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#437261 How AI Will Make Drug Discovery ...

If you had to guess how long it takes for a drug to go from an idea to your pharmacy, what would you guess? Three years? Five years? How about the cost? $30 million? $100 million?

Well, here’s the sobering truth: 90 percent of all drug possibilities fail. The few that do succeed take an average of 10 years to reach the market and cost anywhere from $2.5 billion to $12 billion to get there.

But what if we could generate novel molecules to target any disease, overnight, ready for clinical trials? Imagine leveraging machine learning to accomplish with 50 people what the pharmaceutical industry can barely do with an army of 5,000.

Welcome to the future of AI and low-cost, ultra-fast, and personalized drug discovery. Let’s dive in.

GANs & Drugs
Around 2012, computer scientist-turned-biophysicist Alex Zhavoronkov started to notice that artificial intelligence was getting increasingly good at image, voice, and text recognition. He knew that all three tasks shared a critical commonality. In each, massive datasets were available, making it easy to train up an AI.

But similar datasets were present in pharmacology. So, back in 2014, Zhavoronkov started wondering if he could use these datasets and AI to significantly speed up the drug discovery process. He’d heard about a new technique in artificial intelligence known as generative adversarial networks (or GANs). By pitting two neural nets against one another (adversarial), the system can start with minimal instructions and produce novel outcomes (generative). At the time, researchers had been using GANs to do things like design new objects or create one-of-a-kind, fake human faces, but Zhavoronkov wanted to apply them to pharmacology.

He figured GANs would allow researchers to verbally describe drug attributes: “The compound should inhibit protein X at concentration Y with minimal side effects in humans,” and then the AI could construct the molecule from scratch. To turn his idea into reality, Zhavoronkov set up Insilico Medicine on the campus of Johns Hopkins University in Baltimore, Maryland, and rolled up his sleeves.

Instead of beginning their process in some exotic locale, Insilico’s “drug discovery engine” sifts millions of data samples to determine the signature biological characteristics of specific diseases. The engine then identifies the most promising treatment targets and—using GANs—generates molecules (that is, baby drugs) perfectly suited for them. “The result is an explosion in potential drug targets and a much more efficient testing process,” says Zhavoronkov. “AI allows us to do with fifty people what a typical drug company does with five thousand.”

The results have turned what was once a decade-long war into a month-long skirmish.

In late 2018, for example, Insilico was generating novel molecules in fewer than 46 days, and this included not just the initial discovery, but also the synthesis of the drug and its experimental validation in computer simulations.

Right now, they’re using the system to hunt down new drugs for cancer, aging, fibrosis, Parkinson’s, Alzheimer’s, ALS, diabetes, and many others. The first drug to result from this work, a treatment for hair loss, is slated to start Phase I trials by the end of 2020.

They’re also in the early stages of using AI to predict the outcomes of clinical trials in advance of the trial. If successful, this technique will enable researchers to strip a bundle of time and money out of the traditional testing process.

Protein Folding
Beyond inventing new drugs, AI is also being used by other scientists to identify new drug targets—that is, the place to which a drug binds in the body and another key part of the drug discovery process.

Between 1980 and 2006, despite an annual investment of $30 billion, researchers only managed to find about five new drug targets a year. The trouble is complexity. Most potential drug targets are proteins, and a protein’s structure—meaning the way a 2D sequence of amino acids folds into a 3D protein—determines its function.

But a protein with merely a hundred amino acids (a rather small protein) can produce a googol-cubed worth of potential shapes—that’s a one followed by three hundred zeroes. This is also why protein-folding has long been considered an intractably hard problem for even the most powerful of supercomputers.

Back in 1994, to monitor supercomputers’ progress in protein-folding, a biannual competition was created. Until 2018, success was fairly rare. But then the creators of DeepMind turned their neural networks loose on the problem. They created an AI that mines enormous datasets to determine the most likely distance between a protein’s base pairs and the angles of their chemical bonds—aka, the basics of protein-folding. They called it AlphaFold.

