A New Implant is Being Developed for Enhancing Human Memory

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Would that it was this easy.

In 1998, Andy Clark and David Chalmers proposed that a computer operates together with our brains as an “extended mind,” potentially offering additional processing capabilities as we work out problems, as well as an annex for our memories containing information, images, and so on. Now a professor of biomedical engineering at the University of Southern California, Theodore Berger, is working to bring to market human memory enhancement in the form of a prosthetic implanted in the brain. He’s already testing it attached to humans.

The prosthetic, which Berger has been working on for ten years, can function as an artificial hippocampus, the area in the brain associated with memory and spatial navigation.



The plan is for the device to convert short-term memory into long-term memory and potentially store it as the hippocampus does. His research has been encouraging so far.

Berger began by teaching a rabbit to associate an audio tone with a puff of air administered to the rabbit’s face, causing it to blink. Electrodes attached to the rabbit allowed Berger to observe patterns of activity firing off in the rabbit’s hippocampus. Berger refers to these patterns as a “space-time code” representing where the neurons are in the rabbit’s brain at a specific moment. Berger watched them evolving as the rabbit learned to associate the tone and puff of air. He told Wired, “As the space-time code propagates into the different layers of the hippocampus, it’s gradually changed into a different space-time code.” Eventually, the tone alone was enough for the hippocampus to produce a recallable space-time code based on the latest incoming version to make the rabbit blink.

The manner in which the hippocampus was processing the rabbit’s memory and producing a recallable space-time code became predictable enough to Berger that he was able to develop a mathematical model representing the process.

Berger then built an artificial rat hippocampus — his experimental prosthesis —to test his observations and model. By training rats to press a lever with electrodes monitoring their hippocampuses, Berger was able to acquire the corresponding space-time codes. Running that code through his mathematical model and sending it back to the rats’ brains, his system was validated as the rats successfully pressed their levers. “They recall the correct code as if they’ve created it themselves. Now we’re putting the memory back into the brain,” Berger reports.

It’s maybe the this last statement that’s so intriguing. Does the brain have some kind of master memory index? Has it somehow integrated the artificial hippocampus’s memories into the rats’ directory? Will it also happen in humans?

Dustin Tyler, a professor of engineering at Case Western Reserve University, cautioned Wired, “All of these prosthetics interfacing with the brain have one fundamental challenge. There are billions of neurons in the brain and trillions of connections between them that make them all work together. Trying to find technology that will go into that mass of neurons and be able to connect with them on a reasonably high-resolution level is tricky.”

Still, Bergen himself is optimistic, telling IEEE Spectrum, “We’re testing it in humans now, and getting good initial results. We’re going to go forward with the goal of commercializing this prosthesis.”

What he envisions bringing to market based on his research is a brain prosthetic for people with memory problems. The tiny device would be implanted in the patient’s own hippocampus from where it would stimulate the neurons responsible for turning short-term memories into long-term memories. He hopes it can help patients suffering from Alzheimer’s, other forms of dementia, stroke victims and people whose brains have been injured.



Berger’s business partner in this is tech entrepreneur Bryan Johnson. After selling his payment gateway Braintree to PayPal for $800, he started a venture capital fund, the OS Fund. Its web site states its mission: “The OS Fund invests in entrepreneurs working towards quantum-leap discoveries that promise to rewrite the operating systems of life.” Johnson sees Berger’s work as one such discovery, and formed kernel to support it, running the company himself with Berger as the company’s Chief Science Officer.



Rats and monkeys — the prosthetic improved the memories of rhesus monkeys attached to their prefrontal cortex — are one thing. The greater number of neurons in human brains is a big issue that needs to be grappled before Berger’s implant will work well for humans: It’s difficult to gain a comprehensive view of what’s going on with larger brains due to their greater number of neurons. (Rat brains have about 200 million neurons; humans have 86 billion.) Berger warns, “Our information will be biased based on the neurons we’re able to record from,” and he looks forward to tools that can capture broader swaths of data going forward. It’s anticipated that they’ll need to pack a greater number of electrodes into prostheses.

Human trials so far have been with in-patient epileptics with electrodes already in place for their epilepsy treatments. Berger’s team has observed and recorded activity in the hippocampus during memory tests, and they’ve been encouragingly successful at enhancing patients’ memories by stimulating neurons there. kernel will be funding additional human trials. [via BigThink]

December 2, 2016 / by / in , , , , , , , ,
These Wearables Detect Health Issues Before They Happen

Technologies created by the federally funded MD2K project could lead to consumer devices that offer health guidance in real time.


wearablesopenerElectrocardiogram data transmitted from MD2K’s AutoSense chest-band is displayed on a smartphone running the mCerebrum software platform. This researcher is also wearing a MotionSense wristband.


Future generations of Apple Watches, Fitbits, or Android Wear gadgets may be able to detect and mitigate health problems rather than simply relay health data, thanks to a federally funded project that is applying big-data tools to mobile sensors.

The project, called MD2K, won $10.8 million from the National Institutes of Health to develop hardware and software that compiles and analyzes health data generated by wearable sensors. MD2K’s ultimate goal is to use these sensors and data to anticipate and prevent “adverse health events,” such as addiction relapse. Though the project is aimed at researchers and clinicians, its tools are freely available, so these innovations could turn up in consumer wearables.

Commercial wearable devices aren’t suitable for research because they only gather a few types of health data about a user, such as number of steps taken and heart rate, and they typically display specific results rather than raw sensor data. In addition, their batteries can’t support a full day’s worth of high-frequency data collection and they don’t quantify the degree of uncertainty associated with their data.  



MD2K’s EasySense wearable is a cardiorespiratory monitor that can measure lung fluid level in congestive heart failure patients.


EasySense uses a circular antenna array to obtain stable measurements irrespective of orientation.

To address these shortcomings, the MD2K team, which spans 12 different universities, produced a set of gadgets capable of collecting a variety of raw, reliable sensor data for 24 hours per charge. MotionSense is a smart watch that deciphers users’ arm movements through sensors and can track heart rate variability. EasySense is a micro-radar sensor worn near the chest to measure heart activity and lung fluid volume. MD2K researchers are also using AutoSense—invented before MD2K was established—a chest-band that gleans electrocardiogram (ECG) and respiration data. All three devices stream data via Wi-Fi to Android phones where an MD2K-built software platform processes the information and translates it into digital biomarkers about the wearer’s health status and risk factors.

