Tag Archives: nature
#431559 Drug Discovery AI to Scour a Universe of ...
On a dark night, away from city lights, the stars of the Milky Way can seem uncountable. Yet from any given location no more than 4,500 are visible to the naked eye. Meanwhile, our galaxy has 100–400 billion stars, and there are even more galaxies in the universe.
The numbers of the night sky are humbling. And they give us a deep perspective…on drugs.
Yes, this includes wow-the-stars-are-freaking-amazing-tonight drugs, but also the kinds of drugs that make us well again when we’re sick. The number of possible organic compounds with “drug-like” properties dwarfs the number of stars in the universe by over 30 orders of magnitude.
Next to this multiverse of possibility, the chemical configurations scientists have made into actual medicines are like the smattering of stars you’d glimpse downtown.
But for good reason.
Exploring all that potential drug-space is as humanly impossible as exploring all of physical space, and even if we could, most of what we’d find wouldn’t fit our purposes. Still, the idea that wonder drugs must surely lurk amid the multitudes is too tantalizing to ignore.
Which is why, Alex Zhavoronkov said at Singularity University’s Exponential Medicine in San Diego last week, we should use artificial intelligence to do more of the legwork and speed discovery. This, he said, could be one of the next big medical applications for AI.
Dogs, Diagnosis, and Drugs
Zhavoronkov is CEO of Insilico Medicine and CSO of the Biogerontology Research Foundation. Insilico is one of a number of AI startups aiming to accelerate drug discovery with AI.
In recent years, Zhavoronkov said, the now-famous machine learning technique, deep learning, has made progress on a number of fronts. Algorithms that can teach themselves to play games—like DeepMind’s AlphaGo Zero or Carnegie Mellon’s poker playing AI—are perhaps the most headline-grabbing of the bunch. But pattern recognition was the thing that kicked deep learning into overdrive early on, when machine learning algorithms went from struggling to tell dogs and cats apart to outperforming their peers and then their makers in quick succession.
[Watch this video for an AI update from Neil Jacobstein, chair of Artificial Intelligence and Robotics at Singularity University.]
In medicine, deep learning algorithms trained on databases of medical images can spot life-threatening disease with equal or greater accuracy than human professionals. There’s even speculation that AI, if we learn to trust it, could be invaluable in diagnosing disease. And, as Zhavoronkov noted, with more applications and a longer track record that trust is coming.
“Tesla is already putting cars on the street,” Zhavoronkov said. “Three-year, four-year-old technology is already carrying passengers from point A to point B, at 100 miles an hour, and one mistake and you’re dead. But people are trusting their lives to this technology.”
“So, why don’t we do it in pharma?”
Trial and Error and Try Again
AI wouldn’t drive the car in pharmaceutical research. It’d be an assistant that, when paired with a chemist or two, could fast-track discovery by screening more possibilities for better candidates.
There’s plenty of room to make things more efficient, according to Zhavoronkov.
Drug discovery is arduous and expensive. Chemists sift tens of thousands of candidate compounds for the most promising to synthesize. Of these, a handful will go on to further research, fewer will make it to human clinical trials, and a fraction of those will be approved.
The whole process can take many years and cost hundreds of millions of dollars.
This is a big data problem if ever there was one, and deep learning thrives on big data. Early applications have shown their worth unearthing subtle patterns in huge training databases. Although drug-makers already use software to sift compounds, such software requires explicit rules written by chemists. AI’s allure is its ability to learn and improve on its own.
“There are two strategies for AI-driven innovation in pharma to ensure you get better molecules and much faster approvals,” Zhavoronkov said. “One is looking for the needle in the haystack, and another one is creating a new needle.”
To find the needle in the haystack, algorithms are trained on large databases of molecules. Then they go looking for molecules with attractive properties. But creating a new needle? That’s a possibility enabled by the generative adversarial networks Zhavoronkov specializes in.
Such algorithms pit two neural networks against each other. One generates meaningful output while the other judges whether this output is true or false, Zhavoronkov said. Together, the networks generate new objects like text, images, or in this case, molecular structures.
“We started employing this particular technology to make deep neural networks imagine new molecules, to make it perfect right from the start. So, to come up with really perfect needles,” Zhavoronkov said. “[You] can essentially go to this [generative adversarial network] and ask it to create molecules that inhibit protein X at concentration Y, with the highest viability, specific characteristics, and minimal side effects.”
