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#437303 The Deck Is Not Rigged: Poker and the ...

Tuomas Sandholm, a computer scientist at Carnegie Mellon University, is not a poker player—or much of a poker fan, in fact—but he is fascinated by the game for much the same reason as the great game theorist John von Neumann before him. Von Neumann, who died in 1957, viewed poker as the perfect model for human decision making, for finding the balance between skill and chance that accompanies our every choice. He saw poker as the ultimate strategic challenge, combining as it does not just the mathematical elements of a game like chess but the uniquely human, psychological angles that are more difficult to model precisely—a view shared years later by Sandholm in his research with artificial intelligence.

“Poker is the main benchmark and challenge program for games of imperfect information,” Sandholm told me on a warm spring afternoon in 2018, when we met in his offices in Pittsburgh. The game, it turns out, has become the gold standard for developing artificial intelligence.

Tall and thin, with wire-frame glasses and neat brow hair framing a friendly face, Sandholm is behind the creation of three computer programs designed to test their mettle against human poker players: Claudico, Libratus, and most recently, Pluribus. (When we met, Libratus was still a toddler and Pluribus didn’t yet exist.) The goal isn’t to solve poker, as such, but to create algorithms whose decision making prowess in poker’s world of imperfect information and stochastic situations—situations that are randomly determined and unable to be predicted—can then be applied to other stochastic realms, like the military, business, government, cybersecurity, even health care.

While the first program, Claudico, was summarily beaten by human poker players—“one broke-ass robot,” an observer called it—Libratus has triumphed in a series of one-on-one, or heads-up, matches against some of the best online players in the United States.

Libratus relies on three main modules. The first involves a basic blueprint strategy for the whole game, allowing it to reach a much faster equilibrium than its predecessor. It includes an algorithm called the Monte Carlo Counterfactual Regret Minimization, which evaluates all future actions to figure out which one would cause the least amount of regret. Regret, of course, is a human emotion. Regret for a computer simply means realizing that an action that wasn’t chosen would have yielded a better outcome than one that was. “Intuitively, regret represents how much the AI regrets having not chosen that action in the past,” says Sandholm. The higher the regret, the higher the chance of choosing that action next time.

It’s a useful way of thinking—but one that is incredibly difficult for the human mind to implement. We are notoriously bad at anticipating our future emotions. How much will we regret doing something? How much will we regret not doing something else? For us, it’s an emotionally laden calculus, and we typically fail to apply it in quite the right way. For a computer, it’s all about the computation of values. What does it regret not doing the most, the thing that would have yielded the highest possible expected value?

The second module is a sub-game solver that takes into account the mistakes the opponent has made so far and accounts for every hand she could possibly have. And finally, there is a self-improver. This is the area where data and machine learning come into play. It’s dangerous to try to exploit your opponent—it opens you up to the risk that you’ll get exploited right back, especially if you’re a computer program and your opponent is human. So instead of attempting to do that, the self-improver lets the opponent’s actions inform the areas where the program should focus. “That lets the opponent’s actions tell us where [they] think they’ve found holes in our strategy,” Sandholm explained. This allows the algorithm to develop a blueprint strategy to patch those holes.

It’s a very human-like adaptation, if you think about it. I’m not going to try to outmaneuver you head on. Instead, I’m going to see how you’re trying to outmaneuver me and respond accordingly. Sun-Tzu would surely approve. Watch how you’re perceived, not how you perceive yourself—because in the end, you’re playing against those who are doing the perceiving, and their opinion, right or not, is the only one that matters when you craft your strategy. Overnight, the algorithm patches up its overall approach according to the resulting analysis.

There’s one final thing Libratus is able to do: play in situations with unknown probabilities. There’s a concept in game theory known as the trembling hand: There are branches of the game tree that, under an optimal strategy, one should theoretically never get to; but with some probability, your all-too-human opponent’s hand trembles, they take a wrong action, and you’re suddenly in a totally unmapped part of the game. Before, that would spell disaster for the computer: An unmapped part of the tree means the program no longer knows how to respond. Now, there’s a contingency plan.

Of course, no algorithm is perfect. When Libratus is playing poker, it’s essentially working in a zero-sum environment. It wins, the opponent loses. The opponent wins, it loses. But while some real-life interactions really are zero-sum—cyber warfare comes to mind—many others are not nearly as straightforward: My win does not necessarily mean your loss. The pie is not fixed, and our interactions may be more positive-sum than not.

