Tag Archives: artificial

#437723 Minuscule RoBeetle Turns Liquid Methanol ...

It’s no secret that one of the most significant constraints on robots is power. Most robots need lots of it, and it has to come from somewhere, with that somewhere usually being a battery because there simply aren’t many other good options. Batteries, however, are famous for having poor energy density, and the smaller your robot is, the more of a problem this becomes. And the issue with batteries goes beyond the battery itself, but also carries over into all the other components that it takes to turn the stored energy into useful work, which again is a particular problem for small-scale robots.

In a paper published this week in Science Robotics, researchers from the University of Southern California, in Los Angeles, demonstrate RoBeetle, an 88-milligram four legged robot that runs entirely on methanol, a power-dense liquid fuel. Without any electronics at all, it uses an exceptionally clever bit of mechanical autonomy to convert methanol vapor directly into forward motion, one millimeter-long step at a time.

It’s not entirely clear from the video how the robot actually works, so let’s go through how it’s put together, and then look at the actuation cycle.

Image: Science Robotics

RoBeetle (A) uses a methanol-based actuation mechanism (B). The robot’s body (C) includes the fuel tank subassembly (D), a tank lid, transmission, and sliding shutter (E), bottom side of the sliding shutter (F), nickel-titanium-platinum composite wire and leaf spring (G), and front legs and hind legs with bioinspired backward-oriented claws (H).

The body of RoBeetle is a boxy fuel tank that you can fill with methanol by poking a syringe through a fuel inlet hole. It’s a quadruped, more or less, with fixed hind legs and two front legs attached to a single transmission that moves them both at once in a sort of rocking forward and up followed by backward and down motion. The transmission is hooked up to a leaf spring that’s tensioned to always pull the legs backward, such that when the robot isn’t being actuated, the spring and transmission keep its front legs more or less vertical and allow the robot to stand. Those horns are primarily there to hold the leaf spring in place, but they’ve got little hooks that can carry stuff, too.

The actuator itself is a nickel-titanium (NiTi) shape-memory alloy (SMA), which is just a wire that gets longer when it heats up and then shrinks back down when it cools. SMAs are fairly common and used for all kinds of things, but what makes this particular SMA a little different is that it’s been messily coated with platinum. The “messily” part is important for a reason that we’ll get to in just a second.

The way that the sliding vent is attached to the transmission is the really clever bit about this robot, because it means that the motion of the wire itself is used to modulate the flow of fuel through a purely mechanical system. Essentially, it’s an actuator and a sensor at the same time.

One end of the SMA wire is attached to the middle of the leaf spring, while the other end runs above the back of the robot where it’s stapled to an anchor block on the robot’s rear end. With the SMA wire hooked up but not actuated (i.e., cold rather than warm), it’s short enough that the leaf spring gets pulled back, rocking the legs forward and up. The last component is embedded in the robot’s back, right along the spine and directly underneath the SMA actuator. It’s a sliding vent attached to the transmission, so that the vent is open when the SMA wire is cold and the leaf spring is pulled back, and closed when the SMA wire is warm and the leaf spring is relaxed. The way that the sliding vent is attached to the transmission is the really clever bit about this robot, because it means that the motion of the wire itself is used to modulate the flow of fuel through a purely mechanical system. Essentially, it’s an actuator and a sensor at the same time.

The actuation cycle that causes the robot to walk begins with a full fuel tank and a cold SMA wire. There’s tension on the leaf spring, pulling the transmission back and rocking the legs forward and upward. The transmission also pulls the sliding vent into the open position, allowing methanol vapor to escape up out of the fuel tank and into the air, where it wafts past the SMA wire that runs directly above the vent.

The platinum facilitates a reaction of the methanol (CH3OH) with oxygen in the air (combustion, although not the dramatic flaming and explosive kind) to generate a couple of water molecules and some carbon dioxide plus a bunch of heat, and this is where the messy platinum coating is important, because messy means lots of surface area for the platinum to interact with as much methanol as possible. In just a second or two the temperature of the SMA wire skyrockets from 50 to 100 ºC and it expands, allowing the leaf spring about 0.1 mm of slack. As the leaf spring relaxes, the transmission moves the legs backwards and downwards, and the robot pulls itself forward about 1.2 mm. At the same time, the transmission is closing off the sliding vent, cutting off the supply of methanol vapor. Without the vapor reacting with the platinum and generating heat, in about a second and a half, the SMA wire cools down. As it does, it shrinks, pulling on the leaf spring and starting the cycle over again. Top speed is 0.76 mm/s (0.05 body-lengths per second).

