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#438006 Smellicopter Drone Uses Live Moth ...

Research into robotic sensing has, understandably I guess, been very human-centric. Most of us navigate and experience the world visually and in 3D, so robots tend to get covered with things like cameras and lidar. Touch is important to us, as is sound, so robots are getting pretty good with understanding tactile and auditory information, too. Smell, though? In most cases, smell doesn’t convey nearly as much information for us, so while it hasn’t exactly been ignored in robotics, it certainly isn’t the sensing modality of choice in most cases.

Part of the problem with smell sensing is that we just don’t have a good way of doing it, from a technical perspective. This has been a challenge for a long time, and it’s why we either bribe or trick animals like dogs, rats, vultures, and other animals to be our sensing systems for airborne chemicals. If only they’d do exactly what we wanted them to do all the time, this would be fine, but they don’t, so it’s not.

Until we get better at making chemical sensors, leveraging biology is the best we can do, and what would be ideal would be some sort of robot-animal hybrid cyborg thing. We’ve seen some attempts at remote controlled insects, but as it turns out, you can simplify things if you don’t use the entire insect, but instead just find a way to use its sensing system. Enter the Smellicopter.

There’s honestly not too much to say about the drone itself. It’s an open-source drone project called Crazyflie 2.0, with some additional off the shelf sensors for obstacle avoidance and stabilization. The interesting bits are a couple of passive fins that keep the drone pointed into the wind, and then the sensor, called an electroantennogram.

Image: UW

The drone’s sensor, called an electroantennogram, consists of a “single excised antenna” from a Manduca sexta hawkmoth and a custom signal processing circuit.

To make one of these sensors, you just, uh, “harvest” an antenna from a live hawkmoth. Obligingly, the moth antenna is hollow, meaning that you can stick electrodes up it. Whenever the olfactory neurons in the antenna (which is still technically alive even though it’s not attached to the moth anymore) encounter an odor that they’re looking for, they produce an electrical signal that the electrodes pick up. Plug the other ends of the electrodes into a voltage amplifier and filter, run it through an analog to digital converter, and you’ve got a chemical sensor that weighs just 1.5 gram and consumes only 2.7 mW of power. It’s significantly more sensitive than a conventional metal-oxide odor sensor, in a much smaller and more efficient form factor, making it ideal for drones.

To localize an odor, the Smellicopter uses a simple bioinspired approach called crosswind casting, which involves moving laterally left and right and then forward when an odor is detected. Here’s how it works:

The vehicle takes off to a height of 40 cm and then hovers for ten seconds to allow it time to orient upwind. The smellicopter starts casting left and right crosswind. When a volatile chemical is detected, the smellicopter will surge 25 cm upwind, and then resume casting. As long as the wind direction is fairly consistent, this strategy will bring the insect or robot increasingly closer to a singular source with each surge.

Since odors are airborne, they need a bit of a breeze to spread very far, and the Smellicopter won’t be able to detect them unless it’s downwind of the source. But, that’s just how odors work— even if you’re right next to the source, if the wind is blowing from you towards the source rather than the other way around, you might not catch a whiff of it.

Whenever the olfactory neurons in the antenna encounter an odor that they’re looking for, they produce an electrical signal that the electrodes pick up

There are a few other constraints to keep in mind with this sensor as well. First, rather than detecting something useful (like explosives), it’s going to detect the smells of pretty flowers, because moths like pretty flowers. Second, the antenna will literally go dead on you within a couple hours, since it only functions while its tissues are alive and metaphorically kicking. Interestingly, it may be possible to use CRISPR-based genetic modification to breed moths with antennae that do respond to useful smells, which would be a neat trick, and we asked the researchers—Melanie Anderson, a doctoral student of mechanical engineering at the University of Washington, in Seattle; Thomas Daniel, a UW professor of biology; and Sawyer Fuller, a UW assistant professor of mechanical engineering—about this, along with some other burning questions, via email.

IEEE Spectrum, asking the important questions first: So who came up with “Smellicopter”?

