From Start-up Nation to Brain Nation: Interview with Israel Brain Technologies founder Dr Rafi Gidron

“Our brain enabled us to produce artificial brains, but did not permit us to enter our own brains. We are strangers to ourselves.”

“Israel lives on its brain. We’re now embarking on the fourth revolution. The first were the agricultural, industrial and information revolutions, and now comes the revolution of the brain. This is a problem that Israel devotes itself to solving as quickly as possible and as strongly as possible. Israel is well-positioned to assume a leadership role in the emerging neurotechnology industry that promises to make the world a better place”

                                                                                 -Israel's President Shimon Peres, 2011
                     

Israel is often referred to as the “Start-up Nation”, but Israel’s president Shimon Peres is seemingly fascinated by a much further frontier than that. From “Start-up Nation” to “Brain Nation” is how the recent non-profit Israel Brain Technologies (IBT) initiative is commonly described. The main goal of the initiative will be to steer Israel’s immense R&D efforts in a more neuro-inspired direction, carrying the ultimate goal of making Israel a leading neurotech hub of the world. 

The initiative was conceived under President Peres’s firm belief in the future of neurotechnology, but was put in motion by one of the most successful entrepreneurs in Israel’s history—Dr Rafi Gidron, who was the official founder of IBT and now serves as its chairman. Gidron founded an optical component company Chromatis in 1998, and sold the company to Lucent just 27 months later for $4.7 billion, in what has since become Israel’s largest exit. 

Gidron strongly supports the President’s vision to turn Israel into the go-to neuro nation. After all, Peres was able to raise $250 million for nanotechnology research, and there isn’t a doubt that he could do the same for neurotech. IBT is now entering its third year of operation, and already over $10 million was raised for areas which form the focus of the initiative: human-machine interface and neurological therapies. 

Currently IBT is generating hype through its $1 million prize offered for yet another brain acronym--the B.R.A.I.N. (Breakthrough Research And Innovation in Neurotechnology) competition, which will see most promising scientists around the globe lock horns over who will be the creator of the most innovative technology around the world in the following spheres:

• Technology for diagnostics and treatment of brain disease
• 
  
• Technology which can improve scientific understanding of the brain
• 
  
• Groundbreaking brain-machine interface technology
• 
  
• Innovative brain stimulation technology
• 
  
• Disruptive neuro-technologies in computation, robotics and communications

Currently a team of leading researchers and neuro-experts around the globe, which include three Nobel laureates Profs Eric Kandel, Daniel Kahneman and Bert Sakmann, are selecting a number of finalists of the Brain Prize, which are to be announced in May of 2013. The winner will be revealed at IBT’s Global Brain Technology conference in October 2013. 

More info at www.IsraelBrain.org

Interview with IBT founder Dr Rafi Gidron

Dr Rafi Gidron may be best known for having orchestrated Israel’s largest start-up exit, but today this serial entrepreneur, angel investor and Columbia PhD graduate holds the key to success of the country’s newest vision: to reenact Israel’s hi-tech triumphs, with neurotechnology as the lead star. Dr Gidron has helped assemble an elite multi-disciplinary team of experts who will be responsible for advancing the Israeli neuro-dream. As IBT chairman he is responsible for moving forward the vision that was inspired by President Shimon Peres, by establishing IBT’s infrastructure and objectives, and building sound financial support around the initiative. A key role which IBT is expected to play is being the mediator between international investors and Israeli technologies, and well as various global foundations and Israeli academia. 

One could almost say Dr Gidron was reared for the role of IBT founder: as an avid brain enthusiast for over 10 years he studied the field in depth, and, during the fruitful time of nanotechnology circa 2003, he was involved in Pres. Shimon Peres’s initiative to advance Israel’s nanotech arena. When Pres. Peres’s vision of Israeli neurotech surfaced, Gidron, having accumulated a wealth of entrepreneurial insight and acumen, instantly saw the opportunity. Like Israel’s president, Dr Gidron agrees that neurotechnology is the ultimate challenge, and the ultimate opportunity, of the 21st century. It just so happens that Israel is excellently positioned to be a globally impacting winner in this space, provided that its journey is in the right hands (it is, trust us). 

