Tag Archives: host
#437957 Meet Assembloids, Mini Human Brains With ...
It’s not often that a twitching, snowman-shaped blob of 3D human tissue makes someone’s day.
But when Dr. Sergiu Pasca at Stanford University witnessed the tiny movement, he knew his lab had achieved something special. You see, the blob was evolved from three lab-grown chunks of human tissue: a mini-brain, mini-spinal cord, and mini-muscle. Each individual component, churned to eerie humanoid perfection inside bubbling incubators, is already a work of scientific genius. But Pasca took the extra step, marinating the three components together inside a soup of nutrients.
The result was a bizarre, Lego-like human tissue that replicates the basic circuits behind how we decide to move. Without external prompting, when churned together like ice cream, the three ingredients physically linked up into a fully functional circuit. The 3D mini-brain, through the information highway formed by the artificial spinal cord, was able to make the lab-grown muscle twitch on demand.
In other words, if you think isolated mini-brains—known formally as brain organoids—floating in a jar is creepy, upgrade your nightmares. The next big thing in probing the brain is assembloids—free-floating brain circuits—that now combine brain tissue with an external output.
The end goal isn’t to freak people out. Rather, it’s to recapitulate our nervous system, from input to output, inside the controlled environment of a Petri dish. An autonomous, living brain-spinal cord-muscle entity is an invaluable model for figuring out how our own brains direct the intricate muscle movements that allow us stay upright, walk, or type on a keyboard.
It’s the nexus toward more dexterous brain-machine interfaces, and a model to understand when brain-muscle connections fail—as in devastating conditions like Lou Gehrig’s disease or Parkinson’s, where people slowly lose muscle control due to the gradual death of neurons that control muscle function. Assembloids are a sort of “mini-me,” a workaround for testing potential treatments on a simple “replica” of a person rather than directly on a human.
From Organoids to Assembloids
The miniature snippet of the human nervous system has been a long time in the making.
It all started in 2014, when Dr. Madeleine Lancaster, then a post-doc at Stanford, grew a shockingly intricate 3D replica of human brain tissue inside a whirling incubator. Revolutionarily different than standard cell cultures, which grind up brain tissue to reconstruct as a flat network of cells, Lancaster’s 3D brain organoids were incredibly sophisticated in their recapitulation of the human brain during development. Subsequent studies further solidified their similarity to the developing brain of a fetus—not just in terms of neuron types, but also their connections and structure.
With the finding that these mini-brains sparked with electrical activity, bioethicists increasingly raised red flags that the blobs of human brain tissue—no larger than the size of a pea at most—could harbor the potential to develop a sense of awareness if further matured and with external input and output.
Despite these concerns, brain organoids became an instant hit. Because they’re made of human tissue—often taken from actual human patients and converted into stem-cell-like states—organoids harbor the same genetic makeup as their donors. This makes it possible to study perplexing conditions such as autism, schizophrenia, or other brain disorders in a dish. What’s more, because they’re grown in the lab, it’s possible to genetically edit the mini-brains to test potential genetic culprits in the search for a cure.
Yet mini-brains had an Achilles’ heel: not all were made the same. Rather, depending on the region of the brain that was reverse engineered, the cells had to be persuaded by different cocktails of chemical soups and maintained in isolation. It was a stark contrast to our own developing brains, where regions are connected through highways of neural networks and work in tandem.
Pasca faced the problem head-on. Betting on the brain’s self-assembling capacity, his team hypothesized that it might be possible to grow different mini-brains, each reflecting a different brain region, and have them fuse together into a synchronized band of neuron circuits to process information. Last year, his idea paid off.
In one mind-blowing study, his team grew two separate portions of the brain into blobs, one representing the cortex, the other a deeper part of the brain known to control reward and movement, called the striatum. Shockingly, when put together, the two blobs of human brain tissue fused into a functional couple, automatically establishing neural highways that resulted in one of the most sophisticated recapitulations of a human brain. Pasca crowned this tissue engineering crème-de-la-crème “assembloids,” a portmanteau between “assemble” and “organoids.”
“We have demonstrated that regionalized brain spheroids can be put together to form fused structures called brain assembloids,” said Pasca at the time.” [They] can then be used to investigate developmental processes that were previously inaccessible.”