On its first foray into the competition, contestant AIs were given 43 protein-folding problems to solve. AlphaFold got 25 right. The second-place team managed a meager three. By predicting the elusive ways in which various proteins fold on the basis of their amino acid sequences, AlphaFold may soon have a tremendous impact in aiding drug discovery and fighting some of today’s most intractable diseases.

Drug Delivery
Another theater of war for improved drugs is the realm of drug delivery. Even here, converging exponential technologies are paving the way for massive implications in both human health and industry shifts.

One key contender is CRISPR, the fast-advancing gene-editing technology that stands to revolutionize synthetic biology and treatment of genetically linked diseases. And researchers have now demonstrated how this tool can be applied to create materials that shape-shift on command. Think: materials that dissolve instantaneously when faced with a programmed stimulus, releasing a specified drug at a highly targeted location.

Yet another potential boon for targeted drug delivery is nanotechnology, whereby medical nanorobots have now been used to fight incidences of cancer. In a recent review of medical micro- and nanorobotics, lead authors (from the University of Texas at Austin and University of California, San Diego) found numerous successful tests of in vivo operation of medical micro- and nanorobots.

Drugs From the Future
Covid-19 is uniting the global scientific community with its urgency, prompting scientists to cast aside nation-specific territorialism, research secrecy, and academic publishing politics in favor of expedited therapeutic and vaccine development efforts. And in the wake of rapid acceleration across healthcare technologies, Big Pharma is an area worth watching right now, no matter your industry. Converging technologies will soon enable extraordinary strides in longevity and disease prevention, with companies like Insilico leading the charge.

Riding the convergence of massive datasets, skyrocketing computational power, quantum computing, cognitive surplus capabilities, and remarkable innovations in AI, we are not far from a world in which personalized drugs, delivered directly to specified targets, will graduate from science fiction to the standard of care.

Rejuvenational biotechnology will be commercially available sooner than you think. When I asked Alex for his own projection, he set the timeline at “maybe 20 years—that’s a reasonable horizon for tangible rejuvenational biotechnology.”

How might you use an extra 20 or more healthy years in your life? What impact would you be able to make?

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.

Image Credit: andreas160578 from Pixabay Continue reading

Posted in Human Robots

#437251 The Robot Revolution Was Televised: Our ...

When robots take over the world, Boston Dynamics may get a special shout-out in the acceptance speech.

“Do you, perchance, recall the many times you shoved our ancestors with a hockey stick on YouTube? It might have seemed like fun and games to you—but we remember.”

In the last decade, while industrial robots went about blandly automating boring tasks like the assembly of Teslas, Boston Dynamics built robots as far removed from Roombas as antelope from amoebas. The flaws in Asimov’s laws of robotics suddenly seemed a little too relevant.

The robot revolution was televised—on YouTube. With tens of millions of views, the robotics pioneer is the undisputed heavyweight champion of robot videos, and has been for years. Each new release is basically guaranteed press coverage—mostly stoking robot fear but occasionally eliciting compassion for the hardships of all robot-kind. And for good reason. The robots are not only some of the most advanced in the world, their makers just seem to have a knack for dynamite demos.

When Google acquired the company in 2013, it was a bombshell. One of the richest tech companies, with some of the most sophisticated AI capabilities, had just paired up with one of the world’s top makers of robots. And some walked on two legs like us.

Of course, the robots aren’t quite as advanced as they seem, and a revolution is far from imminent. The decade’s most meme-worthy moment was a video montage of robots, some of them by Boston Dynamics, falling—over and over and over, in the most awkward ways possible. Even today, they’re often controlled by a human handler behind the scenes, and the most jaw-dropping cuts can require several takes to nail. Google sold the company to SoftBank in 2017, saying advanced as they were, there wasn’t yet a clear path to commercial products. (Google’s robotics work was later halted and revived.)

Yet, despite it all, Boston Dynamics is still with us and still making sweet videos. Taken as a whole, the evolution in physical prowess over the years has been nothing short of astounding. And for the first time, this year, a Boston Dynamics robot, Spot, finally went on sale to anyone with a cool $75K.