An interesting environmental effect is that the speed of the robot can be enhanced by a gentle breeze. This is because air moving over the SMA wire cools it down a bit faster while also blowing away any residual methanol from around the vents, shutting down the reaction more completely. RoBeetle can carry more than its own body weight in fuel, and it takes approximately 155 minutes for a full tank of methanol to completely evaporate. It’s worth noting that despite the very high energy density of methanol, this is actually a stupendously inefficient way of powering a robot, with an estimated end-to-end efficiency of just 0.48 percent. Not 48 percent, mind you, but 0.48 percent, while in general, powering SMAs with electricity is much more efficient.

However, you have to look at the entire system that would be necessary to deliver that electricity, and for a robot as small as RoBeetle, the researchers say that it’s basically impossible. The lightest commercially available battery and power supply that would deliver enough juice to heat up an SMA actuator weighs about 800 mg, nearly 10 times the total weight of RoBeetle itself. From that perspective, RoBeetle’s efficiency is actually pretty good.

Image: A. Kitterman/Science Robotics; adapted from R.L.T./MIT

Comparison of various untethered microrobots and bioinspired soft robots that use different power and actuation strategies.

There are some other downsides to RoBeetle we should mention—it can only move forwards, not backwards, and it can’t steer. Its speed isn’t adjustable, and once it starts walking, it’ll walk until it either breaks or runs out of fuel. The researchers have some ideas about the speed, at least, pointing out that increasing the speed of fuel delivery by using pressurized liquid fuels like butane or propane would increase the actuator output frequency. And the frequency, amplitude, and efficiency of the SMAs themselves can be massively increased “by arranging multiple fiber-like thin artificial muscles in hierarchical configurations similar to those observed in sarcomere-based animal muscle,” making RoBeetle even more beetle-like.

As for sensing, RoBeetle’s 230-mg payload is enough to carry passive sensors, but getting those sensors to usefully interact with the robot itself to enable any kind of autonomy remains a challenge. Mechanically intelligence is certainly possible, though, and we can imagine RoBeetle adopting some of the same sorts of systems that have been proposed for the clockwork rover that JPL wants to use for Venus exploration. The researchers also mention how RoBeetle could potentially serve as a model for microbots capable of aerial locomotion, which is something we’d very much like to see.

“An 88-milligram insect-scale autonomous crawling robot driven by a catalytic artificial muscle,” by Xiufeng Yang, Longlong Chang, and Néstor O. Pérez-Arancibia from University of Southern California, in Los Angeles, was published in Science Robotics. Continue reading

Posted in Human Robots

#437709 iRobot Announces Major Software Update, ...

Since the release of the very first Roomba in 2002, iRobot’s long-term goal has been to deliver cleaner floors in a way that’s effortless and invisible. Which sounds pretty great, right? And arguably, iRobot has managed to do exactly this, with its most recent generation of robot vacuums that make their own maps and empty their own dustbins. For those of us who trust our robots, this is awesome, but iRobot has gradually been realizing that many Roomba users either don’t want this level of autonomy, or aren’t ready for it.

Today, iRobot is announcing a major new update to its app that represents a significant shift of its overall approach to home robot autonomy. Humans are being brought back into the loop through software that tries to learn when, where, and how you clean so that your Roomba can adapt itself to your life rather than the other way around.

To understand why this is such a shift for iRobot, let’s take a very brief look back at how the Roomba interface has evolved over the last couple of decades. The first generation of Roomba had three buttons on it that allowed (or required) the user to select whether the room being vacuumed was small or medium or large in size. iRobot ditched that system one generation later, replacing the room size buttons with one single “clean” button. Programmable scheduling meant that users no longer needed to push any buttons at all, and with Roombas able to find their way back to their docking stations, all you needed to do was empty the dustbin. And with the most recent few generations (the S and i series), the dustbin emptying is also done for you, reducing direct interaction with the robot to once a month or less.

