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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.”
Image Credit: Shahadat Rahman on Unsplash Continue reading
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