Zhavoronkov believes AI can find or fabricate more needles from the array of molecular possibilities, freeing human chemists to focus on synthesizing only the most promising. If it works, he hopes we can increase hits, minimize misses, and generally speed the process up.
Proof’s in the Pudding
Insilico isn’t alone on its drug-discovery quest, nor is it a brand new area of interest.
Last year, a Harvard group published a paper on an AI that similarly suggests drug candidates. The software trained on 250,000 drug-like molecules and used its experience to generate new molecules that blended existing drugs and made suggestions based on desired properties.
An MIT Technology Review article on the subject highlighted a few of the challenges such systems may still face. The results returned aren’t always meaningful or easy to synthesize in the lab, and the quality of these results, as always, is only as good as the data dined upon.
Stanford chemistry professor and Andreesen Horowitz partner, Vijay Pande, said that images, speech, and text—three of the areas deep learning’s made quick strides in—have better, cleaner data. Chemical data, on the other hand, is still being optimized for deep learning. Also, while there are public databases, much data still lives behind closed doors at private companies.
To overcome the challenges and prove their worth, Zhavoronkov said, his company is very focused on validating the tech. But this year, skepticism in the pharmaceutical industry seems to be easing into interest and investment.
AI drug discovery startup Exscientia inked a deal with Sanofi for $280 million and GlaxoSmithKline for $42 million. Insilico is also partnering with GlaxoSmithKline, and Numerate is working with Takeda Pharmaceutical. Even Google may jump in. According to an article in Nature outlining the field, the firm’s deep learning project, Google Brain, is growing its biosciences team, and industry watchers wouldn’t be surprised to see them target drug discovery.
With AI and the hardware running it advancing rapidly, the greatest potential may yet be ahead. Perhaps, one day, all 1060 molecules in drug-space will be at our disposal. “You should take all the data you have, build n new models, and search as much of that 1060 as possible” before every decision you make, Brandon Allgood, CTO at Numerate, told Nature.
Today’s projects need to live up to their promises, of course, but Zhavoronkov believes AI will have a big impact in the coming years, and now’s the time to integrate it. “If you are working for a pharma company, and you’re still thinking, ‘Okay, where is the proof?’ Once there is a proof, and once you can see it to believe it—it’s going to be too late,” he said.
Image Credit: Klavdiya Krinichnaya / Shutterstock.com Continue reading
Posted in Human Robots
#431427 Why the Best Healthcare Hacks Are the ...
Technology has the potential to solve some of our most intractable healthcare problems. In fact, it’s already doing so, with inventions getting us closer to a medical Tricorder, and progress toward 3D printed organs, and AIs that can do point-of-care diagnosis.
No doubt these applications of cutting-edge tech will continue to push the needle on progress in medicine, diagnosis, and treatment. But what if some of the healthcare hacks we need most aren’t high-tech at all?
According to Dr. Darshak Sanghavi, this is exactly the case. In a talk at Singularity University’s Exponential Medicine last week, Sanghavi told the audience, “We often think in extremely complex ways, but I think a lot of the improvements in health at scale can be done in an analog way.”
Sanghavi is the chief medical officer and senior vice president of translation at OptumLabs, and was previously director of preventive and population health at the Center for Medicare and Medicaid Innovation, where he oversaw the development of large pilot programs aimed at improving healthcare costs and quality.
“How can we improve health at scale, not for only a small number of people, but for entire populations?” Sanghavi asked. With programs that benefit a small group of people, he explained, what tends to happen is that the average health of a population improves, but the disparities across the group worsen.
“My mantra became, ‘The denominator is everybody,’” he said. He shared details of some low-tech but crucial fixes he believes could vastly benefit the US healthcare system.
1. Regulatory Hacking
Healthcare regulations are ultimately what drive many aspects of patient care, for better or worse. Worse because the mind-boggling complexity of regulations (exhibit A: the Affordable Care Act is reportedly about 20,000 pages long) can make it hard for people to get the care they need at a cost they can afford, but better because, as Sanghavi explained, tweaking these regulations in the right way can result in across-the-board improvements in a given population’s health.