What’s more, real-life applications have to contend with something that a poker algorithm does not: the weights that are assigned to different elements of a decision. In poker, this is a simple value-maximizing process. But what is value in the human realm? Sandholm had to contend with this before, when he helped craft the world’s first kidney exchange. Do you want to be more efficient, giving the maximum number of kidneys as quickly as possible—or more fair, which may come at a cost to efficiency? Do you want as many lives as possible saved—or do some take priority at the cost of reaching more? Is there a preference for the length of the wait until a transplant? Do kids get preference? And on and on. It’s essential, Sandholm says, to separate means and the ends. To figure out the ends, a human has to decide what the goal is.

“The world will ultimately become a lot safer with the help of algorithms like Libratus,” Sandholm told me. I wasn’t sure what he meant. The last thing that most people would do is call poker, with its competition, its winners and losers, its quest to gain the maximum edge over your opponent, a haven of safety.

“Logic is good, and the AI is much better at strategic reasoning than humans can ever be,” he explained. “It’s taking out irrationality, emotionality. And it’s fairer. If you have an AI on your side, it can lift non-experts to the level of experts. Naïve negotiators will suddenly have a better weapon. We can start to close off the digital divide.”

It was an optimistic note to end on—a zero-sum, competitive game yielding a more ultimately fair and rational world.

I wanted to learn more, to see if it was really possible that mathematics and algorithms could ultimately be the future of more human, more psychological interactions. And so, later that day, I accompanied Nick Nystrom, the chief scientist of the Pittsburgh Supercomputing Center—the place that runs all of Sandholm’s poker-AI programs—to the actual processing center that make undertakings like Libratus possible.

A half-hour drive found us in a parking lot by a large glass building. I’d expected something more futuristic, not the same square, corporate glass squares I’ve seen countless times before. The inside, however, was more promising. First the security checkpoint. Then the ride in the elevator — down, not up, to roughly three stories below ground, where we found ourselves in a maze of corridors with card readers at every juncture to make sure you don’t slip through undetected. A red-lit panel formed the final barrier, leading to a small sliver of space between two sets of doors. I could hear a loud hum coming from the far side.

“Let me tell you what you’re going to see before we walk in,” Nystrom told me. “Once we get inside, it will be too loud to hear.”

I was about to witness the heart of the supercomputing center: 27 large containers, in neat rows, each housing multiple processors with speeds and abilities too great for my mind to wrap around. Inside, the temperature is by turns arctic and tropic, so-called “cold” rows alternating with “hot”—fans operate around the clock to cool the processors as they churn through millions of giga, mega, tera, peta and other ever-increasing scales of data bytes. In the cool rows, robotic-looking lights blink green and blue in orderly progression. In the hot rows, a jumble of multicolored wires crisscrosses in tangled skeins.

In the corners stood machines that had outlived their heyday. There was Sherlock, an old Cray model, that warmed my heart. There was a sad nameless computer, whose anonymity was partially compensated for by the Warhol soup cans adorning its cage (an homage to Warhol’s Pittsburghian origins).

And where does Libratus live, I asked? Which of these computers is Bridges, the computer that runs the AI Sandholm and I had been discussing?

Bridges, it turned out, isn’t a single computer. It’s a system with processing power beyond comprehension. It takes over two and a half petabytes to run Libratus. A single petabyte is a million gigabytes: You could watch over 13 years of HD video, store 10 billion photos, catalog the contents of the entire Library of Congress word for word. That’s a whole lot of computing power. And that’s only to succeed at heads-up poker, in limited circumstances.

Yet despite the breathtaking computing power at its disposal, Libratus is still severely limited. Yes, it beat its opponents where Claudico failed. But the poker professionals weren’t allowed to use many of the tools of their trade, including the opponent analysis software that they depend on in actual online games. And humans tire. Libratus can churn for a two-week marathon, where the human mind falters.

But there’s still much it can’t do: play more opponents, play live, or win every time. There’s more humanity in poker than Libratus has yet conquered. “There’s this belief that it’s all about statistics and correlations. And we actually don’t believe that,” Nystrom explained as we left Bridges behind. “Once in a while correlations are good, but in general, they can also be really misleading.”

Two years later, the Sandholm lab will produce Pluribus. Pluribus will be able to play against five players—and will run on a single computer. Much of the human edge will have evaporated in a short, very short time. The algorithms have improved, as have the computers. AI, it seems, has gained by leaps and bounds.