Melanie Anderson: Tom Daniel coined the term “Smellicopter”. Another runner up was “OdorRotor”!

In general, how much better are moths at odor localization than robots?

Melanie Anderson: Moths are excellent at odor detection and odor localization and need to be in order to find mates and food. Their antennae are much more sensitive and specialized than any portable man-made odor sensor. We can't ask the moths how exactly they search for odors so well, but being able to have the odor sensitivity of a moth on a flying platform is a big step in that direction.

Tom Daniel: Our best estimate is that they outperform robotic sensing by at least three orders of magnitude.

How does the localization behavior of the Smellicopter compare to that of a real moth?

Anderson: The cast-and-surge odor search strategy is a simplified version of what we believe the moth (and many other odor searching animals) are doing. It is a reactive strategy that relies on the knowledge that if you detect odor, you can assume that the source is somewhere up-wind of you. When you detect odor, you simply move upwind, and when you lose the odor signal you cast in a cross-wind direction until you regain the signal.

Can you elaborate on the potential for CRISPR to be able to engineer moths for the detection of specific chemicals?

Anderson: CRISPR is already currently being used to modify the odor detection pathways in moth species. It is one of our future efforts to specifically use this to make the antennae sensitive to other chemicals of interest, such as the chemical scent of explosives.

Sawyer Fuller: We think that one of the strengths of using a moth's antenna, in addition to its speed, is that it may provide a path to both high chemical specificity as well as high sensitivity. By expressing a preponderance of only one or a few chemosensors, we are anticipating that a moth antenna will give a strong response only to that chemical. There are several efforts underway in other research groups to make such specific, sensitive chemical detectors. Chemical sensing is an area where biology exceeds man-made systems in terms of efficiency, small size, and sensitivity. So that's why we think that the approach of trying to leverage biological machinery that already exists has some merit.

You mention that the antennae lifespan can be extended for a few days with ice- how feasible do you think this technology is outside of a research context?

Anderson: The antennae can be stored in tiny vials in a standard refrigerator or just with an ice pack to extend their life to about a week. Additionally, the process for attaching the antenna to the electrical circuit is a teachable skill. It is definitely feasible outside of a research context.

Considering the trajectory that sensor development is on, how long do you think that this biological sensor system will outperform conventional alternatives?

Anderson: It's hard to speak toward what will happen in the future, but currently, the moth antenna still stands out among any commercially-available portable sensors.

There have been some experiments with cybernetic insects; what are the advantages and disadvantages of your approach, as opposed to (say) putting some sort of tracking system on a live moth?

Daniel: I was part of a cyber insect team a number of years ago. The challenge of such research is that the animal has natural reactions to attempts to steer or control it.

Anderson: While moths are better at odor tracking than robots currently, the advantage of the drone platform is that we have control over it. We can tell it to constrain the search to a certain area, and return after it finishes searching.

What can you tell us about the health, happiness, and overall wellfare of the moths in your experiments?

Anderson: The moths are cold anesthetized before the antennae are removed. They are then frozen so that they can be used for teaching purposes or in other research efforts.

What are you working on next?

Daniel: The four big efforts are (1) CRISPR modification, (2) experiments aimed at improving the longevity of the antennal preparation, (3) improved measurements of antennal electrical responses to odors combined with machine learning to see if we can classify different odors, and (4) flight in outdoor environments.

Fuller: The moth's antenna sensor gives us a new ability to sense with a much shorter latency than was previously possible with similarly-sized sensors (e.g. semiconductor sensors). What exactly a robot agent should do to best take advantage of this is an open question. In particular, I think the speed may help it to zero in on plume sources in complex environments much more quickly. Think of places like indoor settings with flow down hallways that splits out at doorways, and in industrial settings festooned with pipes and equipment. We know that it is possible to search out and find odors in such scenarios, as anybody who has had to contend with an outbreak of fruit flies can attest. It is also known that these animals respond very quickly to sudden changes in odor that is present in such turbulent, patchy plumes. Since it is hard to reduce such plumes to a simple model, we think that machine learning may provide insights into how to best take advantage of the improved temporal plume information we now have available.