An adjustment to Medicare hospitalization rules makes for a relevant example. The code was updated to state that if people who left the hospital were re-admitted within 30 days, that hospital had to pay a penalty. The result was hospitals taking more care to ensure patients were released not only in good health, but also with a solid understanding of what they had to do to take care of themselves going forward. “Here, arguably the writing of a few lines of regulatory code resulted in a remarkable decrease in 30-day re-admissions, and the savings of several billion dollars,” Sanghavi said.
2. Long-Term Focus
It’s easy to focus on healthcare hacks that have immediate, visible results—but what about fixes whose benefits take years to manifest? How can we motivate hospitals, regulators, and doctors to take action when they know they won’t see changes anytime soon?
“I call this the reality TV problem,” Sanghavi said. “Reality shows don’t really care about who’s the most talented recording artist—they care about getting the most viewers. That is exactly how we think about health care.”
Sanghavi’s team wanted to address this problem for heart attacks. They found they could reliably determine someone’s 10-year risk of having a heart attack based on a simple risk profile. Rather than monitoring patients’ cholesterol, blood pressure, weight, and other individual factors, the team took the average 10-year risk across entire provider panels, then made providers responsible for controlling those populations.
“Every percentage point you lower that risk, by hook or by crook, you get some people to stop smoking, you get some people on cholesterol medication. It’s patient-centered decision-making, and the provider then makes money. This is the world’s first predictive analytic model, at scale, that’s actually being paid for at scale,” he said.
3. Aligned Incentives
If hospitals are held accountable for the health of the communities they’re based in, those hospitals need to have the right incentives to follow through. “Hospitals have to spend money on community benefit, but linking that benefit to a meaningful population health metric can catalyze significant improvements,” Sanghavi said.
Darshak Sanghavi speaking at Singularity University’s 2017 Exponential Medicine Summit in San Diego, CA.
He used smoking cessation as an example. His team designed a program where hospitals were given a score (determined by the Centers for Disease Control and Prevention) based on the smoking rate in the counties where they’re located, then given monetary incentives to improve their score. Improving their score, in turn, resulted in better health for their communities, which meant fewer patients to treat for smoking-related health problems.
4. Social Determinants of Health
Social determinants of health include factors like housing, income, family, and food security. The answer to getting people to pay attention to these factors at scale, and creating aligned incentives, Sanghavi said, is “Very simple. We just have to measure it to start with, and measure it universally.”
His team was behind a $157 million pilot program called Accountable Health Communities that went live this year. The program requires all Medicare and Medicaid beneficiaries get screened for various social determinants of health. With all that data being collected, analysts can pinpoint local trends, then target funds to address the underlying problem, whether it’s job training, drug use, or nutritional education. “You’re then free to invest the dollars where they’re needed…this is how we can improve health at scale, with very simple changes in the incentive structures that are created,” he said.
5. ‘Securitizing’ Public Health
Sanghavi’s final point tied back to his discussion of aligning incentives. As misguided as it may seem, the reality is that financial incentives can make a huge difference in healthcare outcomes, from both a patient and a provider perspective.
Sanghavi’s team did an experiment in which they created outcome benchmarks for three major health problems that exist across geographically diverse areas: smoking, adolescent pregnancy, and binge drinking. The team proposed measuring the baseline of these issues then creating what they called a social impact bond. If communities were able to lower their frequency of these conditions by a given percent within a stated period of time, they’d get paid for it.
“What that did was essentially say, ‘you have a buyer for this outcome if you can achieve it,’” Sanghavi said. “And you can try to get there in any way you like.” The program is currently in CMS clearance.
AI and Robots Not Required
Using robots to perform surgery and artificial intelligence to diagnose disease will undoubtedly benefit doctors and patients around the US and the world. But Sanghavi’s talk made it clear that our healthcare system needs much more than this, and that improving population health on a large scale is really a low-tech project—one involving more regulatory and financial innovation than technological innovation.
“The things that get measured are the things that get changed,” he said. “If we choose the right outcomes to predict long-term benefit, and we pay for those outcomes, that’s the way to make progress.”
Image Credit: Wonderful Nature / Shutterstock.com Continue reading
Posted in Human Robots
#431385 Here’s How to Get to Conscious ...
