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#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
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#438925 Nanophotonics Could Be the ‘Dark ...
The race to build the first practical quantum computers looks like a two-horse contest between machines built from superconducting qubits and those that use trapped ions. But new research suggests a third contender—machines based on optical technology—could sneak up on the inside.
The most advanced quantum computers today are the ones built by Google and IBM, which rely on superconducting circuits to generate the qubits that form the basis of quantum calculations. They are now able to string together tens of qubits, and while controversial, Google claims its machines have achieved quantum supremacy—the ability to carry out a computation beyond normal computers.
Recently this approach has been challenged by a wave of companies looking to use trapped ion qubits, which are more stable and less error-prone than superconducting ones. While these devices are less developed, engineering giant Honeywell has already released a machine with 10 qubits, which it says is more powerful than a machine made of a greater number of superconducting qubits.
But despite this progress, both of these approaches have some major drawbacks. They require specialized fabrication methods, incredibly precise control mechanisms, and they need to be cooled to close to absolute zero to protect the qubits from any outside interference.
That’s why researchers at Canadian quantum computing hardware and software startup Xanadu are backing an alternative quantum computing approach based on optics, which was long discounted as impractical. In a paper published last week in Nature, they unveiled the first fully programmable and scalable optical chip that can run quantum algorithms. Not only does the system run at room temperature, but the company says it could scale to millions of qubits.
The idea isn’t exactly new. As Chris Lee notes in Ars Technica, people have been experimenting with optical approaches to quantum computing for decades, because encoding information in photons’ quantum states and manipulating those states is relatively easy. The biggest problem was that optical circuits were very large and not readily programmable, which meant you had to build a new computer for every new problem you wanted to solve.
That started to change thanks to the growing maturity of photonic integrated circuits. While early experiments with optical computing involved complex table-top arrangements of lasers, lenses, and detectors, today it’s possible to buy silicon chips not dissimilar to electronic ones that feature hundreds of tiny optical components.
In recent years, the reliability and performance of these devices has improved dramatically, and they’re now regularly used by the telecommunications industry. Some companies believe they could be the future of artificial intelligence too.
This allowed the Xanadu researchers to design a silicon chip that implements a complex optical network made up of beam splitters, waveguides, and devices called interferometers that cause light sources to interact with each other.
The chip can generate and manipulate up to eight qubits, but unlike conventional qubits, which can simultaneously be in two states, these qubits can be in any configuration of three states, which means they can carry more information.
Once the light has travelled through the network, it is then fed out to cutting-edge photon-counting detectors that provide the result. This is one of the potential limitations of the system, because currently these detectors need to be cryogenically cooled, although the rest of the chip does not.
But most importantly, the chip is easily re-programmable, which allows it to tackle a variety of problems. The computation can be controlled by adjusting the settings of these interferometers, but the researchers have also developed a software platform that hides the physical complexity from users and allows them to program it using fairly conventional code.
The company announced that its chips were available on the cloud in September of 2020, but the Nature paper is the first peer-reviewed test of their system. The researchers verified that the computations being done were genuinely quantum mechanical in nature, but they also implemented two more practical algorithms: one for simulating molecules and the other for judging how similar two graphs are, which has applications in a variety of pattern recognition problems.
In an accompanying opinion piece, Ulrik Andersen from the Technical University of Denmark says the quality of the qubits needs to be improved considerably and photon losses reduced if the technology is ever to scale to practical problems. But, he says, this breakthrough suggests optical approaches “could turn out to be the dark horse of quantum computing.”
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#438762 When Robots Enter the World, Who Is ...
Over the last half decade or so, the commercialization of autonomous robots that can operate outside of structured environments has dramatically increased. But this relatively new transition of robotic technologies from research projects to commercial products comes with its share of challenges, many of which relate to the rapidly increasing visibility that these robots have in society.