And if that’s possible for wiring up a lab-grown brain, why wouldn’t it work for larger neural circuits?
Assembloids, Assemble
The new study is the fruition of that idea.
The team started with human skin cells, scraped off of eight healthy people, and transformed them into a stem-cell-like state, called iPSCs. These cells have long been touted as the breakthrough for personalized medical treatment, before each reflects the genetic makeup of its original host.
Using two separate cocktails, the team then generated mini-brains and mini-spinal cords using these iPSCs. The two components were placed together “in close proximity” for three days inside a lab incubator, gently floating around each other in an intricate dance. To the team’s surprise, under the microscope using tracers that glow in the dark, they saw highways of branches extending from one organoid to the other like arms in a tight embrace. When stimulated with electricity, the links fired up, suggesting that the connections weren’t just for show—they’re capable of transmitting information.
“We made the parts,” said Pasca, “but they knew how to put themselves together.”
Then came the ménage à trois. Once the mini-brain and spinal cord formed their double-decker ice cream scoop, the team overlaid them onto a layer of muscle cells—cultured separately into a human-like muscular structure. The end result was a somewhat bizarre and silly-looking snowman, made of three oddly-shaped spherical balls.
Yet against all odds, the brain-spinal cord assembly reached out to the lab-grown muscle. Using a variety of tools, including measuring muscle contraction, the team found that this utterly Frankenstein-like snowman was able to make the muscle component contract—in a way similar to how our muscles twitch when needed.
“Skeletal muscle doesn’t usually contract on its own,” said Pasca. “Seeing that first twitch in a lab dish immediately after cortical stimulation is something that’s not soon forgotten.”
When tested for longevity, the contraption lasted for up to 10 weeks without any sort of breakdown. Far from a one-shot wonder, the isolated circuit worked even better the longer each component was connected.
Pasca isn’t the first to give mini-brains an output channel. Last year, the queen of brain organoids, Lancaster, chopped up mature mini-brains into slices, which were then linked to muscle tissue through a cultured spinal cord. Assembloids are a step up, showing that it’s possible to automatically sew multiple nerve-linked structures together, such as brain and muscle, sans slicing.
The question is what happens when these assembloids become more sophisticated, edging ever closer to the inherent wiring that powers our movements. Pasca’s study targets outputs, but what about inputs? Can we wire input channels, such as retinal cells, to mini-brains that have a rudimentary visual cortex to process those examples? Learning, after all, depends on examples of our world, which are processed inside computational circuits and delivered as outputs—potentially, muscle contractions.
To be clear, few would argue that today’s mini-brains are capable of any sort of consciousness or awareness. But as mini-brains get increasingly more sophisticated, at what point can we consider them a sort of AI, capable of computation or even something that mimics thought? We don’t yet have an answer—but the debates are on.
Image Credit: christitzeimaging.com / Shutterstock.com Continue reading
Posted in Human Robots
#437758 Remotely Operated Robot Takes Straight ...
Roboticists love hard problems. Challenges like the DRC and SubT have helped (and are still helping) to catalyze major advances in robotics, but not all hard problems require a massive amount of DARPA funding—sometimes, a hard problem can just be something very specific that’s really hard for a robot to do, especially relative to the ease with which a moderately trained human might be able to do it. Catching a ball. Putting a peg in a hole. Or using a straight razor to shave someone’s face without Sweeney Todd-izing them.
This particular roboticist who sees straight-razor face shaving as a hard problem that robots should be solving is John Peter Whitney, who we first met back at IROS 2014 in Chicago when (working at Disney Research) he introduced an elegant fluidic actuator system. These actuators use tubes containing a fluid (like air or water) to transmit forces from a primary robot to a secondary robot in a very efficient way that also allows for either compliance or very high fidelity force feedback, depending on the compressibility of the fluid.
Photo: John Peter Whitney/Northeastern University
Barber meets robot: Boston based barber Jesse Cabbage [top, right] observes the machine created by roboticist John Peter Whitney. Before testing the robot on Whitney’s face, they used his arm for a quick practice [bottom].
