Tag Archives: first

#437716 Robotic Tank Is Designed to Crawl ...

Let’s talk about bowels! Most of us have them, most of us use them a lot, and like anything that gets used a lot, they eventually need to get checked out to help make sure that everything will keep working the way it should for as long as you need it to. Generally, this means a colonoscopy, and while there are other ways of investigating what’s going on in your gut, a camera on a flexible tube is still “the gold-standard method of diagnosis and intervention,” according to some robotics researchers who want to change that up a bit.

The University of Colorado’s Advanced Medical Technologies Lab has been working on a tank robot called Endoculus that’s able to actively drive itself through your intestines, rather than being shoved. The good news is that it’s very small, and the bad news is that it’s probably not as small as you’d like it to be.

The reason why a robot like Endoculus is necessary (or at least a good idea) is that trying to stuff a semi-rigid endoscopy tube into the semi-floppy tube that is your intestine doesn’t always go smoothly. Sometimes, the tip of the endoscopy tube can get stuck, and as more tube is fed in, it causes the intestine to distend, which best case is painful and worst case can cause serious internal injuries. One way of solving this is with swallowable camera pills, but those don’t help you with tasks like taking tissue samples. A self-propelled system like Endoculus could reduce risk while also making the procedure faster and cheaper.

Image: Advanced Medical Technologies Lab/University of Colorado

The researchers say that while the width of Endoculus is larger than a traditional endoscope, the device would require “minimal distention during use” and would “not cause pain or harm to the patient.” Future versions of the robot, they add, will “yield a smaller footprint.”

Endoculus gets around with four sets of treads, angled to provide better traction against the curved walls of your gut. The treads are micropillared, or covered with small nubs, which helps them deal with all your “slippery colon mucosa.” Designing the robot was particularly tricky because of the severe constraints on the overall size of the device, which is just 3 centimeters wide and 2.3 cm high. In order to cram the two motors required for full control, they had to be arranged parallel to the treads, resulting in a fairly complex system of 3D-printed worm gears. And to make the robot actually useful, it includes a camera, LED lights, tubes for injecting air and water, and a tool port that can accommodate endoscopy instruments like forceps and snares to retrieve tissue samples.

So far, Endoculus has spent some time inside of a live pig, although it wasn’t able to get that far since pig intestines are smaller than human intestines, and because apparently the pig intestine is spiraled somehow. The pig (and the robot) both came out fine. A (presumably different) pig then provided some intestine that was expanded to human-intestine size, inside of which Endoculus did much better, and was able to zip along at up to 40 millimeters per second without causing any damage. Personally, I’m not sure I’d want a robot to explore my intestine at a speed much higher than that.

The next step with Endoculus is to add some autonomy, which means figuring out how to do localization and mapping using the robot’s onboard camera and IMU. And then of course someone has to be the first human to experience Endoculus directly, which I’d totally volunteer for except the research team is in Colorado and I’m not. Sorry!

“Novel Optimization-Based Design and Surgical Evaluation of a Treaded Robotic Capsule Colonoscope,” by Gregory A. Formosa, J. Micah Prendergast, Steven A. Edmundowicz, and Mark E. Rentschler, from the University of Colorado, was presented at ICRA 2020.

< Back to IEEE Journal Watch 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

#437689 GITAI Sending Autonomous Robot to Space ...

We’ve been keeping a close watch on GITAI since early last year—what caught our interest initially is the history of the company, which includes a bunch of folks who started in the JSK Lab at the University of Tokyo, won the DARPA Robotics Challenge Trials as SCHAFT, got swallowed by Google, narrowly avoided being swallowed by SoftBank, and are now designing robots that can work in space.

The GITAI YouTube channel has kept us more to less up to date on their progress so far, and GITAI has recently announced the next step in this effort: The deployment of one of their robots on board the International Space Station in 2021.

Photo: GITAI

GITAI’s S1 is a task-specific 8-degrees-of-freedom arm with an integrated sensing and computing system and 1-meter reach.

GITAI has been working on a variety of robots for space operations, the most sophisticated of which is a humanoid torso called G1, which is controlled through an immersive telepresence system. What will be launching into space next year is a more task-specific system called the S1, which is an 8-degrees-of-freedom arm with an integrated sensing and computing system that can be wall-mounted and has a 1-meter reach.

