Tag Archives: Resistance

#437471 How Giving Robots a Hybrid, Human-Like ...

Squeezing a lot of computing power into robots without using up too much space or energy is a constant battle for their designers. But a new approach that mimics the structure of the human brain could provide a workaround.

The capabilities of most of today’s mobile robots are fairly rudimentary, but giving them the smarts to do their jobs is still a serious challenge. Controlling a body in a dynamic environment takes a surprising amount of processing power, which requires both real estate for chips and considerable amounts of energy to power them.

As robots get more complex and capable, those demands are only going to increase. Today’s most powerful AI systems run in massive data centers across far more chips than can realistically fit inside a machine on the move. And the slow death of Moore’s Law suggests we can’t rely on conventional processors getting significantly more efficient or compact anytime soon.

That prompted a team from the University of Southern California to resurrect an idea from more than 40 years ago: mimicking the human brain’s division of labor between two complimentary structures. While the cerebrum is responsible for higher cognitive functions like vision, hearing, and thinking, the cerebellum integrates sensory data and governs movement, balance, and posture.

When the idea was first proposed the technology didn’t exist to make it a reality, but in a paper recently published in Science Robotics, the researchers describe a hybrid system that combines analog circuits that control motion and digital circuits that govern perception and decision-making in an inverted pendulum robot.

“Through this cooperation of the cerebrum and the cerebellum, the robot can conduct multiple tasks simultaneously with a much shorter latency and lower power consumption,” write the researchers.

The type of robot the researchers were experimenting with looks essentially like a pole balancing on a pair of wheels. They have a broad range of applications, from hoverboards to warehouse logistics—Boston Dynamics’ recently-unveiled Handle robot operates on the same principles. Keeping them stable is notoriously tough, but the new approach managed to significantly improve all digital control approaches by radically improving the speed and efficiency of computations.

Key to bringing the idea alive was the recent emergence of memristors—electrical components whose resistance relies on previous input, which allows them to combine computing and memory in one place in a way similar to how biological neurons operate.

The researchers used memristors to build an analog circuit that runs an algorithm responsible for integrating data from the robot’s accelerometer and gyroscope, which is crucial for detecting the angle and velocity of its body, and another that controls its motion. One key advantage of this setup is that the signals from the sensors are analog, so it does away with the need for extra circuitry to convert them into digital signals, saving both space and power.

More importantly, though, the analog system is an order of magnitude faster and more energy-efficient than a standard all-digital system, the authors report. This not only lets them slash the power requirements, but also lets them cut the processing loop from 3,000 microseconds to just 6. That significantly improves the robot’s stability, with it taking just one second to settle into a steady state compared to more than three seconds using the digital-only platform.

At the minute this is just a proof of concept. The robot the researchers have built is small and rudimentary, and the algorithms being run on the analog circuit are fairly basic. But the principle is a promising one, and there is currently a huge amount of R&D going into neuromorphic and memristor-based analog computing hardware.

As often turns out to be the case, it seems like we can’t go too far wrong by mimicking the best model of computation we have found so far: our own brains.

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Posted in Human Robots

#437209 A Renaissance of Genomics and Drugs Is ...

The causes of aging are extremely complex and unclear. But with longevity clinical trials increasing, more answers—and questions—are emerging than ever before.

With the dramatic demonetization of genome reading and editing over the past decade, and Big Pharma, startups, and the FDA starting to face aging as a disease, we are starting to turn those answers into practical ways to extend our healthspan.

In this article, I’ll explore how genome sequencing and editing, along with new classes of anti-aging drugs, are augmenting our biology to further extend our healthy lives.

Genome Sequencing and Editing
Your genome is the software that runs your body. A sequence of 3.2 billion letters makes you “you.” These base pairs of A’s, T’s, C’s, and G’s determine your hair color, your height, your personality, your propensity for disease, your lifespan, and so on.

Until recently, it’s been very difficult to rapidly and cheaply “read” these letters—and even more difficult to understand what they mean. Since 2001, the cost to sequence a whole human genome has plummeted exponentially, outpacing Moore’s Law threefold. From an initial cost of $3.7 billion, it dropped to $10 million in 2006, and to $1,500 in 2015.

Today, the cost of genome sequencing has dropped below $600, and according to Illumina, the world’s leading sequencing company, the process will soon cost about $100 and take about an hour to complete.

This represents one of the most powerful and transformative technology revolutions in healthcare. When we understand your genome, we’ll be able to understand how to optimize “you.”