Tom Daniel also points out that the relative simplicity of this project (now that the UW researchers have it all figured out, that is) means that even high school students could potentially get involved in it, even if it’s on a ground robot rather than a drone. All the details are in the paper that was just published in Bioinspiration & Biomimetics. Continue reading

Posted in Human Robots

#437992 This Week’s Awesome Tech Stories From ...

ARTIFICIAL INTELLIGENCE
This Chinese Lab Is Aiming for Big AI Breakthroughs
Will Knight | Wired
“China produces as many artificial intelligence researchers as the US, but it lags in key fields like machine learning. The government hopes to make up ground. …It set AI researchers the goal of making ‘fundamental breakthroughs by 2025’ and called for the country to be ‘the world’s primary innovation center by 2030.’ BAAI opened a year later, in Zhongguancun, a neighborhood of Beijing designed to replicate US innovation hubs such as Boston and Silicon Valley.”

ENVIRONMENT
What Elon Musk’s $100 Million Carbon Capture Prize Could Mean
James Temple | MIT Technology Review
“[Elon Musk] announced on Twitter that he plans to give away $100 million of [his $180 billion net worth] as a prize for the ‘best carbon capture technology.’ …Another $100 million could certainly help whatever venture, or ventures, clinch Musk’s prize. But it’s a tiny fraction of his wealth and will also only go so far. …Money aside, however, one thing Musk has a particular knack for is generating attention. And this is a space in need of it.”

HEALTH
Synthetic Cornea Helped a Legally Blind Man Regain His Sight
Steve Dent | Engadget
“While the implant doesn’t contain any electronics, it could help more people than any robotic eye. ‘After years of hard work, seeing a colleague implant the CorNeat KPro with ease and witnessing a fellow human being regain his sight the following day was electrifying and emotionally moving, there were a lot of tears in the room,’ said CorNeat Vision co-founder Dr. Gilad Litvin.”

BIOTECH
MIT Develops Method for Lab-Grown Plants That May Eventually Lead to Alternatives to Forestry and Farming
Darrell Etherington | TechCrunch
“If the work of these researchers can eventually be used to create a way to produce lab-grown wood for use in construction and fabrication in a way that’s scalable and efficient, then there’s tremendous potential in terms of reducing the impact on forestry globally. Eventually, the team even theorizes you could coax the growth of plant-based materials into specific target shapes, so you could also do some of the manufacturing in the lab, by growing a wood table directly for instance.”

AUTOMATION
FAA Approves First Fully Automated Commercial Drone Flights
Andy Pasztor and Katy Stech Ferek | The Wall Street Journal
“US aviation regulators have approved the first fully automated commercial drone flights, granting a small Massachusetts-based company permission to operate drones without hands-on piloting or direct observation by human controllers or observers. …The company’s Scout drones operate under predetermined flight programs and use acoustic technology to detect and avoid drones, birds, and other obstacles.”

SPACE
China’s Surging Private Space Industry Is Out to Challenge the US
Neel V. Patel | MIT Technology Review
“[The Ceres-1] was a commercial rocket—only the second from a Chinese company ever to go into space. And the launch happened less than three years after the company was founded. The achievement is a milestone for China’s fledgling—but rapidly growing—private space industry, an increasingly critical part of the country’s quest to dethrone the US as the world’s preeminent space power.”

CRYPTOCURRENCY
Janet Yellen Will Consider Limiting Use of Cryptocurrency
Timothy B. Lee | Ars Technica
“Cryptocurrencies could come under renewed regulatory scrutiny over the next four years if Janet Yellen, Joe Biden’s pick to lead the Treasury Department, gets her way. During Yellen’s Tuesday confirmation hearing before the Senate Finance Committee, Sen. Maggie Hassan (D-N.H.) asked Yellen about the use of cryptocurrency by terrorists and other criminals. ‘Cryptocurrencies are a particular concern,’ Yellen responded. ‘I think many are used—at least in a transactions sense—mainly for illicit financing.’i”

SCIENCE
Secret Ingredient Found to Power Supernovas
Thomas Lewton | Quanta
“…Only in the last few years, with the growth of supercomputers, have theorists had enough computing power to model massive stars with the complexity needed to achieve explosions. …These new simulations are giving researchers a better understanding of exactly how supernovas have shaped the universe we see today.”