IBT B.R.A.I.N. Prize finalists are to be announced on May 15th, and winners in October 2013 at IBT’s first-of-a-kind Global Brain Technologies Conference. The project has received over 70 applications: ~40% from the US, ~30% from Israel, ~20% from Europe, and the remainder from the rest of the world. Dr Gidron hopes that this project will bring the world to Israeli brain technology, and Israeli brain technology to the world. In addition to the $1 million prize, the winning project will gain the support of IBT, which will continue as a close cooperation to develop the world’s next breakthrough. For IBT, the B.R.A.I.N. competition will demonstrate Israel’s ability to become a hub connecting and accelerating global neuro-technologies. 

Dr Gidron says that IBT is still in preliminary stages of development, but its chief priorities are to support and nurture the nascent neurotech industry through whatever means possible. As IBT gathers momentum, it continues to attract industry leaders and academic and public sector experts. As of today, two Nobel laureates are already part of IBT’s scientific board. One of the developments which Dr Gidron would like to see in the future is the establishment of a neurotech development facility in Israel by a large multinational corporation (MNC), which would contribute to the country’s impressively high MNC presence in other industries. 

Asked about whether the IBT will be looking to cooperate with other world brain initiatives, like the Human Brain Project and the B.R.A.I.N, Dr Gidron said that this will form an integral part of the mission, and added that he is very excited to see other world leaders share the neurotech vision. He says that collaboration between the IBT and the HBP is currently in the works.

Like many experts in the field, Dr Gidron acknowledges that Israel possesses a particular strength in medical devices, which is why IBT isolated key areas of focus with a particular sway in that direction. In his opinion, the burgeoning defense industry, a strong track record in technological innovation, a vibrant culture of entrepreneurship and risk-taking and the multidisciplinarity of all aspects of life in Israel contribute to its unique edge and its quirky inimitability. 

Dr Gidron ends with a sound bite, “Israel: It's not only a State of Mind. It’s a State of Brain!”. And, in retrospect, perhaps another reason for Israel’s enigmatic success is precisely people like him.

Top Neurotechnology Breakthroughs of 2012-2013

The past two years proved to be very fruitful in the world of neuroscience, with both academia and industry exposing new secrets of the mind and unveiling yet more awe-inspiring gadgets. The year has not only delivered incredible breakthroughs in neuroprosthetics, visual stimulation and mind-reading, but also witnessed a substantial leap forward in our understanding of the “connectome” – the complex universe of neuronal pathways and interactions which shape the mind. Most remarkably, it is becoming increasingly clear that our practical knowledge of grey matter is improving at electric speeds, as more and more life-saving technologies contest to humanity’s neuro-scientific accomplishments.  

Below is a collection of some of last year’s prominent advancements, starting with perhaps the most celebrated: the thought-powered leg. 

Having lost his limb in a motorcycle accident, 31-year-old Zac Vawter was fitted with a bionic replacement, called electromyeloid prosthesis—operated entirely by his mind. The neuroprosthetic was initially developed at the Rehabilitation Institute of Chicago (RIC) in 2005, and has reached the peak of its performance last year, when Vawter demonstrated the bionic leg’s awesome powers by climbing 103 flights of stairs of Chicago’s Willis Tower—even skipping two steps at a time.  The device works owing to “targeted muscle reinnervation” (TMR) –essentially a re-wiring of the patient’s neuronal pathways. When Vawter’s leg was amputated, the nerves of his lower leg were surgically rerouted to his hamstring, where muscle signals powering his neuro-robotic leg now originate. Legs have not been the sole limb eligible for neuro-replacement: in 2001 researchers at the Rehabilitation Centre awed the public when they fitted bionic arms for Jesse Sullivan, a 40-year-old electrician who lost both limbs in a work accident. Hundreds of neuroprosthetics have since been implanted, getting incredibly nifty from year to year. 

Therapeutic neurostimulation has also been hot off the conveyor belt last year. Israeli Brainsway is a developer of a Transcranial Magnetic Stimulation (TMS) device which, in essence, is a fancy name for a deep brain tissue massager. Brainsway’s key technology—Deep TMS System—exploits our knowledge about areas of the brain responsible for depression and other neurological disorders, the likes of which are Alzheimers and schizophrenia. The system comes in the shape of a brain helmet which offers completely non-invasive electromagnetic neurostimulation of grey matter. By stimulating areas responsible for depression, the TMS helmet offers an effective 15-minute anti-depression “cranial massage”. Sounds a little sci-fi? The FDA does not think so—the agency has recently approved Brainsway’s TMS system for the treatment of depression patients who have not responded well to other treatments, and the company is working on expanding their therapeutic targets towards autism and Parkinson’s disease in the near future. 