We’ll know the perfect foods, the perfect drugs, the perfect exercise regimen, and the perfect supplements, just for you.
We’ll understand what microbiome types, or gut flora, are ideal for you (more on this in a later article).
We’ll accurately predict how specific sedatives and medicines will impact you.
We’ll learn which diseases and illnesses you’re most likely to develop and, more importantly, how to best prevent them from developing in the first place (rather than trying to cure them after the fact).

CRISPR Gene Editing
In addition to reading the human genome, scientists can now edit a genome using a naturally occurring biological system discovered in 1987 called CRISPR/Cas9.

Short for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9, the editing system was adapted from a naturally-occurring defense system found in bacteria.

Here’s how it works. The bacteria capture snippets of DNA from invading viruses (or bacteriophage) and use them to create DNA segments known as CRISPR arrays. The CRISPR arrays allow the bacteria to “remember” the viruses (or closely related ones), and defend against future invasions. If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA. The bacteria then use Cas9 to cut the DNA apart, which disables the virus.

Most importantly, CRISPR is cheap, quick, easy to use, and more accurate than all previous gene editing methods. As a result, CRISPR/Cas9 has swept through labs around the world as the way to edit a genome. A short search in the literature will show an exponential rise in the number of CRISPR-related publications and patents.

2018: Filled With CRISPR Breakthroughs
Early results are impressive. Researchers have used CRISPR to genetically engineer cocaine resistance into mice, reverse the gene defect causing Duchenne muscular dystrophy (DMD) in dogs, and reduce genetic deafness in mice.

Already this year, CRISPR-edited immune cells have been shown to successfully kill cancer cells in human patients. Researchers have discovered ways to activate CRISPR with light and use the gene-editing technology to better understand Alzheimer’s disease progression.

With great power comes great responsibility, and the opportunity for moral and ethical dilemmas. In 2015, Chinese scientists sparked global controversy when they first edited human embryo cells in the lab with the goal of modifying genes that would make the child resistant to smallpox, HIV, and cholera. Three years later, in November 2018, researcher He Jiankui informed the world that the first set of CRISPR-engineered female twins had been delivered.

To accomplish his goal, Jiankui deleted a region of a receptor on the surface of white blood cells known as CCR5, introducing a rare, natural genetic variation that makes it more difficult for HIV to infect its favorite target, white blood cells. Because Jiankui forged ethical review documents and misled doctors in the process, he was sentenced to three years in prison and fined $429,000 last December.

Coupled with significant ethical conversations necessary for progress, CRISPR will soon provide us the tools to eliminate diseases, create hardier offspring, produce new environmentally resistant crops, and even wipe out pathogens.

Senolytics, Nutraceuticals, and Pharmaceuticals
Over the arc of your life, the cells in your body divide until they reach what is known as the Hayflick limit, or the number of times a normal human cell population will divide before cell division stops, which is typically about 50 divisions.

What normally follows next is programmed cell death or destruction by the immune system. A very small fraction of cells, however, become senescent cells and evade this fate to linger indefinitely. These lingering cells secrete a potent mix of molecules that triggers chronic inflammation, damages the surrounding tissue structures, and changes the behavior of nearby cells for the worse. Senescent cells appear to be one of the root causes of aging, causing everything from fibrosis and blood vessel calcification to localized inflammatory conditions such as osteoarthritis to diminished lung function.

Fortunately, both the scientific and entrepreneurial communities have begun to work on senolytic therapies, moving the technology for selectively destroying senescent cells out of the laboratory and into a half-dozen startup companies.

Prominent companies in the field include the following:

Unity Biotechnology is developing senolytic medicines to selectively eliminate senescent cells with an initial focus on delivering localized therapy in osteoarthritis, ophthalmology, and pulmonary disease.

Oisin Biotechnologies is pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.

SIWA Therapeutics is working on an immunotherapy approach to the problem of senescent cells.

In recent years, researchers have identified or designed a handful of senolytic compounds that can curb aging by regulating senescent cells. Two of these drugs that have gained mainstay research traction are rapamycin and metformin.

(1) Rapamycin

Originally extracted from bacteria found on Easter Island, rapamycin acts on the m-TOR (mechanistic target of rapamycin) pathway to selectively block a key protein that facilitates cell division. Currently, rapamycin derivatives are widely used for immunosuppression in organ and bone marrow transplants. Research now suggests that use results in prolonged lifespan and enhanced cognitive and immune function.

PureTech Health subsidiary resTORbio (which went public in 2018) is working on a rapamycin-based drug intended to enhance immunity and reduce infection. Their clinical-stage RTB101 drug works by inhibiting part of the mTOR pathway.

