Tag Archives: treatment
#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
#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.
Image credit: NIH/NIAID 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
#436944 Is Digital Learning Still Second Best?
As Covid-19 continues to spread, the world has gone digital on an unprecedented scale. Tens of thousands of employees are working from home, and huge conferences, like the Google I/O and Apple WWDC software extravaganzas, plan to experiment with digital events.
Universities too are sending students home. This might have meant an extended break from school not too long ago. But no more. As lecture halls go empty, an experiment into digital learning at scale is ramping up. In the US alone, over 100 universities, from Harvard to Duke, are offering online classes to students to keep the semester going.
While digital learning has been improving for some time, Covid-19 may not only tip us further into a more digitally connected reality, but also help us better appreciate its benefits. This is important because historically, digital learning has been viewed as inferior to traditional learning. But that may be changing.
The Inversion
We often think about digital technologies as ways to reach people without access to traditional services—online learning for children who don’t have schools nearby or telemedicine for patients with no access to doctors. And while these solutions have helped millions of people, they’re often viewed as “second best” and “better than nothing.” Even in more resource-rich environments, there’s an assumption one should pay more to attend an event in person—a concert, a football game, an exercise class—while digital equivalents are extremely cheap or free. Why is this? And is the situation about to change?
Take the case of Dr. Sanjeev Arora, a professor of medicine at the University of New Mexico. Arora started Project Echo because he was frustrated by how many late-stage cases of hepatitis C he encountered in rural New Mexico. He realized that if he had reached patients sooner, he could have prevented needless deaths. The solution? Digital learning for local health workers.
Project Echo connects rural healthcare practitioners to specialists at top health centers by video. The approach is collaborative: Specialists share best practices and work through cases with participants to apply them in the real world and learn from edge cases. Added to expert presentations, there are lots of opportunities to ask questions and interact with specialists.
The method forms a digital loop of learning, practice, assessment, and adjustment.
Since 2003, Project Echo has scaled to 800 locations in 39 countries and trained over 90,000 healthcare providers. Most notably, a study in The New England Journal of Medicine found that the outcomes of hepatitis C treatment given by Project Echo trained healthcare workers in rural and underserved areas were similar to outcomes at university medical centers. That is, digital learning in this context was equivalent to high quality in-person learning.
If that is possible today, with simple tools, will they surpass traditional medical centers and schools in the future? Can digital learning more generally follow suit and have the same success? Perhaps. Going digital brings its own special toolset to the table too.
The Benefits of Digital
If you’re training people online, you can record the session to better understand their engagement levels—or even add artificial intelligence to analyze it in real time. Ahura AI, for example, founded by Bryan Talebi, aims to upskill workers through online training. Early study of their method suggests they can significantly speed up learning by analyzing users’ real-time emotions—like frustration or distraction—and adjusting the lesson plan or difficulty on the fly.
Other benefits of digital learning include the near-instantaneous download of course materials—rather than printing and shipping books—and being able to more easily report grades and other results, a requirement for many schools and social services organizations. And of course, as other digitized industries show, digital learning can grow and scale further at much lower costs.
To that last point, 360ed, a digital learning startup founded in 2016 by Hla Hla Win, now serves millions of children in Myanmar with augmented reality lesson plans. And Global Startup Ecosystem, founded by Christine Souffrant Ntim and Einstein Kofi Ntim in 2015, is the world’s first and largest digital accelerator program. Their entirely online programs support over 1,000 companies in 90 countries. It’s astonishing how fast both of these organizations have grown.
Notably, both examples include offline experiences too. Many of the 360ed lesson plans come with paper flashcards children use with their smartphones because the online-offline interaction improves learning. The Global Startup Ecosystem also hosts about 10 additional in-person tech summits around the world on various topics through a related initiative.
Looking further ahead, probably the most important benefit of online learning will be its potential to integrate with other digital systems in the workplace.
Imagine a medical center that has perfect information about every patient and treatment in real time and that this information is (anonymously and privately) centralized, analyzed, and shared with medical centers, research labs, pharmaceutical companies, clinical trials, policy makers, and medical students around the world. Just as self-driving cars can learn to drive better by having access to the experiences of other self-driving cars, so too can any group working to solve complex, time-sensitive challenges learn from and build on each other’s experiences.
Why This Matters
While in the long term the world will likely end up combining the best aspects of traditional and digital learning, it’s important in the near term to be more aware of the assumptions we make about digital technologies. Some of the most pioneering work in education, healthcare, and other industries may not be highly visible right now because it is in a virtual setting. Most people are unaware, for example, that the busiest emergency room in rural America is already virtual.
Once they start converging with other digital technologies, these innovations will likely become the mainstream system for all of us. Which raises more questions: What is the best business model for these virtual services? If they start delivering better healthcare and educational outcomes than traditional institutions, should they charge more? Hopefully, we will see an even bigger shift occurring, in which technology allows us to provide high quality education, healthcare, and other services to everyone at more affordable prices than today.
These are some of the topics we can consider as Covid-19 forces us into uncharted territory.
Image Credit: Andras Vas / Unsplash Continue reading