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#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
#437491 3.2 Billion Images and 720,000 Hours of ...
Twitter over the weekend “tagged” as manipulated a video showing US Democratic presidential candidate Joe Biden supposedly forgetting which state he’s in while addressing a crowd.
Biden’s “hello Minnesota” greeting contrasted with prominent signage reading “Tampa, Florida” and “Text FL to 30330.”
The Associated Press’s fact check confirmed the signs were added digitally and the original footage was indeed from a Minnesota rally. But by the time the misleading video was removed it already had more than one million views, The Guardian reports.
A FALSE video claiming Biden forgot what state he was in was viewed more than 1 million times on Twitter in the past 24 hours
In the video, Biden says “Hello, Minnesota.”
The event did indeed happen in MN — signs on stage read MN
But false video edited signs to read Florida pic.twitter.com/LdHQVaky8v
— Donie O'Sullivan (@donie) November 1, 2020
If you use social media, the chances are you see (and forward) some of the more than 3.2 billion images and 720,000 hours of video shared daily. When faced with such a glut of content, how can we know what’s real and what’s not?
While one part of the solution is an increased use of content verification tools, it’s equally important we all boost our digital media literacy. Ultimately, one of the best lines of defense—and the only one you can control—is you.
Seeing Shouldn’t Always Be Believing
Misinformation (when you accidentally share false content) and disinformation (when you intentionally share it) in any medium can erode trust in civil institutions such as news organizations, coalitions and social movements. However, fake photos and videos are often the most potent.
For those with a vested political interest, creating, sharing and/or editing false images can distract, confuse and manipulate viewers to sow discord and uncertainty (especially in already polarized environments). Posters and platforms can also make money from the sharing of fake, sensationalist content.
Only 11-25 percent of journalists globally use social media content verification tools, according to the International Centre for Journalists.
Could You Spot a Doctored Image?
Consider this photo of Martin Luther King Jr.
Dr. Martin Luther King Jr. Giving the middle finger #DopeHistoricPics pic.twitter.com/5W38DRaLHr
— Dope Historic Pics (@dopehistoricpic) December 20, 2013
This altered image clones part of the background over King Jr’s finger, so it looks like he’s flipping off the camera. It has been shared as genuine on Twitter, Reddit, and white supremacist websites.
In the original 1964 photo, King flashed the “V for victory” sign after learning the US Senate had passed the civil rights bill.
“Those who love peace must learn to organize as effectively as those who love war.”
Dr. Martin Luther King Jr.
This photo was taken on June 19th, 1964, showing Dr King giving a peace sign after hearing that the civil rights bill had passed the senate. @snopes pic.twitter.com/LXHmwMYZS5
— Willie's Reserve (@WilliesReserve) January 21, 2019
Beyond adding or removing elements, there’s a whole category of photo manipulation in which images are fused together.
Earlier this year, a photo of an armed man was photoshopped by Fox News, which overlaid the man onto other scenes without disclosing the edits, the Seattle Times reported.
You mean this guy who’s been photoshopped into three separate photos released by Fox News? pic.twitter.com/fAXpIKu77a
— Zander Yates ザンダーイェーツ (@ZanderYates) June 13, 2020
Similarly, the image below was shared thousands of times on social media in January, during Australia’s Black Summer bushfires. The AFP’s fact check confirmed it is not authentic and is actually a combination of several separate photos.
Image is more powerful than screams of Greta. A silent girl is holding a koala. She looks straight at you from the waters of the ocean where they found a refuge. She is wearing a breathing mask. A wall of fire is behind them. I do not know the name of the photographer #Australia pic.twitter.com/CrTX3lltdh
— EVC Music (@EVCMusicUK) January 6, 2020
Fully and Partially Synthetic Content
Online, you’ll also find sophisticated “deepfake” videos showing (usually famous) people saying or doing things they never did. Less advanced versions can be created using apps such as Zao and Reface.
Or, if you don’t want to use your photo for a profile picture, you can default to one of several websites offering hundreds of thousands of AI-generated, photorealistic images of people.
These people don’t exist, they’re just images generated by artificial intelligence. Generated Photos, CC BY
Editing Pixel Values and the (not so) Simple Crop
Cropping can greatly alter the context of a photo, too.
We saw this in 2017, when a US government employee edited official pictures of Donald Trump’s inauguration to make the crowd appear bigger, according to The Guardian. The staffer cropped out the empty space “where the crowd ended” for a set of pictures for Trump.
Views of the crowds at the inaugurations of former US President Barack Obama in 2009 (left) and President Donald Trump in 2017 (right). AP
But what about edits that only alter pixel values such as color, saturation, or contrast?
One historical example illustrates the consequences of this. In 1994, Time magazine’s cover of OJ Simpson considerably “darkened” Simpson in his police mugshot. This added fuel to a case already plagued by racial tension, to which the magazine responded, “No racial implication was intended, by Time or by the artist.”
Tools for Debunking Digital Fakery
For those of us who don’t want to be duped by visual mis/disinformation, there are tools available—although each comes with its own limitations (something we discuss in our recent paper).
Invisible digital watermarking has been proposed as a solution. However, it isn’t widespread and requires buy-in from both content publishers and distributors.
Reverse image search (such as Google’s) is often free and can be helpful for identifying earlier, potentially more authentic copies of images online. That said, it’s not foolproof because it:
Relies on unedited copies of the media already being online.
Doesn’t search the entire web.
Doesn’t always allow filtering by publication time. Some reverse image search services such as TinEye support this function, but Google’s doesn’t.
Returns only exact matches or near-matches, so it’s not thorough. For instance, editing an image and then flipping its orientation can fool Google into thinking it’s an entirely different one.
Most Reliable Tools Are Sophisticated
Meanwhile, manual forensic detection methods for visual mis/disinformation focus mostly on edits visible to the naked eye, or rely on examining features that aren’t included in every image (such as shadows). They’re also time-consuming, expensive, and need specialized expertise.
Still, you can access work in this field by visiting sites such as Snopes.com—which has a growing repository of “fauxtography.”
Computer vision and machine learning also offer relatively advanced detection capabilities for images and videos. But they too require technical expertise to operate and understand.
Moreover, improving them involves using large volumes of “training data,” but the image repositories used for this usually don’t contain the real-world images seen in the news.
If you use an image verification tool such as the REVEAL project’s image verification assistant, you might need an expert to help interpret the results.
The good news, however, is that before turning to any of the above tools, there are some simple questions you can ask yourself to potentially figure out whether a photo or video on social media is fake. Think:
Was it originally made for social media?
How widely and for how long was it circulated?
What responses did it receive?
Who were the intended audiences?
Quite often, the logical conclusions drawn from the answers will be enough to weed out inauthentic visuals. You can access the full list of questions, put together by Manchester Metropolitan University experts, here.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
Image Credit: Simon Steinberger from Pixabay Continue reading