Not any less important on the list of last year’s breakthrough neuro-developments is our newfound mind-reading ability. Using electrodes to detect spikes in brain activity, scientists have been able to map areas of the brain responsible for a plethora of thoughts, actions and emotions. They have now put that knowledge to use, quite literally communicating with a comatose patient with the use of an fMRI scanner. A man believed to be in a vegetative state for 12 years was able to tell doctors he was not in pain, kick-starting what has since become a revolution in our understanding of the comatose state. The occurrence caused medical books to be rewritten, as it gave us the ability to communicate with thousands of patients previously deemed unresponsive.

Since its inception mind-reading wasted no time expanding beyond hospital walls. Last year has brought up the phenomenon of mind-controlled gaming (MCG)—and the dangers this form of entertainment carries with it. Despite its early stages of existence, MCG has gained popularity in recent years, and developers like NeuroSky and Emotiv are already marketing devices which detect and interpret brain waves via external electrodes. The issue is—our understanding of this type of interface is akin to our familiarity with the brain—the foundations are certainly in place, but hardly solid enough to embark on an elaborate build. With that said, an important finding emerged at last year’s Usenix security conference in Seattle: mind-controlled interfaces pose a very realistic threat of “brain leaks”. In other words, in what is probably the most fearsome of worldly exploits, a hacker who gains access to an MCG device can potentially access the user’s thoughts. Particularly at stake is private information such as pin codes and passwords, which can be deduced via spikes in electroencephalography (EEG) readings in response to words and images familiar to the user.

And it looks like the burgeoning thought-stealing market comes with its very own weapon: a memory chip now exists in its literal form. Scientists at the Wake Forest University and the University of Southern California have, in an ingenious set of experiments, demonstrated successful thought implantation in mice. Having observed specific brain activity in mice familiarizing themselves with a maze, scientists then implanted a microchip in the subjects’ brains which could be programmed to stimulate the same set of neurons in a different setting. Thus, once a mouse memorized mazeA, for instance, and was then moved to mazeB, a specific memory pattern could be triggered by the implanted microchip which would bring up memories of the familiar maze. Much to the scientists’ astonishment, the mouse would follow the same familiar trail in any new environment—but only if its “familiarity neurons” were triggered by the microchip. Even more bizarrely, the same implant in a completely new subject’s brain brought up the same hybrid memories. The implications of this research are unfathomable: starting with interfering with harmful memories of trauma or disease, all the way down to sci-fi manipulation of the mind we have for so long anticipated in fear.

And just when you thought neuroscience couldn’t get any more awesomely frightening, false memory implants can now be completed with a full set of artificially-controlled decision making. As a harbinger of what forward-looking science authors have previously dubbed the menticide, scientists have demonstrated the ability to correct the decision-making process in cognitively impaired non-human primates. The MIMO (or multi-input multi-output) prosthesis is able to learn from correct decision-making patterns in the brain, and to “replay” them in primates which were mentally impaired following drug administration. The MIMO was able to improve decision making 10% above the norm—and that is just the beginning. Researchers hope that in the future this type of device will benefit people who have suffered strokes and brain injuries which resulted in diminished cognitive ability.

A similarly wonderful technology which neuroscientists claim is only 5 years away is “webcam vision”—a technology which is based on artificial stimulation of the visual cortex in visually impaired patients. For some time now it has been known that blind people are able to “see” just with their brains, and a prosthetic device which could detect the external environment and generate basic images in the brain is only half a decade away. Currently, a team of scientists at the University of Texas are generating a detailed map of the visual cortex, and are hoping to begin working on a visual prosthetic device in the near future.

