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#437258 This Startup Is 3D Printing Custom ...
Around 1.9 million people in the US are currently living with limb loss. The trauma of losing a limb is just the beginning of what amputees have to face, with the sky-high cost of prosthetics making their circumstance that much more challenging.
Prosthetics can run over $50,000 for a complex limb (like an arm or a leg) and aren’t always covered by insurance. As if shelling out that sum one time wasn’t costly enough, kids’ prosthetics need to be replaced as they outgrow them, meaning the total expense can reach hundreds of thousands of dollars.
A startup called Unlimited Tomorrow is trying to change this, and using cutting-edge technology to do so. Based in Rhinebeck, New York, a town about two hours north of New York City, the company was founded by 23-year-old Easton LaChappelle. He’d been teaching himself the basics of robotics and building prosthetics since grade school (his 8th grade science fair project was a robotic arm) and launched his company in 2014.
After six years of research and development, the company launched its TrueLimb product last month, describing it as an affordable, next-generation prosthetic arm using a custom remote-fitting process where the user never has to leave home.
The technologies used for TrueLimb’s customization and manufacturing are pretty impressive, in that they both cut costs and make the user’s experience a lot less stressful.
For starters, the entire purchase, sizing, and customization process for the prosthetic can be done remotely. Here’s how it works. First, prospective users fill out an eligibility form and give information about their residual limb. If they’re a qualified candidate for a prosthetic, Unlimited Tomorrow sends them a 3D scanner, which they use to scan their residual limb.
The company uses the scans to design a set of test sockets (the component that connects the residual limb to the prosthetic), which are mailed to the user. The company schedules a video meeting with the user for them to try on and discuss the different sockets, with the goal of finding the one that’s most comfortable; new sockets can be made based on the information collected during the video consultation. The user selects their skin tone from a swatch with 450 options, then Unlimited Tomorrow 3D prints and assembles the custom prosthetic and tests it before shipping it out.
“We print the socket, forearm, palm, and all the fingers out of durable nylon material in full color,” LaChappelle told Singularity Hub in an email. “The only components that aren’t 3D printed are the actuators, tendons, electronics, batteries, sensors, and the nuts and bolts. We are an extreme example of final use 3D printing.”
Unlimited Tomorrow’s website lists TrueLimb’s cost as “as low as $7,995.” When you consider the customization and capabilities of the prosthetic, this is incredibly low. According to LaChappelle, the company created a muscle sensor that picks up muscle movement at a higher resolution than the industry standard electromyography sensors. The sensors read signals from nerves in the residual limb used to control motions like fingers bending. This means that when a user thinks about bending a finger, the nerve fires and the prosthetic’s sensors can detect the signal and translate it into the action.
“Working with children using our device, I’ve witnessed a physical moment where the brain “clicks” and starts moving the hand rather than focusing on moving the muscles,” LaChappelle said.
The cost savings come both from the direct-to-consumer model and the fact that Unlimited Tomorrow doesn’t use any outside suppliers. “We create every piece of our product,” LaChappelle said. “We don’t rely on another prosthetic manufacturer to make expensive sensors or electronics. By going direct to consumer, we cut out all the middlemen that usually drive costs up.” Similar devices on the market can cost up to $100,000.
Unlimited Tomorrow is primarily focused on making prosthetics for kids; when they outgrow their first TrueLimb, they send it back, where the company upcycles the expensive quality components and integrates them into a new customized device.
Unlimited Tomorrow isn’t the first to use 3D printing for prosthetics. Florida-based Limbitless Solutions does so too, and industry experts believe the technology is the future of artificial limbs.
“I am constantly blown away by this tech,” LaChappelle said. “We look at technology as the means to augment the human body and empower people.”
Image Credit: Unlimited Tomorrow Continue reading
Posted in Human Robots
#437216 New Report: Tech Could Fuel an Age of ...
With rapid technological progress running headlong into dramatic climate change and widening inequality, most experts agree the coming decade will be tumultuous. But a new report predicts it could actually make or break civilization as we know it.
The idea that humanity is facing a major shake-up this century is not new. The Fourth Industrial Revolution being brought about by technologies like AI, gene editing, robotics, and 3D printing is predicted to cause dramatic social, political, and economic upheaval in the coming decades.
But according to think tank RethinkX, thinking about the coming transition as just another industrial revolution is too simplistic. In a report released last week called Rethinking Humanity, the authors argue that we are about to see a reordering of our relationship with the world as fundamental as when hunter-gatherers came together to build the first civilizations.