The S1 will be living on board a commercially funded, pressurized airlock-extension module called Bishop, developed by NanoRacks. Mounted on the inside of the Bishop module, the S1 will have access to a task board and a small assembly area, where it will demonstrate common crew intra-vehicular activity, or IVA—tasks like flipping switches, turning knobs, and managing cables. It’ll also do some in-space assembly, or ISA, attaching panels to create a solar array.

Here’s a demonstration of some task board activities, conducted on Earth in a mockup of Bishop:

GITAI says that “all operations conducted by the S1 GITAI robotic arm will be autonomous, followed by some teleoperations from Nanoracks’ in-house mission control.” This is interesting, because from what we’ve seen until now, GITAI has had a heavy emphasis on telepresence, with a human in the loop to get stuff done. As GITAI’s founder and CEO Sho Nakanose commented to us a year ago, “Telepresence robots have far better performance and can be made practical much quicker than autonomous robots, so first we are working on making telepresence robots practical.”

So what’s changed? “GITAI has been concentrating on teleoperations to demonstrate the dexterity of our robot, but now it’s time to show our capabilities to do the same this time with autonomy,” Nakanose told us last week. “In an environment with minimum communication latency, it would be preferable to operate a robot more with teleoperations to enhance the capability of the robot, since with the current technology level of AI, what a robot can do autonomously is very limited. However, in an environment where the latency becomes noticeable, it would become more efficient to have a mixture of autonomy and teleoperations depending on the application. Eventually, in an ideal world, a robot will operate almost fully autonomously with minimum human cognizance.”

“In an environment where the latency becomes noticeable, it would become more efficient to have a mixture of autonomy and teleoperations depending on the application. Eventually, in an ideal world, a robot will operate almost fully autonomously with minimum human cognizance.”
—Sho Nakanose, GITAI founder and CEO

Nakanose says that this mission will help GITAI to “acquire the skills, know-how, and experience necessary to prepare a robot to be ISS compatible, prov[ing] the maturity of our technology in the microgravity environment.” Success would mean conducting both IVA and ISA experiments as planned (autonomous and teleop for IVA, fully autonomous for ISA), which would be pretty awesome, but we’re told that GITAI has already received a research and development order for space robots from a private space company, and Nakanose expects that “by the mid-2020s, we will be able to show GITAI's robots working in space on an actual mission.”

NanoRacks is schedule to launch the Bishop module on SpaceX CRS-21 in November. The S1 will be launched separately in 2021, and a NASA astronaut will install the robot and then leave it alone to let it start demonstrating how work in space can be made both safer and cheaper once the humans have gotten out of the way. Continue reading

Posted in Human Robots

#437687 Video Friday: Bittle Is a Palm-Sized ...

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!):

ICRES 2020 – September 28-29, 2020 – Taipei, Taiwan
AUVSI EXPONENTIAL 2020 – October 5-8, 2020 – [Online]
IROS 2020 – October 25-29, 2020 – [Online]
CYBATHLON 2020 – November 13-14, 2020 – [Online]
ICSR 2020 – November 14-16, 2020 – Golden, Colo., USA
Let us know if you have suggestions for next week, and enjoy today's videos.

Rongzhong Li, who is responsible for the adorable robotic cat Nybble, has an updated and even more adorable quadruped that's more robust and agile but only costs around US $200 in kit form on Kickstarter.

Looks like the early bird options are sold out, but a full kit is a $225 pledge, for delivery in December.

[ Kickstarter ]

Thanks Rz!

I still maintain that Stickybot was one of the most elegantly designed robots ever.

[ Stanford ]

With the unpredictable health crisis of COVID-19 continuing to place high demands on hospitals, PAL Robotics have successfully completed testing of their delivery robots in Barcelona hospitals this summer. The TIAGo Delivery and TIAGo Conveyor robots were deployed in Hospital Municipal of Badalona and Hospital Clínic Barcelona following a winning proposal submitted to the European DIH-Hero project. Accerion sensors were integrated onto the TIAGo Delivery Robot and TIAGo Conveyor Robot for use in this project.

