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#437673 Can AI and Automation Deliver a COVID-19 ...
Illustration: Marysia Machulska
Within moments of meeting each other at a conference last year, Nathan Collins and Yann Gaston-Mathé began devising a plan to work together. Gaston-Mathé runs a startup that applies automated software to the design of new drug candidates. Collins leads a team that uses an automated chemistry platform to synthesize new drug candidates.
“There was an obvious synergy between their technology and ours,” recalls Gaston-Mathé, CEO and cofounder of Paris-based Iktos.
In late 2019, the pair launched a project to create a brand-new antiviral drug that would block a specific protein exploited by influenza viruses. Then the COVID-19 pandemic erupted across the world stage, and Gaston-Mathé and Collins learned that the viral culprit, SARS-CoV-2, relied on a protein that was 97 percent similar to their influenza protein. The partners pivoted.
Their companies are just two of hundreds of biotech firms eager to overhaul the drug-discovery process, often with the aid of artificial intelligence (AI) tools. The first set of antiviral drugs to treat COVID-19 will likely come from sifting through existing drugs. Remdesivir, for example, was originally developed to treat Ebola, and it has been shown to speed the recovery of hospitalized COVID-19 patients. But a drug made for one condition often has side effects and limited potency when applied to another. If researchers can produce an antiviral that specifically targets SARS-CoV-2, the drug would likely be safer and more effective than a repurposed drug.
There’s one big problem: Traditional drug discovery is far too slow to react to a pandemic. Designing a drug from scratch typically takes three to five years—and that’s before human clinical trials. “Our goal, with the combination of AI and automation, is to reduce that down to six months or less,” says Collins, who is chief strategy officer at SRI Biosciences, a division of the Silicon Valley research nonprofit SRI International. “We want to get this to be very, very fast.”
That sentiment is shared by small biotech firms and big pharmaceutical companies alike, many of which are now ramping up automated technologies backed by supercomputing power to predict, design, and test new antivirals—for this pandemic as well as the next—with unprecedented speed and scope.
“The entire industry is embracing these tools,” says Kara Carter, president of the International Society for Antiviral Research and executive vice president of infectious disease at Evotec, a drug-discovery company in Hamburg. “Not only do we need [new antivirals] to treat the SARS-CoV-2 infection in the population, which is probably here to stay, but we’ll also need them to treat future agents that arrive.”
There are currentlyabout 200 known viruses that infect humans. Although viruses represent less than 14 percent of all known human pathogens, they make up two-thirds of all new human pathogens discovered since 1980.
Antiviral drugs are fundamentally different from vaccines, which teach a person’s immune system to mount a defense against a viral invader, and antibody treatments, which enhance the body’s immune response. By contrast, antivirals are chemical compounds that directly block a virus after a person has become infected. They do this by binding to specific proteins and preventing them from functioning, so that the virus cannot copy itself or enter or exit a cell.
The SARS-CoV-2 virus has an estimated 25 to 29 proteins, but not all of them are suitable drug targets. Researchers are investigating, among other targets, the virus’s exterior spike protein, which binds to a receptor on a human cell; two scissorlike enzymes, called proteases, that cut up long strings of viral proteins into functional pieces inside the cell; and a polymerase complex that makes the cell churn out copies of the virus’s genetic material, in the form of single-stranded RNA.
But it’s not enough for a drug candidate to simply attach to a target protein. Chemists also consider how tightly the compound binds to its target, whether it binds to other things as well, how quickly it metabolizes in the body, and so on. A drug candidate may have 10 to 20 such objectives. “Very often those objectives can appear to be anticorrelated or contradictory with each other,” says Gaston-Mathé.
Compared with antibiotics, antiviral drug discovery has proceeded at a snail’s pace. Scientists advanced from isolating the first antibacterial molecules in 1910 to developing an arsenal of powerful antibiotics by 1944. By contrast, it took until 1951 for researchers to be able to routinely grow large amounts of virus particles in cells in a dish, a breakthrough that earned the inventors a Nobel Prize in Medicine in 1954.