Results of the drug’s recent clinical trial include decreased incidence of infection, improved influenza vaccination response, and a 30.6 percent decrease in respiratory tract infection.

Impressive, to say the least.

(2) Metformin

Metformin is a widely-used generic drug for mitigating liver sugar production in Type 2 diabetes patients. Researchers have found that metformin also reduces oxidative stress and inflammation, which otherwise increase as we age. There is strong evidence that metformin can augment cellular regeneration and dramatically mitigate cellular senescence by reducing both oxidative stress and inflammation.

Over 100 studies registered on ClinicalTrials.gov are currently following up on strong evidence of metformin’s protective effect against cancer.

(3) Nutraceuticals and NAD+

Beyond cellular senescence, certain critical nutrients and proteins tend to decline as a function of age. Nutraceuticals combat aging by supplementing and replenishing these declining nutrient levels.

NAD+ exists in every cell, participating in every process from DNA repair to creating the energy vital for cellular processes. It’s been shown that NAD+ levels decline as we age.

The Elysium Health Basis supplement aims to elevate NAD+ levels in the body to extend one’s lifespan. Elysium’s first clinical study reports that Basis increases NAD+ levels consistently by a sustained 40 percent.

Conclusion
These are just a taste of the tremendous momentum that longevity and aging technology has right now. As artificial intelligence and quantum computing transform how we decode our DNA and how we discover drugs, genetics and pharmaceuticals will become truly personalized.

The next article in this series will demonstrate how artificial intelligence is converging with genetics and pharmaceuticals to transform how we approach longevity, aging, and vitality.

We are edging closer toward a dramatically extended healthspan—where 100 is the new 60. What will you create, where will you explore, and how will you spend your time if you are able to add an additional 40 healthy years to your life?

Join Me
(1) A360 Executive Mastermind: If you’re an exponentially and abundance-minded entrepreneur who would like coaching directly from me, consider joining my Abundance 360 Mastermind, a highly selective community of 360 CEOs and entrepreneurs who I coach for 3 days every January in Beverly Hills, Ca. Through A360, I provide my members with context and clarity about how converging exponential technologies will transform every industry. I’m committed to running A360 for the course of an ongoing 25-year journey as a “countdown to the Singularity.”

If you’d like to learn more and consider joining our 2021 membership, apply here.

(2) Abundance-Digital Online Community: I’ve also created a Digital/Online community of bold, abundance-minded entrepreneurs called Abundance-Digital. Abundance-Digital is Singularity University’s ‘onramp’ for exponential entrepreneurs—those who want to get involved and play at a higher level. Click here to learn more.

(Both A360 and Abundance-Digital are part of Singularity University—your participation opens you to a global community.)

This article originally appeared on diamandis.com. Read the original article here.

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Posted in Human Robots

#437103 How to Make Sense of Uncertainty in a ...

As the internet churns with information about Covid-19, about the virus that causes the disease, and about what we’re supposed to do to fight it, it can be difficult to see the forest for the trees. What can we realistically expect for the rest of 2020? And how do we even know what’s realistic?

Today, humanity’s primary, ideal goal is to eliminate the virus, SARS-CoV-2, and Covid-19. Our second-choice goal is to control virus transmission. Either way, we have three big aims: to save lives, to return to public life, and to keep the economy functioning.

To hit our second-choice goal—and maybe even our primary goal—countries are pursuing five major public health strategies. Note that many of these advances cross-fertilize: for example, advances in virus testing and antibody testing will drive data-based prevention efforts.

Five major public health strategies are underway to bring Covid-19 under control and to contain the spread of SARS-CoV-2.
These strategies arise from things we can control based on the things that we know at any given moment. But what about the things we can’t control and don’t yet know?

The biology of the virus and how it interacts with our bodies is what it is, so we should seek to understand it as thoroughly as possible. How long any immunity gained from prior infection lasts—and indeed whether people develop meaningful immunity at all after infection—are open questions urgently in need of greater clarity. Similarly, right now it’s important to focus on understanding rather than making assumptions about environmental factors like seasonality.

But the biggest question on everyone’s lips is, “When?” When will we see therapeutic progress against Covid-19? And when will life get “back to normal”? There are lots of models out there on the internet; which of those models are right? The simple answer is “none of them.” That’s right—it’s almost certain that every model you’ve seen is wrong in at least one detail, if not all of them. But modeling is meant to be a tool for deeper thinking, a way to run mental (and computational) experiments before—and while—taking action. As George E. P. Box famously wrote in 1976, “All models are wrong, but some are useful.”