And last but certainly not least, alongside the fascinating annual developments in the sphere of neuroscience runs our continuous effort to fathom the complex macrocosm which unites every neuron, synapse and chemical signal in the brain. A massively ambitious effort to map brain synapses, titled “The Human Connectome Project” has been underway in the neuroscientific community. Not only does the initiative hope to re-create a complex 3D neuronal map of the brain, but it also aims to answer the very basic question of how neuronal synapses—or nerve crossroads—are formed, and what influences this formation. A breakthrough milestone was achieved in this sphere in 2012: scientists were able to unveil key principles which guide the formation of neuronal interceptions, and applied these principles to a computational structural prediction model. In this way they were able to demonstrate that brain neurons grow independently of each other, and form connections once they intercept each other’s paths in the brain. The implications of such a development are not negligible: the breakthrough has brought us eons closer to a realistic possibility of an in silico brain reconstruction.

Last years' key advancements showcased here would probably sound like yet another science fiction novel to the untrained ear, but ironically they are mere specks in the rich and succulent broth of neurotech progress today.  The pace with which the field of neuroscience has been advancing in recent years is unparalleled by any other sphere of knowledge, and the coming decade will inevitably bring about exponential leaps in our abilities to treat, shape and harness the mind. One thing is clear: if the past is any indication of the future, the future is absolutely neuro-tastic. 

How to Increase your Company's Value During Fundraising Rounds by Building a Solid Biotech Brand

A biotech startup is likely to hold immense value which is entirely invisible to investors. This value comes in the form on employees, scientific and managerial know-how, intellectual property tied to the company, and many other features which lay hidden away from investors' sight, contributing nothing to the price tag of the company. 

Imagine shopping for a dress when you could only see 10% of it. It sounds risky and absurd, right? Yet  many biotech investors are "shopping" for new ventures in this way every day. And the truth is, because of the riskiness of such investments, investors are understandably shying away from the biotech sector altogether .

Investors would like to be sure that the management team have what it takes to bring the technology to fruition, that the intellectual property of the company is solid and valuable, and that the founders are experts in their field. Surely, due diligence can solve all that, but many investors won't even enter that stage when there is simply nothing to Google about the company. 

For founders who have passion and faith in their start-up, not maximizing the visibility of the brand's assets, particularly through 100% free and simple online means, is not doing their company justice. This is why collecting all the awesome company features under one brand umbrella, and making them visible to the world, will do huge favors to risk-wary investors, and will absolutely elevate the company above the rest during fundraising. And, when the company's product finally nears the market, the solid biotech brand built from day one will save a colossal amount of marketing effort, and significantly cut marketing costs. 

Bio-Brand your Way Through the Valley of Death and Beyond

A month ago Bioassociate covered a marketing technique for your biotech start-ups: Bio-Branding. Below is a re-run of the article for those who have missed it.

Original article can be found here.

If there is any truth biotech founders may rely on, it is that they will be Googled by potential investors, says Bioassociate's Julia Skripka-Serry. Building a bio-brand from day zero can become the defining factor in a biotech's investability and survival.

Most founders of young biotechs wouldn't consider brand building relevant to their business strategy until at least half a decade post-inception. Branding through the valley of death may seem like a sour paradox, not in the least because most bio-marketing literature out there focuses far too much on the product, and not enough on the components which create the company's intrinsic value.

If you happen to belong to the contingent of brand-skeptical founders, perhaps now is the time for a paradigm shift. Building a company brand from moment zero can become the defining factor in your biotech's investability and survival — unless, of course, you happen to be a serial entrepreneur with millions to spend on your new venture.

Too many biotechs fundraise on an empty stomach

As an unfortunate traditional code of conduct in the biotech world, seed- and early-stage fundraising activity tends to be conducted in stealth mode. Armed with a business plan and a handful of scientific publications, fundraising founders will normally seek direct contact angel / VC investors in hopes that the science and first impressions alone will suffice to build the notion of value. But in an era when roughly 220 new biotechs form annually (US, EU & Canada), a growing biotech pool competes for the same dollar every year. In this environment, a distinguishable brand can easily elevate a company above the competition. And chances are if a technology is ready for financing, the company already holds much more value than its founders may perceive. Unleashing this value is a matter of appropriately disseminating and communicating information.

"If you happen to belong to the contingent of brand-skeptical founders, perhaps now is the time for a paradigm shift."