At the core of their argument is the fact that since the first large human settlements appeared 10,000 years ago, civilization has been built on the back of our ability to extract resources from nature, be they food, energy, or materials. This led to a competitive landscape where the governing logic is grow or die, which has driven all civilizations to date.
That could be about to change thanks to emerging technologies that will fundamentally disrupt the five foundational sectors underpinning society: information, energy, food, transportation, and materials. They predict that across all five, costs will fall by 10 times or more, while production processes will become 10 times more efficient and will use 90 percent fewer natural resources with 10 to 100 times less waste.
They say that this transformation has already happened in information, where the internet has dramatically reduced barriers to communication and knowledge. They predict the combination of cheap solar and grid storage will soon see energy costs drop as low as one cent per kilowatt hour, and they envisage widespread adoption of autonomous electric vehicles and the replacement of car ownership with ride-sharing.
The authors laid out their vision for the future of food in another report last year, where they predicted that traditional agriculture would soon be replaced by industrial-scale brewing of single-celled organisms genetically modified to produce all the nutrients we need. In a similar vein, they believe the same processes combined with additive manufacturing and “nanotechnologies” will allow us to build all the materials required for the modern world from the molecule up rather than extracting scarce natural resources.
They believe this could allow us to shift from a system of production based on extraction to one built on creation, as limitless renewable energy makes it possible to build everything we need from scratch and barriers to movement and information disappear. As a result, a lifestyle worthy of the “American Dream” could be available to anyone for as little as $250/month by 2030.
This will require a fundamental reimagining of our societies, though. All great civilizations have eventually hit fundamental limits on their growth and we are no different, as demonstrated by our growing impact on the environment and the increasing concentration of wealth. Historically this stage of development has lead to a doubling down on old tactics in search of short-term gains, but this invariably leads to the collapse of the civilization.
The authors argue that we’re in a unique position. Because of the technological disruption detailed above, we have the ability to break through the limits on our growth. But only if we change what the authors call our “Organizing System.” They describe this as “the prevailing models of thought, belief systems, myths, values, abstractions, and conceptual frameworks that help explain how the world works and our relationship to it.”
They say that the current hierarchical, centralized system based on nation-states is unfit for the new system of production that is emerging. The cracks are already starting to appear, with problems like disinformation campaigns, fake news, and growing polarization demonstrating how ill-suited our institutions are for dealing with the distributed nature of today’s information systems. And as this same disruption comes to the other foundational sectors the shockwaves could lead to the collapse of civilization as we know it.
Their solution is a conscious shift towards a new way of organizing the world. As emerging technology allows communities to become self-sufficient, flows of physical resources will be replaced by flows of information, and we will require a decentralized but highly networked Organizing System.
The report includes detailed recommendations on how to usher this in. Examples include giving individuals control and ownership of data rights; developing new models for community ownership of energy, information, and transportation networks; and allowing states and cities far greater autonomy on policies like immigration, taxation, education, and public expenditure.
How easy it will be to get people on board with such a shift is another matter. The authors say it may require us to re-examine the foundations of our society, like representative democracy, capitalism, and nation-states. While they acknowledge that these ideas are deeply entrenched, they appear to believe we can reason our way around them.
That seems optimistic. Cultural and societal change can be glacial, and efforts to impose it top-down through reason and logic are rarely successful. The report seems to brush over many of the messy realities of humanity, such as the huge sway that tradition and religion hold over the vast majority of people.
It also doesn’t deal with the uneven distribution of the technology that is supposed to catapult us into this new age. And while the predicted revolutions in transportation, energy, and information do seem inevitable, the idea that in the next decade or two we’ll be able to produce any material we desire using cheap and abundant stock materials seems like a stretch.
Despite the techno-utopianism though, many of the ideas in the report hold promise for building societies that are better adapted for the disruptive new age we are about to enter.
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Posted in Human Robots
#437209 A Renaissance of Genomics and Drugs Is ...
The causes of aging are extremely complex and unclear. But with longevity clinical trials increasing, more answers—and questions—are emerging than ever before.
With the dramatic demonetization of genome reading and editing over the past decade, and Big Pharma, startups, and the FDA starting to face aging as a disease, we are starting to turn those answers into practical ways to extend our healthspan.