Whether it's because of their appearance of agency, or because of their history in popular culture, robots frequently inspire people’s imagination. Sometimes this is a good thing, like when it leads to innovative new use cases. And sometimes this is a bad thing, like when it leads to use cases that could be classified as irresponsible or unethical. Can the people selling robots do anything about the latter? And even if they can, should they?
Roboticists understand that robots, fundamentally, are tools. We build them, we program them, and even the autonomous ones are just following the instructions that we’ve coded into them. However, that same appearance of agency that makes robots so compelling means that it may not be clear to people without much experience with or exposure to real robots that a robot itself isn’t inherently good or bad—rather, as a tool, a robot is a reflection of its designers and users.
This can put robotics companies into a difficult position. When they sell a robot to someone, that person can, hypothetically, use the robot in any way they want. Of course, this is the case with every tool, but it’s the autonomous aspect that makes robots unique. I would argue that autonomy brings with it an implied association between a robot and its maker, or in this case, the company that develops and sells it. I’m not saying that this association is necessarily a reasonable one, but I think that it exists, even if that robot has been sold to someone else who has assumed full control over everything it does.
“All of our buyers, without exception, must agree that Spot will not be used to harm or intimidate people or animals, as a weapon or configured to hold a weapon”
—Robert Playter, Boston Dynamics
Robotics companies are certainly aware of this, because many of them are very careful about who they sell their robots to, and very explicit about what they want their robots to be doing. But once a robot is out in the wild, as it were, how far should that responsibility extend? And realistically, how far can it extend? Should robotics companies be held accountable for what their robots do in the world, or should we accept that once a robot is sold to someone else, responsibility is transferred as well? And what can be done if a robot is being used in an irresponsible or unethical way that could have a negative impact on the robotics community?
For perspective on this, we contacted folks from three different robotics companies, each of which has experience selling distinctive mobile robots to commercial end users. We asked them the same five questions about the responsibility that robotics companies have regarding the robots that they sell, and here’s what they had to say:
Do you have any restrictions on what people can do with your robots? If so, what are they, and if not, why not?
Péter Fankhauser, CEO, ANYbotics:
We closely work together with our customers to make sure that our solution provides the right approach for their problem. Thereby, the target use case is clear from the beginning and we do not work with customers interested in using our robot ANYmal outside the intended target applications. Specifically, we strictly exclude any military or weaponized uses and since the foundation of ANYbotics it is close to our heart to make human work easier, safer, and more enjoyable.
Robert Playter, CEO, Boston Dynamics:
Yes, we have restrictions on what people can do with our robots, which are outlined in our Terms and Conditions of Sale. All of our buyers, without exception, must agree that Spot will not be used to harm or intimidate people or animals, as a weapon or configured to hold a weapon. Spot, just like any product, must be used in compliance with the law.
Ryan Gariepy, CTO, Clearpath Robotics:
We do have strict restrictions and KYC processes which are based primarily on Canadian export control regulations. They depend on the type of equipment sold as well as where it is going. More generally, we also will not sell or support a robot if we know that it will create an uncontrolled safety hazard or if we have reason to believe that the buyer is unqualified to use the product. And, as always, we do not support using our products for the development of fully autonomous weapons systems.
More broadly, if you sell someone a robot, why should they be restricted in what they can do with it?
Péter Fankhauser, ANYbotics: We see the robot less as a simple object but more as an artificial workforce. This implies to us that the usage is closely coupled with the transfer of the robot and both the customer and the provider agree what the robot is expected to do. This approach is supported by what we hear from our customers with an increasing interest to pay for the robots as a service or per use.
Robert Playter, Boston Dynamics: We’re offering a product for sale. We’re going to do the best we can to stop bad actors from using our technology for harm, but we don’t have the control to regulate every use. That said, we believe that our business will be best served if our technology is used for peaceful purposes—to work alongside people as trusted assistants and remove them from harm’s way. We do not want to see our technology used to cause harm or promote violence. Our restrictions are similar to those of other manufacturers or technology companies that take steps to reduce or eliminate the violent or unlawful use of their products.
