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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.

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Posted in Human Robots

#435110 5 Coming Breakthroughs in Energy and ...

The energy and transportation industries are being aggressively disrupted by converging exponential technologies.

In just five days, the sun provides Earth with an energy supply exceeding all proven reserves of oil, coal, and natural gas. Capturing just 1 part in 8,000 of this available solar energy would allow us to meet 100 percent of our energy needs.

As we leverage renewable energy supplied by the sun, wind, geothermal sources, and eventually fusion, we are rapidly heading towards a future where 100 percent of our energy needs will be met by clean tech in just 30 years.

During the past 40 years, solar prices have dropped 250-fold. And as these costs plummet, solar panel capacity continues to grow exponentially.

On the heels of energy abundance, we are additionally witnessing a new transportation revolution, which sets the stage for a future of seamlessly efficient travel at lower economic and environmental costs.

Top 5 Transportation Breakthroughs (2019-2024)
Entrepreneur and inventor Ramez Naam is my go-to expert on all things energy and environment. Currently serving as the Energy Co-Chair at Singularity University, Naam is the award-winning author of five books, including the Nexus series of science fiction novels. Having spent 13 years at Microsoft, his software has touched the lives of over a billion people. Naam holds over 20 patents, including several shared with co-inventor Bill Gates.

In the next five years, he forecasts five respective transportation and energy trends, each poised to disrupt major players and birth entirely new business models.

Let’s dive in.

Autonomous cars drive 1 billion miles on US roads. Then 10 billion

Alphabet’s Waymo alone has already reached 10 million miles driven in the US. The 600 Waymo vehicles on public roads drive a total of 25,000 miles each day, and computer simulations provide an additional 25,000 virtual cars driving constantly. Since its launch in December, the Waymo One service has transported over 1,000 pre-vetted riders in the Phoenix area.

With more training miles, the accuracy of these cars continues to improve. Since last year, GM Cruise has improved its disengagement rate by 321 percent since last year, trailing close behind with only one human intervention per 5,025 miles self-driven.

Autonomous taxis as a service in top 20 US metro areas

Along with its first quarterly earnings released last week, Lyft recently announced that it would expand its Waymo partnership with the upcoming deployment of 10 autonomous vehicles in the Phoenix area. While individuals previously had to partake in Waymo’s “early rider program” prior to trying Waymo One, the Lyft partnership will allow anyone to ride in a self-driving vehicle without a prior NDA.

Strategic partnerships will grow increasingly essential between automakers, self-driving tech companies, and rideshare services. Ford is currently working with Volkswagen, and Nvidia now collaborates with Daimler (Mercedes) and Toyota. Just last week, GM Cruise raised another $1.15 billion at a $19 billion valuation as the company aims to launch a ride-hailing service this year.

“They’re going to come to the Bay Area, Los Angeles, Houston, other cities with relatively good weather,” notes Naam. “In every major city within five years in the US and in some other parts of the world, you’re going to see the ability to hail an autonomous vehicle as a ride.”

Cambrian explosion of vehicle formats

Naam explains, “If you look today at the average ridership of a taxi, a Lyft, or an Uber, it’s about 1.1 passengers plus the driver. So, why do you need a large four-seater vehicle for that?”

Small electric, autonomous pods that seat as few as two people will begin to emerge, satisfying the majority of ride-hailing demands we see today. At the same time, larger communal vehicles will appear, such as Uber Express, that will undercut even the cheapest of transportation methods—buses, trams, and the like. Finally, last-mile scooter transit (or simply short-distance walks) might connect you to communal pick-up locations.

By 2024, an unimaginably diverse range of vehicles will arise to meet every possible need, regardless of distance or destination.

Drone delivery for lightweight packages in at least one US city

Wing, the Alphabet drone delivery startup, recently became the first company to gain approval from the Federal Aviation Administration (FAA) to make deliveries in the US. Having secured approval to deliver to 100 homes in Canberra, Australia, Wing additionally plans to begin delivering goods from local businesses in the suburbs of Virginia.

The current state of drone delivery is best suited for lightweight, urgent-demand payloads like pharmaceuticals, thumb drives, or connectors. And as Amazon continues to decrease its Prime delivery times—now as speedy as a one-day turnaround in many cities—the use of drones will become essential.

Robotic factories drive onshoring of US factories… but without new jobs

The supply chain will continue to shorten and become more agile with the re-onshoring of manufacturing jobs in the US and other countries. Naam reasons that new management and software jobs will drive this shift, as these roles develop the necessary robotics to manufacture goods. Equally as important, these robotic factories will provide a more humane setting than many of the current manufacturing practices overseas.

Top 5 Energy Breakthroughs (2019-2024)

First “1 cent per kWh” deals for solar and wind signed

Ten years ago, the lowest price of solar and wind power fell between 10 to 12 cents per kilowatt hour (kWh), over twice the price of wholesale power from coal or natural gas.

