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#436962 Scientists Engineered Neurons to Make ...
Electricity plays a surprisingly powerful role in our bodies. While most people are aware that it plays a crucial role in carrying signals to and from our nerves, our bodies produce electric fields that can do everything from helping heal wounds to triggering the release of hormones.
Electric fields can influence a host of important cellular behavior, like directional migration, proliferation, division, or even differentiation into different cell types. The work of Michael Levin at Tufts University even suggests that electrical fields may play a crucial role in the way our bodies organize themselves.
This has prompted considerable interest in exploiting our body’s receptiveness to electrical stimulation for therapeutic means, but given the diffuse nature of electrical fields a key challenge is finding a way to localize these effects. Conductive polymers have proven a useful tool in this regard thanks to their good electrical properties and biocompatibility, and have been used in everything from neural implants to biosensors.
But now, a team at Stanford University has developed a way to genetically engineer neurons to build the materials into their own cell membranes. The approach could make it possible to target highly specific groups of cells, providing unprecedented control over the body’s response to electrical stimulation.
In a paper in Science, the team explained how they used re-engineered viruses to deliver DNA that hijacks cells’ biosynthesis machinery to create an enzyme that assembles electroactive polymers onto their membranes. This changes the electrical properties of the cells, which the team demonstrated could be used to control their behavior.
They used the approach to modulate neuronal firing in cultures of rat hippocampal neurons, mouse brain slices, and even human cortical spheroids. Most impressively, they showed that they could coax the neurons of living C. elegans worms to produce the polymers in large enough quantities to alter their behavior without impairing the cells’ natural function.
Translating the idea to humans poses major challenges, not least because the viruses used to deliver the genetic changes are still a long way from being approved for clinical use. But the ability to precisely target specific cells using a genetic approach holds enormous promise for bioelectronic medicine, Kevin Otto and Christine Schmidt from the University of Florida say in an accompanying perspective.
Interest is booming in therapies that use electrical stimulation of neural circuits as an alternative to drugs for diseases as varied as arthritis, Alzheimer’s, diabetes, and cardiovascular disease, and hundreds of clinical trials are currently underway.
At present these approaches rely on electrodes that can provide some level of localization, but because different kinds of nerve cells are often packed closely together it’s proven hard to stimulate exactly the right nerves, say Otto and Schmidt. This new approach makes it possible to boost the conductivity of specific cell types, which could make these kinds of interventions dramatically more targeted.
Besides disease-focused bioelectronic interventions, Otto and Schmidt say the approach could prove invaluable for helping to interface advanced prosthetics with patients’ nervous systems by making it possible to excite sensory neurons without accidentally triggering motor neurons, or vice versa.
More speculatively, the approach could one day help create far more efficient bridges between our minds and machines. One of the major challenges for brain-machine interfaces is recording from specific neurons, something that a genetically targeted approach might be able to help greatly with.
If the researchers can replicate the ability to build electronic-tissue “composites” in humans, we may be well on our way to the cyborg future predicted by science fiction.
Image Credit: Gerd Altmann from Pixabay Continue reading
#436946 Coronavirus May Mean Automation Is ...
We’re in the midst of a public health emergency, and life as we know it has ground to a halt. The places we usually go are closed, the events we were looking forward to are canceled, and some of us have lost our jobs or fear losing them soon.
But although it may not seem like it, there are some silver linings; this crisis is bringing out the worst in some (I’m looking at you, toilet paper hoarders), but the best in many. Italians on lockdown are singing together, Spaniards on lockdown are exercising together, this entrepreneur made a DIY ventilator and put it on YouTube, and volunteers in Italy 3D printed medical valves for virus treatment at a fraction of their usual cost.
Indeed, if you want to feel like there’s still hope for humanity instead of feeling like we’re about to snowball into terribleness as a species, just look at these examples—and I’m sure there are many more out there. There’s plenty of hope and opportunity to be found in this crisis.
Peter Xing, a keynote speaker and writer on emerging technologies and associate director in technology and growth initiatives at KPMG, would agree. Xing believes the coronavirus epidemic is presenting us with ample opportunities for increased automation and remote delivery of goods and services. “The upside right now is the burgeoning platform of the digital transformation ecosystem,” he said.
In a thought-provoking talk at Singularity University’s COVID-19 virtual summit this week, Xing explained how the outbreak is accelerating our transition to a highly-automated society—and painted a picture of what the future may look like.
Confronting Scarcity
You’ve probably seen them by now—the barren shelves at your local grocery store. Whether you were in the paper goods aisle, the frozen food section, or the fresh produce area, it was clear something was amiss; the shelves were empty. One of the most inexplicable items people have been panic-bulk-buying is toilet paper.
Xing described this toilet paper scarcity as a prisoner’s dilemma, pointing out that we have a scarcity problem right now in terms of our mindset, not in terms of actual supply shortages. “It’s a prisoner’s dilemma in that we’re all prisoners in our homes right now, and we can either hoard or not hoard, and the outcomes depend on how we collaborate with each other,” he said. “But it’s not a zero-sum game.”