Image: iRobot

iRobot CEO Colin Angle believes that working toward more intelligent human-robot collaboration is “the brave new frontier” of AI. “This whole journey has been earning the right to take this next step, because a robot can’t be responsive if it’s incompetent,” he says. “But thinking that autonomy was the destination was where I was just completely wrong.”

The point that the top-end Roombas are at now reflects a goal that iRobot has been working toward since 2002: With autonomy, scheduling, and the clean base to empty the bin, you can set up your Roomba to vacuum when you’re not home, giving you cleaner floors every single day without you even being aware that the Roomba is hard at work while you’re out. It’s not just hands-off, it’s brain-off. No noise, no fuss, just things being cleaner thanks to the efforts of a robot that does its best to be invisible to you. Personally, I’ve been completely sold on this idea for home robots, and iRobot CEO Colin Angle was as well.

“I probably told you that the perfect Roomba is the Roomba that you never see, you never touch, you just come home everyday and it’s done the right thing,” Angle told us. “But customers don’t want that—they want to be able to control what the robot does. We started to hear this a couple years ago, and it took a while before it sunk in, but it made sense.”

How? Angle compares it to having a human come into your house to clean, but you weren’t allowed to tell them where or when to do their job. Maybe after a while, you’ll build up the amount of trust necessary for that to work, but in the short term, it would likely be frustrating. And people get frustrated with their Roombas for this reason. “The desire to have more control over what the robot does kept coming up, and for me, it required a pretty big shift in my view of what intelligence we were trying to build. Autonomy is not intelligence. We need to do something more.”

That something more, Angle says, is a partnership as opposed to autonomy. It’s an acknowledgement that not everyone has the same level of trust in robots as the people who build them. It’s an understanding that people want to have a feeling of control over their homes, that they have set up the way that they want, and that they’ve been cleaning the way that they want, and a robot shouldn’t just come in and do its own thing.

This change in direction also represents a substantial shift in resources for iRobot, and the company has pivoted two-thirds of its engineering organization to focus on software-based collaborative intelligence rather than hardware.

“Until the robot proves that it knows enough about your home and about the way that you want your home cleaned,” Angle says, “you can’t move forward.” He adds that this is one of those things that seem obvious in retrospect, but even if they’d wanted to address the issue before, they didn’t have the technology to solve the problem. Now they do. “This whole journey has been earning the right to take this next step, because a robot can’t be responsive if it’s incompetent,” Angle says. “But thinking that autonomy was the destination was where I was just completely wrong.”

The previous iteration of the iRobot app (and Roombas themselves) are built around one big fat CLEAN button. The new approach instead tries to figure out in much more detail where the robot should clean, and when, using a mixture of autonomous technology and interaction with the user.

Where to Clean
Knowing where to clean depends on your Roomba having a detailed and accurate map of its environment. For several generations now, Roombas have been using visual mapping and localization (VSLAM) to build persistent maps of your home. These maps have been used to tell the Roomba to clean in specific rooms, but that’s about it. With the new update, Roombas with cameras will be able to recognize some objects and features in your home, including chairs, tables, couches, and even countertops. The robots will use these features to identify where messes tend to happen so that they can focus on those areas—like around the dining room table or along the front of the couch.

We should take a minute here to clarify how the Roomba is using its camera. The original (primary?) purpose of the camera was for VSLAM, where the robot would take photos of your home, downsample them into QR-code-like patterns of light and dark, and then use those (with the assistance of other sensors) to navigate. Now the camera is also being used to take pictures of other stuff around your house to make that map more useful.

Photo: iRobot

The robots will now try to fit into the kinds of cleaning routines that many people already have established. For example, the app may suggest an “after dinner” routine that cleans just around the kitchen and dining room table.

This is done through machine learning using a library of images of common household objects from a floor perspective that iRobot had to develop from scratch. Angle clarified for us that this is all done via a neural net that runs on the robot, and that “no recognizable images are ever stored on the robot or kept, and no images ever leave the robot.” Worst case, if all the data iRobot has about your home gets somehow stolen, the hacker would only know that (for example) your dining room has a table in it and the approximate size and location of that table, because the map iRobot has of your place only stores symbolic representations rather than images.