Today, the gap between solar/wind power and fossil fuel-generated electricity is nearly negligible in many parts of the world. In G20 countries, fossil fuel electricity costs between 5 to 17 cents per kWh, while the average cost per kWh of solar power in the US stands at under 10 cents.

Spanish firm Solarpack Corp Technological recently won a bid in Chile for a 120 MW solar power plant supplying energy at 2.91 cents per kWh. This deal will result in an estimated 25 percent drop in energy costs for Chilean businesses by 2021.

Naam indicates, “We will see the first unsubsidized 1.0 cent solar deals in places like Chile, Mexico, the Southwest US, the Middle East, and North Africa, and we’ll see similar prices for wind in places like Mexico, Brazil, and the US Great Plains.”

Solar and wind will reach >15 percent of US electricity, and begin to drive all growth

Just over eight percent of energy in the US comes from solar and wind sources. In total, 17 percent of American energy is derived from renewable sources, while a whopping 63 percent is sourced from fossil fuels, and 17 percent from nuclear.

Last year in the U.K., twice as much energy was generated from wind than from coal. For over a week in May, the U.K. went completely coal-free, using wind and solar to supply 35 percent and 21 percent of power, respectively. While fossil fuels remain the primary electricity source, this week-long experiment highlights the disruptive potential of solar and wind power that major countries like the U.K. are beginning to emphasize.

“Solar and wind are still a relatively small part of the worldwide power mix, only about six percent. Within five years, it’s going to be 15 percent in the US and more than close to that worldwide,” Naam predicts. “We are nearing the point where we are not building any new fossil fuel power plants.”

It will be cheaper to build new solar/wind/batteries than to run on existing coal

Last October, Northern Indiana utility company NIPSCO announced its transition from a 65 percent coal-powered state to projected coal-free status by 2028. Importantly, this decision was made purely on the basis of financials, with an estimated $4 billion in cost savings for customers. The company has already begun several initiatives in solar, wind, and batteries.

NextEra, the largest power generator in the US, has taken on a similar goal, making a deal last year to purchase roughly seven million solar panels from JinkoSolar over four years. Leading power generators across the globe have vocalized a similar economic case for renewable energy.

ICE car sales have now peaked. All car sales growth will be electric

While electric vehicles (EV) have historically been more expensive for consumers than internal combustion engine-powered (ICE) cars, EVs are cheaper to operate and maintain. The yearly cost of operating an EV in the US is about $485, less than half the $1,117 cost of operating a gas-powered vehicle.

And as battery prices continue to shrink, the upfront costs of EVs will decline until a long-term payoff calculation is no longer required to determine which type of car is the better investment. EVs will become the obvious choice.

Many experts including Naam believe that ICE-powered vehicles peaked worldwide in 2018 and will begin to decline over the next five years, as has already been demonstrated in the past five months. At the same time, EVs are expected to quadruple their market share to 1.6 percent this year.

New storage technologies will displace Li-ion batteries for tomorrow’s most demanding applications

Lithium ion batteries have dominated the battery market for decades, but Naam anticipates new storage technologies will take hold for different contexts. Flow batteries, which can collect and store solar and wind power at large scales, will supply city grids. Already, California’s Independent System Operator, the nonprofit that maintains the majority of the state’s power grid, recently installed a flow battery system in San Diego.

Solid-state batteries, which consist of entirely solid electrolytes, will supply mobile devices in cars. A growing body of competitors, including Toyota, BMW, Honda, Hyundai, and Nissan, are already working on developing solid-state battery technology. These types of batteries offer up to six times faster charging periods, three times the energy density, and eight years of added lifespan, compared to lithium ion batteries.

Final Thoughts
Major advancements in transportation and energy technologies will continue to converge over the next five years. A case in point, Tesla’s recent announcement of its “robotaxi” fleet exemplifies the growing trend towards joint priority of sustainability and autonomy.

On the connectivity front, 5G and next-generation mobile networks will continue to enable the growth of autonomous fleets, many of which will soon run on renewable energy sources. This growth demands important partnerships between energy storage manufacturers, automakers, self-driving tech companies, and ridesharing services.

In the eco-realm, increasingly obvious economic calculi will catalyze consumer adoption of autonomous electric vehicles. In just five years, Naam predicts that self-driving rideshare services will be cheaper than owning a private vehicle for urban residents. And by the same token, plummeting renewable energy costs will make these fuels far more attractive than fossil fuel-derived electricity.

As universally optimized AI systems cut down on traffic, aggregate time spent in vehicles will decimate, while hours in your (or not your) car will be applied to any number of activities as autonomous systems steer the way. All the while, sharing an electric vehicle will cut down not only on your carbon footprint but on the exorbitant costs swallowed by your previous SUV. How will you spend this extra time and money? What new natural resources will fuel your everyday life?

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