In this article, I’ll explore how genome sequencing and editing, along with new classes of anti-aging drugs, are augmenting our biology to further extend our healthy lives.
Genome Sequencing and Editing
Your genome is the software that runs your body. A sequence of 3.2 billion letters makes you “you.” These base pairs of A’s, T’s, C’s, and G’s determine your hair color, your height, your personality, your propensity for disease, your lifespan, and so on.
Until recently, it’s been very difficult to rapidly and cheaply “read” these letters—and even more difficult to understand what they mean. Since 2001, the cost to sequence a whole human genome has plummeted exponentially, outpacing Moore’s Law threefold. From an initial cost of $3.7 billion, it dropped to $10 million in 2006, and to $1,500 in 2015.
Today, the cost of genome sequencing has dropped below $600, and according to Illumina, the world’s leading sequencing company, the process will soon cost about $100 and take about an hour to complete.
This represents one of the most powerful and transformative technology revolutions in healthcare. When we understand your genome, we’ll be able to understand how to optimize “you.”
We’ll know the perfect foods, the perfect drugs, the perfect exercise regimen, and the perfect supplements, just for you.
We’ll understand what microbiome types, or gut flora, are ideal for you (more on this in a later article).
We’ll accurately predict how specific sedatives and medicines will impact you.
We’ll learn which diseases and illnesses you’re most likely to develop and, more importantly, how to best prevent them from developing in the first place (rather than trying to cure them after the fact).
CRISPR Gene Editing
In addition to reading the human genome, scientists can now edit a genome using a naturally occurring biological system discovered in 1987 called CRISPR/Cas9.
Short for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9, the editing system was adapted from a naturally-occurring defense system found in bacteria.
Here’s how it works. The bacteria capture snippets of DNA from invading viruses (or bacteriophage) and use them to create DNA segments known as CRISPR arrays. The CRISPR arrays allow the bacteria to “remember” the viruses (or closely related ones), and defend against future invasions. If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA. The bacteria then use Cas9 to cut the DNA apart, which disables the virus.
Most importantly, CRISPR is cheap, quick, easy to use, and more accurate than all previous gene editing methods. As a result, CRISPR/Cas9 has swept through labs around the world as the way to edit a genome. A short search in the literature will show an exponential rise in the number of CRISPR-related publications and patents.
2018: Filled With CRISPR Breakthroughs
Early results are impressive. Researchers have used CRISPR to genetically engineer cocaine resistance into mice, reverse the gene defect causing Duchenne muscular dystrophy (DMD) in dogs, and reduce genetic deafness in mice.
Already this year, CRISPR-edited immune cells have been shown to successfully kill cancer cells in human patients. Researchers have discovered ways to activate CRISPR with light and use the gene-editing technology to better understand Alzheimer’s disease progression.
With great power comes great responsibility, and the opportunity for moral and ethical dilemmas. In 2015, Chinese scientists sparked global controversy when they first edited human embryo cells in the lab with the goal of modifying genes that would make the child resistant to smallpox, HIV, and cholera. Three years later, in November 2018, researcher He Jiankui informed the world that the first set of CRISPR-engineered female twins had been delivered.
To accomplish his goal, Jiankui deleted a region of a receptor on the surface of white blood cells known as CCR5, introducing a rare, natural genetic variation that makes it more difficult for HIV to infect its favorite target, white blood cells. Because Jiankui forged ethical review documents and misled doctors in the process, he was sentenced to three years in prison and fined $429,000 last December.
Coupled with significant ethical conversations necessary for progress, CRISPR will soon provide us the tools to eliminate diseases, create hardier offspring, produce new environmentally resistant crops, and even wipe out pathogens.
Senolytics, Nutraceuticals, and Pharmaceuticals
Over the arc of your life, the cells in your body divide until they reach what is known as the Hayflick limit, or the number of times a normal human cell population will divide before cell division stops, which is typically about 50 divisions.
What normally follows next is programmed cell death or destruction by the immune system. A very small fraction of cells, however, become senescent cells and evade this fate to linger indefinitely. These lingering cells secrete a potent mix of molecules that triggers chronic inflammation, damages the surrounding tissue structures, and changes the behavior of nearby cells for the worse. Senescent cells appear to be one of the root causes of aging, causing everything from fibrosis and blood vessel calcification to localized inflammatory conditions such as osteoarthritis to diminished lung function.