“We cannot be conscious of what we are not conscious of.” – Julian Jaynes, The Origin of Consciousness in the Breakdown of the Bicameral Mind
Unlike the director leads you to believe, the protagonist of Ex Machina, Andrew Garland’s 2015 masterpiece, isn’t Caleb, a young programmer tasked with evaluating machine consciousness. Rather, it’s his target Ava, a breathtaking humanoid AI with a seemingly child-like naïveté and an enigmatic mind.
Like most cerebral movies, Ex Machina leaves the conclusion up to the viewer: was Ava actually conscious? In doing so, it also cleverly avoids a thorny question that has challenged most AI-centric movies to date: what is consciousness, and can machines have it?
Hollywood producers aren’t the only people stumped. As machine intelligence barrels forward at breakneck speed—not only exceeding human performance on games such as DOTA and Go, but doing so without the need for human expertise—the question has once more entered the scientific mainstream.
Are machines on the verge of consciousness?
This week, in a review published in the prestigious journal Science, cognitive scientists Drs. Stanislas Dehaene, Hakwan Lau and Sid Kouider of the Collège de France, University of California, Los Angeles and PSL Research University, respectively, argue: not yet, but there is a clear path forward.
The reason? Consciousness is “resolutely computational,” the authors say, in that it results from specific types of information processing, made possible by the hardware of the brain.
There is no magic juice, no extra spark—in fact, an experiential component (“what is it like to be conscious?”) isn’t even necessary to implement consciousness.
If consciousness results purely from the computations within our three-pound organ, then endowing machines with a similar quality is just a matter of translating biology to code.
Much like the way current powerful machine learning techniques heavily borrow from neurobiology, the authors write, we may be able to achieve artificial consciousness by studying the structures in our own brains that generate consciousness and implementing those insights as computer algorithms.
From Brain to Bot
Without doubt, the field of AI has greatly benefited from insights into our own minds, both in form and function.
For example, deep neural networks, the architecture of algorithms that underlie AlphaGo’s breathtaking sweep against its human competitors, are loosely based on the multi-layered biological neural networks that our brain cells self-organize into.
Reinforcement learning, a type of “training” that teaches AIs to learn from millions of examples, has roots in a centuries-old technique familiar to anyone with a dog: if it moves toward the right response (or result), give a reward; otherwise ask it to try again.
In this sense, translating the architecture of human consciousness to machines seems like a no-brainer towards artificial consciousness. There’s just one big problem.
“Nobody in AI is working on building conscious machines because we just have nothing to go on. We just don’t have a clue about what to do,” said Dr. Stuart Russell, the author of Artificial Intelligence: A Modern Approach in a 2015 interview with Science.
Multilayered consciousness
The hard part, long before we can consider coding machine consciousness, is figuring out what consciousness actually is.
To Dehaene and colleagues, consciousness is a multilayered construct with two “dimensions:” C1, the information readily in mind, and C2, the ability to obtain and monitor information about oneself. Both are essential to consciousness, but one can exist without the other.
Say you’re driving a car and the low fuel light comes on. Here, the perception of the fuel-tank light is C1—a mental representation that we can play with: we notice it, act upon it (refill the gas tank) and recall and speak about it at a later date (“I ran out of gas in the boonies!”).
“The first meaning we want to separate (from consciousness) is the notion of global availability,” explains Dehaene in an interview with Science. When you’re conscious of a word, your whole brain is aware of it, in a sense that you can use the information across modalities, he adds.
But C1 is not just a “mental sketchpad.” It represents an entire architecture that allows the brain to draw multiple modalities of information from our senses or from memories of related events, for example.
Unlike subconscious processing, which often relies on specific “modules” competent at a defined set of tasks, C1 is a global workspace that allows the brain to integrate information, decide on an action, and follow through until the end.
Like The Hunger Games, what we call “conscious” is whatever representation, at one point in time, wins the competition to access this mental workspace. The winners are shared among different brain computation circuits and are kept in the spotlight for the duration of decision-making to guide behavior.
Because of these features, C1 consciousness is highly stable and global—all related brain circuits are triggered, the authors explain.
For a complex machine such as an intelligent car, C1 is a first step towards addressing an impending problem, such as a low fuel light. In this example, the light itself is a type of subconscious signal: when it flashes, all of the other processes in the machine remain uninformed, and the car—even if equipped with state-of-the-art visual processing networks—passes by gas stations without hesitation.