Since MD2K’s work is open-source, manufacturers such as Apple, Garmin, and Samsung could use the project’s designs to build similar sensors and apps for their own wearable devices. For example, MD2K’s MotionSense “HRV” wristband has three types of LED sensors (red, infra-red, and green) embedded in its underside, while most fitness trackers and commercial smart watches, such as the Apple Watch, have only green LEDs. Because the MD2K gadget can calculate differences in the ways a user’s blood absorbs its various sensor lights, it is able to compute heart rate variability, i.e., variations in the time interval between heartbeats, instead of just measuring a user’s heart rate in terms of beats per minute, as most of today’s wearables do.


MD2K researchers are using this AutoSense chest-band to monitor study participants’ heart activity and respiration.

This heart-rate variability data, along with respiratory signals, can help gauge a person’s stress levels. Emre Ertin, an Ohio State University professor who developed MD2K’s wearable gadgets, says manufacturers could easily implement this “stress biomarker” in their devices. Some commercial wearables, such as the Spire “mindfulness and activity tracker” and Fitbit’s more expensive models, claim to detect stress (through tense breathing), but other popular wearables, including the Apple Watch, Garmin’s “vivo” series, and Samsung’s GearFit2, do not.

Academics at Northwestern and Ohio State universities are already using the MD2K wearables to understand when and why abstinent smokers relapse and to assess congestion in congestive heart failure patients so they can avoid hospitalization. The smoking cessation study pulls information from multiple sources, including the MotionSense wristband’s accelerometer and gyrometer, which evaluate the wearer’s wrist position and movement to identify smoking gestures; the gadget’s heart-rate variability sensors, which assess stress; and the GPS in the user’s smartphone, which yields clues about location. MD2K researchers then examine the data to see which environments and behaviors trigger smoking lapses. Eventually, they will leverage that knowledge to launch “just-in-time” interventions in the form of pop-up messages or surveys on the participant’s smartphone.

It seems inevitable that these advances will trickle down to consumer wearables, but some experts advise caution. “If you take one thousand people who are trying to quit smoking and add an intervention that is digital and mobile, you’ll get some uptake because these people were previously using nothing [to guard against relapse],” says Joseph Kvedar, who heads the Boston-based Partners HealthCare SystemCenter for Connected Health and teaches at Harvard Medical School. “But I don’t think anyone really knows how effective any of these things are, long term.” [MIT Technology Review]

November 30, 2016 / by / in , , , , , , , ,
Brain Implants that Augment the Human Brain Using AI

You probably clicked on this article because the idea of using brain implants to allow artificial intelligence (AI) to read your brain sounds futuristic and fascinating. It is fascinating, but it’s not as futuristic as you might think. Before we start talking about brain implants and how to augment the human brain using AI, we need to put some context around human intelligence and why we might want to tinker with it.

We floated the idea before that gene editing techniques could allow us to promote genetic intelligence by performing gene editing at the germline. That’s one approach. As controversial as it might be, some solid scientific research shows that genetics does play a role in intelligence. For those of us who are already alive and well, this sort of intelligence enhancement won’t work. This is where we might look towards augmented intelligence. This sort of augmentation of the brain will firstly be preventative in that it will look to assist those who have age associated brain disorders as an example. In order for augmented intelligence to be feasible though, we need a read/write interface to the human brain. One company called Kernel might be looking to address this with a technology that takes a page out of science fiction.


The advanced intelligence of tomorrow is a collaboration between the natural and the artificial. United, unheard of possibilities abound. We’re building off two decades of breakthrough research, working closely with private partners and scientists to get usable solutions in the hands of people everywhere. We’re starting with potential applications for patients with cognitive disorders.


To understand Kernel we must first understand the founder of Kernel, Bryan Johnson, a 39 year old man who exemplifies the American entrepreneurial success story. Growing up in the small city of Provo Utah, he hustled his way around as a serial entrepreneur from selling cell phones to establishing a VOIP company. He came up with his biggest idea while working a part-time job selling credit card processing services to businesses. The end result was a payment processing company called Braintree which he sold to eBay for $800 million in 2013.

Mr. Johnson then took some of his proceeds and founded a VC fund called OS Funds. “OS” stands for “operating system” and OS Funds then set out to invest in “entrepreneurs who are working towards quantum-leap discoveries that promise to reinvent the operating systems of life“. OS Funds managed to do just that by investing in ambitious startups like artificial intelligence pioneer Vicarious, drone delivery startup Matternet, nanobot factory Ginkgo Bioworks, and Human Longevity which wants to extend the lifespan of humans. Not content to just rest on his laurels, Mr. Johnson then went on to sink $100 million into a new startup he started this year called Kernel which wants to do nothing less than augment the human brain with artificial intelligence. In August of this year, Kernel came out of stealth mode and posted this cryptic video on their website:


If you can’t be asked to spend 44 seconds to watch the video, here’s what it says along with some cool futuristic animations:


Exploring our universe is extending the life of our earth. Understanding our genetic code is extending the life of our body. And now, we are unlocking our neural code to extend the life of our mind. So, what will it mean to live?

Kernel’s technology is centered around a researcher named Theodore Berger who has been working for the past 35 years to learn how to store brain memories on computer ships. Sound crazy? In a recent interview with MIT Technology Review, he stated “They told me I was nuts a long time ago”. The article goes on to state that “Berger is shedding the loony label and increasingly taking on the role of a visionary pioneer“. If $100 million in backing isn’t a total vindication of Dr. Berger’s “loony label”, then what else is? That’s the equivalent to the amount of money Illumina sunk into Helix.

Dr. Berger’s research has moved across the spectrum  from giving monkeys cocaine and seeing how they recall memories, to testing the memory process of people with epilepsy who have electrodes temporarily implanted in their brain. In the human tests, these electrodes were used to record signals sent to the hippocampus (shown highlighted in the below diagram):


Female Hippocampus Brain Anatomy - blue conceptFemale Hippocampus Brain Anatomy

Why the hippocampus? If we start to think of the brain as a sort of computer, the hippocampus is where short-term memories in RAM are converted to long term memories and then stored on the brain’s “hard drive” where long term memories are stored. It’s those long term memories that Dr. Berger is targeting. The ability to create a bridge between the hippocampus and a chip will allow for “memory implants” that can enhance the memory of those who are suffering from memory loss that accompanies aging. Since the way the brain works is often seen as a black box with 100 billion neurons firing away, Kernel is using machine learning in order to figure out how the brain goes about writing and retrieving memories. Kernel is actually using artificial intelligence to understand real intelligence which will lead to brain augmentation in the form of brain implants.