Image Credit: Ricardo Gomez Angel / Unsplash 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

Posted in Human Robots

#437974 China Wants to Be the World’s AI ...

China’s star has been steadily rising for decades. Besides slashing extreme poverty rates from 88 percent to under 2 percent in just 30 years, the country has become a global powerhouse in manufacturing and technology. Its pace of growth may slow due to an aging population, but China is nonetheless one of the world’s biggest players in multiple cutting-edge tech fields.

One of these fields, and perhaps the most significant, is artificial intelligence. The Chinese government announced a plan in 2017 to become the world leader in AI by 2030, and has since poured billions of dollars into AI projects and research across academia, government, and private industry. The government’s venture capital fund is investing over $30 billion in AI; the northeastern city of Tianjin budgeted $16 billion for advancing AI; and a $2 billion AI research park is being built in Beijing.

On top of these huge investments, the government and private companies in China have access to an unprecedented quantity of data, on everything from citizens’ health to their smartphone use. WeChat, a multi-functional app where people can chat, date, send payments, hail rides, read news, and more, gives the CCP full access to user data upon request; as one BBC journalist put it, WeChat “was ahead of the game on the global stage and it has found its way into all corners of people’s existence. It could deliver to the Communist Party a life map of pretty much everybody in this country, citizens and foreigners alike.” And that’s just one (albeit big) source of data.

Many believe these factors are giving China a serious leg up in AI development, even providing enough of a boost that its progress will surpass that of the US.

But there’s more to AI than data, and there’s more to progress than investing billions of dollars. Analyzing China’s potential to become a world leader in AI—or in any technology that requires consistent innovation—from multiple angles provides a more nuanced picture of its strengths and limitations. In a June 2020 article in Foreign Affairs, Oxford fellows Carl Benedikt Frey and Michael Osborne argued that China’s big advantages may not actually be that advantageous in the long run—and its limitations may be very limiting.

Moving the AI Needle
To get an idea of who’s likely to take the lead in AI, it could help to first consider how the technology will advance beyond its current state.

To put it plainly, AI is somewhat stuck at the moment. Algorithms and neural networks continue to achieve new and impressive feats—like DeepMind’s AlphaFold accurately predicting protein structures or OpenAI’s GPT-3 writing convincing articles based on short prompts—but for the most part these systems’ capabilities are still defined as narrow intelligence: completing a specific task for which the system was painstakingly trained on loads of data.

(It’s worth noting here that some have speculated OpenAI’s GPT-3 may be an exception, the first example of machine intelligence that, while not “general,” has surpassed the definition of “narrow”; the algorithm was trained to write text, but ended up being able to translate between languages, write code, autocomplete images, do math, and perform other language-related tasks it wasn’t specifically trained for. However, all of GPT-3’s capabilities are limited to skills it learned in the language domain, whether spoken, written, or programming language).

Both AlphaFold’s and GPT-3’s success was due largely to the massive datasets they were trained on; no revolutionary new training methods or architectures were involved. If all it was going to take to advance AI was a continuation or scaling-up of this paradigm—more input data yields increased capability—China could well have an advantage.

But one of the biggest hurdles AI needs to clear to advance in leaps and bounds rather than baby steps is precisely this reliance on extensive, task-specific data. Other significant challenges include the technology’s fast approach to the limits of current computing power and its immense energy consumption.

Thus, while China’s trove of data may give it an advantage now, it may not be much of a long-term foothold on the climb to AI dominance. It’s useful for building products that incorporate or rely on today’s AI, but not for pushing the needle on how artificially intelligent systems learn. WeChat data on users’ spending habits, for example, would be valuable in building an AI that helps people save money or suggests items they might want to purchase. It will enable (and already has enabled) highly tailored products that will earn their creators and the companies that use them a lot of money.

