Tag Archives: death
#439077 How Scientists Grew Human Muscles in Pig ...
The little pigs bouncing around the lab looked exceedingly normal. Yet their adorable exterior hid a remarkable secret: each piglet carried two different sets of genes. For now, both sets came from their own species. But one day, one of those sets may be human.
The piglets are chimeras—creatures with intermingled sets of genes, as if multiple entities were seamlessly mashed together. Named after the Greek lion-goat-serpent monsters, chimeras may hold the key to an endless supply of human organs and tissues for transplant. The crux is growing these human parts in another animal—one close enough in size and function to our own.
Last week, a team from the University of Minnesota unveiled two mind-bending chimeras. One was joyous little piglets, each propelled by muscles grown from a different pig. Another was pig embryos, transplanted into surrogate pigs, that developed human muscles for more than 20 days.
The study, led by Drs. Mary and Daniel Garry at the University of Minnesota, had a therapeutic point: engineering a brilliant way to replace muscle loss, especially for the muscles around our skeletons that allow us to move and navigate the world. Trauma and injury, such as from firearm wounds or car crashes, can damage muscle tissue beyond the point of repair. Unfortunately, muscles are also stubborn in that donor tissue from cadavers doesn’t usually “take” at the injury site. For now, there are no effective treatments for severe muscle death, called volumetric muscle loss.
The new human-pig hybrids are designed to tackle this problem. Muscle wasting aside, the study also points to a clever “hack” that increases the amount of human tissue inside a growing pig embryo.
If further improved, the technology could “provide an unlimited supply of organs for transplantation,” said Dr. Mary Garry to Inverse. What’s more, because the human tissue can be sourced from patients themselves, the risk of rejection by the immune system is relatively low—even when grown inside a pig.
“The shortage of organs for heart transplantation, vascular grafting, and skeletal muscle is staggering,” said Garry. Human-animal chimeras could have a “seismic impact” that transforms organ transplantation and helps solve the organ shortage crisis.
That is, if society accepts the idea of a semi-humanoid pig.
Wait…But How?
The new study took a page from previous chimera recipes.
The main ingredients and steps go like this: first, you need an embryo that lacks the ability to develop a tissue or organ. This leaves an “empty slot” of sorts that you can fill with another set of genes—pig, human, or even monkey.
Second, you need to fine-tune the recipe so that the embryos “take” the new genes, incorporating them into their bodies as if they were their own. Third, the new genes activate to instruct the growing embryo to make the necessary tissue or organs without harming the overall animal. Finally, the foreign genes need to stay put, without cells migrating to another body part—say, the brain.
Not exactly straightforward, eh? The piglets are technological wonders that mix cutting-edge gene editing with cloning technologies.
The team went for two chimeras: one with two sets of pig genes, the other with a pig and human mix. Both started with a pig embryo that can’t make its own skeletal muscles (those are the muscles surrounding your bones). Using CRISPR, the gene-editing Swiss Army Knife, they snipped out three genes that are absolutely necessary for those muscles to develop. Like hitting a bullseye with three arrows simultaneously, it’s already a technological feat.
Here’s the really clever part: the muscles around your bones have a slightly different genetic makeup than the ones that line your blood vessels or the ones that pump your heart. While the resulting pig embryos had severe muscle deformities as they developed, their hearts beat as normal. This means the gene editing cut only impacted skeletal muscles.
Then came step two: replacing the missing genes. Using a microneedle, the team injected a fertilized and slightly developed pig egg—called a blastomere—into the embryo. If left on its natural course, a blastomere eventually develops into another embryo. This step “smashes” the two sets of genes together, with the newcomer filling the muscle void. The hybrid embryo was then placed into a surrogate, and roughly four months later, chimeric piglets were born.
Equipped with foreign DNA, the little guys nevertheless seemed totally normal, nosing around the lab and running everywhere without obvious clumsy stumbles. Under the microscope, their “xenomorph” muscles were indistinguishable from run-of-the-mill average muscle tissue—no signs of damage or inflammation, and as stretchy and tough as muscles usually are. What’s more, the foreign DNA seemed to have only developed into muscles, even though they were prevalent across the body. Extensive fishing experiments found no trace of the injected set of genes inside blood vessels or the brain.