In an article he wrote on Medium about this incredible endeavor, Mr. Johnson states that the quest to enhance human intelligence “may be the largest market in history”. He also talks about he plans to “optimize for long term value creation by raising approximately a billion dollars from public and private sources” and that “each market approved product we create will require approximately $200M and 7–10 years”.

If Kernel can learn how to interpret the signals being sent to the hippocampus at 100% percent accuracy, then the “read/write” ability is covered. At the moment he claims to be more in the 80% range. Kind of like a 4-5 drink night out. If this whole thing works out, we’ll all be able to walk around with brain implants that give us the memory of an elephant and hopefully never have to worry about where we put our car keys. But that’s not all this means. Here’s where things can get a whole lot more interesting.

There’s been a lot of banter these days about the idea that we might be living in a simulation. The general idea is that if we can engineer our own simulations that are indistinguishable from our present reality, then it makes it likely that we are presently in a simulation. Then when Elon Musk came out and said recently that we’re almost certainly living in a simulation, everyone starts to think that maybe the idea isn’t so loony. If we think about what’s needed for this to happen in our present reality, virtual reality goggles aren’t going to cut it. You can take the goggles off anytime and you’re back in your living room.

The one thing that would make a simulation truly convincing would be a brain interface that would allow for every single one of your sensory inputs to be fed a stream of data. That’s the ultimate brain augmentation, the ability to plug a real-time data feed into our brain. That’s the direction Kernel is heading towards because if we can give the brain a place to store memories, we can speak the brain’s language and begin making it remember things that never happened, or forget things that did happen. Maybe psychologists are going the way of radiologists, or maybe we’ve read too many science fiction books, but some of the possible directions this could take are truly amazing to think about. This is exactly the sort of potential that led the founder of Kernel, Mr. Bryan Johnson, to state “We are at one of the most exciting moments in history“.


November 29, 2016 / by / in , , , , , , , , , ,
Researchers uncover algorithm which may solve human intelligence

02-35-54 Wikimedia Commons 


If we have the algorithm, we also have the key to true artificial intelligence.


The key element which separates today’s artificial intelligence (AI) systems and what we consider to be human thought and learning processes could be boiled down to no more than an algorithm.

That’s according to a recent paper published in the journal Frontiers in Systems Neuroscience, which suggests that despite the complexity of the human brain, an algorithm may be all it takes for our technological creations to mimic our way of thinking.

As reported by Business Insider, the idea that human thought can be whittled down to an algorithm lies in the “Theory of Connectivity,” which proposes that human intelligence is rooted in “a power-of-two-based permutation logic (N = 2i-1)” algorithm, capable of producing perceptions, memories, generalized knowledge and flexible actions, according to the paper.

First proposed in 2015, the theory suggests that how we acquire and process knowledge can be explained by how different neurons interact and align in separate areas of the brain.

It may also be that our brain power is based on “a relatively simple mathematical logic,” according to Dr. Joe Tsien, neuroscientist at the Medical College of Georgia at Augusta University and author of the paper.

The logic proposed, N = 2i-1, relates to how groups of similar neurons come together to handle tasks such as recognizing food, shelter, and threats. These cliques then cluster together to form functional connectivity motifs (FCMs), which handle additional ideas and conclusions.

The more complex the task, the larger the group of FCMs.


In order to test the theory and how many cliques are necessary to create an FCM, the researchers analyzed how the algorithm performed in seven different regions of the brain, all of which handled primal, basic responses such as food, shelter, and fear in lab mice and hamsters.

By offering different food combinations and monitoring brain responses, the team was able to document 15 unique combinations of neuron clusters.

Furthermore, these cliques “appear prewired,” according to the researchers, as they appeared immediately when the food choices did.

“The fundamental mathematical rule even remained largely intact when the NMDA receptor, a master switch for learning and memory, was disabled after the brain matured,” the scientists say.

Such research is an important step in improving our understanding of how the brain, and mind, works — and therefore how this scientific understanding could hypothetically be implied to future AI projects. It may not give us the key to improving our own intelligence, but if the basic components of how the brain is wired could be applied to artificial intelligence models, then who knows how far future AI will advance.

Originally published on ZDNet.

November 29, 2016 / by / in , , , , , , , ,
Caltech scientists use bacterial protein to merge silicon and carbon and create new organosilicon compounds
Could lead to products that are more environmentally friendly and potentially much less expensive; raises questions about alien lifeforms


Artist rendering of organosilicon-based life (credit: Lei Chen and Yan Liang ( for Caltech)

Scientists at Caltech have “bred” a bacterial protein with the ability to make silicon-carbon bonds, with applications in several industries — something only chemists could do before. The research was published in the Nov. 24 issue of the journal Science.

Molecules with silicon-carbon (organosilicon) compounds are found in pharmaceuticals and many other products, including agricultural chemicals, paints, semiconductors, and computer and TV screens. Currently, these products are made synthetically, since silicon-carbon bonds are not found in nature.

The new research demonstrates that biology can be used to manufacture these bonds in ways that are more environmentally friendly and potentially much less expensive, according to the researchers.


Caltech | Bringing Silicon to Life: Scientists Persuade Nature to Make Silicon-Carbon Bonds


Directed evolution

The key to this research involves deliberate messing with nature: a method called directed evolution* pioneered in the early 1990s by Frances Arnold, Caltech’s Dick and Barbara Dickinson Professor of Chemical Engineering, Bioengineering and Biochemistry, and principal investigator of this project.


An example of directed evolution with comparison to natural evolution. The inner cycle indicates the 3 stages of the directed evolution cycle with the natural process being mimicked in parentheses. The outer circle demonstrates steps a typical experiment. The red symbols indicate functional variants, the pale symbols indicate variants with reduced function. (credit: Thomas Shafee CC)

Directed evolution has been used for years to make enzymes for household products, like detergents; and for “green” sustainable routes to making pharmaceuticals, agricultural chemicals, and fuels.