Xing referenced a CNN article about why toilet paper, of all things, is one of the items people have been panic-buying most (I, too, have been utterly baffled by this phenomenon). But maybe there’d be less panic if we knew more about the production methods and supply chain involved in manufacturing toilet paper. It turns out it’s a highly automated process (you can learn more about it in this documentary by National Geographic) and requires very few people (though it does require about 27,000 trees a day—so stop bulk-buying it! Just stop!).
The supply chain limitation here is in the raw material; we certainly can’t keep cutting down this many trees a day forever. But—somewhat ironically, given the Costco cartloads of TP people have been stuffing into their trunks and backseats—thanks to automation, toilet paper isn’t something stores are going to stop receiving anytime soon.
Automation For All
Now we have a reason to apply this level of automation to, well, pretty much everything.
Though our current situation may force us into using more robots and automated systems sooner than we’d planned, it will end up saving us money and creating opportunity, Xing believes. He cited “fast-casual” restaurants (Chipotle, Panera, etc.) as a prime example.
Currently, people in the US spend much more to eat at home than we do to eat in fast-casual restaurants if you take into account the cost of the food we’re preparing plus the value of the time we’re spending on cooking, grocery shopping, and cleaning up after meals. According to research from investment management firm ARK Invest, taking all these costs into account makes for about $12 per meal for food cooked at home.
That’s the same as or more than the cost of grabbing a burrito or a sandwich at the joint around the corner. As more of the repetitive, low-skill tasks involved in preparing fast casual meals are automated, their cost will drop even more, giving us more incentive to forego home cooking. (But, it’s worth noting that these figures don’t take into account that eating at home is, in most cases, better for you since you’re less likely to fill your food with sugar, oil, or various other taste-enhancing but health-destroying ingredients—plus, there are those of us who get a nearly incomparable amount of joy from laboring over then savoring a homemade meal).
Now that we’re not supposed to be touching each other or touching anything anyone else has touched, but we still need to eat, automating food preparation sounds appealing (and maybe necessary). Multiple food delivery services have already implemented a contactless delivery option, where customers can choose to have their food left on their doorstep.
Besides the opportunities for in-restaurant automation, “This is an opportunity for automation to happen at the last mile,” said Xing. Delivery drones, robots, and autonomous trucks and vans could all play a part. In fact, use of delivery drones has ramped up in China since the outbreak.
Speaking of deliveries, service robots have steadily increased in numbers at Amazon; as of late 2019, the company employed around 650,000 humans and 200,000 robots—and costs have gone down as robots have gone up.
ARK Invest’s research predicts automation could add $800 billion to US GDP over the next 5 years and $12 trillion during the next 15 years. On this trajectory, GDP would end up being 40 percent higher with automation than without it.
Automating Ourselves?
This is all well and good, but what do these numbers and percentages mean for the average consumer, worker, or citizen?
“The benefits of automation aren’t being passed on to the average citizen,” said Xing. “They’re going to the shareholders of the companies creating the automation.” This is where policies like universal basic income and universal healthcare come in; in the not-too-distant future, we may see more movement toward measures like these (depending how the election goes) that spread the benefit of automation out rather than concentrating it in a few wealthy hands.
In the meantime, though, some people are benefiting from automation in ways that maybe weren’t expected. We’re in the midst of what’s probably the biggest remote-work experiment in US history, not to mention remote learning. Tools that let us digitally communicate and collaborate, like Slack, Zoom, Dropbox, and Gsuite, are enabling remote work in a way that wouldn’t have been possible 20 or even 10 years ago.
In addition, Xing said, tools like DataRobot and H2O.ai are democratizing artificial intelligence by allowing almost anyone, not just data scientists or computer engineers, to run machine learning algorithms. People are codifying the steps in their own repetitive work processes and having their computers take over tasks for them.
As 3D printing gets cheaper and more accessible, it’s also being more widely adopted, and people are finding more applications (case in point: the Italians mentioned above who figured out how to cheaply print a medical valve for coronavirus treatment).
The Mother of Invention
This movement towards a more automated society has some positives: it will help us stay healthy during times like the present, it will drive down the cost of goods and services, and it will grow our GDP in the long run. But by leaning into automation, will we be enabling a future that keeps us more physically, psychologically, and emotionally distant from each other?
We’re in a crisis, and desperate times call for desperate measures. We’re sheltering in place, practicing social distancing, and trying not to touch each other. And for most of us, this is really unpleasant and difficult. We can’t wait for it to be over.
For better or worse, this pandemic will likely make us pick up the pace on our path to automation, across many sectors and processes. The solutions people implement during this crisis won’t disappear when things go back to normal (and, depending who you talk to, they may never really do so).
But let’s make sure to remember something. Even once robots are making our food and drones are delivering it, and our computers are doing data entry and email replies on our behalf, and we all have 3D printers to make anything we want at home—we’re still going to be human. And humans like being around each other. We like seeing one another’s faces, hearing one another’s voices, and feeling one another’s touch—in person, not on a screen or in an app.
No amount of automation is going to change that, and beyond lowering costs or increasing GDP, our greatest and most crucial responsibility will always be to take care of each other.