So does that mean that, ultimately, the algorithmic can indeed beat out the human, that computation can untangle the web of human interaction by discerning “the little tactics of deception, of asking yourself what is the other man going to think I mean to do,” as von Neumann put it?

Long before I’d spoken to Sandholm, I’d met Kevin Slavin, a polymath of sorts whose past careers have including founding a game design company and an interactive art space and launching the Playful Systems group at MIT’s Media Lab. Slavin has a decidedly different view from the creators of Pluribus. “On the one hand, [von Neumann] was a genius,” Kevin Slavin reflects. “But the presumptuousness of it.”

Slavin is firmly on the side of the gambler, who recognizes uncertainty for what it is and thus is able to take calculated risks when necessary, all the while tampering confidence at the outcome. The most you can do is put yourself in the path of luck—but to think you can guess with certainty the actual outcome is a presumptuousness the true poker player foregoes. For Slavin, the wonder of computers is “That they can generate this fabulous, complex randomness.” His opinion of the algorithmic assaults on chance? “This is their moment,” he said. “But it’s the exact opposite of what’s really beautiful about a computer, which is that it can do something that’s actually unpredictable. That, to me, is the magic.”

Will they actually succeed in making the unpredictable predictable, though? That’s what I want to know. Because everything I’ve seen tells me that absolute success is impossible. The deck is not rigged.

“It’s an unbelievable amount of work to get there. What do you get at the end? Let’s say they’re successful. Then we live in a world where there’s no God, agency, or luck,” Slavin responded.

“I don’t want to live there,’’ he added “I just don’t want to live there.”

Luckily, it seems that for now, he won’t have to. There are more things in life than are yet written in the algorithms. We have no reliable lie detection software—whether in the face, the skin, or the brain. In a recent test of bluffing in poker, computer face recognition failed miserably. We can get at discomfort, but we can’t get at the reasons for that discomfort: lying, fatigue, stress—they all look much the same. And humans, of course, can also mimic stress where none exists, complicating the picture even further.

Pluribus may turn out to be powerful, but von Neumann’s challenge still stands: The true nature of games, the most human of the human, remains to be conquered.

This article was originally published on Undark. Read the original article.

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#437261 How AI Will Make Drug Discovery ...

If you had to guess how long it takes for a drug to go from an idea to your pharmacy, what would you guess? Three years? Five years? How about the cost? $30 million? $100 million?

Well, here’s the sobering truth: 90 percent of all drug possibilities fail. The few that do succeed take an average of 10 years to reach the market and cost anywhere from $2.5 billion to $12 billion to get there.

But what if we could generate novel molecules to target any disease, overnight, ready for clinical trials? Imagine leveraging machine learning to accomplish with 50 people what the pharmaceutical industry can barely do with an army of 5,000.

Welcome to the future of AI and low-cost, ultra-fast, and personalized drug discovery. Let’s dive in.

GANs & Drugs
Around 2012, computer scientist-turned-biophysicist Alex Zhavoronkov started to notice that artificial intelligence was getting increasingly good at image, voice, and text recognition. He knew that all three tasks shared a critical commonality. In each, massive datasets were available, making it easy to train up an AI.

But similar datasets were present in pharmacology. So, back in 2014, Zhavoronkov started wondering if he could use these datasets and AI to significantly speed up the drug discovery process. He’d heard about a new technique in artificial intelligence known as generative adversarial networks (or GANs). By pitting two neural nets against one another (adversarial), the system can start with minimal instructions and produce novel outcomes (generative). At the time, researchers had been using GANs to do things like design new objects or create one-of-a-kind, fake human faces, but Zhavoronkov wanted to apply them to pharmacology.

He figured GANs would allow researchers to verbally describe drug attributes: “The compound should inhibit protein X at concentration Y with minimal side effects in humans,” and then the AI could construct the molecule from scratch. To turn his idea into reality, Zhavoronkov set up Insilico Medicine on the campus of Johns Hopkins University in Baltimore, Maryland, and rolled up his sleeves.

Instead of beginning their process in some exotic locale, Insilico’s “drug discovery engine” sifts millions of data samples to determine the signature biological characteristics of specific diseases. The engine then identifies the most promising treatment targets and—using GANs—generates molecules (that is, baby drugs) perfectly suited for them. “The result is an explosion in potential drug targets and a much more efficient testing process,” says Zhavoronkov. “AI allows us to do with fifty people what a typical drug company does with five thousand.”