In directed evolution, new and better enzymes are created in labs by artificial selection, similar to the way that breeders modify corn, cows, or cats. Enzymes are a class of proteins that catalyze, or facilitate, chemical reactions. The directed evolution process begins with an enzyme that scientists want to enhance. The DNA coding for the enzyme is mutated in more-or-less random ways, and the resulting enzymes are tested for a desired trait. The top-performing enzyme is then mutated again, and the process is repeated until an enzyme that performs much better than the original is created.


Going where no enzyme has gone before

In the new study, the goal was not just to improve an enzyme’s biological function but to actually persuade it to do something that it had not done before. The researchers’ first step was to find a suitable candidate, an enzyme showing potential for making the silicon-carbon bonds.

“It’s like breeding a racehorse,” says Arnold, who is also the director of the Donna and Benjamin M. Rosen Bioengineering Center at Caltech. “A good breeder recognizes the inherent ability of a horse to become a racer and has to bring that out in successive generations. We just do it with proteins.”


An Icelandic hot spring (credit: Nordic Visitor)

The ideal candidate turned out to be a protein from a bacterium, Rhodothermus marinus, that grows in hot springs in Iceland. That protein, called cytochrome c, normally shuttles electrons to other proteins, but the researchers found that it also happens to act like an enzyme to create silicon-carbon bonds at low levels. The scientists then mutated the DNA coding for that protein within a region that specifies an iron-containing portion of the protein thought to be responsible for its silicon-carbon bond-forming activity. Next, they tested these mutant enzymes for their ability to make organosilicon compounds better than the original.


cytochrome c (credit: Caltech)


After only three rounds, they had created an enzyme that can selectively make silicon-carbon bonds 15 times more efficiently than the best catalyst invented by chemists. Furthermore, the enzyme is highly selective, which means that it makes fewer unwanted byproducts that have to be chemically separated out.

“This iron-based, genetically encoded catalyst is nontoxic, cheaper, and easier to modify compared to other catalysts used in chemical synthesis,” says Jennifer Kan, a postdoctoral scholar in Arnold’s lab and lead author of the new study. “The new reaction can also be done at room temperature and in water.”

The synthetic process for making silicon-carbon bonds often uses precious metals and toxic solvents, and requires extra processing to remove unwanted byproducts, all of which add to the cost of making these compounds.


Could life on Earth (or elsewhere) have evolved based on silicon-carbon?

The study is the first to show that nature can adapt to incorporate silicon into carbon-based molecules, the building blocks of life.

Carbon and silicon are chemically very similar, and silicon is the second most abundant element in Earth’s crust. They can both form bonds to four atoms simultaneously, making them well suited to form the long chains of molecules found in life, such as proteins and DNA. Science-fiction authors have imagined alien worlds with silicon-based life, like the lumpy Horta creatures portrayed in an episode of the 1960s TV series Star Trek.

“This study shows how quickly nature can adapt to new challenges,” says Arnold. “The DNA-encoded catalytic machinery of the cell can rapidly learn to promote new chemical reactions when we provide new reagents and the appropriate incentive in the form of artificial selection.”

However, no living organism is known [yet] to put silicon-carbon bonds together, even though silicon is so abundant, all around us, in rocks and all over the beach,” says Kan.

What about other planets (Mars has both silicon and carbon, for example) and asteroids? And could alien life have evolved silicon-carbon semiconductor brains? It would also be interesting to see if such a lifeform could be invented on Earth.

This research is funded by the National Science Foundation, the Caltech Innovation Initiative program, and the Jacobs Institute for Molecular Engineering for Medicine at Caltech.

* Not to be confused with a transhumanist concept for controlling human evolution.


Abstract of Directed evolution of cytochrome c for carbon–silicon bond formation: Bringing silicon to life

Enzymes that catalyze carbon–silicon bond formation are unknown in nature, despite the natural abundance of both elements. Such enzymes would expand the catalytic repertoire of biology, enabling living systems to access chemical space previously only open to synthetic chemistry. We have discovered that heme proteins catalyze the formation of organosilicon compounds under physiological conditions via carbene insertion into silicon–hydrogen bonds. The reaction proceeds both in vitro and in vivo, accommodating a broad range of substrates with high chemo- and enantioselectivity. Using directed evolution, we enhanced the catalytic function of cytochrome c from Rhodothermus marinus to achieve more than 15-fold higher turnover than state-of-the-art synthetic catalysts. This carbon–silicon bond-forming biocatalyst offers an environmentally friendly and highly efficient route to producing enantiopure organosilicon molecules.

November 29, 2016 / by / in , , , , , , , , , ,
New unique brain ‘fingerprint’ method can identify a person with nearly 100% accuracy

Could provide biomarkers to help researchers determine how factors such as disease, the environment, and different experiences impact the brain and change over time.





A research team led by Carnegie Mellon University used diffusion MRI to measure the local connectome of 699 brains from five data sets. The local connectome comprises the point-by-point connections along all of the white matter pathways in the brain, as opposed to the connections between brain regions. To create a fingerprint, they used diffusion MRI data to calculate the distribution of water diffusion along the cerebral white matter’s fibers. (credit: Carnegie Mellon University)

Researchers have “fingerprinted” the white matter of the human brain using a new diffusion MRI method, mapping the brain’s connections (the connectome) at a more detailed level than ever before. They confirmed that structural connections in the brain are unique to each individual person and the connections were able to identify a person with nearly 100% accuracy.

The new method could provide biomarkers to help researchers determine how factors such as disease, the environment, genetic and social factors, and different experiences impact the brain and change over time.

“This means that many of your life experiences are somehow reflected in the connectivity of your brain,” said Timothy Verstynen, an assistant professor of psychology at Carnegie Mellon University and senior author of the study, published in open-access PLOS Computational Biology.


The local connectome: a personal biomarker



Demonstrating the level of detail, one local connectome fingerprint is shown in different zoom-in resolutions. A local connectome fingerprint has a total of 513,316 entries of scalar values. (credit: Fang-Cheng Yeh et al./PLoS Comput Biol)

For the study, the researchers used diffusion MRI to measure the local connectome of 699 brains from five data sets. The local connectome is the point-by-point connections along all of the white matter pathways in the brain, as opposed to the connections between brain regions. To create a fingerprint for each person, they used the diffusion MRI data to calculate the distribution of water diffusion along the cerebral white matter’s fibers.*

The measurements revealed the local connectome is highly unique to an individual and can be used as a personal biomarker for human identity. To test the uniqueness, the team ran more than 17,000 identification tests. With nearly 100 percent accuracy, they were able to tell whether two local connectomes, or brain “fingerprints,” came from the same person or not.

