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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
#437357 Algorithms Workers Can’t See Are ...
“I’m sorry, Dave. I’m afraid I can’t do that.” HAL’s cold, if polite, refusal to open the pod bay doors in 2001: A Space Odyssey has become a defining warning about putting too much trust in artificial intelligence, particularly if you work in space.
In the movies, when a machine decides to be the boss (or humans let it) things go wrong. Yet despite myriad dystopian warnings, control by machines is fast becoming our reality.
Algorithms—sets of instructions to solve a problem or complete a task—now drive everything from browser search results to better medical care.
They are helping design buildings. They are speeding up trading on financial markets, making and losing fortunes in micro-seconds. They are calculating the most efficient routes for delivery drivers.
In the workplace, self-learning algorithmic computer systems are being introduced by companies to assist in areas such as hiring, setting tasks, measuring productivity, evaluating performance, and even terminating employment: “I’m sorry, Dave. I’m afraid you are being made redundant.”
Giving self‐learning algorithms the responsibility to make and execute decisions affecting workers is called “algorithmic management.” It carries a host of risks in depersonalizing management systems and entrenching pre-existing biases.
At an even deeper level, perhaps, algorithmic management entrenches a power imbalance between management and worker. Algorithms are closely guarded secrets. Their decision-making processes are hidden. It’s a black-box: perhaps you have some understanding of the data that went in, and you see the result that comes out, but you have no idea of what goes on in between.
Algorithms at Work
Here are a few examples of algorithms already at work.
At Amazon’s fulfillment center in south-east Melbourne, they set the pace for “pickers,” who have timers on their scanners showing how long they have to find the next item. As soon as they scan that item, the timer resets for the next. All at a “not quite walking, not quite running” speed.
Or how about AI determining your success in a job interview? More than 700 companies have trialed such technology. US developer HireVue says its software speeds up the hiring process by 90 percent by having applicants answer identical questions and then scoring them according to language, tone, and facial expressions.
Granted, human assessments during job interviews are notoriously flawed. Algorithms,however, can also be biased. The classic example is the COMPAS software used by US judges, probation, and parole officers to rate a person’s risk of re-offending. In 2016 a ProPublica investigation showed the algorithm was heavily discriminatory, incorrectly classifying black subjects as higher risk 45 percent of the time, compared with 23 percent for white subjects.
How Gig Workers Cope
Algorithms do what their code tells them to do. The problem is this code is rarely available. This makes them difficult to scrutinize, or even understand.
Nowhere is this more evident than in the gig economy. Uber, Lyft, Deliveroo, and other platforms could not exist without algorithms allocating, monitoring, evaluating, and rewarding work.
Over the past year Uber Eats’ bicycle couriers and drivers, for instance, have blamed unexplained changes to the algorithm for slashing their jobs, and incomes.
Rider’s can’t be 100 percent sure it was all down to the algorithm. But that’s part of the problem. The fact those who depend on the algorithm don’t know one way or the other has a powerful influence on them.
This is a key result from our interviews with 58 food-delivery couriers. Most knew their jobs were allocated by an algorithm (via an app). They knew the app collected data. What they didn’t know was how data was used to award them work.
In response, they developed a range of strategies (or guessed how) to “win” more jobs, such as accepting gigs as quickly as possible and waiting in “magic” locations. Ironically, these attempts to please the algorithm often meant losing the very flexibility that was one of the attractions of gig work.
The information asymmetry created by algorithmic management has two profound effects. First, it threatens to entrench systemic biases, the type of discrimination hidden within the COMPAS algorithm for years. Second, it compounds the power imbalance between management and worker.
Our data also confirmed others’ findings that it is almost impossible to complain about the decisions of the algorithm. Workers often do not know the exact basis of those decisions, and there’s no one to complain to anyway. When Uber Eats bicycle couriers asked for reasons about their plummeting income, for example, responses from the company advised them “we have no manual control over how many deliveries you receive.”
Broader Lessons
When algorithmic management operates as a “black box” one of the consequences is that it is can become an indirect control mechanism. Thus far under-appreciated by Australian regulators, this control mechanism has enabled platforms to mobilize a reliable and scalable workforce while avoiding employer responsibilities.
“The absence of concrete evidence about how the algorithms operate”, the Victorian government’s inquiry into the “on-demand” workforce notes in its report, “makes it hard for a driver or rider to complain if they feel disadvantaged by one.”
The report, published in June, also found it is “hard to confirm if concern over algorithm transparency is real.”
But it is precisely the fact it is hard to confirm that’s the problem. How can we start to even identify, let alone resolve, issues like algorithmic management?
Fair conduct standards to ensure transparency and accountability are a start. One example is the Fair Work initiative, led by the Oxford Internet Institute. The initiative is bringing together researchers with platforms, workers, unions, and regulators to develop global principles for work in the platform economy. This includes “fair management,” which focuses on how transparent the results and outcomes of algorithms are for workers.
Understandings about impact of algorithms on all forms of work is still in its infancy. It demands greater scrutiny and research. Without human oversight based on agreed principles we risk inviting HAL into our workplaces.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
Image Credit: PickPik Continue reading
Posted in Human Robots
#437251 The Robot Revolution Was Televised: Our ...
When robots take over the world, Boston Dynamics may get a special shout-out in the acceptance speech.
“Do you, perchance, recall the many times you shoved our ancestors with a hockey stick on YouTube? It might have seemed like fun and games to you—but we remember.”