Another useful new feature is intended to help manage the “evil Roomba places” (as Angle puts it) that every home has that cause Roombas to get stuck. If the place is evil enough that Roomba has to call you for help because it gave up completely, Roomba will now remember, and suggest that either you make some changes or that it stops cleaning there, which seems reasonable.

When to Clean
It turns out that the primary cause of mission failure for Roombas is not that they get stuck or that they run out of battery—it’s user cancellation, usually because the robot is getting in the way or being noisy when you don’t want it to be. “If you kill a Roomba’s job because it annoys you,” points out Angle, “how is that robot being a good partner? I think it’s an epic fail.” Of course, it’s not the robot’s fault, because Roombas only clean when we tell them to, which Angle says is part of the problem. “People actually aren’t very good at making their own schedules—they tend to oversimplify, and not think through what their schedules are actually about, which leads to lots of [figurative] Roomba death.”

To help you figure out when the robot should actually be cleaning, the new app will look for patterns in when you ask the robot to clean, and then recommend a schedule based on those patterns. That might mean the robot cleans different areas at different times every day of the week. The app will also make scheduling recommendations that are event-based as well, integrated with other smart home devices. Would you prefer the Roomba to clean every time you leave the house? The app can integrate with your security system (or garage door, or any number of other things) and take care of that for you.

More generally, Roomba will now try to fit into the kinds of cleaning routines that many people already have established. For example, the app may suggest an “after dinner” routine that cleans just around the kitchen and dining room table. The app will also, to some extent, pay attention to the environment and season. It might suggest increasing your vacuuming frequency if pollen counts are especially high, or if it’s pet shedding season and you have a dog. Unfortunately, Roomba isn’t (yet?) capable of recognizing dogs on its own, so the app has to cheat a little bit by asking you some basic questions.

A Smarter App

Image: iRobot

The previous iteration of the iRobot app (and Roombas themselves) are built around one big fat CLEAN button. The new approach instead tries to figure out in much more detail where the robot should clean, and when, using a mixture of autonomous technology and interaction with the user.

The app update, which should be available starting today, is free. The scheduling and recommendations will work on every Roomba model, although for object recognition and anything related to mapping, you’ll need one of the more recent and fancier models with a camera. Future app updates will happen on a more aggressive schedule. Major app releases should happen every six months, with incremental updates happening even more frequently than that.

Angle also told us that overall, this change in direction also represents a substantial shift in resources for iRobot, and the company has pivoted two-thirds of its engineering organization to focus on software-based collaborative intelligence rather than hardware. “It’s not like we’re done doing hardware,” Angle assured us. “But we do think about hardware differently. We view our robots as platforms that have longer life cycles, and each platform will be able to support multiple generations of software. We’ve kind of decoupled robot intelligence from hardware, and that’s a change.”

Angle believes that working toward more intelligent collaboration between humans and robots is “the brave new frontier of artificial intelligence. I expect it to be the frontier for a reasonable amount of time to come,” he adds. “We have a lot of work to do to create the type of easy-to-use experience that consumer robots need.” Continue reading

Posted in Human Robots

#437707 Video Friday: This Robot Will Restock ...

Video Friday is your weekly selection of awesome robotics videos, collected by your Automaton bloggers. We’ll also be posting a weekly calendar of upcoming robotics events for the next few months; here's what we have so far (send us your events!):

CLAWAR 2020 – August 24-26, 2020 – [Online Conference]
ICUAS 2020 – September 1-4, 2020 – Athens, Greece
ICRES 2020 – September 28-29, 2020 – Taipei, Taiwan
AUVSI EXPONENTIAL 2020 – October 5-8, 2020 – [Online Conference]
IROS 2020 – October 25-29, 2020 – Las Vegas, Nev., USA
CYBATHLON 2020 – November 13-14, 2020 – [Online Event]
ICSR 2020 – November 14-16, 2020 – Golden, Colo., USA
Let us know if you have suggestions for next week, and enjoy today's videos.