The results have turned what was once a decade-long war into a month-long skirmish.

In late 2018, for example, Insilico was generating novel molecules in fewer than 46 days, and this included not just the initial discovery, but also the synthesis of the drug and its experimental validation in computer simulations.

Right now, they’re using the system to hunt down new drugs for cancer, aging, fibrosis, Parkinson’s, Alzheimer’s, ALS, diabetes, and many others. The first drug to result from this work, a treatment for hair loss, is slated to start Phase I trials by the end of 2020.

They’re also in the early stages of using AI to predict the outcomes of clinical trials in advance of the trial. If successful, this technique will enable researchers to strip a bundle of time and money out of the traditional testing process.

Protein Folding
Beyond inventing new drugs, AI is also being used by other scientists to identify new drug targets—that is, the place to which a drug binds in the body and another key part of the drug discovery process.

Between 1980 and 2006, despite an annual investment of $30 billion, researchers only managed to find about five new drug targets a year. The trouble is complexity. Most potential drug targets are proteins, and a protein’s structure—meaning the way a 2D sequence of amino acids folds into a 3D protein—determines its function.

But a protein with merely a hundred amino acids (a rather small protein) can produce a googol-cubed worth of potential shapes—that’s a one followed by three hundred zeroes. This is also why protein-folding has long been considered an intractably hard problem for even the most powerful of supercomputers.

Back in 1994, to monitor supercomputers’ progress in protein-folding, a biannual competition was created. Until 2018, success was fairly rare. But then the creators of DeepMind turned their neural networks loose on the problem. They created an AI that mines enormous datasets to determine the most likely distance between a protein’s base pairs and the angles of their chemical bonds—aka, the basics of protein-folding. They called it AlphaFold.

On its first foray into the competition, contestant AIs were given 43 protein-folding problems to solve. AlphaFold got 25 right. The second-place team managed a meager three. By predicting the elusive ways in which various proteins fold on the basis of their amino acid sequences, AlphaFold may soon have a tremendous impact in aiding drug discovery and fighting some of today’s most intractable diseases.

Drug Delivery
Another theater of war for improved drugs is the realm of drug delivery. Even here, converging exponential technologies are paving the way for massive implications in both human health and industry shifts.

One key contender is CRISPR, the fast-advancing gene-editing technology that stands to revolutionize synthetic biology and treatment of genetically linked diseases. And researchers have now demonstrated how this tool can be applied to create materials that shape-shift on command. Think: materials that dissolve instantaneously when faced with a programmed stimulus, releasing a specified drug at a highly targeted location.

Yet another potential boon for targeted drug delivery is nanotechnology, whereby medical nanorobots have now been used to fight incidences of cancer. In a recent review of medical micro- and nanorobotics, lead authors (from the University of Texas at Austin and University of California, San Diego) found numerous successful tests of in vivo operation of medical micro- and nanorobots.

Drugs From the Future
Covid-19 is uniting the global scientific community with its urgency, prompting scientists to cast aside nation-specific territorialism, research secrecy, and academic publishing politics in favor of expedited therapeutic and vaccine development efforts. And in the wake of rapid acceleration across healthcare technologies, Big Pharma is an area worth watching right now, no matter your industry. Converging technologies will soon enable extraordinary strides in longevity and disease prevention, with companies like Insilico leading the charge.

Riding the convergence of massive datasets, skyrocketing computational power, quantum computing, cognitive surplus capabilities, and remarkable innovations in AI, we are not far from a world in which personalized drugs, delivered directly to specified targets, will graduate from science fiction to the standard of care.

Rejuvenational biotechnology will be commercially available sooner than you think. When I asked Alex for his own projection, he set the timeline at “maybe 20 years—that’s a reasonable horizon for tangible rejuvenational biotechnology.”

How might you use an extra 20 or more healthy years in your life? What impact would you be able to make?

Join Me
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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

#437202 Scientists Used Dopamine to Seamlessly ...

In just half a decade, neuromorphic devices—or brain-inspired computing—already seem quaint. The current darling? Artificial-biological hybrid computing, uniting both man-made computer chips and biological neurons seamlessly into semi-living circuits.