And the lag between the discovery of a virus and the creation of a treatment can be heartbreaking. According to the World Health Organization, 71 million people worldwide have chronic hepatitis C, a major cause of liver cancer. The virus that causes the infection was discovered in 1989, but effective antiviral drugs didn’t hit the market until 2014.
While many antibiotics work on a range of microbes, most antivirals are highly specific to a single virus—what those in the business call “one bug, one drug.” It takes a detailed understanding of a virus to develop an antiviral against it, says Che Colpitts, a virologist at Queen’s University, in Canada, who works on antivirals against RNA viruses. “When a new virus emerges, like SARS-CoV-2, we’re at a big disadvantage.”
Making drugs to stop viruses is hard for three main reasons. First, viruses are the Spartans of the pathogen world: They’re frugal, brutal, and expert at evading the human immune system. About 20 to 250 nanometers in diameter, viruses rely on just a few parts to operate, hijacking host cells to reproduce and often destroying those cells upon departure. They employ tricks to camouflage their presence from the host’s immune system, including preventing infected cells from sending out molecular distress beacons. “Viruses are really small, so they only have a few components, so there’s not that many drug targets available to start with,” says Colpitts.
Second, viruses replicate quickly, typically doubling in number in hours or days. This constant copying of their genetic material enables viruses to evolve quickly, producing mutations able to sidestep drug effects. The virus that causes AIDS soon develops resistance when exposed to a single drug. That’s why a cocktail of antiviral drugs is used to treat HIV infection.
Finally, unlike bacteria, which can exist independently outside human cells, viruses invade human cells to propagate, so any drug designed to eliminate a virus needs to spare the host cell. A drug that fails to distinguish between a virus and a cell can cause serious side effects. “Discriminating between the two is really quite difficult,” says Evotec’s Carter, who has worked in antiviral drug discovery for over three decades.
And then there’s the money barrier. Developing antivirals is rarely profitable. Health-policy researchers at the London School of Economics recently estimated that the average cost of developing a new drug is US $1 billion, and up to $2.8 billion for cancer and other specialty drugs. Because antivirals are usually taken for only short periods of time or during short outbreaks of disease, companies rarely recoup what they spent developing the drug, much less turn a profit, says Carter.
To change the status quo, drug discovery needs fresh approaches that leverage new technologies, rather than incremental improvements, says Christian Tidona, managing director of BioMed X, an independent research institute in Heidelberg, Germany. “We need breakthroughs.”
Putting Drug Development on Autopilot
Earlier this year, SRI Biosciences and Iktos began collaborating on a way to use artificial intelligence and automated chemistry to rapidly identify new drugs to target the COVID-19 virus. Within four months, they had designed and synthesized a first round of antiviral candidates. Here’s how they’re doing it.
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STEP 1: Iktos’s AI platform uses deep-learning algorithms in an iterative process to come up with new molecular structures likely to bind to and disable a specific coronavirus protein. Illustrations: Chris Philpot
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STEP 2: SRI Biosciences’s SynFini system is a three-part automated chemistry suite for producing new compounds. Starting with a target compound from Iktos, SynRoute uses machine learning to analyze and optimize routes for creating that compound, with results in about 10 seconds. It prioritizes routes based on cost, likelihood of success, and ease of implementation.
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STEP 3: SynJet, an automated inkjet printer platform, tests the routes by printing out tiny quantities of chemical ingredients to see how they react. If the right compound is produced, the platform tests it.
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STEP 4: AutoSyn, an automated tabletop chemical plant, synthesizes milligrams to grams of the desired compound for further testing. Computer-selected “maps” dictate paths through the plant’s modular components.
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STEP 5: The most promising compounds are tested against live virus samples.
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Iktos’s AI platform was created by a medicinal chemist and an AI expert. To tackle SARS-CoV-2, the company used generative models—deep-learning algorithms that generate new data—to “imagine” molecular structures with a good chance of disabling a key coronavirus protein.