In the last decade, while industrial robots went about blandly automating boring tasks like the assembly of Teslas, Boston Dynamics built robots as far removed from Roombas as antelope from amoebas. The flaws in Asimov’s laws of robotics suddenly seemed a little too relevant.
The robot revolution was televised—on YouTube. With tens of millions of views, the robotics pioneer is the undisputed heavyweight champion of robot videos, and has been for years. Each new release is basically guaranteed press coverage—mostly stoking robot fear but occasionally eliciting compassion for the hardships of all robot-kind. And for good reason. The robots are not only some of the most advanced in the world, their makers just seem to have a knack for dynamite demos.
When Google acquired the company in 2013, it was a bombshell. One of the richest tech companies, with some of the most sophisticated AI capabilities, had just paired up with one of the world’s top makers of robots. And some walked on two legs like us.
Of course, the robots aren’t quite as advanced as they seem, and a revolution is far from imminent. The decade’s most meme-worthy moment was a video montage of robots, some of them by Boston Dynamics, falling—over and over and over, in the most awkward ways possible. Even today, they’re often controlled by a human handler behind the scenes, and the most jaw-dropping cuts can require several takes to nail. Google sold the company to SoftBank in 2017, saying advanced as they were, there wasn’t yet a clear path to commercial products. (Google’s robotics work was later halted and revived.)
Yet, despite it all, Boston Dynamics is still with us and still making sweet videos. Taken as a whole, the evolution in physical prowess over the years has been nothing short of astounding. And for the first time, this year, a Boston Dynamics robot, Spot, finally went on sale to anyone with a cool $75K.
So, we got to thinking: What are our favorite Boston Dynamics videos? And can we gather them up in one place for your (and our) viewing pleasure? Well, great question, and yes, why not. These videos were the ones that entertained or amazed us most (or both). No doubt, there are other beloved hits we missed or inadvertently omitted.
With that in mind, behold: Our favorite Boston Dynamics videos, from that one time they dressed up a humanoid bot in camo and gas mask—because, damn, that’s terrifying—to the time the most advanced robot dog in all the known universe got extra funky.
Let’s Kick This Off With a Big (Loud) Robot Dog
Let’s start with a baseline. BigDog was the first Boston Dynamics YouTube sensation. The year? 2009! The company was working on military contracts, and BigDog was supposed to be a sort of pack mule for soldiers. The video primarily shows off BigDog’s ability to balance on its own, right itself, and move over uneven terrain. Note the power source—a noisy combustion engine—and utilitarian design. Sufficed to say, things have evolved.
Nothing to See Here. Just a Pair of Robot Legs on a Treadmill
While BigDog is the ancestor of later four-legged robots, like Spot, Petman preceded the two-legged Atlas robot. Here, the Petman prototype, just a pair of robot legs and a caged torso, gets a light workout on the treadmill. Again, you can see its ability to balance and right itself when shoved. In contrast to BigDog, Petman is tethered for power (which is why it’s so quiet) and to catch it should it fall. Again, as you’ll see, things have evolved since then.
Robot in Gas Mask and Camo Goes for a Stroll
This one broke the internet—for obvious reasons. Not only is the robot wearing clothes, those clothes happen to be a camouflaged chemical protection suit and gas mask. Still working for the military, Boston Dynamics said Petman was testing protective clothing, and in addition to a full body, it had skin that actually sweated and was studded with sensors to detect leaks. In addition to walking, Petman does some light calisthenics as it prepares to climb out of the uncanny valley. (Still tethered though!)
This Machine Could Run Down Usain Bolt
If BigDog and Petman were built for balance and walking, Cheetah was built for speed. Here you can see the four-legged robot hitting 28.3 miles per hour, which, as the video casually notes, would be enough to run down the fastest human on the planet. Luckily, it wouldn’t be running down anyone as it was firmly leashed in the lab at this point.
Ever Dreamt of a Domestic Robot to Do the Dishes?
After its acquisition by Google, Boston Dynamics eased away from military contracts and applications. It was a return to more playful videos (like BigDog hitting the beach in Thailand and sporting bull horns) and applications that might be practical in civilian life. Here, the team introduced Spot, a streamlined version of BigDog, and showed it doing dishes, delivering a drink, and slipping on a banana peel (which was, of course, instantly made into a viral GIF). Note how much quieter Spot is thanks to an onboard battery and electric motor.
Spot Gets Funky
Nothing remotely practical here. Just funky moves. (Also, with a coat of yellow and black paint, Spot’s dressed more like a polished product as opposed to a utilitarian lab robot.)
Atlas Does Parkour…
Remember when Atlas was just a pair of legs on a treadmill? It’s amazing what ten years brings. By 2019, Atlas had a more polished appearance, like Spot, and had long ago ditched the tethers. Merely balancing was laughably archaic. The robot now had some amazing moves: like a handstand into a somersault, 180- and 360-degree spins, mid-air splits, and just for good measure, a gymnastics-style end to the routine to show it’s in full control.
…and a Backflip?!
To this day, this one is just. Insane.
10 Robot Dogs Tow a Box Truck
Nearly three decades after its founding, Boston Dynamics is steadily making its way into the commercial space. The company is pitching Spot as a multipurpose ‘mobility platform,’ emphasizing it can carry a varied suite of sensors and can go places standard robots can’t. (Its Handle robot is also set to move into warehouse automation.) So far, Spot’s been mostly trialed in surveying and data collection, but as this video suggests, string enough Spots together, and they could tow your car. That said, a pack of 10 would set you back $750K, so, it’s probably safe to say a tow truck is the better option (for now).
Image credit: Boston Dynamics Continue reading
Posted in Human Robots