Growing in the spotlight: building a brand in the "Googlosphere"

Your web search results talk, and if there is any truth biotech founders may rely on, it is that they will be Googled by potential investors. Has your company's founding scientist published breakthrough scientific material? Get him to summarize and publish it on a company blog (in layman's terms!). Has the therapeutic compound you are working on achieved outstanding results in pivotal trials? Let the world know about it on your company's LinkedIn page. Or, perhaps, your key technology is in-licensed and the management holds a wealth of experience in commercializing projects? Consider contributing a thought-leadership article on pharmaphorum. Not only will this visibility give the company street cred, but it will help people understand the technology. Scientific journals aren't titled Harry Potter and Nature Biotechnology for a reason – perhaps if scientific publications were thrilling (and cheap!) reads, investors wouldn't liken biotech investment to a trip to Vegas.

Tools for web supremacy

A "Bio-brand" is essentially a collective of all the components which speak the company name. This includes the founders' and employees' reputation and expertise, intellectual property, publications, peer reviews and, most of all, the company's presence in the Googlosphere.

"In truth, like in all aspects of marketing, the most successful campaign is the one that never ends."

Blogger, LinkedIn, Facebook, Twitter, a wealth of online forums and leading websites which appreciate expert-based contribution are all valuable and completely free tools for establishing a solid company brand and for boosting the company's visibility in search results.

Last time I checked, there seemed to be an infinity of such tools — thus, the question is, when can you stop building the brand? In truth, like in all aspects of marketing, the most successful campaign is the one that never ends. But this means that you can tailor brand building around your availability, and do a little at a time to contribute to continuous brand growth.

Investors like to bet on the jockey, rather than the horse

An important side-note to keep in mind is that technology does not found itself, and investors tend to care immensely about a company's management. If every founder and employee published at least one thought-leadership article before fundraising, each would create a personal brand under the company umbrella, and the "sum of the jockeys" would contribute to a nifty initial value. It's no surprise that many leading companies request that their employees tweet and blog under the company brand: a personal brand is, rather bluntly, a personal price tag. And the sum of price tags is the worth of the shop.

It is likely that company founders can already boast an abundance of value-creating information. They have certainly produced presentations, articles and personal notes in the past. Now it is just a matter of putting this information online and tying it to the company name.

Would you read this?

It is worth mentioning that screaming your company's name for no apparent reason is a faux pas: unlike other industries, marketing in biotech is 99% information-driven, where advertisements are value-carrying words, rather than shrewd slogans and subliminal imagery. When releasing information to the great wide web, put yourself in the shoes of the investor.

Below is a typical life science investor's due diligence checklist:

It is astounding how many of those boxes an online search can help tick off. Keep these items in mind when producing online information, and watch your company's value grow in the investor's eyes.

"...screaming your company's name for no apparent reason is a faux pas..."

Much of your brand value should eventually come from the outside

Naturally, the valuable information you release will attract other experts who will share and cite it. In a world where much importance is put on assessing and validating our sources, brand value is directly proportional to the quality of the places you contribute to and the brand value of the people/entities which refer you.

But ultimately, for a fund-seeking biotech, external value assessment and scientific evaluation is a powerful value-creating step. Larger-cap companies normally benefit from getting picked up and valuated by independent analysts, but companies of smaller scale are finding it increasingly useful to commission analyst coverage. Not only does a valuation report generate a wealth of information for online use, but it also expands the potential investor pool to those investors who would not have advanced time and money towards conducting due diligence on your company.

Unlike all the other steps I mentioned, a valuation report isn't free, but it is certainly one of the only affordable and worthwhile options for brand building which I would recommend.

Sign up for our free Bio-Branding Webinar

We will be giving away our trade secrets in a free Elsevier Webinar, coming soon. Subscribe on our home page for an invitation.

Introducing Bio-Branding: A Brand New Service

A solid biotech brand is an empire of expertise in the "Googlosphere" which can easily elevate one brand above another during fundraising rounds. Bioassociate is now offering a service which lays solid foundations for companies' brand empires, and increases biotech startups' visibility through 100% expert-based, qualitative and informative content branding. 

Get in touch with us if you would like to learn more, and to arrange a free consultation. 

Israel's Reign in the Golden Age of Neuroscience is Ready!

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AbbVie's Latest Drug Deal Marks A Shift In The Celiac Disease Therapeutics Field

Bioassociate's latest Seeking Alpha article is on AbbVie's latest therapeutic venture. Below is a re-run of the article, and the original can be found here. 

