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#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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#435161 Less Like Us: An Alternate Theory of ...
The question of whether an artificial general intelligence will be developed in the future—and, if so, when it might arrive—is controversial. One (very uncertain) estimate suggests 2070 might be the earliest we could expect to see such technology.
Some futurists point to Moore’s Law and the increasing capacity of machine learning algorithms to suggest that a more general breakthrough is just around the corner. Others suggest that extrapolating exponential improvements in hardware is unwise, and that creating narrow algorithms that can beat humans at specialized tasks brings us no closer to a “general intelligence.”
But evolution has produced minds like the human mind at least once. Surely we could create artificial intelligence simply by copying nature, either by guided evolution of simple algorithms or wholesale emulation of the human brain.
Both of these ideas are far easier to conceive of than they are to achieve. The 302 neurons of the nematode worm’s brain are still an extremely difficult engineering challenge, let alone the 86 billion in a human brain.
Leaving aside these caveats, though, many people are worried about artificial general intelligence. Nick Bostrom’s influential book on superintelligence imagines it will be an agent—an intelligence with a specific goal. Once such an agent reaches a human level of intelligence, it will improve itself—increasingly rapidly as it gets smarter—in pursuit of whatever goal it has, and this “recursive self-improvement” will lead it to become superintelligent.
This “intelligence explosion” could catch humans off guard. If the initial goal is poorly specified or malicious, or if improper safety features are in place, or if the AI decides it would prefer to do something else instead, humans may be unable to control our own creation. Bostrom gives examples of how a seemingly innocuous goal, such as “Make everyone happy,” could be misinterpreted; perhaps the AI decides to drug humanity into a happy stupor, or convert most of the world into computing infrastructure to pursue its goal.
Drexler and Comprehensive AI Services
These are increasingly familiar concerns for an AI that behaves like an agent, seeking to achieve its goal. There are dissenters to this picture of how artificial general intelligence might arise. One notable alternative point of view comes from Eric Drexler, famous for his work on molecular nanotechnology and Engines of Creation, the book that popularized it.
With respect to AI, Drexler believes our view of an artificial intelligence as a single “agent” that acts to maximize a specific goal is too narrow, almost anthropomorphizing AI, or modeling it as a more realistic route towards general intelligence. Instead, he proposes “Comprehensive AI Services” (CAIS) as an alternative route to artificial general intelligence.
What does this mean? Drexler’s argument is that we should look more closely at how machine learning and AI algorithms are actually being developed in the real world. The optimization effort is going into producing algorithms that can provide services and perform tasks like translation, music recommendations, classification, medical diagnoses, and so forth.
AI-driven improvements in technology, argues Drexler, will lead to a proliferation of different algorithms: technology and software improvement, which can automate increasingly more complicated tasks. Recursive improvement in this regime is already occurring—take the newer versions of AlphaGo, which can learn to improve themselves by playing against previous versions.
Many Smart Arms, No Smart Brain
Instead of relying on some unforeseen breakthrough, the CAIS model of AI just assumes that specialized, narrow AI will continue to improve at performing each of its tasks, and the range of tasks that machine learning algorithms will be able to perform will become wider. Ultimately, once a sufficient number of tasks have been automated, the services that an AI will provide will be so comprehensive that they will resemble a general intelligence.
One could then imagine a “general” intelligence as simply an algorithm that is extremely good at matching the task you ask it to perform to the specialized service algorithm that can perform that task. Rather than acting like a single brain that strives to achieve a particular goal, the central AI would be more like a search engine, looking through the tasks it can perform to find the closest match and calling upon a series of subroutines to achieve the goal.
For Drexler, this is inherently a safety feature. Rather than Bostrom’s single, impenetrable, conscious and superintelligent brain (which we must try to psychoanalyze in advance without really knowing what it will look like), we have a network of capabilities. If you don’t want your system to perform certain tasks, you can simply cut it off from access to those services. There is no superintelligent consciousness to outwit or “trap”: more like an extremely high-level programming language that can respond to complicated commands by calling upon one of the myriad specialized algorithms that have been developed by different groups.
This skirts the complex problem of consciousness and all of the sticky moral quandaries that arise in making minds that might be like ours. After all, if you could simulate a human mind, you could simulate it experiencing unimaginable pain. Black Mirror-esque dystopias where emulated minds have no rights and are regularly “erased” or forced to labor in dull and repetitive tasks, hove into view.
Drexler argues that, in this world, there is no need to ever build a conscious algorithm. Yet it seems likely that, at some point, humans will attempt to simulate our own brains, if only in the vain attempt to pursue immortality. This model cannot hold forever. Yet its proponents argue that any world in which we could develop general AI would probably also have developed superintelligent capabilities in a huge range of different tasks, such as computer programming, natural language understanding, and so on. In other words, CAIS arrives first.
The Future In Our Hands?
Drexler argues that his model already incorporates many of the ideas from general AI development. In the marketplace, algorithms compete all the time to perform these services: they undergo the same evolutionary pressures that lead to “higher intelligence,” but the behavior that’s considered superior is chosen by humans, and the nature of the “general intelligence” is far more shaped by human decision-making and human programmers. Development in AI services could still be rapid and disruptive.
But in Drexler’s case, the research and development capacity comes from humans and organizations driven by the desire to improve algorithms that are performing individualized and useful tasks, rather than from a conscious AI recursively reprogramming and improving itself.
In other words, this vision does not absolve us of the responsibility of making our AI safe; if anything, it gives us a greater degree of responsibility. As more and more complex “services” are automated, performing what used to be human jobs at superhuman speed, the economic disruption will be severe.
Equally, as machine learning is trusted to carry out more complex decisions, avoiding algorithmic bias becomes crucial. Shaping each of these individual decision-makers—and trying to predict the complex ways they might interact with each other—is no less daunting a task than specifying the goal for a hypothetical, superintelligent, God-like AI. Arguably, the consequences of the “misalignment” of these services algorithms are already multiplying around us.
The CAIS model bridges the gap between real-world AI, machine learning developments, and real-world safety considerations, as well as the speculative world of superintelligent agents and the safety considerations involved with controlling their behavior. We should keep our minds open as to what form AI and machine learning will take, and how it will influence our societies—and we must take care to ensure that the systems we create don’t end up forcing us all to live in a world of unintended consequences.
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