Here, we’re seeking useful insights, as opposed to exact predictions, which is why we’re pulling back from quantitative details to get at the mindsets that will support agency and hope. To that end, I’ve been putting together timelines that I believe will yield useful expectations for the next year or two—and asking how optimistic I need to be in order to believe a particular timeline.

For a moderately optimistic scenario to be relevant, breakthroughs in science and technology come at paces expected based on previous efforts and assumptions that turn out to be basically correct; accessibility of those breakthroughs increases at a reasonable pace; regulation achieves its desired effects, without major surprises; and compliance with regulations is reasonably high.

In contrast, if I’m being highly optimistic, breakthroughs in science and technology and their accessibility come more quickly than they ever have before; regulation is evidence-based and successful in the first try or two; and compliance with those regulations is high and uniform. If I’m feeling not-so-optimistic, then I anticipate serious setbacks to breakthroughs and accessibility (with the overturning of many important assumptions), repeated failure of regulations to achieve their desired outcomes, and low compliance with those regulations.

The following scenarios outline the things that need to happen in the fight against Covid-19, when I expect to see them, and how confident I feel in those expectations. They focus on North America and Europe because there are data missing about China’s 2019 outbreak and other regions are still early in their outbreaks. Perhaps the most important thing to keep in mind throughout: We know more today than we did yesterday, but we still have much to learn. New knowledge derived from greater study and debate will almost certainly inspire ongoing course corrections.

As you dive into the scenarios below, practice these three mindset shifts. First, defeating Covid-19 will be a marathon, not a sprint. We shouldn’t expect life to look like 2019 for the next year or two—if ever. As Ed Yong wrote recently in The Atlantic, “There won’t be an obvious moment when everything is under control and regular life can safely resume.” Second, remember that you have important things to do for at least a year. And third, we are all in this together. There is no “us” and “them.” We must all be alert, responsive, generous, and strong throughout 2020 and 2021—and willing to throw away our assumptions when scientific evidence invalidates them.

The Middle Way: Moderate Optimism
Let’s start with the case in which I have the most confidence: moderate optimism.

This timeline considers milestones through late 2021, the earliest that I believe vaccines will become available. The “normal” timeline for developing a vaccine for diseases like seasonal flu is 18 months, which leads to my projection that we could potentially have vaccines as soon as 18 months from the first quarter of 2020. While Melinda Gates agrees with that projection, others (including AI) believe that 3 to 5 years is far more realistic, based on past vaccine development and the need to test safety and efficacy in humans. However, repurposing existing vaccines against other diseases—or piggybacking off clever synthetic platforms—could lead to vaccines being available sooner. I tried to balance these considerations for this moderately optimistic scenario. Either way, deploying vaccines at the end of 2021 is probably much later than you may have been led to believe by the hype engine. Again, if you take away only one message from this article, remember that the fight against Covid-19 is a marathon, not a sprint.

Here, I’ve visualized a moderately optimistic scenario as a baseline. Think of these timelines as living guides, as opposed to exact predictions. There are still many unknowns. More or less optimistic views (see below) and new information could shift these timelines forward or back and change the details of the strategies.
Based on current data, I expect that the first wave of Covid-19 cases (where we are now) will continue to subside in many areas, leading governments to ease restrictions in an effort to get people back to work. We’re already seeing movement in that direction, with a variety of benchmarks and changes at state and country levels around the world. But depending on the details of the changes, easing restrictions will probably cause a second wave of sickness (see Germany and Singapore), which should lead governments to reimpose at least some restrictions.

In tandem, therapeutic efforts will be transitioning from emergency treatments to treatments that have been approved based on safety and efficacy data in clinical trials. In a moderately optimistic scenario, assuming clinical trials currently underway yield at least a few positive results, this shift to mostly approved therapies could happen as early as the third or fourth quarter of this year and continue from there. One approval that should come rather quickly is for plasma therapies, in which the blood from people who have recovered from Covid-19 is used as a source of antibodies for people who are currently sick.

Companies around the world are working on both viral and antibody testing, focusing on speed, accuracy, reliability, and wide accessibility. While these tests are currently being run in hospitals and research laboratories, at-home testing is a critical component of the mass testing we’ll need to keep viral spread in check. These are needed to minimize the impact of asymptomatic cases, test the assumption that infection yields resistance to subsequent infection (and whether it lasts), and construct potential immunity passports if this assumption holds. Testing is also needed for contact tracing efforts to prevent further spread and get people back to public life. Finally, it’s crucial to our fundamental understanding of the biology of SARS-CoV-2 and Covid-19.