Compared to its relative prevalence, Celiac disease is the most common disease that has zero treatments on the market. To make matters worse, only four companies are developing drugs for treatment of Celiac, and until a few days ago, this entire field has been flying under the radar.

This changed on May 15, when AbbVie (ABBV) announced it will pay $70 million to secure rights to an early-stage therapy for celiac disease developed by Alvine Pharmaceuticals. Under the terms of the agreement, AbbVie holds an exclusive option to either acquire the drug (named ALV003) or equity in Alvine upon successful completion of a Phase 2b study that will be conducted by the latter. Should AbbVie exercise its option, Alvine would receive additional undisclosed payments.

Celiac disease is an autoimmune disorder that affects the small intestine of people with a genetic predisposition. The autoimmune reaction is triggered by gluten proteins (gliadins) that are found in common grains, such as wheat, barley, and rye. If untreated, Celiac-related inflammation can result in severe damage of the digestive tract tissue and can lead to anemia, infertility, osteoporosis, neurological dysfunction, and cancer.

Today, treatment means only one thing - a life-long gluten-free diet. However, the 6 million celiac patients in the U.S. and Europe are having a hard time maintaining a 100% gluten-free diet, as accidental gluten cross-contamination cannot be completely avoided. This results in a significant unmet need for non-dietary therapies to treat Celiac, and consequently, a big and untapped market - according to a GlobalDatareport, Celiac disease therapeutics in the seven major markets would generate revenues of more than $650 million by 2019.

Alvine's AVL003 contains two recombinant enzymes that break down gluten in the intestines. Following a six-week phase IIa study, Alvine reported that AVL003 reduced the gliadin-related intestinal inflammation among Celiac patients that consumed gluten. AbbVie's deal makes it the first big pharma player to join the Celiac therapeutics field, and according to the sum it is willing to risk on a drug that completed a single efficacy clinical study, it looks like it means business.

Besides Alvine, three other companies are developing celiac disease therapies. Alba Therapeutics, with a drug that inhibits the gut's permeability to gluten, and ImmusanT, which develops a vaccine for induction of gluten tolerance, are both private companies. The third company is BioLine Rx (BLRX), whose Celiac targeting drug, BL-7010, is expected to commence clinical development later this year.

BL-7010 is a non-absorbable, high molecular weight polymer that binds gliadins in the gastrointestinal tract and neutralizes their harmful effect in Celiac patients. In-vivo data for this drug includes high specificity to gliadins, prevention of pathological damage and reduction of intestinal inflammation, with no toxic effects. According to BLRX, results from a pilot clinical study with BL-7010 are expected mid-2014. Considering the current low price of BioLine's stock, the very short clinical trials with Celiac drugs and the very few competitors in the Celiac therapeutics field, BL-7010 could very well be BioLine's joker card.

As of now, the research and development of Celiac therapeutics is being performed solely by small biotechs. AbbVie's recent deal, that included a considerable upfront payment for a drug that completed only one clinical efficacy study, implies that big partnering opportunities are available for the other few companies in the race for a Celiac drug.

Israel's Reign in the Golden Age of Neuroscience: Introduction

Bioassociate has been working hard on interviewing Israel's most prominent neuroscientists and leaders of exciting young neurotech companies. Our latest report, titled "Israel's Reign in the Golden Age of Neuroscience" was written in conjunction with President Shimon Peres's Israel Brain Technologies initiative, which aims to make Israel a leading global neurotech hub. 

Below is an introduction to Bioassociate's latest white paper, which will be ready shortly. If you would like to receive a free copy of the report, make sure to subscribe to our mailing list on the Bioassociate homepage - www.Bioassociate.com

The blind can see, the deaf can hear, and the paralyzed can walk—without a doubt, the Golden Age of Neuroscience is upon us. And if that weren’t enough, mind control, telepathy and in fact elaborate real-life Avatar scenarios are so nigh that scores of the neurotech-savvy have begun to pre-order their titanium thought defense helmets. So awesome have the leaps of neurotechnology been in recent years that the media has struggled to deliver this industry a deserved timely coverage, and public awareness has just barely caught up with humanity’s neuro-prowess of late. 