For a new drug target, the software proposes and evaluates roughly 1 million compounds, says Gaston-Mathé. It’s an iterative process: At each step, the system generates 100 virtual compounds, which are tested in silico with predictive models to see how closely they meet the objectives. The test results are then used to design the next batch of compounds. “It’s like we have a very, very fast chemist who is designing compounds, testing compounds, getting back the data, then designing another batch of compounds,” he says.
The computer isn’t as smart as a human chemist, Gaston-Mathé notes, but it’s much faster, so it can explore far more of what people in the field call “chemical space”—the set of all possible organic compounds. Unexplored chemical space is huge: Biochemists estimate that there are at least 1063 possible druglike molecules, and that 99.9 percent of all possible small molecules or compounds have never been synthesized.
Still, designing a chemical compound isn’t the hardest part of creating a new drug. After a drug candidate is designed, it must be synthesized, and the highly manual process for synthesizing a new chemical hasn’t changed much in 200 years. It can take days to plan a synthesis process and then months to years to optimize it for manufacture.
That’s why Gaston-Mathé was eager to send Iktos’s AI-generated designs to Collins’s team at SRI Biosciences. With $13.8 million from the Defense Advanced Research Projects Agency, SRI Biosciences spent the last four years automating the synthesis process. The company’s automated suite of three technologies, called SynFini, can produce new chemical compounds in just hours or days, says Collins.
First, machine-learning software devises possible routes for making a desired molecule. Next, an inkjet printer platform tests the routes by printing out and mixing tiny quantities of chemical ingredients to see how they react with one another; if the right compound is produced, the platform runs tests on it. Finally, a tabletop chemical plant synthesizes milligrams to grams of the desired compound.
Less than four months after Iktos and SRI Biosciences announced their collaboration, they had designed and synthesized a first round of antiviral candidates for SARS-CoV-2. Now they’re testing how well the compounds work on actual samples of the virus.
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63 possible druglike molecules, 99.9 percent have never been synthesized.
Theirs isn’t the only collaborationapplying new tools to drug discovery. In late March, Alex Zhavoronkov, CEO of Hong Kong–based Insilico Medicine, came across a YouTube video showing three virtual-reality avatars positioning colorful, sticklike fragments in the side of a bulbous blue protein. The three researchers were using VR to explore how compounds might bind to a SARS-CoV-2 enzyme. Zhavoronkov contacted the startup that created the simulation—Nanome, in San Diego—and invited it to examine Insilico’s AI-generated molecules in virtual reality.
Insilico runs an AI platform that uses biological data to train deep-learning algorithms, then uses those algorithms to identify molecules with druglike features that will likely bind to a protein target. A four-day training sprint in late January yielded 100 molecules that appear to bind to an important SARS-CoV-2 protease. The company recently began synthesizing some of those molecules for laboratory testing.
Nanome’s VR software, meanwhile, allows researchers to import a molecular structure, then view and manipulate it on the scale of individual atoms. Like human chess players who use computer programs to explore potential moves, chemists can use VR to predict how to make molecules more druglike, says Nanome CEO Steve McCloskey. “The tighter the interface between the human and the computer, the more information goes both ways,” he says.
Zhavoronkov sent data about several of Insilico’s compounds to Nanome, which re-created them in VR. Nanome’s chemist demonstrated chemical tweaks to potentially improve each compound. “It was a very good experience,” says Zhavoronkov.
Meanwhile, in March, Takeda Pharmaceutical Co., of Japan, invited Schrödinger, a New York–based company that develops chemical-simulation software, to join an alliance working on antivirals. Schrödinger’s AI focuses on the physics of how proteins interact with small molecules and one another.
The software sifts through billions of molecules per week to predict a compound’s properties, and it optimizes for multiple desired properties simultaneously, says Karen Akinsanya, chief biomedical scientist and head of discovery R&D at Schrödinger. “There’s a huge sense of urgency here to come up with a potent molecule, but also to come up with molecules that are going to be well tolerated” by the body, she says. Drug developers are seeking compounds that can be broadly used and easily administered, such as an oral drug rather than an intravenous drug, she adds.