Fortunately, both the scientific and entrepreneurial communities have begun to work on senolytic therapies, moving the technology for selectively destroying senescent cells out of the laboratory and into a half-dozen startup companies.
Prominent companies in the field include the following:
Unity Biotechnology is developing senolytic medicines to selectively eliminate senescent cells with an initial focus on delivering localized therapy in osteoarthritis, ophthalmology, and pulmonary disease.
Oisin Biotechnologies is pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.
SIWA Therapeutics is working on an immunotherapy approach to the problem of senescent cells.
In recent years, researchers have identified or designed a handful of senolytic compounds that can curb aging by regulating senescent cells. Two of these drugs that have gained mainstay research traction are rapamycin and metformin.
(1) Rapamycin
Originally extracted from bacteria found on Easter Island, rapamycin acts on the m-TOR (mechanistic target of rapamycin) pathway to selectively block a key protein that facilitates cell division. Currently, rapamycin derivatives are widely used for immunosuppression in organ and bone marrow transplants. Research now suggests that use results in prolonged lifespan and enhanced cognitive and immune function.
PureTech Health subsidiary resTORbio (which went public in 2018) is working on a rapamycin-based drug intended to enhance immunity and reduce infection. Their clinical-stage RTB101 drug works by inhibiting part of the mTOR pathway.
Results of the drug’s recent clinical trial include decreased incidence of infection, improved influenza vaccination response, and a 30.6 percent decrease in respiratory tract infection.
Impressive, to say the least.
(2) Metformin
Metformin is a widely-used generic drug for mitigating liver sugar production in Type 2 diabetes patients. Researchers have found that metformin also reduces oxidative stress and inflammation, which otherwise increase as we age. There is strong evidence that metformin can augment cellular regeneration and dramatically mitigate cellular senescence by reducing both oxidative stress and inflammation.
Over 100 studies registered on ClinicalTrials.gov are currently following up on strong evidence of metformin’s protective effect against cancer.
(3) Nutraceuticals and NAD+
Beyond cellular senescence, certain critical nutrients and proteins tend to decline as a function of age. Nutraceuticals combat aging by supplementing and replenishing these declining nutrient levels.
NAD+ exists in every cell, participating in every process from DNA repair to creating the energy vital for cellular processes. It’s been shown that NAD+ levels decline as we age.
The Elysium Health Basis supplement aims to elevate NAD+ levels in the body to extend one’s lifespan. Elysium’s first clinical study reports that Basis increases NAD+ levels consistently by a sustained 40 percent.
Conclusion
These are just a taste of the tremendous momentum that longevity and aging technology has right now. As artificial intelligence and quantum computing transform how we decode our DNA and how we discover drugs, genetics and pharmaceuticals will become truly personalized.
The next article in this series will demonstrate how artificial intelligence is converging with genetics and pharmaceuticals to transform how we approach longevity, aging, and vitality.
We are edging closer toward a dramatically extended healthspan—where 100 is the new 60. What will you create, where will you explore, and how will you spend your time if you are able to add an additional 40 healthy years to your life?
Join Me
(1) A360 Executive Mastermind: If you’re an exponentially and abundance-minded entrepreneur who would like coaching directly from me, consider joining my Abundance 360 Mastermind, a highly selective community of 360 CEOs and entrepreneurs who I coach for 3 days every January in Beverly Hills, Ca. Through A360, I provide my members with context and clarity about how converging exponential technologies will transform every industry. I’m committed to running A360 for the course of an ongoing 25-year journey as a “countdown to the Singularity.”
If you’d like to learn more and consider joining our 2021 membership, apply here.
(2) Abundance-Digital Online Community: I’ve also created a Digital/Online community of bold, abundance-minded entrepreneurs called Abundance-Digital. Abundance-Digital is Singularity University’s ‘onramp’ for exponential entrepreneurs—those who want to get involved and play at a higher level. Click here to learn more.
(Both A360 and Abundance-Digital are part of Singularity University—your participation opens you to a global community.)
This article originally appeared on diamandis.com. Read the original article here.
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Posted in Human Robots
#437202 Scientists Used Dopamine to Seamlessly ...
In just half a decade, neuromorphic devices—or brain-inspired computing—already seem quaint. The current darling? Artificial-biological hybrid computing, uniting both man-made computer chips and biological neurons seamlessly into semi-living circuits.