Whitney is now at Northeastern University, in Boston, and he recently gave a talk at the RSS workshop on “Reacting to Contact,” where he suggested that straight razor shaving would be an interesting and valuable problem for robotics to work toward, due to its difficulty and requirement for an extremely high level of both performance and reliability.
Now, a straight razor is sort of like a safety razor, except with the safety part removed, which in fact does make it significantly less safe for humans, much less robots. Also not ideal for those worried about safety is that as part of the process the razor ends up in distressingly close proximity to things like the artery that is busily delivering your brain’s entire supply of blood, which is very close to the top of the list of things that most people want to keep blades very far away from. But that didn’t stop Whitney from putting his whiskers where his mouth is and letting his robotic system mediate the ministrations of a professional barber. It’s not an autonomous robotic straight-razor shave (because Whitney is not totally crazy), but it’s a step in that direction, and requires that the hardware Whitney developed be dead reliable.
Perhaps that was a poor choice of words. But, rest assured that Whitney lived long enough to answer our questions after. Here’s the video; it’s part of a longer talk, but it should start in the right spot, at about 23:30.
If Whitney looked a little bit nervous to you, that’s because he was. “This was the first time I’d ever been shaved by someone (something?!) else with a straight razor,” he told us, and while having a professional barber at the helm was some comfort, “the lack of feeling and control on my part was somewhat unsettling.” Whitney says that the barber, Jesse Cabbage of Dentes Barbershop in Somerville, Mass., was surprised by how well he could feel the tactile sensations being transmitted from the razor. “That’s one of the reasons we decided to make this video,” Whitney says. “I can’t show someone how something feels, so the next best thing is to show a delicate task that either from experience or intuition makes it clear to the viewer that the system must have these properties—otherwise the task wouldn’t be possible.”
And as for when Whitney might be comfortable getting shaved by a robotic system without a human in the loop? It’s going to take a lot of work, as do most other hard problems in robotics. “There are two parts to this,” he explains. “One is fault-tolerance of the components themselves (software, electronics, etc.) and the second is the quality of the perception and planning algorithms.”
He offers a comparison to self-driving cars, in which similar (or greater) risks are incurred: “To learn how to perceive, interpret, and adapt, we need a very high-fidelity model of the problem, or a wealth of data and experience, or both” he says. “But in the case of shaving we are greatly lacking in both!” He continues with the analogy: “I think there is a natural progression—the community started with autonomous driving of toy cars on closed courses and worked up to real cars carrying human passengers; in robotic manipulation we are beginning to move out of the ‘toy car’ stage and so I think it’s good to target high-consequence hard problems to help drive progress.”
The ultimate goal is much more general than the creation of a dedicated straight razor shaving robot. This particular hardware system is actually a testbed for exploring MRI-compatible remote needle biopsy.
Of course, the ultimate goal here is much more general than the creation of a dedicated straight razor shaving robot; it’s a challenge that includes a host of sub-goals that will benefit robotics more generally. This particular hardware system Whitney is developing is actually a testbed for exploring MRI-compatible remote needle biopsy, and he and his students are collaborating with Brigham and Women’s Hospital in Boston on adapting this technology to prostate biopsy and ablation procedures. They’re also exploring how delicate touch can be used as a way to map an environment and localize within it, especially where using vision may not be a good option. “These traits and behaviors are especially interesting for applications where we must interact with delicate and uncertain environments,” says Whitney. “Medical robots, assistive and rehabilitation robots and exoskeletons, and shared-autonomy teleoperation for delicate tasks.”
A paper with more details on this robotic system, “Series Elastic Force Control for Soft Robotic Fluid Actuators,” is available on arXiv. 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.
5/5
STEP 5: The most promising compounds are tested against live virus samples.
Previous
Next
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
Posted in Human Robots
#437667 17 Teams to Take Part in DARPA’s ...
Among all of the other in-person events that have been totally wrecked by COVID-19 is the Cave Circuit of the DARPA Subterranean Challenge. DARPA has already hosted the in-person events for the Tunnel and Urban SubT circuits (see our previous coverage here), and the plan had always been for a trio of events representing three uniquely different underground environments in advance of the SubT Finals, which will somehow combine everything into one bonkers course.