Image Credit: Gritt Zheng on Unsplash Continue reading
#436578 AI Just Discovered a New Antibiotic to ...
Penicillin, one of the greatest discoveries in the history of medicine, was a product of chance.
After returning from summer vacation in September 1928, bacteriologist Alexander Fleming found a colony of bacteria he’d left in his London lab had sprouted a fungus. Curiously, wherever the bacteria contacted the fungus, their cell walls broke down and they died. Fleming guessed the fungus was secreting something lethal to the bacteria—and the rest is history.
Fleming’s discovery of penicillin and its later isolation, synthesis, and scaling in the 1940s released a flood of antibiotic discoveries in the next few decades. Bacteria and fungi had been waging an ancient war against each other, and the weapons they’d evolved over eons turned out to be humanity’s best defense against bacterial infection and disease.
In recent decades, however, the flood of new antibiotics has slowed to a trickle.
Their development is uneconomical for drug companies, and the low-hanging fruit has long been picked. We’re now facing the emergence of strains of super bacteria resistant to one or more antibiotics and an aging arsenal to fight them with. Gone unchallenged, an estimated 700,000 deaths worldwide due to drug resistance could rise to as many as 10 million in 2050.
Increasingly, scientists warn the tide is turning, and we need a new strategy to keep pace with the remarkably quick and boundlessly creative tactics of bacterial evolution.
But where the golden age of antibiotics was sparked by serendipity, human intelligence, and natural molecular weapons, its sequel may lean on the uncanny eye of artificial intelligence to screen millions of compounds—and even design new ones—in search of the next penicillin.
Hal Discovers a Powerful Antibiotic
In a paper published this week in the journal, Cell, MIT researchers took a step in this direction. The team says their machine learning algorithm discovered a powerful new antibiotic.
Named for the AI in 2001: A Space Odyssey, the antibiotic, halicin, successfully wiped out dozens of bacterial strains, including some of the most dangerous drug-resistant bacteria on the World Health Organization’s most wanted list. The bacteria also failed to develop resistance to E. coli during a month of observation, in stark contrast to existing antibiotic ciprofloxacin.
“In terms of antibiotic discovery, this is absolutely a first,” Regina Barzilay, a senior author on the study and computer science professor at MIT, told The Guardian.
The algorithm that discovered halicin was trained on the molecular features of 2,500 compounds. Nearly half were FDA-approved drugs, and another 800 naturally occurring. The researchers specifically tuned the algorithm to look for molecules with antibiotic properties but whose structures would differ from existing antibiotics (as halicin’s does). Using another machine learning program, they screened the results for those likely to be safe for humans.
Early study suggests halicin attacks the bacteria’s cell membranes, disrupting their ability to produce energy. Protecting the cell membrane from halicin might take more than one or two genetic mutations, which could account for its impressive ability to prevent resistance.
“I think this is one of the more powerful antibiotics that has been discovered to date,” James Collins, an MIT professor of bioengineering and senior author told The Guardian. “It has remarkable activity against a broad range of antibiotic-resistant pathogens.”
Beyond tests in petri-dish bacterial colonies, the team also tested halicin in mice. The antibiotic cleared up infections of a strain of bacteria resistant to all known antibiotics in a day. The team plans further study in partnership with a pharmaceutical company or nonprofit, and they hope to eventually prove it safe and effective for use in humans.
This last bit remains the trickiest step, given the cost of getting a new drug approved. But Collins hopes algorithms like theirs will help. “We could dramatically reduce the cost required to get through clinical trials,” he told the Financial Times.
A Universe of Drugs Awaits
The bigger story may be what happens next.
How many novel antibiotics await discovery, and how far can AI screening take us? The initial 6,000 compounds scanned by Barzilay and Collins’s team is a drop in the bucket.
They’ve already begun digging deeper by setting the algorithm loose on 100 million molecules from an online library of 1.5 billion compounds called the ZINC15 database. This first search took three days and turned up 23 more candidates that, like halicin, differ structurally from existing antibiotics and may be safe for humans. Two of these—which the team will study further—appear to be especially powerful.
Even more ambitiously, Barzilay hopes the approach can find or even design novel antibiotics that kill bad bacteria with alacrity while sparing the good guys. In this way, a round of antibiotics would cure whatever ails you without taking out your whole gut microbiome in the process.
All this is part of a larger movement to use machine learning algorithms in the long, expensive process of drug discovery. Other players in the area are also training AI on the vast possibility space of drug-like compounds. Last fall, one of the leaders in the area, Insilico, was challenged by a partner to see just how fast their method could do the job. The company turned out a new a proof-of-concept drug candidate in only 46 days.
The field is still developing, however, and it has yet to be seen exactly how valuable these approaches will be in practice. Barzilay is optimistic though.
“There is still a question of whether machine-learning tools are really doing something intelligent in healthcare, and how we can develop them to be workhorses in the pharmaceuticals industry,” she said. “This shows how far you can adapt this tool.”
Image Credit: Halicin (top row) prevented the development of antibiotic resistance in E. coli, while ciprofloxacin (bottom row) did not. Collins Lab at MIT Continue reading