Curiously, they discovered that identical twins only share about 12 percent of structural connectivity patterns and the brain’s unique local connectome is sculpted over time, changing at an average rate of 13 percent every 100 days.


Decoding unexplored connectome data

“The most exciting part is that we can apply this new method to existing data and reveal new information that is already sitting there unexplored. The higher specificity allows us to reliably study how genetic and environmental factors shape the human brain over time, thereby opening a gate to understand how the human brain functions or dysfunctions,” said Fang-Cheng (Frank) Yeh, the study’s first author and now an assistant professor of neurological surgery at the University of Pittsburgh.

So we can start to look at how shared experiences — for example, poverty, or people who have the same pathological disease — are reflected in their brain connections, which could lead to new medical biomarkers for certain health concerns.

The team included researchers at the U.S. Army Research Laboratory, the University of Pittsburgh, the National Taiwan University, and the University of California, Santa Barbara. The Army Research Laboratory funded this research, which was supported by NSF BIGDATA, WU-Minn Consortium, the Ruentex Group, the Ministry of Economic Affairs, Taiwan, and National Institutes of Health.

* The local connectome is defined as the degree of connectivity between adjacent voxels within a white matter fascicle measured by the density of the diffusing water. A collection of these density measurements provides a high-dimensional feature vector that can describe the unique configuration of the structural connectome within an individual, providing a novel approach for comparing differences and similarities between individuals as pairwise distances. To evaluate the performance of this approach, the researchers used four independently collected diffusion MRI datasets with repeat scans at different time intervals (ranging from the same day to a year) to examine whether local connectome fingerprints can reliably distinguish the difference between within-subject and between-subject scans.


Abstract of Quantifying Differences and Similarities in Whole-Brain White Matter Architecture Using Local Connectome Fingerprints


Quantifying differences or similarities in connectomes has been a challenge due to the immense complexity of global brain networks. Here we introduce a noninvasive method that uses diffusion MRI to characterize whole-brain white matter architecture as a single local connectome fingerprint that allows for a direct comparison between structural connectomes. In four independently acquired data sets with repeated scans (total N = 213), we show that the local connectome fingerprint is highly specific to an individual, allowing for an accurate self-versus-others classification that achieved 100% accuracy across 17,398 identification tests. The estimated classification error was approximately one thousand times smaller than fingerprints derived from diffusivity-based measures or region-to-region connectivity patterns for repeat scans acquired within 3 months. The local connectome fingerprint also revealed neuroplasticity within an individual reflected as a decreasing trend in self-similarity across time, whereas this change was not observed in the diffusivity measures. Moreover, the local connectome fingerprint can be used as a phenotypic marker, revealing 12.51% similarity between monozygotic twins, 5.14% between dizygotic twins, and 4.51% between none-twin siblings, relative to differences between unrelated subjects. This novel approach opens a new door for probing the influence of pathological, genetic, social, or environmental factors on the unique configuration of the human connectome.



November 29, 2016 / by / in , , , , , , , , ,
Disrupting the brain’s internal clock causes depressive-like behavior in mice


Credit: Martha Sexton/public domain 


Disruptions of daily rhythms of the body’s master internal clock cause depression- and anxiety-like behaviors in mice, reports a new study in Biological Psychiatry. The findings provide insight into the role of the brain’s internal time keeping system in the development of mood disorders, such as bipolar disorder and major depressive disorder, which have been associated with disturbed daily (circadian) rhythms.

“Our data show that perturbing circadian rhythms in otherwise totally undisturbed animals is enough to cause behaviors similar to human depression,” commented first author Dr. Dominic Landgraf of the University of California, San Diego.

Inherent circadian clocks help us function throughout the day, by telling us when to sleep, wake and eat, as well as by synchronizing our bodily processes. “It is perhaps not surprising that disruptions of our natural synchronization can have heavy impacts on our physical and mental health,” Dr. Landgraf added.

However, until now researchers did not know if disturbed circadian rhythms were a cause or consequence of mood disorders. In the new study, a team led by David K. Welsh has shown for the first time a causal relationship between functioning circadian clocks and mood regulation.

The researchers developed a new genetic mouse model by suppressing Bmal1, one of the master genes that drives circadian rhythms, in the suprachiasmatic nucleus (SCN), which serves as the brain’s central clock regulator. Diminished Bmal1 expression reduced the strength of the clock signals produced by the SCN by about 80%. Targeting this particular brain region allowed the researchers to focus on the specific effects of the SCN circadian rhythms, and to avoid alterations in other brain regions that have confounded previous studies.

In behavioral tests, mice with reduced circadian rhythms, relative to control mice, were less motivated to escape an uncomfortable situation, which is commonly interpreted as despair or hopelessness in the animal. The mice also showed increased aversion to brightly lit areas, considered to be an indicator of anxiety-like behavior.

In addition to the altered behavior, mice with reduced circadian rhythms gained more weight than normal mice, even though they consumed the same amount of food. This finding suggests that disrupted SCN circadian rhythms could lead to metabolic abnormalities observed in many depressed patients.

Importantly, the findings show that even though the SCN does not directly regulate mood, alterations to circadian rhythms in the SCN are sufficient to cause depression- and anxiety-like behaviors in mice.

“We have long known that disruptions in circadian rhythms may contribute to depression, particularly in people at risk for major depression or bipolar disorder,” said Dr. John Krystal, Editor of Biological Psychiatry. “This new study provides additional evidence implicating the Bmal1 gene in the relationship between these circadian rhythms and mood.”

According to Dr. Landgraf, the results are an important step toward developing new depression treatments that directly target the circadian clock in humans.

More information: Dominic Landgraf et al. Genetic Disruption of Circadian Rhythms in the Suprachiasmatic Nucleus Causes Helplessness, Behavioral Despair, and Anxiety-like Behavior in Mice, Biological Psychiatry (2016). DOI: 10.1016/j.biopsych.2016.03.1050

November 29, 2016 / by / in , , , , , , , ,
What Could CRISPR Do Tomorrow?