So, we got to thinking: What are our favorite Boston Dynamics videos? And can we gather them up in one place for your (and our) viewing pleasure? Well, great question, and yes, why not. These videos were the ones that entertained or amazed us most (or both). No doubt, there are other beloved hits we missed or inadvertently omitted.

With that in mind, behold: Our favorite Boston Dynamics videos, from that one time they dressed up a humanoid bot in camo and gas mask—because, damn, that’s terrifying—to the time the most advanced robot dog in all the known universe got extra funky.

Let’s Kick This Off With a Big (Loud) Robot Dog
Let’s start with a baseline. BigDog was the first Boston Dynamics YouTube sensation. The year? 2009! The company was working on military contracts, and BigDog was supposed to be a sort of pack mule for soldiers. The video primarily shows off BigDog’s ability to balance on its own, right itself, and move over uneven terrain. Note the power source—a noisy combustion engine—and utilitarian design. Sufficed to say, things have evolved.

Nothing to See Here. Just a Pair of Robot Legs on a Treadmill
While BigDog is the ancestor of later four-legged robots, like Spot, Petman preceded the two-legged Atlas robot. Here, the Petman prototype, just a pair of robot legs and a caged torso, gets a light workout on the treadmill. Again, you can see its ability to balance and right itself when shoved. In contrast to BigDog, Petman is tethered for power (which is why it’s so quiet) and to catch it should it fall. Again, as you’ll see, things have evolved since then.

Robot in Gas Mask and Camo Goes for a Stroll
This one broke the internet—for obvious reasons. Not only is the robot wearing clothes, those clothes happen to be a camouflaged chemical protection suit and gas mask. Still working for the military, Boston Dynamics said Petman was testing protective clothing, and in addition to a full body, it had skin that actually sweated and was studded with sensors to detect leaks. In addition to walking, Petman does some light calisthenics as it prepares to climb out of the uncanny valley. (Still tethered though!)

This Machine Could Run Down Usain Bolt
If BigDog and Petman were built for balance and walking, Cheetah was built for speed. Here you can see the four-legged robot hitting 28.3 miles per hour, which, as the video casually notes, would be enough to run down the fastest human on the planet. Luckily, it wouldn’t be running down anyone as it was firmly leashed in the lab at this point.

Ever Dreamt of a Domestic Robot to Do the Dishes?
After its acquisition by Google, Boston Dynamics eased away from military contracts and applications. It was a return to more playful videos (like BigDog hitting the beach in Thailand and sporting bull horns) and applications that might be practical in civilian life. Here, the team introduced Spot, a streamlined version of BigDog, and showed it doing dishes, delivering a drink, and slipping on a banana peel (which was, of course, instantly made into a viral GIF). Note how much quieter Spot is thanks to an onboard battery and electric motor.

Spot Gets Funky
Nothing remotely practical here. Just funky moves. (Also, with a coat of yellow and black paint, Spot’s dressed more like a polished product as opposed to a utilitarian lab robot.)

Atlas Does Parkour…
Remember when Atlas was just a pair of legs on a treadmill? It’s amazing what ten years brings. By 2019, Atlas had a more polished appearance, like Spot, and had long ago ditched the tethers. Merely balancing was laughably archaic. The robot now had some amazing moves: like a handstand into a somersault, 180- and 360-degree spins, mid-air splits, and just for good measure, a gymnastics-style end to the routine to show it’s in full control.

…and a Backflip?!
To this day, this one is just. Insane.

10 Robot Dogs Tow a Box Truck
Nearly three decades after its founding, Boston Dynamics is steadily making its way into the commercial space. The company is pitching Spot as a multipurpose ‘mobility platform,’ emphasizing it can carry a varied suite of sensors and can go places standard robots can’t. (Its Handle robot is also set to move into warehouse automation.) So far, Spot’s been mostly trialed in surveying and data collection, but as this video suggests, string enough Spots together, and they could tow your car. That said, a pack of 10 would set you back $750K, so, it’s probably safe to say a tow truck is the better option (for now).