We need tests that are very reliable, both in the clinic and at home. So, don’t go buying any at-home test kits just yet, even if you find them online. Wait for reliable test kits and deeper understanding of how a test result translates to everyday realities. If we’re moderately optimistic, in-clinic testing will rapidly expand this quarter and/or next, with the possibility of broadly available, high-quality at-home sampling (and perhaps even analysis) thereafter.

Note that testing is not likely to be a “one-and-done” endeavor, as a person’s infection and immunity status change over time. Expect to be testing yourself—and your family—often as we move later into 2020.

Testing data are also going to inform distancing requirements at the country and local levels. In this scenario, restrictions—at some level of stringency—could persist at least through the end of 2020, as most countries are way behind the curve on testing (Iceland is an informative exception). Governments will likely continue to ask citizens to work from home if at all possible; to wear masks or face coverings in public; to employ heightened hygiene and social distancing in workplaces; and to restrict travel and social gatherings. So while it’s likely we’ll be eating in local restaurants again in 2020 in this scenario, at least for a little while, it’s not likely we’ll be heading to big concerts any time soon.

The Extremes: High and Low Optimism
How would high and low levels of optimism change our moderately optimistic timeline? The milestones are the same, but the time required to achieve them is shorter or longer, respectively. Quantifying these shifts is less important than acknowledging and incorporating a range of possibilities into our view. It pays to pay attention to our bias. Here are a few examples of reasonable possibilities that could shift the moderately optimistic timeline.

When vaccines become available
Vaccine repurposing could shorten the time for vaccines to become available; today, many vaccine candidates are in various stages of testing. On the other hand, difficulties in manufacture and distribution, or faster-than-expected mutation of SARS-CoV-2, could slow vaccine development. Given what we know now, I am not strongly concerned about either of these possibilities—drug companies are rapidly expanding their capabilities, and viral mutation isn’t an urgent concern at this time based on sequencing data—but they could happen.

At first, governments will likely supply vaccines to essential workers such as healthcare workers, but it is essential that vaccines become widely available around the world as quickly and as safely as possible. Overall, I suggest a dose of skepticism when reading highly optimistic claims about a vaccine (or multiple vaccines) being available in 2020. Remember, a vaccine is a knockout punch, not a first line of defense for an outbreak.

When testing hits its stride
While I am confident that testing is a critical component of our response to Covid-19, reliability is incredibly important to testing for SARS-CoV-2 and for immunity to the disease, particularly at home. For an individual, a false negative (being told you don’t have antibodies when you really do) could be just as bad as a false positive (being told you do have antibodies when you really don’t). Those errors are compounded when governments are trying to make evidence-based policies for social and physical distancing.

If you’re highly optimistic, high-quality testing will ramp up quickly as companies and scientists innovate rapidly by cleverly combining multiple test modalities, digital signals, and cutting-edge tech like CRISPR. Pop-up testing labs could also take some pressure off hospitals and clinics.

If things don’t go well, reliability issues could hinder testing, manufacturing bottlenecks could limit availability, and both could hamstring efforts to control spread and ease restrictions. And if it turns out that immunity to Covid-19 isn’t working the way we assumed, then we must revisit our assumptions about our path(s) back to public life, as well as our vaccine-development strategies.

How quickly safe and effective treatments appear
Drug development is known to be long, costly, and fraught with failure. It’s not uncommon to see hope in a drug spike early only to be dashed later on down the road. With that in mind, the number of treatments currently under investigation is astonishing, as is the speed through which they’re proceeding through testing. Breakthroughs in a therapeutic area—for example in treating the seriously ill or in reducing viral spread after an infection takes hold—could motivate changes in the focus of distancing regulations.

While speed will save lives, we cannot overlook the importance of knowing a treatment’s efficacy (does it work against Covid-19?) and safety (does it make you sick in a different, or worse, way?). Repurposing drugs that have already been tested for other diseases is speeding innovation here, as is artificial intelligence.

Remarkable collaborations among governments and companies, large and small, are driving innovation in therapeutics and devices such as ventilators for treating the sick.

Whether government policies are effective and responsive
Those of us who have experienced lockdown are eager for it to be over. Businesses, economists, and governments are also eager to relieve the terrible pressure that is being exerted on the global economy. However, lifting restrictions will almost certainly lead to a resurgence in sickness.

Here, the future is hard to model because there are many, many factors at play, and at play differently in different places—including the extent to which individuals actually comply with regulations.

Reliable testing—both in the clinic and at home—is crucial to designing and implementing restrictions, monitoring their effectiveness, and updating them; delays in reliable testing could seriously hamper this design cycle. Lack of trust in governments and/or companies could also suppress uptake. That said, systems are already in place for contact tracing in East Asia. Other governments could learn important lessons, but must also earn—and keep—their citizens’ trust.