Schrödinger evaluated four protein targets and performed virtual screens for two of them, a computing-intensive process. In June, Google Cloud donated the equivalent of 16 million hours of Nvidia GPU time for the company’s calculations. Next, the alliance’s drug companies will synthesize and test the most promising compounds identified by the virtual screens.
Other companies, including Amazon Web Services, IBM, and Intel, as well as several U.S. national labs are also donating time and resources to the Covid-19 High Performance Computing Consortium. The consortium is supporting 87 projects, which now have access to 6.8 million CPU cores, 50,000 GPUs, and 600 petaflops of computational resources.
While advanced technologies could transform early drug discovery, any new drug candidate still has a long road after that. It must be tested in animals, manufactured in large batches for clinical trials, then tested in a series of trials that, for antivirals, lasts an average of seven years.
In May, the BioMed X Institute in Germany launched a five-year project to build a Rapid Antiviral Response Platform, which would speed drug discovery all the way through manufacturing for clinical trials. The €40 million ($47 million) project, backed by drug companies, will identify outside-the-box proposals from young scientists, then provide space and funding to develop their ideas.
“We’ll focus on technologies that allow us to go from identification of a new virus to 10,000 doses of a novel potential therapeutic ready for trials in less than six months,” says BioMed X’s Tidona, who leads the project.
While a vaccine will likely arrive long before a bespoke antiviral does, experts expect COVID-19 to be with us for a long time, so the effort to develop a direct-acting, potent antiviral continues. Plus, having new antivirals—and tools to rapidly create more—can only help us prepare for the next pandemic, whether it comes next month or in another 102 years.
“We’ve got to start thinking differently about how to be more responsive to these kinds of threats,” says Collins. “It’s pushing us out of our comfort zones.”
This article appears in the October 2020 print issue as “Automating Antivirals.” Continue reading
Posted in Human Robots
#437477 If a Robot Is Conscious, Is It OK to ...
In the Star Trek: The Next Generation episode “The Measure of a Man,” Data, an android crew member of the Enterprise, is to be dismantled for research purposes unless Captain Picard can argue that Data deserves the same rights as a human being. Naturally the question arises: What is the basis upon which something has rights? What gives an entity moral standing?
The philosopher Peter Singer argues that creatures that can feel pain or suffer have a claim to moral standing. He argues that nonhuman animals have moral standing, since they can feel pain and suffer. Limiting it to people would be a form of speciesism, something akin to racism and sexism.
Without endorsing Singer’s line of reasoning, we might wonder if it can be extended further to an android robot like Data. It would require that Data can either feel pain or suffer. And how you answer that depends on how you understand consciousness and intelligence.
As real artificial intelligence technology advances toward Hollywood’s imagined versions, the question of moral standing grows more important. If AIs have moral standing, philosophers like me reason, it could follow that they have a right to life. That means you cannot simply dismantle them, and might also mean that people shouldn’t interfere with their pursuing their goals.
Two Flavors of Intelligence and a Test
IBM’s Deep Blue chess machine was successfully trained to beat grandmaster Gary Kasparov. But it could not do anything else. This computer had what’s called domain-specific intelligence.
On the other hand, there’s the kind of intelligence that allows for the ability to do a variety of things well. It is called domain-general intelligence. It’s what lets people cook, ski, and raise children—tasks that are related, but also very different.
Artificial general intelligence, AGI, is the term for machines that have domain-general intelligence. Arguably no machine has yet demonstrated that kind of intelligence. This summer, a startup called OpenAI released a new version of its Generative Pre-Training language model. GPT-3 is a natural language processing system, trained to read and write so that it can be easily understood by people.
It drew immediate notice, not just because of its impressive ability to mimic stylistic flourishes and put together plausible content, but also because of how far it had come from a previous version. Despite this impressive performance, GPT-3 doesn’t actually know anything beyond how to string words together in various ways. AGI remains quite far off.
Named after pioneering AI researcher Alan Turing, the Turing test helps determine when an AI is intelligent. Can a person conversing with a hidden AI tell whether it’s an AI or a human being? If he can’t, then for all practical purposes, the AI is intelligent. But this test says nothing about whether the AI might be conscious.
