on to a very specific sequence of DNA and cut it, inactivating genes with ease. This has great promise for targeted gene therapy to cure genetic diseases, and for discovering the causes of disease. The technology can also be tweaked to latch on without cutting, labeling DNA with a fluorescent probe that allows researchers to locate and track a gene among thousands in the nucleus of a living, dividing cell. The newly developed technique now makes it easier to create the RNA guides that allow CRISPR-Cas9 to target DNA so precisely. In fact, for less than $100 in supplies, anyone can make tens of thousands of such precisely guided probes covering an organism’s entire genome.The process, which they refer to as CRISPR-EATING – for “Everything Available Turned Into New Guides” – is reported in a paper to appear in the August 10 issue of the journal Developmental Cell.

As proof of principle, the researchers turned the entire genome of the common gut bacterium E. coli into a library of 40,000 RNA guides that covered 88 percent of the bacterial genome. Each RNA guide is a segment of 20 RNA base pairs: the template used by CRISPR-Cas9 as it seeks out complementary DNA to bind and cut. These libraries can be employed in traditional CRISPR-Cas9 editing to target any specific DNA sequence in the genome and cut it, which is what researchers do to pin down the function of a gene: knock it out and see what bad things happen in the cell. This can help pinpoint the cause of a disease, for example. The process is called genetic screening and is done in batches: each of the thousands of probes is introduced into a single cell on a plate filled with hundreds of thousands of cells. “We can make these libraries for a lot less money, which makes genetic screening potentially accessible in organisms less well studied,” such as those that have not yet had their genomes sequenced, said first author Andrew Lane, a UC Berkeley post-doctoral fellow.

Real-time cell monitoring
But Lane and colleague Rebecca Heald, UC Berkeley professor of molecular and cell biology, developed the technology in order to track chromosomes in real-time in living cells, in particular during cell division, a process known as mitosis. This is part of a larger project by Heald to find out what regulates the size of the nucleus and other subcellular components as organisms grow from just a few cells to many cells. “This technology will allow us to paint a whole chromosome and look at it live and really follow it in the nucleus during the cell cycle or as it goes through developmental transitions, for example in an embryo, to see how it changes in size and structure,” Heald said. The new technique uses standard PCR (polymerase chain reaction) to generate many short lengths of DNA from whatever segment of DNA a researcher is interested in, up to and including an entire genome. These fragments are then precisely snipped at a region called a PAM, which is critical to CRISPR binding. Simple restriction enzymes are then used to cut each piece 20 base pairs from the PAM end, generating the exact size of RNA guide that CRISPR uses in searching the genome for complementary sites. These guide RNAs are then easily incorporated into the CRISPR-Cas9 complex, yielding tens of thousands of probes for labeling or cutting DNA. “By using the genome itself as a source for guide RNAs, their approach puts the creation of libraries that target contiguous regions in reach of almost any lab,” said Jacob Corn, managing and scientific director of the Innovative Genomics Initiative at UC Berkeley. “This could be very useful for genome imaging and certain kinds of screens, and I’m very interested to see how it enables biological discovery using Cas9 tools.”

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