CRISPR is the newest, most efficient and most accurate method to edit a cell’s genome. We have to understand it and prepare for the medical revolution it brings upon us, so here I summarized everything to know about this genome editing method from DNA-scissors to currently unimaginable possibilities, such as having an army of gene-edited soldiers. Here, let me show you the myriad of wonderful opportunities as well as the frightening ethical challenges what the CRISPR/Cas9 gene editing method could bring into healthcare in the future.


If such examples as the complete eradication of malaria, the possible end of cancer and the treatment of deadly genetic diseases are the most likely scenarios happening very soon, imagine the scope of results we might get to. Perfect humans? Eternal youth and beauty? Living for hundreds of years?

All of it is possible if we open the door of genome editing. But we have the utmost responsibility not to turn it into Pandora’s Box and let various monsters created through the inobservance of bioethical questions into the world.




1) We start “small”: let’s treat HIV

HIV inserts its DNA into the genome of the host, and while it can lay dormant for years and certain medical treatments can moderate its effects, there is no way to make the virus permanently inactive. In 2015, scientists used CRISPR to cut HIV cells out of living cells of patients in a laboratory – proving that it is possible. This year, they carried out a lab experiment with rats which had HIV in 99 per cent of their cells. By injecting CRISPR into the rats’ tails, they were able to remove 48 per cent of the virus from the DNA of their body cells. Although the experiments are still in their infancy, it seems that CRISPR could mean the ultimate solution to cure HIV and ultimately AIDS.



2) Drugs of the New Age

CRISPR/CAS9 could also mean a revolution for the pharmaceutical industry. New types of drugs may be developed for treating diseases which were previously thought deadly and incurable. Pharmaceutical giant Bayer AG and start-up CRISPR Therapeutics recently announced a $300 million joint venture to develop CRISPR-based drugs to treat heart disease, blood disorders, and blindness. Their cooperation could mean the dawn of a new drug development era focusing more on genetic methods. And who knows? Maybe in a couple of decades, it will be possible to treat cancer or AIDS through a pill or an injection.


CRISPR/CAS9-Drug Development


3) The Arrival of Superplants

If you think about GMOs and the Flavr Savr Tomato, plants are somehow always in the first row when it comes to genetic modification. It is no different with CRISPR. Researchers are currently experimenting with ways to improve crop disease resistance and environmental stress tolerance using the gene-editing tool. A research team from Rutgers is working on a long-term project to genetically modify wine grapes and turfgrass in such a way that the methods can be implemented in a variety of other crops. Imagine having jasmines blossoming the whole year in Scandinavian countries or harvest pumpkins in February. We have unlimited possibilities…




4) Boosting Human Intelligence?

In the era of smart phones, smart homes, smart cars and artificial intelligence – which is feared by many since it might be able to take over the world (Stephen Hawking even said that the development of full artificial intelligence could spell the end of the human race. Elon Musk agreed) –, it seems to be a smart idea to try to boost the intelligence of actual people as well.

A recent study identified 74 genetic variants—spelling mistakes in single nucleotides in the six billion letter human genome—which can be used to predict nearly 20 percent of the variation in school years completed, a quantitative trait of fortitude which is correlated to general intelligence, and which you can learn about by sequencing your own genome.

“In my opinion, CRISPR could in principle be used to boost the expected intelligence of an embryo by a considerable amount,” said James J. Lee, a researcher at University of Minnesota, one of the authors of that study. So, caution is necessary here. And not only because some will – rightfully! – think that intelligence is more than couple of genes in the right sequence. What about creative intelligence? What about the randomly wandering thoughts? What about the ability to produce memories? All these questions need to be studied, and it is still not sure whether they can be studied from the point of view of genetics – yet.




5) Editing humans?

And here we are. We arrived at the most problematic issue of genetic editing. To the human being and to what a lot of people consider already as the territory of the Gods. The editing of the genome of humans.

There are tremendous bioethical issues about human genetic editing starting from the pre-selection of embryos who could live and who will be condemned to death until the effective designing of babies. But I have to tell you that it is not a distant possibility in the future, it is already happening.

During pregnancy, there are lots of tests pregnant women go through. Many of them examine whether the foetus has any deadly genetic disease. For example, if the little embryo is diagnosed with Down-syndrome, the mother could decide to terminate the pregnancy. And in most cases, they do so.

Thus, whether you like it or not, whether you fee adverse and negative about it or not – it is already happening.

Moreover, researchers at the Francis Crick Institute in London want to genetically modify human embryos to learn more about the earliest stages of human life and potentially reduce the number of miscarriages.


CRISPR/CAS9 - Editing Humans


6) Designing babies?

Imagine the following scenario: you and your wife decided to have a kid. After going to the bedroom and having done the usual procedure, you call a genetic designer and ask for a personal appointment. Then you sit down at the kitchen table and start to talk about how your kid should look like and what traits should he or she have. You decide you would like to have a nice and healthy boy with plenty of blond hair (no, not like Donald Trumps’). He should be very intelligent, he should have great eye-sight, and he should have a great immune system, be muscular, be tall and have a nice smile.

And imagine a darker scenario. What if with the advancement of biotechnology, in a fully controlled society, a leader decides about the biological “casts” of people – producing humans who are working as blue-collar laborers, producing humans who are white-collar laborers or producing killing-machines – genetically modified soldiers with the inability to empathy or free will.

Are we far away from this? Should we be far away from this?

Chinese researchers reported using CRISPR to edit the genome of human embryos in April 2015, however they sparked a worldwide debate over how this technology could (or should) be used.

The gene-editing of embryos carries huge risks as CRISPR can accidentally edit genes that have a DNA sequence similar to its target, and cause irreversible mutations in the embryos. It is a scary and very alarming outcome, and we should definitely do everything in our power to avoid such scenarios.



7) Eternal Youth and Living Forever?

And what happens, if we are able to eradicate diseases and to design perfectly healthy humans? What if we also find the gene which is responsible for aging and we will be able to cut it out with the help of CRISPR? Are we going to live for two- or three hundred years and die looking like our 22-year-old selves?

How could we deal with such a scenario? Can we even deal with the possibility that it is already imaginable with the recent scientific method? It would completely change our perception about our species, our relation to nature – even life and death itself. And what if something goes wrong? What are the consequences to such a scenario? If we cut malaria genes out of mosquitoes, what if we kill them by accident? What will bats eat then? And what if something bigger happens? What if we condemn humanity to death?

Can we even think about such issues buried in our little universes?