A Better Human-Pig Hybrid
Confident in their recipe, the team next repeated the experiment with human cells, with a twist. Instead of using controversial human embryonic stem cells, which are obtained from aborted fetuses, they relied on induced pluripotent stem cells (iPSCs). These are skin cells that have been reverted back into a stem cell state.
Unlike previous attempts at making human chimeras, the team then scoured the genetic landscape of how pig and human embryos develop to find any genetic “brakes” that could derail the process. One gene, TP53, stood out, which was then promptly eliminated with CRISPR.
This approach provides a way for future studies to similarly increase the efficiency of interspecies chimeras, the team said.
The human-pig embryos were then carefully grown inside surrogate pigs for less than a month, and extensively analyzed. By day 20, the hybrids had already grown detectable human skeletal muscle. Similar to the pig-pig chimeras, the team didn’t detect any signs that the human genes had sprouted cells that would eventually become neurons or other non-muscle cells.
For now, human-animal chimeras are not allowed to grow to term, in part to stem the theoretical possibility of engineering humanoid hybrid animals (shudder). However, a sentient human-pig chimera is something that the team specifically addressed. Through multiple experiments, they found no trace of human genes in the embryos’ brain stem cells 20 and 27 days into development. Similarly, human donor genes were absent in cells that would become the hybrid embryos’ reproductive cells.
Despite bioethical quandaries and legal restrictions, human-animal chimeras have taken off, both as a source of insight into human brain development and a well of personalized organs and tissues for transplant. In 2019, Japan lifted its ban on developing human brain cells inside animal embryos, as well as the term limit—to global controversy. There’s also the question of animal welfare, given that hybrid clones will essentially become involuntary organ donors.
As the debates rage on, scientists are nevertheless pushing the limits of human-animal chimeras, while treading as carefully as possible.
“Our data…support the feasibility of the generation of these interspecies chimeras, which will serve as a model for translational research or, one day, as a source for xenotransplantation,” the team said.
Image Credit: Christopher Carson on Unsplash Continue reading
Posted in Human Robots
#438785 Video Friday: A Blimp For Your Cat
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!):
HRI 2021 – March 8-11, 2021 – [Online Conference]
RoboSoft 2021 – April 12-16, 2021 – [Online Conference]
ICRA 2021 – May 30-5, 2021 – Xi'an, China
Let us know if you have suggestions for next week, and enjoy today's videos.
Shiny robotic cat toy blimp!
I am pretty sure this is Google Translate getting things wrong, but the About page mentions that the blimp will “take you to your destination after appearing in the death of God.”
[ NTT DoCoMo ] via [ RobotStart ]
If you have yet to see this real-time video of Perseverance landing on Mars, drop everything and watch it.
During the press conference, someone commented that this is the first time anyone on the team who designed and built this system has ever seen it in operation, since it could only be tested at the component scale on Earth. This landing system has blown my mind since Curiosity.
Here's a better look at where Percy ended up:
[ NASA ]
The fact that Digit can just walk up and down wet, slippery, muddy hills without breaking a sweat is (still) astonishing.
[ Agility Robotics ]
SkyMul wants drones to take over the task of tying rebar, which looks like just the sort of thing we'd rather robots be doing so that we don't have to:
The tech certainly looks promising, and SkyMul says that they're looking for some additional support to bring things to the pilot stage.
[ SkyMul ]
Thanks Eohan!
Flatcat is a pet-like, playful robot that reacts to touch. Flatcat feels everything exactly: Cuddle with it, romp around with it, or just watch it do weird things of its own accord. We are sure that flatcat will amaze you, like us, and caress your soul.
I don't totally understand it, but I want it anyway.
[ Flatcat ]
Thanks Oswald!
This is how I would have a romantic dinner date if I couldn't get together in person. Herman the UR3 and an OptiTrack system let me remotely make a romantic meal!