With C1 in place, the fuel tank would alert the car computer (allowing the light to enter the car’s “conscious mind”), which in turn checks the built-in GPS to search for the next gas station.
“We think in a machine this would translate into a system that takes information out of whatever processing module it’s encapsulated in, and make it available to any of the other processing modules so they can use the information,” says Dehaene. “It’s a first sense of consciousness.”
Meta-cognition
In a way, C1 reflects the mind’s capacity to access outside information. C2 goes introspective.
The authors define the second facet of consciousness, C2, as “meta-cognition:” reflecting on whether you know or perceive something, or whether you just made an error (“I think I may have filled my tank at the last gas station, but I forgot to keep a receipt to make sure”). This dimension reflects the link between consciousness and sense of self.
C2 is the level of consciousness that allows you to feel more or less confident about a decision when making a choice. In computational terms, it’s an algorithm that spews out the probability that a decision (or computation) is correct, even if it’s often experienced as a “gut feeling.”
C2 also has its claws in memory and curiosity. These self-monitoring algorithms allow us to know what we know or don’t know—so-called “meta-memory,” responsible for that feeling of having something at the tip of your tongue. Monitoring what we know (or don’t know) is particularly important for children, says Dehaene.
“Young children absolutely need to monitor what they know in order to…inquire and become curious and learn more,” he explains.
The two aspects of consciousness synergize to our benefit: C1 pulls relevant information into our mental workspace (while discarding other “probable” ideas or solutions), while C2 helps with long-term reflection on whether the conscious thought led to a helpful response.
Going back to the low fuel light example, C1 allows the car to solve the problem in the moment—these algorithms globalize the information, so that the car becomes aware of the problem.
But to solve the problem, the car would need a “catalog of its cognitive abilities”—a self-awareness of what resources it has readily available, for example, a GPS map of gas stations.
“A car with this sort of self-knowledge is what we call having C2,” says Dehaene. Because the signal is globally available and because it’s being monitored in a way that the machine is looking at itself, the car would care about the low gas light and behave like humans do—lower fuel consumption and find a gas station.
“Most present-day machine learning systems are devoid of any self-monitoring,” the authors note.
But their theory seems to be on the right track. The few examples whereby a self-monitoring system was implemented—either within the structure of the algorithm or as a separate network—the AI has generated “internal models that are meta-cognitive in nature, making it possible for an agent to develop a (limited, implicit, practical) understanding of itself.”
Towards conscious machines
Would a machine endowed with C1 and C2 behave as if it were conscious? Very likely: a smartcar would “know” that it’s seeing something, express confidence in it, report it to others, and find the best solutions for problems. If its self-monitoring mechanisms break down, it may also suffer “hallucinations” or even experience visual illusions similar to humans.
Thanks to C1 it would be able to use the information it has and use it flexibly, and because of C2 it would know the limit of what it knows, says Dehaene. “I think (the machine) would be conscious,” and not just merely appearing so to humans.
If you’re left with a feeling that consciousness is far more than global information sharing and self-monitoring, you’re not alone.
“Such a purely functional definition of consciousness may leave some readers unsatisfied,” the authors acknowledge.
“But we’re trying to take a radical stance, maybe simplifying the problem. Consciousness is a functional property, and when we keep adding functions to machines, at some point these properties will characterize what we mean by consciousness,” Dehaene concludes.
Image Credit: agsandrew / Shutterstock.com Continue reading
Posted in Human Robots
#431243 Does Our Survival Depend on Relentless ...
Malthus had a fever dream in the 1790s. While the world was marveling in the first manifestations of modern science and technology and the industrial revolution that was just beginning, he was concerned. He saw the exponential growth in the human population as a terrible problem for the species—an existential threat. He was afraid the human population would overshoot the availability of resources, and then things would really hit the fan.
“Famine seems to be the last, the most dreadful resource of nature. The power of population is so superior to the power of the earth to produce subsistence for man, that premature death must in some shape or other visit the human race. The vices of mankind are active and able ministers of depopulation.”
So Malthus wrote in his famous text, an essay on the principles of population.
