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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.

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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).

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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

#437157 A Human-Centric World of Work: Why It ...

Long before coronavirus appeared and shattered our pre-existing “normal,” the future of work was a widely discussed and debated topic. We’ve watched automation slowly but surely expand its capabilities and take over more jobs, and we’ve wondered what artificial intelligence will eventually be capable of.

The pandemic swiftly turned the working world on its head, putting millions of people out of a job and forcing millions more to work remotely. But essential questions remain largely unchanged: we still want to make sure we’re not replaced, we want to add value, and we want an equitable society where different types of work are valued fairly.

To address these issues—as well as how the pandemic has impacted them—this week Singularity University held a digital summit on the future of work. Forty-three speakers from multiple backgrounds, countries, and sectors of the economy shared their expertise on everything from work in developing markets to why we shouldn’t want to go back to the old normal.

Gary Bolles, SU’s chair for the Future of Work, kicked off the discussion with his thoughts on a future of work that’s human-centric, including why it matters and how to build it.

What Is Work?
“Work” seems like a straightforward concept to define, but since it’s constantly shifting shape over time, let’s make sure we’re on the same page. Bolles defined work, very basically, as human skills applied to problems.

“It doesn’t matter if it’s a dirty floor or a complex market entry strategy or a major challenge in the world,” he said. “We as humans create value by applying our skills to solve problems in the world.” You can think of the problems that need solving as the demand and human skills as the supply, and the two are in constant oscillation, including, every few decades or centuries, a massive shift.

We’re in the midst of one of those shifts right now (and we already were, long before the pandemic). Skills that have long been in demand are declining. The World Economic Forum’s 2018 Future of Jobs report listed things like manual dexterity, management of financial and material resources, and quality control and safety awareness as declining skills. Meanwhile, skills the next generation will need include analytical thinking and innovation, emotional intelligence, creativity, and systems analysis.

Along Came a Pandemic
With the outbreak of coronavirus and its spread around the world, the demand side of work shrunk; all the problems that needed solving gave way to the much bigger, more immediate problem of keeping people alive. But as a result, tens of millions of people around the world are out of work—and those are just the ones that are being counted, and they’re a fraction of the true total. There are additional millions in seasonal or gig jobs or who work in informal economies now without work, too.

“This is our opportunity to focus,” Bolles said. “How do we help people re-engage with work? And make it better work, a better economy, and a better set of design heuristics for a world that we all want?”

Bolles posed five key questions—some spurred by impact of the pandemic—on which future of work conversations should focus to make sure it’s a human-centric future.

1. What does an inclusive world of work look like? Rather than seeing our current systems of work as immutable, we need to actually understand those systems and how we want to change them.

2. How can we increase the value of human work? We know that robots and software are going to be fine in the future—but for humans to be fine, we need to design for that very intentionally.

3. How can entrepreneurship help create a better world of work? In many economies the new value that’s created often comes from younger companies; how do we nurture entrepreneurship?

4. What will the intersection of workplace and geography look like? A large percentage of the global workforce is now working from home; what could some of the outcomes of that be? How does gig work fit in?

5. How can we ensure a healthy evolution of work and life? The health and the protection of those at risk is why we shut down our economies, but we need to find a balance that allows people to work while keeping them safe.

Problem-Solving Doesn’t End
The end result these questions are driving towards, and our overarching goal, is maximizing human potential. “If we come up with ways we can continue to do that, we’ll have a much more beneficial future of work,” Bolles said. “We should all be talking about where we can have an impact.”

One small silver lining? We had plenty of problems to solve in the world before ever hearing about coronavirus, and now we have even more. Is the pace of automation accelerating due to the virus? Yes. Are companies finding more ways to automate their processes in order to keep people from getting sick? They are.

But we have a slew of new problems on our hands, and we’re not going to stop needing human skills to solve them (not to mention the new problems that will surely emerge as second- and third-order effects of the shutdowns). If Bolles’ definition of work holds up, we’ve got ours cut out for us.

In an article from April titled The Great Reset, Bolles outlined three phases of the unemployment slump (we’re currently still in the first phase) and what we should be doing to minimize the damage. “The evolution of work is not about what will happen 10 to 20 years from now,” he said. “It’s about what we could be doing differently today.”