Expect to see restrictions descend and then lift in response to changes in the number of Covid-19 cases and in the effectiveness of our prevention strategies. Also expect country-specific and perhaps even area-specific responses that differ from each other. The benefit of this approach? Governments around the world are running perhaps hundreds of real-time experiments and design cycles in balancing health and the economy, and we can learn from the results.

A Way Out
As Jeremy Farrar, head of the Wellcome Trust, told Science magazine, “Science is the exit strategy.” Some of our greatest technological assistance is coming from artificial intelligence, digital tools for collaboration, and advances in biotechnology.

Our exit strategy also needs to include empathy and future visioning—because in the midst of this crisis, we are breaking ground for a new, post-Covid future.

What do we want that future to look like? How will the hard choices we make now about data ethics impact the future of surveillance? Will we continue to embrace inclusiveness and mass collaboration? Perhaps most importantly, will we lay the foundation for successfully confronting future challenges? Whether we’re thinking about the next pandemic (and there will be others) or the cascade of catastrophes that climate change is bringing ever closer—it’s important to remember that we all have the power to become agents of that change.

Special thanks to Ola Kowalewski and Jason Dorrier for significant conversations.

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Posted in Human Robots

#436911 Scientists Linked Artificial and ...

Scientists have linked up two silicon-based artificial neurons with a biological one across multiple countries into a fully-functional network. Using standard internet protocols, they established a chain of communication whereby an artificial neuron controls a living, biological one, and passes on the info to another artificial one.

Whoa.

We’ve talked plenty about brain-computer interfaces and novel computer chips that resemble the brain. We’ve covered how those “neuromorphic” chips could link up into tremendously powerful computing entities, using engineered communication nodes called artificial synapses.

As Moore’s law is dying, we even said that neuromorphic computing is one path towards the future of extremely powerful, low energy consumption artificial neural network-based computing—in hardware—that could in theory better link up with the brain. Because the chips “speak” the brain’s language, in theory they could become neuroprosthesis hubs far more advanced and “natural” than anything currently possible.

This month, an international team put all of those ingredients together, turning theory into reality.

The three labs, scattered across Padova, Italy, Zurich, Switzerland, and Southampton, England, collaborated to create a fully self-controlled, hybrid artificial-biological neural network that communicated using biological principles, but over the internet.

The three-neuron network, linked through artificial synapses that emulate the real thing, was able to reproduce a classic neuroscience experiment that’s considered the basis of learning and memory in the brain. In other words, artificial neuron and synapse “chips” have progressed to the point where they can actually use a biological neuron intermediary to form a circuit that, at least partially, behaves like the real thing.

That’s not to say cyborg brains are coming soon. The simulation only recreated a small network that supports excitatory transmission in the hippocampus—a critical region that supports memory—and most brain functions require enormous cross-talk between numerous neurons and circuits. Nevertheless, the study is a jaw-dropping demonstration of how far we’ve come in recreating biological neurons and synapses in artificial hardware.

And perhaps one day, the currently “experimental” neuromorphic hardware will be integrated into broken biological neural circuits as bridges to restore movement, memory, personality, and even a sense of self.

The Artificial Brain Boom
One important thing: this study relies heavily on a decade of research into neuromorphic computing, or the implementation of brain functions inside computer chips.

The best-known example is perhaps IBM’s TrueNorth, which leveraged the brain’s computational principles to build a completely different computer than what we have today. Today’s computers run on a von Neumann architecture, in which memory and processing modules are physically separate. In contrast, the brain’s computing and memory are simultaneously achieved at synapses, small “hubs” on individual neurons that talk to adjacent ones.

Because memory and processing occur on the same site, biological neurons don’t have to shuttle data back and forth between processing and storage compartments, massively reducing processing time and energy use. What’s more, a neuron’s history will also influence how it behaves in the future, increasing flexibility and adaptability compared to computers. With the rise of deep learning, which loosely mimics neural processing as the prima donna of AI, the need to reduce power while boosting speed and flexible learning is becoming ever more tantamount in the AI community.

Neuromorphic computing was partially born out of this need. Most chips utilize special ingredients that change their resistance (or other physical characteristics) to mimic how a neuron might adapt to stimulation. Some chips emulate a whole neuron, that is, how it responds to a history of stimulation—does it get easier or harder to fire? Others imitate synapses themselves, that is, how easily they will pass on the information to another neuron.