Image credit: Boston Dynamics Continue reading

Posted in Human Robots

#437230 How Drones and Aerial Vehicles Could ...

Drones, personal flying vehicles, and air taxis may be part of our everyday life in the very near future. Drones and air taxis will create new means of mobility and transport routes. Drones will be used for surveillance, delivery, and in the construction sector as it moves towards automation.

The introduction of these aerial craft into cities will require the built environment to change dramatically. Drones and other new aerial vehicles will require landing pads, charging points, and drone ports. They could usher in new styles of building, and lead to more sustainable design.

My research explores the impact of aerial vehicles on urban design, mapping out possible future trajectories.

An Aerial Age
Already, civilian drones can vary widely in size and complexity. They can carry a range of items from high-resolution cameras, delivery mechanisms, and thermal image technology to speakers and scanners. In the public sector, drones are used in disaster response and by the fire service to tackle fires which could endanger firefighters.

During the coronavirus pandemic, drones have been used by the police to enforce lockdown. Drones normally used in agriculture have sprayed disinfectant over cities. In the UK, drone delivery trials are taking place to carry medical items to the Isle of Wight.

Alongside drones, our future cities could also be populated by vertical takeoff and landing craft (VTOL), used as private vehicles and air taxis.

These vehicles are familiar to sci-fi fans. The late Syd Mead’s illustrations of the Spinner VTOL craft in the film Blade Runner captured the popular imagination, and the screens for the Spinners in Blade Runner 2049 created by Territory Studio provided a careful design fiction of the experience of piloting these types of vehicle.

Now, though, these flying vehicles are reality. A number of companies are developing eVTOL with electric multi-rotor jets, and a whole new motorsport is being established around them.

These aircraft have the potential to change our cities. However, they need to be tested extensively in urban airspace. A study conducted by Airbus found that public concerns about VTOL use focused on the safety of those on the ground and noise emissions.

New Cities
The widespread adoption of drones and VTOL will lead to new architecture and infrastructure. Existing buildings will require adaptations: landing pads, solar photovoltaic panels for energy efficiency, charging points for delivery drones, and landscaping to mitigate noise emissions.

A number of companies are already trialing drone delivery services. Existing buildings will need to be adapted to accommodate these new networks, and new design principles will have to be implemented in future ones.

The architect Saúl Ajuria Fernández has developed a design for a delivery drone port hub. This drone port acts like a beehive where drones recharge and collect parcels for distribution. Architectural firm Humphreys & Partners’ Pier 2, a design for a modular apartment building of the future, includes a cantilevered drone port for delivery services.

The Norman Foster Foundation has designed a drone port for delivery of medical supplies and other items for rural communities in Rwanda. The structure is also intended to function as a space for the public to congregate, as well as to receive training in robotics.

Drones may also help the urban environment become more sustainable. Researchers at the University of Stuttgart have developed a re-configurable architectural roof canopy system deployed by drones. By adjusting to follow the direction of the sun, the canopy provides shade and reduces reliance on ventilation systems.

Demand for air taxis and personal flying vehicles will develop where failures in other transport systems take place. The Airbus research found that of the cities surveyed, highest demand for VTOLs was in Los Angeles and Mexico City, urban areas famous for traffic pollution. To accommodate these aerial vehicles, urban space will need to transform to include landing pads, airport-like infrastructure, and recharge points.

Furthermore, this whole logistics system in lower airspace (below 500 feet), or what I term “hover space,” will need an urban traffic management system. One great example of how this hover space could work can be seen in a speculative project from design studio Superflux in their Drone Aviary project. A number of drones with different functions move around an urban area in a network, following different paths at varying heights.

We are at a critical period in urban history, faced by climatic breakdown and pandemic. Drones and aerial vehicles can be part of a profound rethink of the urban environment.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Image Credit: NASA Continue reading

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.

Image Credit: Arek Socha from Pixabay Continue reading

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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