Ryan Gariepy, Clearpath Robotics: Assuming the organization doing the restricting is a private organization and the robot and its software is sold vs. leased or “managed,” there aren't strong legal reasons to restrict use. That being said, the manufacturer likewise has no obligation to continue supporting that specific robot or customer going forward. However, given that we are only at the very edge of how robots will reshape a great deal of society, it is in the best interest for the manufacturer and user to be honest with each other about their respective goals. Right now, you're not only investing in the initial purchase and relationship, you're investing in the promise of how you can help each other succeed in the future.
“If a robot is being used in a way that is irresponsible due to safety: intervene! If it’s unethical: speak up!”
—Péter Fankhauser, ANYbotics
What can you realistically do to make sure that people who buy your robots use them in the ways that you intend?
Péter Fankhauser, ANYbotics: We maintain a close collaboration with our customers to ensure their success with our solution. So for us, we have refrained from technical solutions to block unintended use.
Robert Playter, Boston Dynamics: We vet our customers to make sure that their desired applications are things that Spot can support, and are in alignment with our Terms and Conditions of Sale. We’ve turned away customers whose applications aren’t a good match with our technology. If customers misuse our technology, we’re clear in our Terms of Sale that their violations may void our warranty and prevent their robots from being updated, serviced, repaired, or replaced. We may also repossess robots that are not purchased, but leased. Finally, we will refuse future sales to customers that violate our Terms of Sale.
Ryan Gariepy, Clearpath Robotics: We typically work with our clients ahead of the purchase to make sure their expectations match reality, in particular on aspects like safety, supervisory requirements, and usability. It's far worse to sell a robot that'll sit on a shelf or worse, cause harm, then to not sell a robot at all, so we prefer to reduce the risk of this situation in advance of receiving an order or shipping a robot.
How do you evaluate the merit of edge cases, for example if someone wants to use your robot in research or art that may push the boundaries of what you personally think is responsible or ethical?
Péter Fankhauser, ANYbotics: It’s about the dialog, understanding, and figuring out alternatives that work for all involved parties and the earlier you can have this dialog the better.
Robert Playter, Boston Dynamics: There’s a clear line between exploring robots in research and art, and using the robot for violent or illegal purposes.
Ryan Gariepy, Clearpath Robotics: We have sold thousands of robots to hundreds of clients, and I do not recall the last situation that was not covered by a combination of export control and a general evaluation of the client's goals and expectations. I'm sure this will change as robots continue to drop in price and increase in flexibility and usability.
“You're not only investing in the initial purchase and relationship, you're investing in the promise of how you can help each other succeed in the future.”
—Ryan Gariepy, Clearpath Robotics
What should roboticists do if we see a robot being used in a way that we feel is unethical or irresponsible?
Péter Fankhauser, ANYbotics: If it’s irresponsible due to safety: intervene! If it’s unethical: speak up!
Robert Playter, Boston Dynamics: We want robots to be beneficial for humanity, which includes the notion of not causing harm. As an industry, we think robots will achieve long-term commercial viability only if people see robots as helpful, beneficial tools without worrying if they’re going to cause harm.
Ryan Gariepy, Clearpath Robotics: On a one off basis, they should speak to a combination of the user, the supplier or suppliers, the media, and, if safety is an immediate concern, regulatory or government agencies. If the situation in question risks becoming commonplace and is not being taken seriously, they should speak up more generally in appropriate forums—conferences, industry groups, standards bodies, and the like.
As more and more robots representing different capabilities become commercially available, these issues are likely to come up more frequently. The three companies we talked to certainly don’t represent every viewpoint, and we did reach out to other companies who declined to comment. But I would think (I would hope?) that everyone in the robotics community can agree that robots should be used in a way that makes people’s lives better. What “better” means in the context of art and research and even robots in the military may not always be easy to define, and inevitably there’ll be disagreement as to what is ethical and responsible, and what isn’t.