[ PAL Robotics ]

Energy Robotics, a leading developer of software solutions for mobile robots used in industrial applications, announced that its remote sensing and inspection solution for Boston Dynamics’s agile mobile robot Spot was successfully deployed at Merck’s thermal exhaust treatment plant at its headquarters in Darmstadt, Germany. Energy Robotics equipped Spot with sensor technology and remote supervision functions to support the inspection mission.

Combining Boston Dynamics’ intuitive controls, robotic intelligence and open interface with Energy Robotics’ control and autonomy software, user interface and encrypted cloud connection, Spot can be taught to autonomously perform a specific inspection round while being supervised remotely from anywhere with internet connectivity. Multiple cameras and industrial sensors enable the robot to find its way around while recording and transmitting information about the facility’s onsite equipment operations.

Spot reads the displays of gauges in its immediate vicinity and can also zoom in on distant objects using an externally-mounted optical zoom lens. In the thermal exhaust treatment facility, for instance, it monitors cooling water levels and notes whether condensation water has accumulated. Outside the facility, Spot monitors pipe bridges for anomalies.

Among the robot’s many abilities, it can detect defects of wires or the temperature of pump components using thermal imaging. The robot was put through its paces on a comprehensive course that tested its ability to handle special challenges such as climbing stairs, scaling embankments and walking over grating.

[ Energy Robotics ]

Thanks Stefan!

Boston Dynamics really should give Dr. Guero an Atlas just to see what he can do with it.

[ DrGuero ]

World's First Socially Distanced Birthday Party: Located in London, the robotic arm was piloted in real time to light the candles on the cake by the founder of Extend Robotics, Chang Liu, who was sat 50 miles away in Reading. Other team members in Manchester and Reading were also able to join in the celebration as the robot was used to accurately light the candles on the birthday cake.

[ Extend Robotics ]

The Robocon in-person competition was canceled this year, but check out Tokyo University's robots in action:

[ Robocon ]

Sphero has managed to pack an entire Sphero into a much smaller sphere.

[ Sphero ]

Squishy Robotics, a small business funded by the National Science Foundation (NSF), is developing mobile sensor robots for use in disaster rescue, remote monitoring, and space exploration. The shape-shifting, mobile, senor robots from UC-Berkeley spin-off Squishy Robotics can be dropped from airplanes or drones and can provide first responders with ground-based situational awareness during fires, hazardous materials (HazMat) release, and natural and man-made disasters.

[ Squishy Robotics ]

Meet Jasper, the small girl with big dreams to FLY. Created by UTS Animal Logic Academy in partnership with the Royal Australian Air Force to encourage girls to soar above the clouds. Jasper was created using a hybrid of traditional animation techniques and technology such as robotics and 3D printing. A KUKA QUANTEC robot is used during the film making to help the Australian Royal Airforce tell their story in a unique way. UTS adapted their High Accurate robot to film consistent paths, creating a video with physical sets and digital characters.

[ AU AF ]

Impressive what the Ghost Robotics V60 can do without any vision sensors on it.

[ Ghost Robotics ]

Is your job moving tiny amounts of liquid around? Would you rather be doing something else? ABB’s YuMi got you.

[ Yumi ]

For his PhD work at the Media Lab, Biomechatronics researcher Roman Stolyarov developed a terrain-adaptive control system for robotic leg prostheses. as a way to help people with amputations feel as able-bodied and mobile as possible, by allowing them to walk seamlessly regardless of the ground terrain.

[ MIT ]

This robot collects data on each cow when she enters to be milked. Milk samples and 3D photos can be taken to monitor the cow’s health status. The Ontario Dairy Research Centre in Elora, Ontario, is leading dairy innovation through education and collaboration. It is a state-of-the-art 175,000 square foot facility for discovery, learning and outreach. This centre is a partnership between the Agricultural Research Institute of Ontario, OMAFRA, the University of Guelph and the Ontario dairy industry.

[ University of Guleph ]

Australia has one of these now, should the rest of us panic?

[ Boeing ]

Daimler and Torc are developing Level 4 automated trucks for the real world. Here is a glimpse into our closed-course testing, routes on public highways in Virginia, and self-driving capabilities development. Our year of collaborating on the future of transportation culminated in the announcement of our new truck testing center in New Mexico.

[ Torc Robotics ] 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.

1/5

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

2/5

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.

3/5

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.

4/5

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.

Out of 10
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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