Where are our finest philosophers to offer some insight about it? Because we not only need science, but also philosophy, religion and ethics to keep up with the rapid developments and offer advice.




What Can We and What Should We Do?

When the Chinese researchers reported using CRISPR to edit the genome of human embryos in April 2015, the world’s foremost geneticists, biotechnologists, and bioethicists decided to gather and discuss the issue with immense significance.  They gathered in Washington to discuss the future of gene editing, agreed that basic research should progress but there should be a moratorium on editing human embryos on pregnancies.

But CRISPR itself cannot be stopped from other types of research apparently. Couple of months after the Chinese experiments were reported, in February 2016, UK scientists have been allowed by the Human Fertilisation and Embryology Authority (HFEA) to use the CRISPR on unused human embryos. In June, 2016 it was reported that a United States advisory committee has green-lighted the use of CRISPR in human trials.

Genome editing did not appear overnight. Eric Meslin, the director of the Indiana University Center for Bioethics reminded here that we’ve been talking about manipulation of the genome for 40 years, since the 70s. There was steps like the sheep clone Dolly, patients dying from gene therapy treatments, the stem cell debate of the early 2000s—all of these echoes are present whenever the ethics of CRISPR come up, he added.




Bioethicists usually strike a balance between regulation and permission—too much permission, and researchers can ignore societal constructs of morality; too much restriction means progress slows down, and scientists start to operate outside that agreement in shady, grey cellars financed by evil-minded billionaires. They believe that bioethicists need to be more–not less–involved in the conversation about CRISPR. However, the most important issue is that for technologies that have the capacity to disrupt the world of research and medicine as we know it, everyone–researchers, politicians, sociologists, theologians, average citizens all over the world–must be drawn in to the discussion.

David Lemberg, the founding editor of Bioethics Today and associate faculty professor in the Department of Community Health at National University says that the role for bioethicists—and of all stakeholders representing numerous interest groups—is to oversee research and to limit its conduct based on the precautionary principle.

“Just because we can do a thing does not mean we should do the thing”, he added. And I completely agree with his statement. Although we need to facilitate the advance of such research methods in curing diseases, but an army of bioethicists are needed to make sure we keep human values we are meant to keep.

And if you want to see what the topic is about in a nutshell, check out this awesome video, we were referring to through the whole time:


[The Medical Futurist]


November 29, 2016 / by / in , , , , , , , , , ,
What can you achieve with CRISPR therapy today?


CRISPR is the newest, most efficient and most accurate method to edit a cell’s genome. It opens up a myriad of wonderful opportunities as well as frightening ethical challenges in healthcare. We have to understand it and prepare for the medical revolution it brings upon us, so here I summarised everything to know about this genome editing method from DNA-scissors to currently unimaginable possibilities, such as having an army of gene-edited soldiers. Let me introduce you, what can you achieve with CRISPR therapy today.



CRISPR therapy


1) The Gene-Editing Tool

So you should know that scientists around the world are already using this technique in several of their projects. In addition, global research and development companies started using CRISPR/Cas 9 for the development of drugs to treat a number of life-threatening medical conditions, including sickle-cell anaemia and cancer.

For example, Columbia University Medical Center (CUMC) and University of Iowa scientists have used CRISPR to repair a genetic mutation responsible for retinitis pigmentosa (RP), an inherited condition that causes the retina to degrade and leads to blindness in at least 1.5 million cases worldwide. The researchers published their study about it in Scientific Reports.

The authors of the study said that: “We still have some way to go, but we believe that the first therapeutic use of CRISPR will be to treat an eye disease. Here we have demonstrated that the initial steps are feasible”.



2) The Tool Turning Genes On and Off

In 2013, a researcher called Stanley Qi, working currently at Stanford University, found a way to “mess up” the working of the DNA scissors, actually blunting them, and so creating a “dead” version of Cas9 that can’t cut anything at all.

The team developed ways of using the blunted enzyme to switch genes off (CRISPRi, where the i stands for interference) or on (CRISPRa, where the a stands for activation), or to tune their activity over a 1,000-fold range. They used these techniques to quickly and thoroughly screen human cells for genes that they need to grow, or to deal with a bacterial toxin.

Now, instead of a precise and versatile set of scissors, which can cut any gene you want, you have a precise and versatile delivery system, which can control any gene you want. You don’t just have an editor, but you have a tiny entity controlled from outside. It is genius and scary at the same time.


CRISPR therapy - genome editing


3) The Tool Treating Huntington’s Disease

One recent breakthrough is the use of a CRISPR formed from mouth bacterium that is capable of breaking RNA, the part of cells that help transform genes into usable proteins. The RNA version of CRISPR was developed by researchers at the Massachusetts Institute of Technology (MIT). It is based on a certain enzyme known as C2c2, which helps keep bacteria protected against other microbes such as viruses.

By manipulating the RNA, researchers could influence gene activity as well as the production of protein in the body. This would effectively grant them the ability to turn the process up or down, or even switch it on or off to suit their purposes without affecting the genetic codes stored in the RNA. This whole method means that it is now becoming increasingly possible to develop better forms of treatment that can target specific malignancies in the body, such as Huntington’s disease.



4) The Tool Against Malaria

The World Health Organisation (WHO) estimates that about 3.2 billion people – nearly half of the world’s population – are at risk of malaria. In 2015, there were roughly 214 million malaria cases and an estimated 438 000 malaria deaths, thus it is overtly important to fight and prevent the disease. One of the best methods is to somehow fight off its primary transmitter, infected mosquitoes.

Researchers have used gene-editing to create mosquitoes that are almost entirely resistant to the parasite that causes malaria. They used CRISPR to remove a segment of mosquito DNA, and when the mosquitoes’ genetic system tried to repair the genome, it was tricked into replacing it with a DNA construct engineered by the scientists. They found that 99 per cent of the offspring of the genetically modified insects also had the malaria-resistant genes. So some genetic change had occurred.


CRISPR therapy - Against Malaria-spreading Mosquitos


5) The ultimate weapon against cancer

As a very simple explanation, cancer occurs when cells refuse to die and keep multiplying in various places in our bodies, while hiding from our immune system. With CRISPR, we will have the chance to edit our cells in our immune systems to improve them against cancer cells and to help them kill these malevolent entities in time. In the future, getting rid of cancer could mean just an injection as now against mumps which was a deadly disease for children in the 1800s.