Although single neuromorphic chips have proven to be far more efficient and powerful than current computer chips running machine learning algorithms in toy problems, so far few people have tried putting the artificial components together with biological ones in the ultimate test.

That’s what this study did.

A Hybrid Network
Still with me? Let’s talk network.

It’s gonna sound complicated, but remember: learning is the formation of neural networks, and neurons that fire together wire together. To rephrase: when learning, neurons will spontaneously organize into networks so that future instances will re-trigger the entire network. To “wire” together, downstream neurons will become more responsive to their upstream neural partners, so that even a whisper will cause them to activate. In contrast, some types of stimulation will cause the downstream neuron to “chill out” so that only an upstream “shout” will trigger downstream activation.

Both these properties—easier or harder to activate downstream neurons—are essentially how the brain forms connections. The “amping up,” in neuroscience jargon, is long-term potentiation (LTP), whereas the down-tuning is LTD (long-term depression). These two phenomena were first discovered in the rodent hippocampus more than half a century ago, and ever since have been considered as the biological basis of how the brain learns and remembers, and implicated in neurological problems such as addition (seriously, you can’t pass Neuro 101 without learning about LTP and LTD!).

So it’s perhaps especially salient that one of the first artificial-brain hybrid networks recapitulated this classic result.

To visualize: the three-neuron network began in Switzerland, with an artificial neuron with the badass name of “silicon spiking neuron.” That neuron is linked to an artificial synapse, a “memristor” located in the UK, which is then linked to a biological rat neuron cultured in Italy. The rat neuron has a “smart” microelectrode, controlled by the artificial synapse, to stimulate it. This is the artificial-to-biological pathway.

Meanwhile, the rat neuron in Italy also has electrodes that listen in on its electrical signaling. This signaling is passed back to another artificial synapse in the UK, which is then used to control a second artificial neuron back in Switzerland. This is the biological-to-artificial pathway back. As a testimony in how far we’ve come in digitizing neural signaling, all of the biological neural responses are digitized and sent over the internet to control its far-out artificial partner.

Here’s the crux: to demonstrate a functional neural network, just having the biological neuron passively “pass on” electrical stimulation isn’t enough. It has to show the capacity to learn, that is, to be able to mimic the amping up and down-tuning that are LTP and LTD, respectively.

You’ve probably guessed the results: certain stimulation patterns to the first artificial neuron in Switzerland changed how the artificial synapse in the UK operated. This, in turn, changed the stimulation to the biological neuron, so that it either amped up or toned down depending on the input.

Similarly, the response of the biological neuron altered the second artificial synapse, which then controlled the output of the second artificial neuron. Altogether, the biological and artificial components seamlessly linked up, over thousands of miles, into a functional neural circuit.

Cyborg Mind-Meld
So…I’m still picking my jaw up off the floor.

It’s utterly insane seeing a classic neuroscience learning experiment repeated with an integrated network with artificial components. That said, a three-neuron network is far from the thousands of synapses (if not more) needed to truly re-establish a broken neural circuit in the hippocampus, which DARPA has been aiming to do. And LTP/LTD has come under fire recently as the de facto brain mechanism for learning, though so far they remain cemented as neuroscience dogma.

However, this is one of the few studies where you see fields coming together. As Richard Feynman famously said, “What I cannot recreate, I cannot understand.” Even though neuromorphic chips were built on a high-level rather than molecular-level understanding of how neurons work, the study shows that artificial versions can still synapse with their biological counterparts. We’re not just on the right path towards understanding the brain, we’re recreating it, in hardware—if just a little.

While the study doesn’t have immediate use cases, practically it does boost both the neuromorphic computing and neuroprosthetic fields.

“We are very excited with this new development,” said study author Dr. Themis Prodromakis at the University of Southampton. “On one side it sets the basis for a novel scenario that was never encountered during natural evolution, where biological and artificial neurons are linked together and communicate across global networks; laying the foundations for the Internet of Neuro-electronics. On the other hand, it brings new prospects to neuroprosthetic technologies, paving the way towards research into replacing dysfunctional parts of the brain with AI chips.”

Image Credit: Gerd Altmann from Pixabay Continue reading

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#436578 AI Just Discovered a New Antibiotic to ...

Penicillin, one of the greatest discoveries in the history of medicine, was a product of chance.

After returning from summer vacation in September 1928, bacteriologist Alexander Fleming found a colony of bacteria he’d left in his London lab had sprouted a fungus. Curiously, wherever the bacteria contacted the fungus, their cell walls broke down and they died. Fleming guessed the fungus was secreting something lethal to the bacteria—and the rest is history.