It sounds crazy, but a new study in Nature Materials shows that it’s possible to get an artificial neuron to communicate directly with a biological one using not just electricity, but dopamine—a chemical the brain naturally uses to change how neural circuits behave, most known for signaling reward.
Because these chemicals, known as “neurotransmitters,” are how biological neurons functionally link up in the brain, the study is a dramatic demonstration that it’s possible to connect artificial components with biological brain cells into a functional circuit.
The team isn’t the first to pursue hybrid neural circuits. Previously, a different team hooked up two silicon-based artificial neurons with a biological one into a circuit using electrical protocols alone. Although a powerful demonstration of hybrid computing, the study relied on only one-half of the brain’s computational ability: electrical computing.
The new study now tackles the other half: chemical computing. It adds a layer of compatibility that lays the groundwork not just for brain-inspired computers, but also for brain-machine interfaces and—perhaps—a sort of “cyborg” future. After all, if your brain can’t tell the difference between an artificial neuron and your own, could you? And even if you did, would you care?
Of course, that scenario is far in the future—if ever. For now, the team, led by Dr. Alberto Salleo, professor of materials science and engineering at Stanford University, collectively breathed a sigh of relief that the hybrid circuit worked.
“It’s a demonstration that this communication melding chemistry and electricity is possible,” said Salleo. “You could say it’s a first step toward a brain-machine interface, but it’s a tiny, tiny very first step.”
Neuromorphic Computing
The study grew from years of work into neuromorphic computing, or data processing inspired by the brain.
The blue-sky idea was inspired by the brain’s massive parallel computing capabilities, along with vast energy savings. By mimicking these properties, scientists reasoned, we could potentially turbo-charge computing. Neuromorphic devices basically embody artificial neural networks in physical form—wouldn’t hardware that mimics how the brain processes information be even more efficient and powerful?
These explorations led to novel neuromorphic chips, or artificial neurons that “fire” like biological ones. Additional work found that it’s possible to link these chips up into powerful circuits that run deep learning with ease, with bioengineered communication nodes called artificial synapses.
As a potential computing hardware replacement, these systems have proven to be incredibly promising. Yet scientists soon wondered: given their similarity to biological brains, can we use them as “replacement parts” for brains that suffer from traumatic injuries, aging, or degeneration? Can we hook up neuromorphic components to the brain to restore its capabilities?
Buzz & Chemistry
Theoretically, the answer’s yes.
But there’s a huge problem: current brain-machine interfaces only use electrical signals to mimic neural computation. The brain, in contrast, has two tricks up its sleeve: electricity and chemicals, or electrochemical.
Within a neuron, electricity travels up its incoming branches, through the bulbous body, then down the output branches. When electrical signals reach the neuron’s outgoing “piers,” dotted along the output branch, however, they hit a snag. A small gap exists between neurons, so to get to the other side, the electrical signals generally need to be converted into little bubble ships, packed with chemicals, and set sail to the other neuronal shore.
In other words, without chemical signals, the brain can’t function normally. These neurotransmitters don’t just passively carry information. Dopamine, for example, can dramatically change how a neural circuit functions. For an artificial-biological hybrid neural system, the absence of chemistry is like nixing international cargo vessels and only sticking with land-based trains and highways.
“To emulate biological synaptic behavior, the connectivity of the neuromorphic device must be dynamically regulated by the local neurotransmitter activity,” the team said.
Let’s Get Electro-Chemical
The new study started with two neurons: the upstream, an immortalized biological cell that releases dopamine; and the downstream, an artificial neuron that the team previously introduced in 2017, made of a mix of biocompatible and electrical-conducting materials.
Rather than the classic neuron shape, picture more of a sandwich with a chunk bitten out in the middle (yup, I’m totally serious). Each of the remaining parts of the sandwich is a soft electrode, made of biological polymers. The “bitten out” part has a conductive solution that can pass on electrical signals.
The biological cell sits close to the first electrode. When activated, it dumps out boats of dopamine, which drift to the electrode and chemically react with it—mimicking the process of dopamine docking onto a biological neuron. This, in turn, generates a current that’s passed on to the second electrode through the conductive solution channel. When this current reaches the second electrode, it changes the electrode’s conductance—that is, how well it can pass on electrical information. This second step is analogous to docked dopamine “ships” changing how likely it is that a biological neuron will fire in the future.
In other words, dopamine release from the biological neuron interacts with the artificial one, so that the chemicals change how the downstream neuron behaves in a somewhat lasting way—a loose mimic of what happens inside the brain during learning.