It sounds crazy, but a new study in Nature Materials shows that it’s possible to get an artificial neuron to communicate directly with a biological one using not just electricity, but dopamine—a chemical the brain naturally uses to change how neural circuits behave, most known for signaling reward.

Because these chemicals, known as “neurotransmitters,” are how biological neurons functionally link up in the brain, the study is a dramatic demonstration that it’s possible to connect artificial components with biological brain cells into a functional circuit.

The team isn’t the first to pursue hybrid neural circuits. Previously, a different team hooked up two silicon-based artificial neurons with a biological one into a circuit using electrical protocols alone. Although a powerful demonstration of hybrid computing, the study relied on only one-half of the brain’s computational ability: electrical computing.

The new study now tackles the other half: chemical computing. It adds a layer of compatibility that lays the groundwork not just for brain-inspired computers, but also for brain-machine interfaces and—perhaps—a sort of “cyborg” future. After all, if your brain can’t tell the difference between an artificial neuron and your own, could you? And even if you did, would you care?

Of course, that scenario is far in the future—if ever. For now, the team, led by Dr. Alberto Salleo, professor of materials science and engineering at Stanford University, collectively breathed a sigh of relief that the hybrid circuit worked.

“It’s a demonstration that this communication melding chemistry and electricity is possible,” said Salleo. “You could say it’s a first step toward a brain-machine interface, but it’s a tiny, tiny very first step.”

Neuromorphic Computing
The study grew from years of work into neuromorphic computing, or data processing inspired by the brain.

The blue-sky idea was inspired by the brain’s massive parallel computing capabilities, along with vast energy savings. By mimicking these properties, scientists reasoned, we could potentially turbo-charge computing. Neuromorphic devices basically embody artificial neural networks in physical form—wouldn’t hardware that mimics how the brain processes information be even more efficient and powerful?

These explorations led to novel neuromorphic chips, or artificial neurons that “fire” like biological ones. Additional work found that it’s possible to link these chips up into powerful circuits that run deep learning with ease, with bioengineered communication nodes called artificial synapses.

As a potential computing hardware replacement, these systems have proven to be incredibly promising. Yet scientists soon wondered: given their similarity to biological brains, can we use them as “replacement parts” for brains that suffer from traumatic injuries, aging, or degeneration? Can we hook up neuromorphic components to the brain to restore its capabilities?

Buzz & Chemistry
Theoretically, the answer’s yes.

But there’s a huge problem: current brain-machine interfaces only use electrical signals to mimic neural computation. The brain, in contrast, has two tricks up its sleeve: electricity and chemicals, or electrochemical.

Within a neuron, electricity travels up its incoming branches, through the bulbous body, then down the output branches. When electrical signals reach the neuron’s outgoing “piers,” dotted along the output branch, however, they hit a snag. A small gap exists between neurons, so to get to the other side, the electrical signals generally need to be converted into little bubble ships, packed with chemicals, and set sail to the other neuronal shore.

In other words, without chemical signals, the brain can’t function normally. These neurotransmitters don’t just passively carry information. Dopamine, for example, can dramatically change how a neural circuit functions. For an artificial-biological hybrid neural system, the absence of chemistry is like nixing international cargo vessels and only sticking with land-based trains and highways.

“To emulate biological synaptic behavior, the connectivity of the neuromorphic device must be dynamically regulated by the local neurotransmitter activity,” the team said.

Let’s Get Electro-Chemical
The new study started with two neurons: the upstream, an immortalized biological cell that releases dopamine; and the downstream, an artificial neuron that the team previously introduced in 2017, made of a mix of biocompatible and electrical-conducting materials.

Rather than the classic neuron shape, picture more of a sandwich with a chunk bitten out in the middle (yup, I’m totally serious). Each of the remaining parts of the sandwich is a soft electrode, made of biological polymers. The “bitten out” part has a conductive solution that can pass on electrical signals.

The biological cell sits close to the first electrode. When activated, it dumps out boats of dopamine, which drift to the electrode and chemically react with it—mimicking the process of dopamine docking onto a biological neuron. This, in turn, generates a current that’s passed on to the second electrode through the conductive solution channel. When this current reaches the second electrode, it changes the electrode’s conductance—that is, how well it can pass on electrical information. This second step is analogous to docked dopamine “ships” changing how likely it is that a biological neuron will fire in the future.