[ Dave's Armoury ]
Here, we propose a novel design of deformable propellers inspired by dragonfly wings. The structure of these propellers includes a flexible segment similar to the nodus on a dragonfly wing. This flexible segment can bend, twist and even fold upon collision, absorbing force upon impact and protecting the propeller from damage.
[ Paper ]
Thanks Van!
In the 1970s, The CIA created the world's first miniaturized unmanned aerial vehicle, or UAV, which was intended to be a clandestine listening device. The Insectothopter was never deployed operationally, but was still revolutionary for its time.
It may never have been deployed (not that they'll admit to, anyway), but it was definitely operational and could fly controllably.
[ CIA ]
Research labs are starting to get Digits, which means we're going to get a much better idea of what its limitations are.
[ Ohio State ]
This video shows the latest achievements for LOLA walking on undetected uneven terrain. The robot is technically blind, not using any camera-based or prior information on the terrain.
[ TUM ]
We define “robotic contact juggling” to be the purposeful control of the motion of a three-dimensional smooth object as it rolls freely on a motion-controlled robot manipulator, or “hand.” While specific examples of robotic contact juggling have been studied before, in this paper we provide the first general formulation and solution method for the case of an arbitrary smooth object in single-point rolling contact on an arbitrary smooth hand.
[ Paper ]
Thanks Fan!
A couple of new cobots from ABB, designed to work safely around humans.
[ ABB ]
Thanks Fan!
It's worth watching at least a little bit of Adam Savage testing Spot's new arm, because we get to see Spot try, fail, and eventually succeed at an autonomous door-opening behavior at the 10 minute mark.
[ Tested ]
SVR discusses diversity with guest speakers Dr. Michelle Johnson from the GRASP Lab at UPenn; Dr Ariel Anders from Women in Robotics and first technical hire at Robust.ai; Alka Roy from The Responsible Innovation Project; and Kenechukwu C. Mbanesi and Kenya Andrews from Black in Robotics. The discussion here is moderated by Dr. Ken Goldberg—artist, roboticist and Director of the CITRIS People and Robots Lab—and Andra Keay from Silicon Valley Robotics.
[ SVR ]
RAS presents a Soft Robotics Debate on Bioinspired vs. Biohybrid Design.
In this debate, we will bring together experts in Bioinspiration and Biohybrid design to discuss the necessary steps to make more competent soft robots. We will try to answer whether bioinspired research should focus more on developing new bioinspired material and structures or on the integration of living and artificial structures in biohybrid designs.
[ RAS SoRo ]
IFRR presents a Colloquium on Human Robot Interaction.
Across many application domains, robots are expected to work in human environments, side by side with people. The users will vary substantially in background, training, physical and cognitive abilities, and readiness to adopt technology. Robotic products are expected to not only be intuitive, easy to use, and responsive to the needs and states of their users, but they must also be designed with these differences in mind, making human-robot interaction (HRI) a key area of research.
[ IFRR ]
Vijay Kumar, Nemirovsky Family Dean and Professor at Penn Engineering, gives an introduction to ENIAC day and David Patterson, Pardee Professor of Computer Science, Emeritus at the University of California at Berkeley, speaks about the legacy of the ENIAC and its impact on computer architecture today. This video is comprised of lectures one and two of nine total lectures in the ENIAC Day series.
There are more interesting ENIAC videos at the link below, but we'll highlight this particular one, about the women of the ENIAC, also known as the First Programmers.
[ ENIAC Day ] Continue reading
Posted in Human Robots
#438553 New Drone Software Handles Motor ...
Good as some drones are becoming at obstacle avoidance, accidents do still happen. And as far as robots go, drones are very much on the fragile side of things. Any sort of significant contact between a drone and almost anything else usually results in a catastrophic, out-of-control spin followed by a death plunge to the ground. Bad times. Bad, expensive times.
A few years ago, we saw some interesting research into software that can keep the most common drone form factor, the quadrotor, aloft and controllable even after the failure of one motor. The big caveat to that software was that it relied on GPS for state estimation, meaning that without a GPS signal, the drone is unable to get the information it needs to keep itself under control. In a paper recently accepted to RA-L, researchers at the University of Zurich report that they have developed a vision-based system that brings state estimation completely on-board. The upshot: potentially any drone with some software and a camera can keep itself safe even under the most challenging conditions.