But that’s not all. Chemical signaling is especially powerful in the brain because it’s flexible. Dopamine, for example, only grabs onto the downstream neurons for a bit before it returns back to its upstream neuron—that is, recycled or destroyed. This means that its effect is temporary, giving the neural circuit breathing room to readjust its activity.
The Stanford team also tried reconstructing this quirk in their hybrid circuit. They crafted a microfluidic channel that shuttles both dopamine and its byproduct away from the artificial neurons after they’ve done their job for recycling.
Putting It All Together
After confirming that biological cells can survive happily on top of the artificial one, the team performed a few tests to see if the hybrid circuit could “learn.”
They used electrical methods to first activate the biological dopamine neuron, and watched the artificial one. Before the experiment, the team wasn’t quite sure what to expect. Theoretically, it made sense that dopamine would change the artificial neuron’s conductance, similar to learning. But “it was hard to know whether we’d achieve the outcome we predicted on paper until we saw it happen in the lab,” said study author Scott Keene.
On the first try, however, the team found that the burst of chemical signaling was able to change the artificial neuron’s conductance long-term, similar to the neuroscience dogma “neurons that fire together, wire together.” Activating the upstream biological neuron with chemicals also changed the artificial neuron’s conductance in a way that mimicked learning.
“That’s when we realized the potential this has for emulating the long-term learning process of a synapse,” said Keene.
Visualizing under an electron microscope, the team found that, similar to its biological counterpart, the hybrid synapse was able to efficiently recycle dopamine with timescales similar to the brain after some calibration. By playing with how much dopamine accumulates at the artificial neuron, the team found that they loosely mimic a learning rule called spike learning—a darling of machine learning inspired by the brain’s computation.
A Hybrid Future?
Unfortunately for cyborg enthusiasts, the work is still in its infancy.
For one, the artificial neurons are still rather bulky compared to biological ones. This means that they can’t capture and translate information from a single “boat” of dopamine. It’s also unclear if, and how, a hybrid synapse can work inside a living brain. Given the billions of synapses firing away in our heads, it’ll be a challenge to find-and-replace those that need replacement, and be able to control our memories and behaviors similar to natural ones.
That said, we’re inching ever closer to full-capability artificial-biological hybrid circuits.
“The neurotransmitter-mediated neuromorphic device presented in this work constitutes a fundamental building block for artificial neural networks that can be directly modulated based on biological feedback from live neurons,” the authors concluded. “[It] is a crucial first step in realizing next-generation adaptive biohybrid interfaces.”
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Posted in Human Robots
#437171 Scientists Tap the World’s Most ...
In The Hitchhiker’s Guide to the Galaxy by Douglas Adams, the haughty supercomputer Deep Thought is asked whether it can find the answer to the ultimate question concerning life, the universe, and everything. It replies that, yes, it can do it, but it’s tricky and it’ll have to think about it. When asked how long it will take it replies, “Seven-and-a-half million years. I told you I’d have to think about it.”
Real-life supercomputers are being asked somewhat less expansive questions but tricky ones nonetheless: how to tackle the Covid-19 pandemic. They’re being used in many facets of responding to the disease, including to predict the spread of the virus, to optimize contact tracing, to allocate resources and provide decisions for physicians, to design vaccines and rapid testing tools, and to understand sneezes. And the answers are needed in a rather shorter time frame than Deep Thought was proposing.
The largest number of Covid-19 supercomputing projects involves designing drugs. It’s likely to take several effective drugs to treat the disease. Supercomputers allow researchers to take a rational approach and aim to selectively muzzle proteins that SARS-CoV-2, the virus that causes Covid-19, needs for its life cycle.
The viral genome encodes proteins needed by the virus to infect humans and to replicate. Among these are the infamous spike protein that sniffs out and penetrates its human cellular target, but there are also enzymes and molecular machines that the virus forces its human subjects to produce for it. Finding drugs that can bind to these proteins and stop them from working is a logical way to go.
The Summit supercomputer at Oak Ridge National Laboratory has a peak performance of 200,000 trillion calculations per second—equivalent to about a million laptops. Image credit: Oak Ridge National Laboratory, U.S. Dept. of Energy, CC BY
I am a molecular biophysicist. My lab, at the Center for Molecular Biophysics at the University of Tennessee and Oak Ridge National Laboratory, uses a supercomputer to discover drugs. We build three-dimensional virtual models of biological molecules like the proteins used by cells and viruses, and simulate how various chemical compounds interact with those proteins. We test thousands of compounds to find the ones that “dock” with a target protein. Those compounds that fit, lock-and-key style, with the protein are potential therapies.