While the SubT Urban Circuit event snuck in just under the lockdown wire in late February, DARPA made the difficult (but prudent) decision to cancel the in-person Cave Circuit event. What this means is that there will be no Systems Track Cave competition, which is a serious disappointment—we were very much looking forward to watching teams of robots navigating through an entirely unpredictable natural environment with a lot of verticality. Fortunately, DARPA is still running a Virtual Cave Circuit, and 17 teams will be taking part in this competition featuring a simulated cave environment that’s as dynamic and detailed as DARPA can make it.
From DARPA’s press releases:
DARPA’s Subterranean (SubT) Challenge will host its Cave Circuit Virtual Competition, which focuses on innovative solutions to map, navigate, and search complex, simulated cave environments November 17. Qualified teams have until Oct. 15 to develop and submit software-based solutions for the Cave Circuit via the SubT Virtual Portal, where their technologies will face unknown cave environments in the cloud-based SubT Simulator. Until then, teams can refine their roster of selected virtual robot models, choose sensor payloads, and continue to test autonomy approaches to maximize their score.
The Cave Circuit also introduces new simulation capabilities, including digital twins of Systems Competition robots to choose from, marsupial-style platforms combining air and ground robots, and breadcrumb nodes that can be dropped by robots to serve as communications relays. Each robot configuration has an associated cost, measured in SubT Credits – an in-simulation currency – based on performance characteristics such as speed, mobility, sensing, and battery life.
Each team’s simulated robots must navigate realistic caves, with features including natural terrain and dynamic rock falls, while they search for and locate various artifacts on the course within five meters of accuracy to score points during a 60-minute timed run. A correct report is worth one point. Each course contains 20 artifacts, which means each team has the potential for a maximum score of 20 points. Teams can leverage numerous practice worlds and even build their own worlds using the cave tiles found in the SubT Tech Repo to perfect their approach before they submit one official solution for scoring. The DARPA team will then evaluate the solution on a set of hidden competition scenarios.
Of the 17 qualified teams (you can see all of them here), there are a handful that we’ll quickly point out. Team BARCS, from Michigan Tech, was the winner of the SubT Virtual Urban Circuit, meaning that they may be the team to beat on Cave as well, although the course is likely to be unique enough that things will get interesting. Some Systems Track teams to watch include Coordinated Robotics, CTU-CRAS-NORLAB, MARBLE, NUS SEDS, and Robotika, and there are also a handful of brand new teams as well.
Now, just because there’s no dedicated Cave Circuit for the Systems Track teams, it doesn’t mean that there won’t be a Cave component (perhaps even a significant one) in the final event, which as far as we know is still scheduled to happen in fall of next year. We’ve heard that many of the Systems Track teams have been testing out their robots in caves anyway, and as the virtual event gets closer, we’ll be doing a sort of Virtual Systems Track series that highlights how different teams are doing mock Cave Circuits in caves they’ve found for themselves.
For more, we checked in with DARPA SubT program manager Dr. Timothy H. Chung.
IEEE Spectrum: Was it a difficult decision to cancel the Systems Track for Cave?
Tim Chung: The decision to go virtual only was heart wrenching, because I think DARPA’s role is to offer up opportunities that may be unimaginable for some of our competitors, like opening up a cave-type site for this competition. We crawled and climbed through a number of these sites, and I share the sense of disappointment that both our team and the competitors have that we won’t be able to share all the advances that have been made since the Urban Circuit. But what we’ve been able to do is pour a lot of our energy and the insights that we got from crawling around in those caves into what’s going to be a really great opportunity on the Virtual Competition side. And whether it’s a global pandemic, or just lack of access to physical sites like caves, virtual environments are an opportunity that we want to develop.
“The simulator offers us a chance to look at where things could be … it really allows for us to find where some of those limits are in the technology based only on our imagination.”
—Timothy H. Chung, DARPA
What kind of new features will be included in the Virtual Cave Circuit for this competition?
I’m really excited about these particular features because we’re seeing an opportunity for increased synergy between the physical and the virtual. The first I’d say is that we scanned some of the Systems Track robots using photogrammetry and combined that with some additional models that we got from the systems competitors themselves to turn their systems robots into virtual models. We often talk about the sim to real transfer and how successful we can get a simulation to transfer over to the physical world, but now we’ve taken something from the physical world and made it virtual. We’ve validated the controllers as well as the kinematics of the robots, we’ve iterated with the systems competitors themselves, and now we have these 13 robots (air and ground) in the SubT Tech Repo that now all virtual competitors can take advantage of.