Fleming’s discovery of penicillin and its later isolation, synthesis, and scaling in the 1940s released a flood of antibiotic discoveries in the next few decades. Bacteria and fungi had been waging an ancient war against each other, and the weapons they’d evolved over eons turned out to be humanity’s best defense against bacterial infection and disease.

In recent decades, however, the flood of new antibiotics has slowed to a trickle.

Their development is uneconomical for drug companies, and the low-hanging fruit has long been picked. We’re now facing the emergence of strains of super bacteria resistant to one or more antibiotics and an aging arsenal to fight them with. Gone unchallenged, an estimated 700,000 deaths worldwide due to drug resistance could rise to as many as 10 million in 2050.

Increasingly, scientists warn the tide is turning, and we need a new strategy to keep pace with the remarkably quick and boundlessly creative tactics of bacterial evolution.

But where the golden age of antibiotics was sparked by serendipity, human intelligence, and natural molecular weapons, its sequel may lean on the uncanny eye of artificial intelligence to screen millions of compounds—and even design new ones—in search of the next penicillin.

Hal Discovers a Powerful Antibiotic
In a paper published this week in the journal, Cell, MIT researchers took a step in this direction. The team says their machine learning algorithm discovered a powerful new antibiotic.

Named for the AI in 2001: A Space Odyssey, the antibiotic, halicin, successfully wiped out dozens of bacterial strains, including some of the most dangerous drug-resistant bacteria on the World Health Organization’s most wanted list. The bacteria also failed to develop resistance to E. coli during a month of observation, in stark contrast to existing antibiotic ciprofloxacin.

“In terms of antibiotic discovery, this is absolutely a first,” Regina Barzilay, a senior author on the study and computer science professor at MIT, told The Guardian.

The algorithm that discovered halicin was trained on the molecular features of 2,500 compounds. Nearly half were FDA-approved drugs, and another 800 naturally occurring. The researchers specifically tuned the algorithm to look for molecules with antibiotic properties but whose structures would differ from existing antibiotics (as halicin’s does). Using another machine learning program, they screened the results for those likely to be safe for humans.

Early study suggests halicin attacks the bacteria’s cell membranes, disrupting their ability to produce energy. Protecting the cell membrane from halicin might take more than one or two genetic mutations, which could account for its impressive ability to prevent resistance.

“I think this is one of the more powerful antibiotics that has been discovered to date,” James Collins, an MIT professor of bioengineering and senior author told The Guardian. “It has remarkable activity against a broad range of antibiotic-resistant pathogens.”

Beyond tests in petri-dish bacterial colonies, the team also tested halicin in mice. The antibiotic cleared up infections of a strain of bacteria resistant to all known antibiotics in a day. The team plans further study in partnership with a pharmaceutical company or nonprofit, and they hope to eventually prove it safe and effective for use in humans.

This last bit remains the trickiest step, given the cost of getting a new drug approved. But Collins hopes algorithms like theirs will help. “We could dramatically reduce the cost required to get through clinical trials,” he told the Financial Times.

A Universe of Drugs Awaits
The bigger story may be what happens next.

How many novel antibiotics await discovery, and how far can AI screening take us? The initial 6,000 compounds scanned by Barzilay and Collins’s team is a drop in the bucket.

They’ve already begun digging deeper by setting the algorithm loose on 100 million molecules from an online library of 1.5 billion compounds called the ZINC15 database. This first search took three days and turned up 23 more candidates that, like halicin, differ structurally from existing antibiotics and may be safe for humans. Two of these—which the team will study further—appear to be especially powerful.

Even more ambitiously, Barzilay hopes the approach can find or even design novel antibiotics that kill bad bacteria with alacrity while sparing the good guys. In this way, a round of antibiotics would cure whatever ails you without taking out your whole gut microbiome in the process.

All this is part of a larger movement to use machine learning algorithms in the long, expensive process of drug discovery. Other players in the area are also training AI on the vast possibility space of drug-like compounds. Last fall, one of the leaders in the area, Insilico, was challenged by a partner to see just how fast their method could do the job. The company turned out a new a proof-of-concept drug candidate in only 46 days.

The field is still developing, however, and it has yet to be seen exactly how valuable these approaches will be in practice. Barzilay is optimistic though.

“There is still a question of whether machine-learning tools are really doing something intelligent in healthcare, and how we can develop them to be workhorses in the pharmaceuticals industry,” she said. “This shows how far you can adapt this tool.”

Image Credit: Halicin (top row) prevented the development of antibiotic resistance in E. coli, while ciprofloxacin (bottom row) did not. Collins Lab at MIT Continue reading

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