We’ll keep on talking about it, though, and do our best to help the robotics community to continue growing and evolving in a positive way. Let us know what you think in the comments. Continue reading
Posted in Human Robots
#437978 How Mirroring the Architecture of the ...
While AI can carry out some impressive feats when trained on millions of data points, the human brain can often learn from a tiny number of examples. New research shows that borrowing architectural principles from the brain can help AI get closer to our visual prowess.
The prevailing wisdom in deep learning research is that the more data you throw at an algorithm, the better it will learn. And in the era of Big Data, that’s easier than ever, particularly for the large data-centric tech companies carrying out a lot of the cutting-edge AI research.
Today’s largest deep learning models, like OpenAI’s GPT-3 and Google’s BERT, are trained on billions of data points, and even more modest models require large amounts of data. Collecting these datasets and investing the computational resources to crunch through them is a major bottleneck, particularly for less well-resourced academic labs.
It also means today’s AI is far less flexible than natural intelligence. While a human only needs to see a handful of examples of an animal, a tool, or some other category of object to be able pick it out again, most AI need to be trained on many examples of an object in order to be able to recognize it.
There is an active sub-discipline of AI research aimed at what is known as “one-shot” or “few-shot” learning, where algorithms are designed to be able to learn from very few examples. But these approaches are still largely experimental, and they can’t come close to matching the fastest learner we know—the human brain.
This prompted a pair of neuroscientists to see if they could design an AI that could learn from few data points by borrowing principles from how we think the brain solves this problem. In a paper in Frontiers in Computational Neuroscience, they explained that the approach significantly boosts AI’s ability to learn new visual concepts from few examples.
“Our model provides a biologically plausible way for artificial neural networks to learn new visual concepts from a small number of examples,” Maximilian Riesenhuber, from Georgetown University Medical Center, said in a press release. “We can get computers to learn much better from few examples by leveraging prior learning in a way that we think mirrors what the brain is doing.”
Several decades of neuroscience research suggest that the brain’s ability to learn so quickly depends on its ability to use prior knowledge to understand new concepts based on little data. When it comes to visual understanding, this can rely on similarities of shape, structure, or color, but the brain can also leverage abstract visual concepts thought to be encoded in a brain region called the anterior temporal lobe (ATL).
“It is like saying that a platypus looks a bit like a duck, a beaver, and a sea otter,” said paper co-author Joshua Rule, from the University of California Berkeley.
The researchers decided to try and recreate this capability by using similar high-level concepts learned by an AI to help it quickly learn previously unseen categories of images.
Deep learning algorithms work by getting layers of artificial neurons to learn increasingly complex features of an image or other data type, which are then used to categorize new data. For instance, early layers will look for simple features like edges, while later ones might look for more complex ones like noses, faces, or even more high-level characteristics.
First they trained the AI on 2.5 million images across 2,000 different categories from the popular ImageNet dataset. They then extracted features from various layers of the network, including the very last layer before the output layer. They refer to these as “conceptual features” because they are the highest-level features learned, and most similar to the abstract concepts that might be encoded in the ATL.
They then used these different sets of features to train the AI to learn new concepts based on 2, 4, 8, 16, 32, 64, and 128 examples. They found that the AI that used the conceptual features yielded much better performance than ones trained using lower-level features on lower numbers of examples, but the gap shrunk as they were fed more training examples.
While the researchers admit the challenge they set their AI was relatively simple and only covers one aspect of the complex process of visual reasoning, they said that using a biologically plausible approach to solving the few-shot problem opens up promising new avenues in both neuroscience and AI.
“Our findings not only suggest techniques that could help computers learn more quickly and efficiently, they can also lead to improved neuroscience experiments aimed at understanding how people learn so quickly, which is not yet well understood,” Riesenhuber said.
As the researchers note, the human visual system is still the gold standard when it comes to understanding the world around us. Borrowing from its design principles might turn out to be a profitable direction for future research.
Image Credit: Gerd Altmann from Pixabay Continue reading
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