Tokyo startup Telexistence has recently unveiled a new robot called the Model-T, an advanced teleoperated humanoid that can use tools and grasp a wide range of objects. Japanese convenience store chain FamilyMart plans to test the Model-T to restock shelves in up to 20 stores by 2022. In the trial, a human “pilot” will operate the robot remotely, handling items like beverage bottles, rice balls, sandwiches, and bento boxes.

With Model-T and AWP, FamilyMart and TX aim to realize a completely new store operation by remoteizing and automating the merchandise restocking work, which requires a large number of labor-hours. As a result, stores can operate with less number of workers and enable them to recruit employees regardless of the store’s physical location.

[ Telexistence ]

Quadruped dance-off should be a new robotics competition at IROS or ICRA.

I dunno though, that moonwalk might keep Spot in the lead…

[ Unitree ]

Through a hybrid of simulation and real-life training, this air muscle robot is learning to play table tennis.

Table tennis requires to execute fast and precise motions. To gain precision it is necessary to explore in this high-speed regimes, however, exploration can be safety-critical at the same time. The combination of RL and muscular soft robots allows to close this gap. While robots actuated by pneumatic artificial muscles generate high forces that are required for e.g. smashing, they also offer safe execution of explosive motions due to antagonistic actuation.

To enable practical training without real balls, we introduce Hybrid Sim and Real Training (HYSR) that replays prerecorded real balls in simulation while executing actions on the real system. In this manner, RL can learn the challenging motor control of the PAM-driven robot while executing ~15000 hitting motions.

[ Max Planck Institute ]

Thanks Dieter!

Anthony Cowley wrote in to share his recent thesis work on UPSLAM, a fast and lightweight SLAM technique that records data in panoramic depth images (just PNGs) that are easy to visualize and even easier to share between robots, even on low-bandwidth networks.

[ UPenn ]

Thanks Anthony!

GITAI’s G1 is the space dedicated general-purpose robot. G1 robot will enable automation of various tasks internally & externally on space stations and for lunar base development.

[ Gitai ]

The University of Michigan has a fancy new treadmill that’s built right into the floor, which proves to be a bit much for Mini Cheetah.

But Cassie Blue won’t get stuck on no treadmill! She goes for a 0.3 mile walk across campus, which ends when a certain someone ran the gantry into Cassie Blue’s foot.

[ Michigan Robotics ]

Some serious quadruped research going on at UT Austin Human Centered Robotics Lab.

[ HCRL ]

Will Burrard-Lucas has spent lockdown upgrading his slightly indestructible BeetleCam wildlife photographing robot.

[ Will Burrard-Lucas ]

Teleoperated surgical robots are becoming commonplace in operating rooms, but many are massive (sometimes taking up an entire room) and are difficult to manipulate, especially if a complication arises and the robot needs to removed from the patient. A new collaboration between the Wyss Institute, Harvard University, and Sony Corporation has created the mini-RCM, a surgical robot the size of a tennis ball that weighs as much as a penny, and performed significantly better than manually operated tools in delicate mock-surgical procedures. Importantly, its small size means it is more comparable to the human tissues and structures on which it operates, and it can easily be removed by hand if needed.

[ Harvard Wyss ]

Yaskawa appears to be working on a robot that can scan you with a temperature gun and then jam a mask on your face?

[ Motoman ]

Maybe we should just not have people working in mines anymore, how about that?

[ Exyn ]

Many current human-robot interactive systems tend to use accurate and fast – but also costly – actuators and tracking systems to establish working prototypes that are safe to use and deploy for user studies. This paper presents an embedded framework to build a desktop space for human-robot interaction, using an open-source robot arm, as well as two RGB cameras connected to a Raspberry Pi-based controller that allow a fast yet low-cost object tracking and manipulation in 3D. We show in our evaluations that this facilitates prototyping a number of systems in which user and robot arm can commonly interact with physical objects.

[ Paper ]

IBM Research is proud to host professor Yoshua Bengio — one of the world’s leading experts in AI — in a discussion of how AI can contribute to the fight against COVID-19.

[ IBM Research ]

Ira Pastor, ideaXme life sciences ambassador interviews Professor Dr. Hiroshi Ishiguro, the Director of the Intelligent Robotics Laboratory, of the Department of Systems Innovation, in the Graduate School of Engineering Science, at Osaka University, Japan.