In other words, dopamine release from the biological neuron interacts with the artificial one, so that the chemicals change how the downstream neuron behaves in a somewhat lasting way—a loose mimic of what happens inside the brain during learning.

But that’s not all. Chemical signaling is especially powerful in the brain because it’s flexible. Dopamine, for example, only grabs onto the downstream neurons for a bit before it returns back to its upstream neuron—that is, recycled or destroyed. This means that its effect is temporary, giving the neural circuit breathing room to readjust its activity.

The Stanford team also tried reconstructing this quirk in their hybrid circuit. They crafted a microfluidic channel that shuttles both dopamine and its byproduct away from the artificial neurons after they’ve done their job for recycling.

Putting It All Together
After confirming that biological cells can survive happily on top of the artificial one, the team performed a few tests to see if the hybrid circuit could “learn.”

They used electrical methods to first activate the biological dopamine neuron, and watched the artificial one. Before the experiment, the team wasn’t quite sure what to expect. Theoretically, it made sense that dopamine would change the artificial neuron’s conductance, similar to learning. But “it was hard to know whether we’d achieve the outcome we predicted on paper until we saw it happen in the lab,” said study author Scott Keene.

On the first try, however, the team found that the burst of chemical signaling was able to change the artificial neuron’s conductance long-term, similar to the neuroscience dogma “neurons that fire together, wire together.” Activating the upstream biological neuron with chemicals also changed the artificial neuron’s conductance in a way that mimicked learning.

“That’s when we realized the potential this has for emulating the long-term learning process of a synapse,” said Keene.

Visualizing under an electron microscope, the team found that, similar to its biological counterpart, the hybrid synapse was able to efficiently recycle dopamine with timescales similar to the brain after some calibration. By playing with how much dopamine accumulates at the artificial neuron, the team found that they loosely mimic a learning rule called spike learning—a darling of machine learning inspired by the brain’s computation.

A Hybrid Future?
Unfortunately for cyborg enthusiasts, the work is still in its infancy.

For one, the artificial neurons are still rather bulky compared to biological ones. This means that they can’t capture and translate information from a single “boat” of dopamine. It’s also unclear if, and how, a hybrid synapse can work inside a living brain. Given the billions of synapses firing away in our heads, it’ll be a challenge to find-and-replace those that need replacement, and be able to control our memories and behaviors similar to natural ones.

That said, we’re inching ever closer to full-capability artificial-biological hybrid circuits.

“The neurotransmitter-mediated neuromorphic device presented in this work constitutes a fundamental building block for artificial neural networks that can be directly modulated based on biological feedback from live neurons,” the authors concluded. “[It] is a crucial first step in realizing next-generation adaptive biohybrid interfaces.”

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Posted in Human Robots

#437171 Scientists Tap the World’s Most ...

In The Hitchhiker’s Guide to the Galaxy by Douglas Adams, the haughty supercomputer Deep Thought is asked whether it can find the answer to the ultimate question concerning life, the universe, and everything. It replies that, yes, it can do it, but it’s tricky and it’ll have to think about it. When asked how long it will take it replies, “Seven-and-a-half million years. I told you I’d have to think about it.”

Real-life supercomputers are being asked somewhat less expansive questions but tricky ones nonetheless: how to tackle the Covid-19 pandemic. They’re being used in many facets of responding to the disease, including to predict the spread of the virus, to optimize contact tracing, to allocate resources and provide decisions for physicians, to design vaccines and rapid testing tools, and to understand sneezes. And the answers are needed in a rather shorter time frame than Deep Thought was proposing.

The largest number of Covid-19 supercomputing projects involves designing drugs. It’s likely to take several effective drugs to treat the disease. Supercomputers allow researchers to take a rational approach and aim to selectively muzzle proteins that SARS-CoV-2, the virus that causes Covid-19, needs for its life cycle.

The viral genome encodes proteins needed by the virus to infect humans and to replicate. Among these are the infamous spike protein that sniffs out and penetrates its human cellular target, but there are also enzymes and molecular machines that the virus forces its human subjects to produce for it. Finding drugs that can bind to these proteins and stop them from working is a logical way to go.