But data quantity isn’t what’s going to advance AI. As Frey and Osborne put it, “Data efficiency is the holy grail of further progress in artificial intelligence.”

To that end, research teams in academia and private industry are working on ways to make AI less data-hungry. New training methods like one-shot learning and less-than-one-shot learning have begun to emerge, along with myriad efforts to make AI that learns more like the human brain.

While not insignificant, these advancements still fall into the “baby steps” category. No one knows how AI is going to progress beyond these small steps—and that uncertainty, in Frey and Osborne’s opinion, is a major speed bump on China’s fast-track to AI dominance.

How Innovation Happens
A lot of great inventions have happened by accident, and some of the world’s most successful companies started in garages, dorm rooms, or similarly low-budget, nondescript circumstances (including Google, Facebook, Amazon, and Apple, to name a few). Innovation, the authors point out, often happens “through serendipity and recombination, as inventors and entrepreneurs interact and exchange ideas.”

Frey and Osborne argue that although China has great reserves of talent and a history of building on technologies conceived elsewhere, it doesn’t yet have a glowing track record in terms of innovation. They note that of the 100 most-cited patents from 2003 to present, none came from China. Giants Tencent, Alibaba, and Baidu are all wildly successful in the Chinese market, but they’re rooted in technologies or business models that came out of the US and were tweaked for the Chinese population.

“The most innovative societies have always been those that allowed people to pursue controversial ideas,” Frey and Osborne write. China’s heavy censorship of the internet and surveillance of citizens don’t quite encourage the pursuit of controversial ideas. The country’s social credit system rewards people who follow the rules and punishes those who step out of line. Frey adds that top-down execution of problem-solving is effective when the problem at hand is clearly defined—and the next big leaps in AI are not.

It’s debatable how strongly a culture of social conformism can impact technological innovation, and of course there can be exceptions. But a relevant historical example is the Soviet Union, which, despite heavy investment in science and technology that briefly rivaled the US in fields like nuclear energy and space exploration, ended up lagging far behind primarily due to political and cultural factors.

Similarly, China’s focus on computer science in its education system could give it an edge—but, as Frey told me in an email, “The best students are not necessarily the best researchers. Being a good researcher also requires coming up with new ideas.”

Winner Take All?
Beyond the question of whether China will achieve AI dominance is the issue of how it will use the powerful technology. Several of the ways China has already implemented AI could be considered morally questionable, from facial recognition systems used aggressively against ethnic minorities to smart glasses for policemen that can pull up information about whoever the wearer looks at.

This isn’t to say the US would use AI for purely ethical purposes. The military’s Project Maven, for example, used artificially intelligent algorithms to identify insurgent targets in Iraq and Syria, and American law enforcement agencies are also using (mostly unregulated) facial recognition systems.

It’s conceivable that “dominance” in AI won’t go to one country; each nation could meet milestones in different ways, or meet different milestones. Researchers from both countries, at least in the academic sphere, could (and likely will) continue to collaborate and share their work, as they’ve done on many projects to date.

If one country does take the lead, it will certainly see some major advantages as a result. Brookings Institute fellow Indermit Gill goes so far as to say that whoever leads in AI in 2030 will “rule the world” until 2100. But Gill points out that in addition to considering each country’s strengths, we should consider how willing they are to improve upon their weaknesses.

While China leads in investment and the US in innovation, both nations are grappling with huge economic inequalities that could negatively impact technological uptake. “Attitudes toward the social change that accompanies new technologies matter as much as the technologies, pointing to the need for complementary policies that shape the economy and society,” Gill writes.

Will China’s leadership be willing to relax its grip to foster innovation? Will the US business environment be enough to compete with China’s data, investment, and education advantages? And can both countries find a way to distribute technology’s economic benefits more equitably?

Time will tell, but it seems we’ve got our work cut out for us—and China does too.

Image Credit: Adam Birkett on Unsplash 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.

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