Two Kinds of Consciousness
There are two parts to consciousness. First, there’s the what-it’s-like-for-me aspect of an experience, the sensory part of consciousness. Philosophers call this phenomenal consciousness. It’s about how you experience a phenomenon, like smelling a rose or feeling pain.
In contrast, there’s also access consciousness. That’s the ability to report, reason, behave, and act in a coordinated and responsive manner to stimuli based on goals. For example, when I pass the soccer ball to my friend making a play on the goal, I am responding to visual stimuli, acting from prior training, and pursuing a goal determined by the rules of the game. I make the pass automatically, without conscious deliberation, in the flow of the game.
Blindsight nicely illustrates the difference between the two types of consciousness. Someone with this neurological condition might report, for example, that they cannot see anything in the left side of their visual field. But if asked to pick up a pen from an array of objects in the left side of their visual field, they can reliably do so. They cannot see the pen, yet they can pick it up when prompted—an example of access consciousness without phenomenal consciousness.
Data is an android. How do these distinctions play out with respect to him?
The Data Dilemma
The android Data demonstrates that he is self-aware in that he can monitor whether or not, for example, he is optimally charged or there is internal damage to his robotic arm.
Data is also intelligent in the general sense. He does a lot of distinct things at a high level of mastery. He can fly the Enterprise, take orders from Captain Picard and reason with him about the best path to take.
He can also play poker with his shipmates, cook, discuss topical issues with close friends, fight with enemies on alien planets, and engage in various forms of physical labor. Data has access consciousness. He would clearly pass the Turing test.
However, Data most likely lacks phenomenal consciousness—he does not, for example, delight in the scent of roses or experience pain. He embodies a supersized version of blindsight. He’s self-aware and has access consciousness—can grab the pen—but across all his senses he lacks phenomenal consciousness.
Now, if Data doesn’t feel pain, at least one of the reasons Singer offers for giving a creature moral standing is not fulfilled. But Data might fulfill the other condition of being able to suffer, even without feeling pain. Suffering might not require phenomenal consciousness the way pain essentially does.
For example, what if suffering were also defined as the idea of being thwarted from pursuing a just cause without causing harm to others? Suppose Data’s goal is to save his crewmate, but he can’t reach her because of damage to one of his limbs. Data’s reduction in functioning that keeps him from saving his crewmate is a kind of nonphenomenal suffering. He would have preferred to save the crewmate, and would be better off if he did.
In the episode, the question ends up resting not on whether Data is self-aware—that is not in doubt. Nor is it in question whether he is intelligent—he easily demonstrates that he is in the general sense. What is unclear is whether he is phenomenally conscious. Data is not dismantled because, in the end, his human judges cannot agree on the significance of consciousness for moral standing.
Should an AI Get Moral Standing?
Data is kind; he acts to support the well-being of his crewmates and those he encounters on alien planets. He obeys orders from people and appears unlikely to harm them, and he seems to protect his own existence. For these reasons he appears peaceful and easier to accept into the realm of things that have moral standing.
But what about Skynet in the Terminator movies? Or the worries recently expressed by Elon Musk about AI being more dangerous than nukes, and by Stephen Hawking on AI ending humankind?
Human beings don’t lose their claim to moral standing just because they act against the interests of another person. In the same way, you can’t automatically say that just because an AI acts against the interests of humanity or another AI it doesn’t have moral standing. You might be justified in fighting back against an AI like Skynet, but that does not take away its moral standing. If moral standing is given in virtue of the capacity to nonphenomenally suffer, then Skynet and Data both get it even if only Data wants to help human beings.
There are no artificial general intelligence machines yet. But now is the time to consider what it would take to grant them moral standing. How humanity chooses to answer the question of moral standing for nonbiological creatures will have big implications for how we deal with future AIs—whether kind and helpful like Data, or set on destruction, like Skynet.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
Image Credit: Ico Maker / Shutterstock.com Continue reading
Posted in Human Robots
#437182 MIT’s Tiny New Brain Chip Aims for AI ...