We also have additional robot capability. Those comms bread crumbs are common among many of the competitors, so we’ve adopted that in the virtual world, and now you have comms relay nodes that are baked in to the SubT Simulator—you can have either six or twelve comms nodes that you can drop from a variety of our ground robot platforms. We have the marsupial deployment capability now, so now we have parent ground robots that can be mixed and matched with different child drones to become marsupial pairs.
And this is something I’ve been planning for for a while: we now have the ability to trigger things like rock falls. They still don’t quite look like Indiana Jones with the boulder coming down the corridor, but this comes really close. In addition to it just being an interesting and realistic consideration, we get to really dynamically test and stress the robots’ ability to navigate and recognize that something has changed in the environment and respond to it.
Image: DARPA
DARPA is still running a Virtual Cave Circuit, and 17 teams will be taking part in this competition featuring a simulated cave environment.
No simulation is perfect, so can you talk to us about what kinds of things aren’t being simulated right now? Where does the simulator not match up to reality?
I think that question is foundational to any conversation about simulation. I’ll give you a couple of examples:
We have the ability to represent wholesale damage to a robot, but it’s not at the actuator or component level. So there’s not a reliability model, although I think that would be really interesting to incorporate so that you could do assessments on things like mean time to failure. But if a robot falls off a ledge, it can be disabled by virtue of being too damaged to continue.
With communications, and this is one that’s near and dear not only to my heart but also to all of those that have lived through developing communication systems and robotic systems, we’ve gone through and conducted RF surveys of underground environments to get a better handle on what propagation effects are. There’s a lot of research that has gone into this, and trying to carry through some of that realism, we do have path loss models for RF communications baked into the SubT Simulator. For example, when you drop a bread crumb node, it’s using a path loss model so that it can represent the degradation of signal as you go farther into a cave. Now, we’re not modeling it at the Maxwell equations level, which I think would be awesome, but we’re not quite there yet.
We do have things like battery depletion, sensor degradation to the extent that simulators can degrade sensor inputs, and things like that. It’s just amazing how close we can get in some places, and how far away we still are in others, and I think showing where the limits are of how far you can get simulation is all part and parcel of why SubT Challenge wants to have both System and Virtual tracks. Simulation can be an accelerant, but it’s not going to be the panacea for development and innovation, and I think all the competitors are cognizant those limitations.
One of the most amazing things about the SubT Virtual Track is that all of the robots operate fully autonomously, without the human(s) in the loop that the System Track teams have when they compete. Why make the Virtual Track even more challenging in that way?
I think it’s one of the defining, delineating attributes of the Virtual Track. Our continued vision for the simulation side is that the simulator offers us a chance to look at where things could be, and allows for us to explore things like larger scales, or increased complexity, or types of environments that we can’t physically gain access to—it really allows for us to find where some of those limits are in the technology based only on our imagination, and this is one of the intrinsic values of simulation.
But I think finding a way to incorporate human input, or more generally human factors like teleoperation interfaces and the in-situ stress that you might not be able to recreate in the context of a virtual competition provided a good reason for us to delineate the two competitions, with the Virtual Competition really being about the role of fully autonomous or self-sufficient systems going off and doing their solution without human guidance, while also acknowledging that the real world has conditions that would not necessarily be represented by a fully simulated version. Having said that, I think cognitive engineering still has an incredibly important role to play in human robot interaction.
What do we have to look forward to during the Virtual Competition Showcase?
We have a number of additional features and capabilities that we’ve baked into the simulator that will allow for us to derive some additional insights into our competition runs. Those insights might involve things like the performance of one or more robots in a given scenario, or the impact of the environment on different types of robots, and what I can tease is that this will be an opportunity for us to showcase both the technology and also the excitement of the robots competing in the virtual environment. I’m trying not to give too many spoilers, but we’ll have an opportunity to really get into the details.
Check back as we get closer to the 17 November event for more on the DARPA SubT Challenge. Continue reading
Posted in Human Robots