But Malthus was wrong. Not just in his proposed solution, which was to stop giving aid and food to the poor so that they wouldn’t explode in population. His prediction was also wrong: there was no great, overwhelming famine that caused the population to stay at the levels of the 1790s. Instead, the world population—with a few dips—has continued to grow exponentially ever since. And it’s still growing.
There have concurrently been developments in agriculture and medicine and, in the 20th century, the Green Revolution, in which Norman Borlaug ensured that countries adopted high-yield varieties of crops—the first precursors to modern ideas of genetically engineering food to produce better crops and more growth. The world was able to produce an astonishing amount of food—enough, in the modern era, for ten billion people. It is only a grave injustice in the way that food is distributed that means 12 percent of the world goes hungry, and we still have starvation. But, aside from that, we were saved by the majesty of another kind of exponential growth; the population grew, but the ability to produce food grew faster.
In so much of the world around us today, there’s the same old story. Take exploitation of fossil fuels: here, there is another exponential race. The exponential growth of our ability to mine coal, extract natural gas, refine oil from ever more complex hydrocarbons: this is pitted against our growing appetite. The stock market is built on exponential growth; you cannot provide compound interest unless the economy grows by a certain percentage a year.
“This relentless and ruthless expectation—that technology will continue to improve in ways we can’t foresee—is not just baked into share prices, but into the very survival of our species.”
When the economy fails to grow exponentially, it’s considered a crisis: a financial catastrophe. This expectation penetrates down to individual investors. In the cryptocurrency markets—hardly immune from bubbles, the bull-and-bear cycle of economics—the traders’ saying is “Buy the hype, sell the news.” Before an announcement is made, the expectation of growth, of a boost—the psychological shift—is almost invariably worth more than whatever the major announcement turns out to be. The idea of growth is baked into the share price, to the extent that even good news can often cause the price to dip when it’s delivered.
In the same way, this relentless and ruthless expectation—that technology will continue to improve in ways we can’t foresee—is not just baked into share prices, but into the very survival of our species. A third of Earth’s soil has been acutely degraded due to agriculture; we are looming on the brink of a topsoil crisis. In less relentless times, we may have tried to solve the problem by letting the fields lie fallow for a few years. But that’s no longer an option: if we do so, people will starve. Instead, we look to a second Green Revolution—genetically modified crops, or hydroponics—to save us.
Climate change is considered by many to be an existential threat. The Intergovernmental Panel on Climate Change has already put their faith in the exponential growth of technology. Many of the scenarios where they can successfully imagine the human race dealing with the climate crisis involve the development and widespread deployment of carbon capture and storage technology. Our hope for the future already has built-in expectations of exponential growth in our technology in this field. Alongside this, to reduce carbon emissions to zero on the timescales we need to, we will surely require new technologies in renewable energy, energy efficiency, and electrification of the transport system.
Without exponential growth in technology continuing, then, we are doomed. Humanity finds itself on a treadmill that’s rapidly accelerating, with the risk of plunging into the abyss if we can’t keep up the pace. Yet this very acceleration could also pose an existential threat. As our global system becomes more interconnected and complex, chaos theory takes over: the economics of a town in Macedonia can influence a US presidential election; critical infrastructure can be brought down by cybercriminals.
New threats, such as biotechnology, nanotechnology, or a generalized artificial intelligence, could put incredible power—power over the entire species—into the hands of a small number of people. We are faced with a paradox: the continued existence of our system depends on the exponential growth of our capacities outpacing the exponential growth of our needs and desires. Yet this very growth will create threats that are unimaginably larger than any humans have faced before in history.
“It is necessary that we understand the consequences and prospects for exponential growth: that we understand the nature of the race that we’re in.”
Neo-Luddites may find satisfaction in rejecting the ill-effects of technology, but they will still live in a society where technology is the lifeblood that keeps the whole system pumping. Now, more than ever, it is necessary that we understand the consequences and prospects for exponential growth: that we understand the nature of the race that we’re in.
If we decide that limitless exponential growth on a finite planet is unsustainable, we need to plan for the transition to a new way of living before our ability to accelerate runs out. If we require new technologies or fields of study to enable this growth to continue, we must focus our efforts on these before anything else. If we want to survive the 21st century without major catastrophe, we don’t have a choice but to understand it. Almost by default, we’re all accelerationists now.
Image Credit: focal point / Shutterstock.com Continue reading
Posted in Human Robots