The Summit supercomputer at Oak Ridge National Laboratory has a peak performance of 200,000 trillion calculations per second—equivalent to about a million laptops. Image credit: Oak Ridge National Laboratory, U.S. Dept. of Energy, CC BY

I am a molecular biophysicist. My lab, at the Center for Molecular Biophysics at the University of Tennessee and Oak Ridge National Laboratory, uses a supercomputer to discover drugs. We build three-dimensional virtual models of biological molecules like the proteins used by cells and viruses, and simulate how various chemical compounds interact with those proteins. We test thousands of compounds to find the ones that “dock” with a target protein. Those compounds that fit, lock-and-key style, with the protein are potential therapies.

The top-ranked candidates are then tested experimentally to see if they indeed do bind to their targets and, in the case of Covid-19, stop the virus from infecting human cells. The compounds are first tested in cells, then animals, and finally humans. Computational drug discovery with high-performance computing has been important in finding antiviral drugs in the past, such as the anti-HIV drugs that revolutionized AIDS treatment in the 1990s.

World’s Most Powerful Computer
Since the 1990s the power of supercomputers has increased by a factor of a million or so. Summit at Oak Ridge National Laboratory is presently the world’s most powerful supercomputer, and has the combined power of roughly a million laptops. A laptop today has roughly the same power as a supercomputer had 20-30 years ago.

However, in order to gin up speed, supercomputer architectures have become more complicated. They used to consist of single, very powerful chips on which programs would simply run faster. Now they consist of thousands of processors performing massively parallel processing in which many calculations, such as testing the potential of drugs to dock with a pathogen or cell’s proteins, are performed at the same time. Persuading those processors to work together harmoniously is a pain in the neck but means we can quickly try out a lot of chemicals virtually.

Further, researchers use supercomputers to figure out by simulation the different shapes formed by the target binding sites and then virtually dock compounds to each shape. In my lab, that procedure has produced experimentally validated hits—chemicals that work—for each of 16 protein targets that physician-scientists and biochemists have discovered over the past few years. These targets were selected because finding compounds that dock with them could result in drugs for treating different diseases, including chronic kidney disease, prostate cancer, osteoporosis, diabetes, thrombosis and bacterial infections.

Scientists are using supercomputers to find ways to disable the various proteins—including the infamous spike protein (green protrusions)—produced by SARS-CoV-2, the virus responsible for Covid-19. Image credit: Thomas Splettstoesser scistyle.com, CC BY-ND

Billions of Possibilities
So which chemicals are being tested for Covid-19? A first approach is trying out drugs that already exist for other indications and that we have a pretty good idea are reasonably safe. That’s called “repurposing,” and if it works, regulatory approval will be quick.

But repurposing isn’t necessarily being done in the most rational way. One idea researchers are considering is that drugs that work against protein targets of some other virus, such as the flu, hepatitis or Ebola, will automatically work against Covid-19, even when the SARS-CoV-2 protein targets don’t have the same shape.

Our own work has now expanded to about 10 targets on SARS-CoV-2, and we’re also looking at human protein targets for disrupting the virus’s attack on human cells. Top-ranked compounds from our calculations are being tested experimentally for activity against the live virus. Several of these have already been found to be active.The best approach is to check if repurposed compounds will actually bind to their intended target. To that end, my lab published a preliminary report of a supercomputer-driven docking study of a repurposing compound database in mid-February. The study ranked 8,000 compounds in order of how well they bind to the viral spike protein. This paper triggered the establishment of a high-performance computing consortium against our viral enemy, announced by President Trump in March. Several of our top-ranked compounds are now in clinical trials.

Also, we and others are venturing out into the wild world of new drug discovery for Covid-19—looking for compounds that have never been tried as drugs before. Databases of billions of these compounds exist, all of which could probably be synthesized in principle but most of which have never been made. Billion-compound docking is a tailor-made task for massively parallel supercomputing.

Dawn of the Exascale Era
Work will be helped by the arrival of the next big machine at Oak Ridge, called Frontier, planned for next year. Frontier should be about 10 times more powerful than Summit. Frontier will herald the “exascale” supercomputing era, meaning machines capable of 1,000,000,000,000,000,000 calculations per second.

Although some fear supercomputers will take over the world, for the time being, at least, they are humanity’s servants, which means that they do what we tell them to. Different scientists have different ideas about how to calculate which drugs work best—some prefer artificial intelligence, for example—so there’s quite a lot of arguing going on.

Hopefully, scientists armed with the most powerful computers in the world will, sooner rather than later, find the drugs needed to tackle Covid-19. If they do, then their answers will be of more immediate benefit, if less philosophically tantalizing, than the answer to the ultimate question provided by Deep Thought, which was, maddeningly, simply 42.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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#437157 A Human-Centric World of Work: Why It ...