[ ideaXme ]

A CVPR talk from Stanford’s Chelsea Finn on “Generalization in Visuomotor Learning.”

[ Stanford ] Continue reading

Posted in Human Robots

#437701 Robotics, AI, and Cloud Computing ...

IBM must be brimming with confidence about its new automated system for performing chemical synthesis because Big Blue just had twenty or so journalists demo the complex technology live in a virtual room.

IBM even had one of the journalists choose the molecule for the demo: a molecule in a potential Covid-19 treatment. And then we watched as the system synthesized and tested the molecule and provided its analysis in a PDF document that we all saw in the other journalist’s computer. It all worked; again, that’s confidence.

The complex system is based upon technology IBM started developing three years ago that uses artificial intelligence (AI) to predict chemical reactions. In August 2018, IBM made this service available via the Cloud and dubbed it RXN for Chemistry.

Now, the company has added a new wrinkle to its Cloud-based AI: robotics. This new and improved system is no longer named simply RXN for Chemistry, but RoboRXN for Chemistry.

All of the journalists assembled for this live demo of RoboRXN could watch as the robotic system executed various steps, such as moving the reactor to a small reagent and then moving the solvent to a small reagent. The robotic system carried out the entire set of procedures—completing the synthesis and analysis of the molecule—in eight steps.

Image: IBM Research

IBM RXN helps predict chemical reaction outcomes or design retrosynthesis in seconds.

In regular practice, a user will be able to suggest a combination of molecules they would like to test. The AI will pick up the order and task a robotic system to run the reactions necessary to produce and test the molecule. Users will be provided analyses of how well their molecules performed.

Back in March of this year, Silicon Valley-based startup Strateos demonstrated something similar that they had developed. That system also employed a robotic system to help researchers working from the Cloud create new chemical compounds. However, what distinguishes IBM’s system is its incorporation of a third element: the AI.

The backbone of IBM’s AI model is a machine learning translation method that treats chemistry like language translation. It translates the language of chemistry by converting reactants and reagents to products through the use of Statistical Machine Intelligence and Learning Engine (SMILE) representation to describe chemical entities.

IBM has also leveraged an automatic data driven strategy to ensure the quality of its data. Researchers there used millions of chemical reactions to teach the AI system chemistry, but contained within that data set were errors. So, how did IBM clean this so-called noisy data to eliminate the potential for bad models?

According to Alessandra Toniato, a researcher at IBM Zurichh, the team implemented what they dubbed the “forgetting experiment.”

Toniato explains that, in this approach, they asked the AI model how sure it was that the chemical examples it was given were examples of correct chemistry. When faced with this choice, the AI identified chemistry that it had “never learnt,” “forgotten six times,” or “never forgotten.” Those that were “never forgotten” were examples that were clean, and in this way they were able to clean the data that AI had been presented.

While the AI has always been part of the RXN for Chemistry, the robotics is the newest element. The main benefit that turning over the carrying out of the reactions to a robotic system is expected to yield is to free up chemists from doing the often tedious process of having to design a synthesis from scratch, says Matteo Manica, a research staff member in Cognitive Health Care and Life Sciences at IBM Research Zürich.

“In this demo, you could see how the system is synergistic between a human and AI,” said Manica. “Combine that with the fact that we can run all these processes with a robotic system 24/7 from anywhere in the world, and you can see how it will really help up to speed up the whole process.”

There appear to be two business models that IBM is pursuing with its latest technology. One is to deploy the entire system on the premises of a company. The other is to offer licenses to private Cloud installations.

Photo: Michael Buholzer

Teodoro Laino of IBM Research Europe.

“From a business perspective you can think of having a system like we demonstrated being replicated on the premise within companies or research groups that would like to have the technology available at their disposal,” says Teodoro Laino, distinguished RSM, manager at IBM Research Europe. “On the other hand, we are also pushing at bringing the entire system to a service level.”

Just as IBM is brimming with confidence about its new technology, the company also has grand aspirations for it.

Laino adds: “Our aim is to provide chemical services across the world, a sort of Amazon of chemistry, where instead of looking for chemistry already in stock, you are asking for chemistry on demand.”

< Back to IEEE COVID-19 Resources Continue reading

Posted in Human Robots

#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

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