The top-ranked candidates are then tested experimentally to see if they indeed do bind to their targets and, in the case of Covid-19, stop the virus from infecting human cells. The compounds are first tested in cells, then animals, and finally humans. Computational drug discovery with high-performance computing has been important in finding antiviral drugs in the past, such as the anti-HIV drugs that revolutionized AIDS treatment in the 1990s.
World’s Most Powerful Computer
Since the 1990s the power of supercomputers has increased by a factor of a million or so. Summit at Oak Ridge National Laboratory is presently the world’s most powerful supercomputer, and has the combined power of roughly a million laptops. A laptop today has roughly the same power as a supercomputer had 20-30 years ago.
However, in order to gin up speed, supercomputer architectures have become more complicated. They used to consist of single, very powerful chips on which programs would simply run faster. Now they consist of thousands of processors performing massively parallel processing in which many calculations, such as testing the potential of drugs to dock with a pathogen or cell’s proteins, are performed at the same time. Persuading those processors to work together harmoniously is a pain in the neck but means we can quickly try out a lot of chemicals virtually.
Further, researchers use supercomputers to figure out by simulation the different shapes formed by the target binding sites and then virtually dock compounds to each shape. In my lab, that procedure has produced experimentally validated hits—chemicals that work—for each of 16 protein targets that physician-scientists and biochemists have discovered over the past few years. These targets were selected because finding compounds that dock with them could result in drugs for treating different diseases, including chronic kidney disease, prostate cancer, osteoporosis, diabetes, thrombosis and bacterial infections.
Scientists are using supercomputers to find ways to disable the various proteins—including the infamous spike protein (green protrusions)—produced by SARS-CoV-2, the virus responsible for Covid-19. Image credit: Thomas Splettstoesser scistyle.com, CC BY-ND
Billions of Possibilities
So which chemicals are being tested for Covid-19? A first approach is trying out drugs that already exist for other indications and that we have a pretty good idea are reasonably safe. That’s called “repurposing,” and if it works, regulatory approval will be quick.
But repurposing isn’t necessarily being done in the most rational way. One idea researchers are considering is that drugs that work against protein targets of some other virus, such as the flu, hepatitis or Ebola, will automatically work against Covid-19, even when the SARS-CoV-2 protein targets don’t have the same shape.
Our own work has now expanded to about 10 targets on SARS-CoV-2, and we’re also looking at human protein targets for disrupting the virus’s attack on human cells. Top-ranked compounds from our calculations are being tested experimentally for activity against the live virus. Several of these have already been found to be active.The best approach is to check if repurposed compounds will actually bind to their intended target. To that end, my lab published a preliminary report of a supercomputer-driven docking study of a repurposing compound database in mid-February. The study ranked 8,000 compounds in order of how well they bind to the viral spike protein. This paper triggered the establishment of a high-performance computing consortium against our viral enemy, announced by President Trump in March. Several of our top-ranked compounds are now in clinical trials.
Also, we and others are venturing out into the wild world of new drug discovery for Covid-19—looking for compounds that have never been tried as drugs before. Databases of billions of these compounds exist, all of which could probably be synthesized in principle but most of which have never been made. Billion-compound docking is a tailor-made task for massively parallel supercomputing.
Dawn of the Exascale Era
Work will be helped by the arrival of the next big machine at Oak Ridge, called Frontier, planned for next year. Frontier should be about 10 times more powerful than Summit. Frontier will herald the “exascale” supercomputing era, meaning machines capable of 1,000,000,000,000,000,000 calculations per second.
Although some fear supercomputers will take over the world, for the time being, at least, they are humanity’s servants, which means that they do what we tell them to. Different scientists have different ideas about how to calculate which drugs work best—some prefer artificial intelligence, for example—so there’s quite a lot of arguing going on.
Hopefully, scientists armed with the most powerful computers in the world will, sooner rather than later, find the drugs needed to tackle Covid-19. If they do, then their answers will be of more immediate benefit, if less philosophically tantalizing, than the answer to the ultimate question provided by Deep Thought, which was, maddeningly, simply 42.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
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Posted in Human Robots