The human brain operates on roughly 20 watts of power (a third of a 60-watt light bulb) in a space the size of, well, a human head. The biggest machine learning algorithms use closer to a nuclear power plant’s worth of electricity and racks of chips to learn.
That’s not to slander machine learning, but nature may have a tip or two to improve the situation. Luckily, there’s a branch of computer chip design heeding that call. By mimicking the brain, super-efficient neuromorphic chips aim to take AI off the cloud and put it in your pocket.
The latest such chip is smaller than a piece of confetti and has tens of thousands of artificial synapses made out of memristors—chip components that can mimic their natural counterparts in the brain.
In a recent paper in Nature Nanotechnology, a team of MIT scientists say their tiny new neuromorphic chip was used to store, retrieve, and manipulate images of Captain America’s Shield and MIT’s Killian Court. Whereas images stored with existing methods tended to lose fidelity over time, the new chip’s images remained crystal clear.
“So far, artificial synapse networks exist as software. We’re trying to build real neural network hardware for portable artificial intelligence systems,” Jeehwan Kim, associate professor of mechanical engineering at MIT said in a press release. “Imagine connecting a neuromorphic device to a camera on your car, and having it recognize lights and objects and make a decision immediately, without having to connect to the internet. We hope to use energy-efficient memristors to do those tasks on-site, in real-time.”
A Brain in Your Pocket
Whereas the computers in our phones and laptops use separate digital components for processing and memory—and therefore need to shuttle information between the two—the MIT chip uses analog components called memristors that process and store information in the same place. This is similar to the way the brain works and makes memristors far more efficient. To date, however, they’ve struggled with reliability and scalability.
To overcome these challenges, the MIT team designed a new kind of silicon-based, alloyed memristor. Ions flowing in memristors made from unalloyed materials tend to scatter as the components get smaller, meaning the signal loses fidelity and the resulting computations are less reliable. The team found an alloy of silver and copper helped stabilize the flow of silver ions between electrodes, allowing them to scale the number of memristors on the chip without sacrificing functionality.
While MIT’s new chip is promising, there’s likely a ways to go before memristor-based neuromorphic chips go mainstream. Between now and then, engineers like Kim have their work cut out for them to further scale and demonstrate their designs. But if successful, they could make for smarter smartphones and other even smaller devices.
“We would like to develop this technology further to have larger-scale arrays to do image recognition tasks,” Kim said. “And some day, you might be able to carry around artificial brains to do these kinds of tasks, without connecting to supercomputers, the internet, or the cloud.”
Special Chips for AI
The MIT work is part of a larger trend in computing and machine learning. As progress in classical chips has flagged in recent years, there’s been an increasing focus on more efficient software and specialized chips to continue pushing the pace.
Neuromorphic chips, for example, aren’t new. IBM and Intel are developing their own designs. So far, their chips have been based on groups of standard computing components, such as transistors (as opposed to memristors), arranged to imitate neurons in the brain. These chips are, however, still in the research phase.
Graphics processing units (GPUs)—chips originally developed for graphics-heavy work like video games—are the best practical example of specialized hardware for AI and were heavily used in this generation of machine learning early on. In the years since, Google, NVIDIA, and others have developed even more specialized chips that cater more specifically to machine learning.
The gains from such specialized chips are already being felt.
In a recent cost analysis of machine learning, research and investment firm ARK Invest said cost declines have far outpaced Moore’s Law. In a particular example, they found the cost to train an image recognition algorithm (ResNet-50) went from around $1,000 in 2017 to roughly $10 in 2019. The fall in cost to actually run such an algorithm was even more dramatic. It took $10,000 to classify a billion images in 2017 and just $0.03 in 2019.
Some of these declines can be traced to better software, but according to ARK, specialized chips have improved performance by nearly 16 times in the last three years.
As neuromorphic chips—and other tailored designs—advance further in the years to come, these trends in cost and performance may continue. Eventually, if all goes to plan, we might all carry a pocket brain that can do the work of today’s best AI.
Image credit: Peng Lin Continue reading
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.”
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