Long before coronavirus appeared and shattered our pre-existing “normal,” the future of work was a widely discussed and debated topic. We’ve watched automation slowly but surely expand its capabilities and take over more jobs, and we’ve wondered what artificial intelligence will eventually be capable of.

The pandemic swiftly turned the working world on its head, putting millions of people out of a job and forcing millions more to work remotely. But essential questions remain largely unchanged: we still want to make sure we’re not replaced, we want to add value, and we want an equitable society where different types of work are valued fairly.

To address these issues—as well as how the pandemic has impacted them—this week Singularity University held a digital summit on the future of work. Forty-three speakers from multiple backgrounds, countries, and sectors of the economy shared their expertise on everything from work in developing markets to why we shouldn’t want to go back to the old normal.

Gary Bolles, SU’s chair for the Future of Work, kicked off the discussion with his thoughts on a future of work that’s human-centric, including why it matters and how to build it.

What Is Work?
“Work” seems like a straightforward concept to define, but since it’s constantly shifting shape over time, let’s make sure we’re on the same page. Bolles defined work, very basically, as human skills applied to problems.

“It doesn’t matter if it’s a dirty floor or a complex market entry strategy or a major challenge in the world,” he said. “We as humans create value by applying our skills to solve problems in the world.” You can think of the problems that need solving as the demand and human skills as the supply, and the two are in constant oscillation, including, every few decades or centuries, a massive shift.

We’re in the midst of one of those shifts right now (and we already were, long before the pandemic). Skills that have long been in demand are declining. The World Economic Forum’s 2018 Future of Jobs report listed things like manual dexterity, management of financial and material resources, and quality control and safety awareness as declining skills. Meanwhile, skills the next generation will need include analytical thinking and innovation, emotional intelligence, creativity, and systems analysis.

Along Came a Pandemic
With the outbreak of coronavirus and its spread around the world, the demand side of work shrunk; all the problems that needed solving gave way to the much bigger, more immediate problem of keeping people alive. But as a result, tens of millions of people around the world are out of work—and those are just the ones that are being counted, and they’re a fraction of the true total. There are additional millions in seasonal or gig jobs or who work in informal economies now without work, too.

“This is our opportunity to focus,” Bolles said. “How do we help people re-engage with work? And make it better work, a better economy, and a better set of design heuristics for a world that we all want?”

Bolles posed five key questions—some spurred by impact of the pandemic—on which future of work conversations should focus to make sure it’s a human-centric future.

1. What does an inclusive world of work look like? Rather than seeing our current systems of work as immutable, we need to actually understand those systems and how we want to change them.

2. How can we increase the value of human work? We know that robots and software are going to be fine in the future—but for humans to be fine, we need to design for that very intentionally.

3. How can entrepreneurship help create a better world of work? In many economies the new value that’s created often comes from younger companies; how do we nurture entrepreneurship?

4. What will the intersection of workplace and geography look like? A large percentage of the global workforce is now working from home; what could some of the outcomes of that be? How does gig work fit in?

5. How can we ensure a healthy evolution of work and life? The health and the protection of those at risk is why we shut down our economies, but we need to find a balance that allows people to work while keeping them safe.

Problem-Solving Doesn’t End
The end result these questions are driving towards, and our overarching goal, is maximizing human potential. “If we come up with ways we can continue to do that, we’ll have a much more beneficial future of work,” Bolles said. “We should all be talking about where we can have an impact.”

One small silver lining? We had plenty of problems to solve in the world before ever hearing about coronavirus, and now we have even more. Is the pace of automation accelerating due to the virus? Yes. Are companies finding more ways to automate their processes in order to keep people from getting sick? They are.

But we have a slew of new problems on our hands, and we’re not going to stop needing human skills to solve them (not to mention the new problems that will surely emerge as second- and third-order effects of the shutdowns). If Bolles’ definition of work holds up, we’ve got ours cut out for us.

In an article from April titled The Great Reset, Bolles outlined three phases of the unemployment slump (we’re currently still in the first phase) and what we should be doing to minimize the damage. “The evolution of work is not about what will happen 10 to 20 years from now,” he said. “It’s about what we could be doing differently today.”

Watch Bolles’ talk and those of dozens of other experts for more insights into building a human-centric future of work here.

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