Watch Bolles’ talk and those of dozens of other experts for more insights into building a human-centric future of work here.

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Posted in Human Robots

#437103 How to Make Sense of Uncertainty in a ...

As the internet churns with information about Covid-19, about the virus that causes the disease, and about what we’re supposed to do to fight it, it can be difficult to see the forest for the trees. What can we realistically expect for the rest of 2020? And how do we even know what’s realistic?

Today, humanity’s primary, ideal goal is to eliminate the virus, SARS-CoV-2, and Covid-19. Our second-choice goal is to control virus transmission. Either way, we have three big aims: to save lives, to return to public life, and to keep the economy functioning.

To hit our second-choice goal—and maybe even our primary goal—countries are pursuing five major public health strategies. Note that many of these advances cross-fertilize: for example, advances in virus testing and antibody testing will drive data-based prevention efforts.

Five major public health strategies are underway to bring Covid-19 under control and to contain the spread of SARS-CoV-2.
These strategies arise from things we can control based on the things that we know at any given moment. But what about the things we can’t control and don’t yet know?

The biology of the virus and how it interacts with our bodies is what it is, so we should seek to understand it as thoroughly as possible. How long any immunity gained from prior infection lasts—and indeed whether people develop meaningful immunity at all after infection—are open questions urgently in need of greater clarity. Similarly, right now it’s important to focus on understanding rather than making assumptions about environmental factors like seasonality.

But the biggest question on everyone’s lips is, “When?” When will we see therapeutic progress against Covid-19? And when will life get “back to normal”? There are lots of models out there on the internet; which of those models are right? The simple answer is “none of them.” That’s right—it’s almost certain that every model you’ve seen is wrong in at least one detail, if not all of them. But modeling is meant to be a tool for deeper thinking, a way to run mental (and computational) experiments before—and while—taking action. As George E. P. Box famously wrote in 1976, “All models are wrong, but some are useful.”

Here, we’re seeking useful insights, as opposed to exact predictions, which is why we’re pulling back from quantitative details to get at the mindsets that will support agency and hope. To that end, I’ve been putting together timelines that I believe will yield useful expectations for the next year or two—and asking how optimistic I need to be in order to believe a particular timeline.

For a moderately optimistic scenario to be relevant, breakthroughs in science and technology come at paces expected based on previous efforts and assumptions that turn out to be basically correct; accessibility of those breakthroughs increases at a reasonable pace; regulation achieves its desired effects, without major surprises; and compliance with regulations is reasonably high.

In contrast, if I’m being highly optimistic, breakthroughs in science and technology and their accessibility come more quickly than they ever have before; regulation is evidence-based and successful in the first try or two; and compliance with those regulations is high and uniform. If I’m feeling not-so-optimistic, then I anticipate serious setbacks to breakthroughs and accessibility (with the overturning of many important assumptions), repeated failure of regulations to achieve their desired outcomes, and low compliance with those regulations.

The following scenarios outline the things that need to happen in the fight against Covid-19, when I expect to see them, and how confident I feel in those expectations. They focus on North America and Europe because there are data missing about China’s 2019 outbreak and other regions are still early in their outbreaks. Perhaps the most important thing to keep in mind throughout: We know more today than we did yesterday, but we still have much to learn. New knowledge derived from greater study and debate will almost certainly inspire ongoing course corrections.

As you dive into the scenarios below, practice these three mindset shifts. First, defeating Covid-19 will be a marathon, not a sprint. We shouldn’t expect life to look like 2019 for the next year or two—if ever. As Ed Yong wrote recently in The Atlantic, “There won’t be an obvious moment when everything is under control and regular life can safely resume.” Second, remember that you have important things to do for at least a year. And third, we are all in this together. There is no “us” and “them.” We must all be alert, responsive, generous, and strong throughout 2020 and 2021—and willing to throw away our assumptions when scientific evidence invalidates them.

The Middle Way: Moderate Optimism
Let’s start with the case in which I have the most confidence: moderate optimism.