A few years ago, we wrote about first author Sihao Sun’s work on high speed controlled flight of a quadrotor with a non-functional motor. But that innovation relied on an external motion capture system. Since then, Sun has moved from Tu Delft to Davide Scaramuzza’s lab at UZH, and it looks like he’s been able to combine his work on controlled spinning flight with the Robotics and Perception Group’s expertise in vision. Now, a downward-facing camera is all it takes for a spinning drone to remain stable and controllable:
Remember, this software isn’t just about guarding against motor failure. Drone motors themselves don’t just up and fail all that often, either with respect to their software or hardware. But they do represent the most likely point of failure for any drone, usually because when you run into something, what ultimately causes your drone to crash is damage to a motor or a propeller that causes loss of control.
The reason that earlier solutions relied on GPS was because the spinning drone needs a method of state estimation—that is, in order to be closed-loop controllable, the drone needs to have a reasonable understanding of what its position is and how that position is changing over time. GPS is an easy way to take care of this, but GPS is also an external system that doesn’t work everywhere. Having a state estimation system that’s completely internal to the drone itself is much more fail safe, and Sun got his onboard system to work through visual feature tracking with a downward-facing camera, even as the drone is spinning at over 20 rad/s.
While the system works well enough with a regular downward-facing camera—something that many consumer drones are equipped with for stabilization purposes—replacing it with an event camera (you remember event cameras, right?) makes the performance even better, especially in low light.
For more details on this, including what you’re supposed to do with a rapidly spinning partially disabled quadrotor (as well as what it’ll take to make this a standard feature on consumer hardware), we spoke with Sihao Sun via email.
IEEE Spectrum: what usually happens when a drone spinning this fast lands? Is there any way to do it safely?
Sihao Sun: Our experience shows that we can safely land the drone while it is spinning. When the range sensor measurements are lower than a threshold (around 10 cm, indicating that the drone is close to the ground), we switch off the rotors. During the landing procedure, despite the fast spinning motion, the thrust direction oscillates around the gravity vector, thus the drone touches the ground with its legs without damaging other components.
Can your system handle more than one motor failure?
Yes, the system can also handle the failure of two opposing rotors. However, if two adjacent rotors or more than two rotors fail, our method cannot save the quadrotor. Some research has shown that it is possible to control a quadrotor with only one remaining rotor. But the drone requires a very special inertial property, which is hard to satisfy in real applications.
How different is your system's performance from a similar system that relies on GPS, in a favorable environment?
In a favorable environment, our system outperforms those relying on GPS signals because it obtains better position estimates. Since a damaged quadrotor spins fast, the accelerometer readings are largely affected by centrifugal forces. When the GPS signal is lost or degraded, a drone relying on GPS needs to integrate these biased accelerometer measurements for position estimation, leading to large position estimation errors. Feeding these erroneous estimates to the flight controller can easily crash the drone.
When you say that your solution requires “only onboard sensors and computation,” are those requirements specialized, or would they be generally compatible with the current generation of recreational and commercial quadrotors?
We use an NVIDIA Jetson TX2 to run our solution, which includes two parts: the control algorithm and the vision-based state estimation algorithm. The control algorithm is lightweight; thus, we believe that it is compatible with the current generation of quadrotors. On the other hand, the vision-based state estimation requires relatively more computational resources, which may not be affordable for cheap recreational platforms. But this is not an issue for commercial quadrotors because many of them have more powerful processors than a TX2.
What else can event cameras be used for, in recreational or commercial applications?
Many drone applications can benefit from event cameras, especially those in high-speed or low-light conditions, such as autonomous drone racing, cave exploration, drone delivery during night time, etc. Event cameras also consume very little power, which is a significant advantage for energy-critical missions, such as planetary aerial vehicles for Mars explorations. Regarding space applications, we are currently collaborating with JPL to explore the use of event cameras to address the key limitations of standard cameras for the next Mars helicopter.
[ UZH RPG ] Continue reading
Posted in Human Robots
#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