And lately, something miraculous happened. After trying traditional cancer-treating methods such as chemotherapy and bone-marrow transplants, doctors decided to use gene-editing technologies in a last-ditch effort to save a girl who was suffering from lymphoblastic leukemia. The doctors altered the immune system, namely T-cells of a donor to more effectively locate and kill leukemia cells – without attacking the patient’s organism. Actually, they did not use CRISPR, but another method, TALEN, but in any case, it turned out to be a huge success.



6) The Shield Against Duchenne Syndrome

Patients with the devastating Duchenne’s Muscular Dystrophy lose the ability to walk by their teens, and often die from one of a number of complications—like respiratory or heart failure—at a young age. The disease is caused by a mutation that prevents the body from producing the dystrophin protein, a critical protein in the development of muscle tissue.

Since the syndrome is retraceable to one specific mutation of a gene, researchers are experimenting with the use of CRISPR in finding a treatment for it. This year, experiments showed that scientists were able to treat mice with the Duchenne’s Muscular Dystrophy through gene editing – thus the technology has great promise in treating people suffering from this deadly illness in the near future.



7) With the Advancement of Research, We Could Have Clinical Trials in 2017 (!!)

The discovery of CRISPR has been having the impact on science as the discovery of the DNA and the Human Genome Project in itself was. Research labs are popping up like mushrooms, such as Intellia Therapeutics or CRISPR Therapeutics. Apparently, it is very sexy to work on CRISPR-related projects.

Editas Medicine is one of the leading genome editing, biotechnological company dedicated to treating patients with genetically-defined diseases by correcting their disease-causing genes. Its mission is to translate the promise of genome editing science into a broad class of transformative genomic medicines to benefit the greatest number of patients. Their areas of research include eye diseases, blood- muscle or lung diseases and cancer.

With the advancement of CRISPR research, it is somehow almost natural that the possibility for clinical trials appeared. Editas Medicine said that the company hopes to start a clinical trial in 2017 to treat a rare form of blindness (leber congenital amaurosis, which affects the light-receiving cells of the retina) using CRISPR. If Editas’s plans move forward, the study would likely be the first to use CRISPR to edit the DNA of a person.



These are only a few examples of the many out there. But I’m sure they will mark the beginning of a new era in genome editing and healthcare in general. However, I also believe that the long-term impacts on society and the ethics of doing research will be of much higher altitude. CRISPR could actually bring tremendous change to our future with designer babies, the eradication of diseases or that of ageing. Exactly due to such impacts, it will also generate huge ethical dilemmas and ultimate questions about our way of life. [The Medical Futurist]

November 29, 2016 / by / in , , , , , , , , ,
Bioprinting Is One Step Closer to Making a Human Kidney





Bioprinting has been all over the news in the past several years with headline-worthy breakthroughs like printed human skin, synthetic bones, and even a fully functional mouse thyroid gland.

3D printing paved the way for bioprinting thanks to the printers’ unique ability to recreate human tissue structures; their software can be written to ‘stack’ cells in precise patterns as directed by a digital model, and they can produce tissue in just hours and make numerous identical samples.

Despite the progress in bioprinting, however, more complex human organs continue to elude scientists, and resting near the top of the ‘more complex’ list are the kidneys.

Kidney basics

The kidneys, bean-shaped and fist-sized, are located below the rib cage on either side of the spine and play a critical role in our day-to-day health. Each kidney cleans the blood by passing fluid and waste products through a biological filter called a nephron that blocks blood cells and important molecules like proteins. Necessary minerals are passed back to the blood, and waste exits the body in urine.

Our kidneys filter 120 to 150 quarts of blood every day, keeping the blood’s composition stable and our bodies functioning properly. Our kidneys prevent waste buildup in the body, stabilize our electrolyte levels, and produce hormones to regulate blood pressure and make red blood cells.

They don’t work for everyone

About 10% of the global population is affected by chronic kidney disease, with millions of people dying each year due to lack of affordable treatment. In the US, treatment of chronic kidney disease costs around $48 billion per year, consuming almost seven percent of the total Medicare budget to care for less than one percent of the covered population. There are over 93,000 people currently on the US kidney transplant waiting list, with wait times ranging up to ten years.

Lacking a donor kidney, patients who can afford it undergo dialysis, which requires them to sit for three to ten hours as blood passes out of their bodies, through a machine that cleans it, then back into their veins. Despite the high cost and time commitment of dialysis, it still doesn’t do as good of a job of cleaning the blood as kidneys do.

A better solution may be near

The kidneys are one of the hardest organs to recreate—if not the hardest. This is due both to the huge number of nephrons contained in each kidney and to the nephrons’ intricate structure.

But scientists at Harvard’s Jennifer Lewis Lab recently took the first step towards creating an artificial kidney that could one day replace biological donor kidneys. Using 3D printing, Lewis and her colleagues were able to re-create the tubule component of the kidney’s nephrons and give it a vascular network for blood flow.

The first step was to print a 3D tissue grid made of layers of gels at room temperature. One gel contains human stem cells, and the other becomes a liquid when cooled.

As the tissue sets, it cools off, which causes the second gel to flow out of the grid, leaving behind channels where blood vessels can grow. An alternative method, developed by researchers at Wake Forest University, is to program the printer software to leave microchannels in the tissue structure.

The material is enclosed in an extracellular matrix, then growth factors are added to the hollow channels to prompt the stem cells to differentiate into specific cell types.

The 3D printed tubules were able to stay alive for over two months.

Steady progress

Last year, scientists at Lawrence Livermore National Laboratory developed a method that allows vascular networks to self-assemble in bioprinted tissues. Until that point, the vascular network was the biggest missing piece for bioprinting organs.

The kidney tissue created at Lewis Lab is significant because of the tubules’ complexity, and the fact they were partially able to function as biological nephrons do.

Bioprinting has a ways to go before being able to create a fully-functional organ, but the technology has other useful applications. Bioprinted nephron tubules could be used for drug toxicity testing, helping determine biological kidneys’ ability to filter certain chemicals, or they could be incorporated into existing dialysis methods to make the procedure more similar to the way our bodies intended.

Individual advancements in bioprinting may seem small, but if they continue at their current pace, we may see printed organs start to take the burden off those donor lists during our lifetime.

This post originally appeared on SingularityHub.

November 28, 2016 / by / in , , , , , , , , ,
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