This timeline considers milestones through late 2021, the earliest that I believe vaccines will become available. The “normal” timeline for developing a vaccine for diseases like seasonal flu is 18 months, which leads to my projection that we could potentially have vaccines as soon as 18 months from the first quarter of 2020. While Melinda Gates agrees with that projection, others (including AI) believe that 3 to 5 years is far more realistic, based on past vaccine development and the need to test safety and efficacy in humans. However, repurposing existing vaccines against other diseases—or piggybacking off clever synthetic platforms—could lead to vaccines being available sooner. I tried to balance these considerations for this moderately optimistic scenario. Either way, deploying vaccines at the end of 2021 is probably much later than you may have been led to believe by the hype engine. Again, if you take away only one message from this article, remember that the fight against Covid-19 is a marathon, not a sprint.

Here, I’ve visualized a moderately optimistic scenario as a baseline. Think of these timelines as living guides, as opposed to exact predictions. There are still many unknowns. More or less optimistic views (see below) and new information could shift these timelines forward or back and change the details of the strategies.
Based on current data, I expect that the first wave of Covid-19 cases (where we are now) will continue to subside in many areas, leading governments to ease restrictions in an effort to get people back to work. We’re already seeing movement in that direction, with a variety of benchmarks and changes at state and country levels around the world. But depending on the details of the changes, easing restrictions will probably cause a second wave of sickness (see Germany and Singapore), which should lead governments to reimpose at least some restrictions.

In tandem, therapeutic efforts will be transitioning from emergency treatments to treatments that have been approved based on safety and efficacy data in clinical trials. In a moderately optimistic scenario, assuming clinical trials currently underway yield at least a few positive results, this shift to mostly approved therapies could happen as early as the third or fourth quarter of this year and continue from there. One approval that should come rather quickly is for plasma therapies, in which the blood from people who have recovered from Covid-19 is used as a source of antibodies for people who are currently sick.

Companies around the world are working on both viral and antibody testing, focusing on speed, accuracy, reliability, and wide accessibility. While these tests are currently being run in hospitals and research laboratories, at-home testing is a critical component of the mass testing we’ll need to keep viral spread in check. These are needed to minimize the impact of asymptomatic cases, test the assumption that infection yields resistance to subsequent infection (and whether it lasts), and construct potential immunity passports if this assumption holds. Testing is also needed for contact tracing efforts to prevent further spread and get people back to public life. Finally, it’s crucial to our fundamental understanding of the biology of SARS-CoV-2 and Covid-19.

We need tests that are very reliable, both in the clinic and at home. So, don’t go buying any at-home test kits just yet, even if you find them online. Wait for reliable test kits and deeper understanding of how a test result translates to everyday realities. If we’re moderately optimistic, in-clinic testing will rapidly expand this quarter and/or next, with the possibility of broadly available, high-quality at-home sampling (and perhaps even analysis) thereafter.

Note that testing is not likely to be a “one-and-done” endeavor, as a person’s infection and immunity status change over time. Expect to be testing yourself—and your family—often as we move later into 2020.

Testing data are also going to inform distancing requirements at the country and local levels. In this scenario, restrictions—at some level of stringency—could persist at least through the end of 2020, as most countries are way behind the curve on testing (Iceland is an informative exception). Governments will likely continue to ask citizens to work from home if at all possible; to wear masks or face coverings in public; to employ heightened hygiene and social distancing in workplaces; and to restrict travel and social gatherings. So while it’s likely we’ll be eating in local restaurants again in 2020 in this scenario, at least for a little while, it’s not likely we’ll be heading to big concerts any time soon.

The Extremes: High and Low Optimism
How would high and low levels of optimism change our moderately optimistic timeline? The milestones are the same, but the time required to achieve them is shorter or longer, respectively. Quantifying these shifts is less important than acknowledging and incorporating a range of possibilities into our view. It pays to pay attention to our bias. Here are a few examples of reasonable possibilities that could shift the moderately optimistic timeline.

When vaccines become available
Vaccine repurposing could shorten the time for vaccines to become available; today, many vaccine candidates are in various stages of testing. On the other hand, difficulties in manufacture and distribution, or faster-than-expected mutation of SARS-CoV-2, could slow vaccine development. Given what we know now, I am not strongly concerned about either of these possibilities—drug companies are rapidly expanding their capabilities, and viral mutation isn’t an urgent concern at this time based on sequencing data—but they could happen.