It is no surprise that we pondered so much of our vast universe before tapping into the microcosmic mystery of the mind: the human brain is riddled with millions of neuronal connections, all intertwined in a jungle so dense that the intricacy of galaxies and nebulas could pale in comparison. Having understood the basic principles which guide brain formation, scientists’ success in elucidating grey matter’s modus operandi has witnessed exponential growth in recent years, and one could safely say that our ability to harness this knowledge is at its most fruitful level yet. Neuroscientists have proudly treated depression, Parkinson’s disease, a range of psychological disorders, blindness, paralysis, and have even been able to communicate with long-comatose patients. Hardly any achievement of the last century could contest to be as jaw-dropping as giving a man thought to be in a decade-long vegetative state the ability to tell his parents he can hear them. 

Israel, a country which boasts the highest R&D per capita spend in the world, is one of only a handful of players actively pursuing a neurotech vision today. Most impressively, the countries or continents with which it shares this vision are at least ten times larger than it, both in size and budget. Thus, in celebration of the unraveling Neuro-Renaissance, and particularly as tribute to Israel’s increased involvement in the ever-expanding neuro-cosm, we present the current global neurotech situation, leading worldwide initiatives to raise awareness and to aid this ever-growing industry, followed by a summary of Israel’s very own academic and commercial neuro-arena. Place your titanium helmet orders!

Make sure to visit and subscribe on www.bioassociate.com to get a free copy

The (understandable) Confusion in Brain Mapping Terminology

The blind can see, the deaf can hear, and the paralyzed can walk—without a doubt, the Golden Age of Neuroscience is upon us. And if that weren’t enough, mind control, telepathy and in fact elaborate real-life Avatar scenarios are so nigh that scores of the neurotech-savvy have begun to pre-order their titanium thought defense helmets. So awesome have the leaps of neurotechnology been in recent years that the media has struggled to deliver this industry a deserved timely coverage, and public awareness has just barely caught up with humanity’s neuro-prowess of late. And what came about was the usual by-product of a much-too-quickly advancing technology: terminology fails. 

(view original image here)

On April 2, 2013 President Barack Obama unveiled the BRAIN (Brain Research through Advancing Innovative Neurotechnologies) initiative, whose final and uttermost objective is to visualize, map, understand and reconstruct the activity of every single neuron in the brain. This knowledge will in the future be applied to the development of new technologies and the treatment of quickly expanding array of neurological disorders.

BRAIN’s near-sighted primary goal will be to sponsor ongoing brain mapping projects, such as the Human Connectome Project, which the initiative claims will help us visualize every neuron in the brain and understand the formation of synapnses (connections) between neurons in live brain tissues. As the Human Connectome Project deals primarily with brain scans of live humans and their brains, this happens to be a feat which, for the time being, any knowledgeable neuroscientists will tell you is utter nonsense.

Here is why. 

The Human Connectome Project (HCP) has been dubbed one of the greatest neuroscience ambitions of the new millennium, much akin to the Human Genome Project a decade ago. The project showcases efforts to fathom the complex macrocosm which unites every axon bundle in the brain with the use of high-resolution fMRI or other non-invasive techniques, and symbolizes the positive level of trust which neuroscientists now assign to neurotechnology. HCP precedes and perhaps supersedes the BRAIN initiative, as already in 2010 it secured grants collectively worth over $40 million from the NIH. Initial 1200 Connectome subjects will be scanned for hours using an fMRI scanner 4 to 8 times as powerful as a standard one, utilizing the power of one nuclear submarine per scan, in hopes to yield insight into the connectivity of nerves within a brain, and how this connectivity varies throughout species and in disease. 

With novel neuro-terminology threatening to become its own language, much confusion and mis-representation surrounds HCP, and naturally the media hype it triggered has seemingly gotten lost in translation –or, rather, in literary terms. In bold truth, the techniques which the HCP is set to exploit are entirely non-invasive brain scans whose resolution is equivalent to that of a rusty security camera. Although general brain regions of humans will be clearly visible, local inter-region synapses, which form 80% of connections in the cerebral cortex, are entirely inaccessible to supracranial scans, as even a light microscope of the highest magnification is insufficient to visualize a single neuron. 