At first, governments will likely supply vaccines to essential workers such as healthcare workers, but it is essential that vaccines become widely available around the world as quickly and as safely as possible. Overall, I suggest a dose of skepticism when reading highly optimistic claims about a vaccine (or multiple vaccines) being available in 2020. Remember, a vaccine is a knockout punch, not a first line of defense for an outbreak.

When testing hits its stride
While I am confident that testing is a critical component of our response to Covid-19, reliability is incredibly important to testing for SARS-CoV-2 and for immunity to the disease, particularly at home. For an individual, a false negative (being told you don’t have antibodies when you really do) could be just as bad as a false positive (being told you do have antibodies when you really don’t). Those errors are compounded when governments are trying to make evidence-based policies for social and physical distancing.

If you’re highly optimistic, high-quality testing will ramp up quickly as companies and scientists innovate rapidly by cleverly combining multiple test modalities, digital signals, and cutting-edge tech like CRISPR. Pop-up testing labs could also take some pressure off hospitals and clinics.

If things don’t go well, reliability issues could hinder testing, manufacturing bottlenecks could limit availability, and both could hamstring efforts to control spread and ease restrictions. And if it turns out that immunity to Covid-19 isn’t working the way we assumed, then we must revisit our assumptions about our path(s) back to public life, as well as our vaccine-development strategies.

How quickly safe and effective treatments appear
Drug development is known to be long, costly, and fraught with failure. It’s not uncommon to see hope in a drug spike early only to be dashed later on down the road. With that in mind, the number of treatments currently under investigation is astonishing, as is the speed through which they’re proceeding through testing. Breakthroughs in a therapeutic area—for example in treating the seriously ill or in reducing viral spread after an infection takes hold—could motivate changes in the focus of distancing regulations.

While speed will save lives, we cannot overlook the importance of knowing a treatment’s efficacy (does it work against Covid-19?) and safety (does it make you sick in a different, or worse, way?). Repurposing drugs that have already been tested for other diseases is speeding innovation here, as is artificial intelligence.

Remarkable collaborations among governments and companies, large and small, are driving innovation in therapeutics and devices such as ventilators for treating the sick.

Whether government policies are effective and responsive
Those of us who have experienced lockdown are eager for it to be over. Businesses, economists, and governments are also eager to relieve the terrible pressure that is being exerted on the global economy. However, lifting restrictions will almost certainly lead to a resurgence in sickness.

Here, the future is hard to model because there are many, many factors at play, and at play differently in different places—including the extent to which individuals actually comply with regulations.

Reliable testing—both in the clinic and at home—is crucial to designing and implementing restrictions, monitoring their effectiveness, and updating them; delays in reliable testing could seriously hamper this design cycle. Lack of trust in governments and/or companies could also suppress uptake. That said, systems are already in place for contact tracing in East Asia. Other governments could learn important lessons, but must also earn—and keep—their citizens’ trust.

Expect to see restrictions descend and then lift in response to changes in the number of Covid-19 cases and in the effectiveness of our prevention strategies. Also expect country-specific and perhaps even area-specific responses that differ from each other. The benefit of this approach? Governments around the world are running perhaps hundreds of real-time experiments and design cycles in balancing health and the economy, and we can learn from the results.

A Way Out
As Jeremy Farrar, head of the Wellcome Trust, told Science magazine, “Science is the exit strategy.” Some of our greatest technological assistance is coming from artificial intelligence, digital tools for collaboration, and advances in biotechnology.

Our exit strategy also needs to include empathy and future visioning—because in the midst of this crisis, we are breaking ground for a new, post-Covid future.

What do we want that future to look like? How will the hard choices we make now about data ethics impact the future of surveillance? Will we continue to embrace inclusiveness and mass collaboration? Perhaps most importantly, will we lay the foundation for successfully confronting future challenges? Whether we’re thinking about the next pandemic (and there will be others) or the cascade of catastrophes that climate change is bringing ever closer—it’s important to remember that we all have the power to become agents of that change.

Special thanks to Ola Kowalewski and Jason Dorrier for significant conversations.

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