In other words, an fMRI scanner does not, and probably never will, visualize single cells and local synapses in the brain. However, HCP may yield great insights into the "connective visuality" of the brain, as vibrant HCP images (such as the one below) show thousands of connections between particular brain regions via axonal bundles (which are cables composed of many nerve cells, a bit like your landline telephone wire, not single brain cells). Scientists say that it is this inter-region connectivity which is responsible for our superior intelligence to other species, as preliminary scans clearly show a much more "connected" human brain in comparison with that of a chimpanzee, for instance. Scientists also believe that comparing such deep brain scan images between healthy and ailed individuals can help us understand neurological disease in the future.

Does this imply that we shall never be able to dwell into the microscopic ecosystem of grey matter? Not at all, although it may take some time until we are able to do so in humans. Non-human species, however can now be studied with a dozen of other, much more invasive techniques you probably wouldn't want performed on yourself. These techniques' findings collectively contribute to the general brain Connectome (note the unnecessary similarity to the Human Connectome Project) across all species-which is, in essence, a brain equivalent of the genome. To make matters more ponderous, Connectomics is the study of the connectome with all the research techniques available today, comprising MRI, electron microscopy, fluorescent cell staining, rendering brains see-through and a fantastical endeavor which goes by the name of optogenetics. 

One rather straight-forward technique used to visualize individual neurons and synapses in the cortical column is, literally, brain carving. A team of researchers at Harvard, led by prominent brain explorer Dr. Lichtman, have been working towards creating the most efficient contraption for slicing off pastrami-thin slices of mouse brain and observing them under a powerful electron microscope. Theoretically, this process may yield a complete 3D cellular reconstruction of a brain, but it would require creating and aligning thousands, if not millions, of brain slices. 

Amongst other, less brute-force neuronal visualization technique is the Clarity Project, which helps visualize neurons in brains of live mice. The Clarity project revolves around scientists' ability to chemically produce completely transparent brains (or other organs) in mice--a technique which was recently developed by Prof Karl Deisseroth and his team at Stanford. The chemical treatment strips away lipids which normally block the passage of light using the detergent SDS.

(original image here)

To help them through the treacherous cranial terrain scientists at Dr Lichtman's Dr Diesseroth's labs utilize fluorescent staining of neurons, which helps isolate single cells spanning a number of brain areas. The staining produces images such as this, termed BrainBows: 

(original here)

But perhaps the most compelling technique developed at Deisseroth's lab is optogenetics - a research tool which revolves around a gene discovered in 2002, encoding light-gated ion channels, or Channelrhodopsins, found in unicellular green algae. Upon activation with a specific-frequency light, the channels open, causing an ion influx into the cell much akin to the mechanism which causes our neurons to fire. Using a different light frequency can also activate a different set of channels—the Halorhodopsins which will cause a negative ion influx into the cell and thus inhibition of the neuron. For algae, this mechanism’s function is to orient the cells towards or away from light. But this mechanism can also be applied to mammalian cells.

(original image here)

In recent years scientists succeeded in engineering rhodopsins from algae into nerve cells of mice, either grown externally or, in fact, in perfectly alive animals. In essence, genes encoding these channels can be “injected” into very specific areas of the brain, which will render those areas light-sensitive. By shining a light with the use of optic cables into those areas, scientists can trigger very specific neurons, and examine the animal’s behavior, thereby demonstrating the role of the specific neurons they are studying.

Click here for a video of an optogenetically-challenged mouse commanded by scientists to go in perpetual circles. 

(original image here)

Ultimately, all the techniques which have armed neuroscience in recent years work towards one ambitious goal: to comptuationally simulate the workings of a brain, which would give us the ability to re-create, and perform "virtual healing", on neurological ailments. A breakthrough milestone was achieved in this sphere of connectomics in 2012: scientists were able to unveil key principles which guide the formation of neuronal interceptions, and applied these principles to a computational structural prediction model. In this way they were able to demonstrate that brain neurons grow independently of each other, and form connections once they intercept each other’s paths in the brain. 

Some might argue that virtually recreating a self-sufficient human brain capable of conscious thought like you and I might not be a great idea, but that's for later debates (we are not there yet).

Bioassociate will soon publish an in-depth report on the Global Neuroscience Revolution, where many recent fascinating developments, techniques and initiatives will be described. If you wish to receive a copy of the report please subscribe to our mailing list on our home page: www.bioassociate.com