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Spider-Man is one of the most popular superheroes of all time. It’s a bit surprising given that one of the more common phobias is arachnophobia—a debilitating fear of spiders.
Perhaps more fantastical is that young Peter Parker, a brainy high school science nerd, seemingly developed overnight the famous web-shooters and the synthetic spider silk that he uses to swing across the cityscape like Tarzan through the jungle.
That’s because scientists have been trying for decades to replicate spider silk, a material that is five times stronger than steel, among its many superpowers. In recent years, researchers have been untangling the protein-based fiber’s structure down to the molecular level, leading to new insights and new potential for eventual commercial uses.
The applications for such a material seem near endless. There’s the more futuristic visions, like enabling robotic “muscles” for human-like movement or ensnaring real-life villains with a Spider-Man-like web. Near-term applications could include the biomedical industry, such as bandages and adhesives, and as a replacement textile for everything from rope to seat belts to parachutes.
Spinning Synthetic Spider Silk
Randy Lewis has been studying the properties of spider silk and developing methods for producing it synthetically for more than three decades. In the 1990s, his research team was behind cloning the first spider silk gene, as well as the first to identify and sequence the proteins that make up the six different silks that web slingers make. Each has different mechanical properties.
“So our thought process was that you could take that information and begin to to understand what made them strong and what makes them stretchy, and why some are are very stretchy and some are not stretchy at all, and some are stronger and some are weaker,” explained Lewis, a biology professor at Utah State University and director of the Synthetic Spider Silk Lab, in an interview with Singularity Hub.
Spiders are naturally territorial and cannibalistic, so any intention to farm silk naturally would likely end in an orgy of arachnid violence. Instead, Lewis and company have genetically modified different organisms to produce spider silk synthetically, including inserting a couple of web-making genes into the genetic code of goats. The goats’ milk contains spider silk proteins.
The lab also produces synthetic spider silk through a fermentation process not entirely dissimilar to brewing beer, but using genetically modified bacteria to make the desired spider silk proteins. A similar technique has been used for years to make a key enzyme in cheese production. More recently, companies are using transgenic bacteria to make meat and milk proteins, entirely bypassing animals in the process.
The same fermentation technology is used by a chic startup called Bolt Threads outside of San Francisco that has raised more than $200 million for fashionable fibers made out of synthetic spider silk it calls Microsilk. (The company is also developing a second leather-like material, Mylo, using the underground root structure of mushrooms known as mycelium.)
Lewis’ lab also uses transgenic silkworms to produce a kind of composite material made up of the domesticated insect’s own silk proteins and those of spider silk. “Those have some fairly impressive properties,” Lewis said.
The researchers are even experimenting with genetically modified alfalfa. One of the big advantages there is that once the spider silk protein has been extracted, the remaining protein could be sold as livestock feed. “That would bring the cost of spider silk protein production down significantly,” Lewis said.
Building a Better Web
Producing synthetic spider silk isn’t the problem, according to Lewis, but the ability to do it at scale commercially remains a sticking point.
Another challenge is “weaving” the synthetic spider silk into usable products that can take advantage of the material’s marvelous properties.
“It is possible to make silk proteins synthetically, but it is very hard to assemble the individual proteins into a fiber or other material forms,” said Markus Buehler, head of the Department of Civil and Environmental Engineering at MIT, in an email to Singularity Hub. “The spider has a complex spinning duct in which silk proteins are exposed to physical forces, chemical gradients, the combination of which generates the assembly of molecules that leads to silk fibers.”
Buehler recently co-authored a paper in the journal Science Advances that found dragline spider silk exhibits different properties in response to changes in humidity that could eventually have applications in robotics.
Specifically, spider silk suddenly contracts and twists above a certain level of relative humidity, exerting enough force to “potentially be competitive with other materials being explored as actuators—devices that move to perform some activity such as controlling a valve,” according to a press release.
Studying Spider Silk Up Close
Recent studies at the molecular level are helping scientists learn more about the unique properties of spider silk, which may help researchers develop materials with extraordinary capabilities.
For example, scientists at Arizona State University used magnetic resonance tools and other instruments to image the abdomen of a black widow spider. They produced what they called the first molecular-level model of spider silk protein fiber formation, providing insights on the nanoparticle structure. The research was published last October in Proceedings of the National Academy of Sciences.
A cross section of the abdomen of a black widow (Latrodectus Hesperus) spider used in this study at Arizona State University. Image Credit: Samrat Amin.
Also in 2018, a study presented in Nature Communications described a sort of molecular clamp that binds the silk protein building blocks, which are called spidroins. The researchers observed for the first time that the clamp self-assembles in a two-step process, contributing to the extensibility, or stretchiness, of spider silk.
Another team put the spider silk of a brown recluse under an atomic force microscope, discovering that each strand, already 1,000 times thinner than a human hair, is made up of thousands of nanostrands. That helps explain its extraordinary tensile strength, though technique is also a factor, as the brown recluse uses a special looping method to reinforce its silk strands. The study also appeared last year in the journal ACS Macro Letters.
Making Spider Silk Stick
Buehler said his team is now trying to develop better and faster predictive methods to design silk proteins using artificial intelligence.
“These new methods allow us to generate new protein designs that do not naturally exist and which can be explored to optimize certain desirable properties like torsional actuation, strength, bioactivity—for example, tissue engineering—and others,” he said.
Meanwhile, Lewis’ lab has discovered a method that allows it to solubilize spider silk protein in what is essentially a water-based solution, eschewing acids or other toxic compounds that are normally used in the process.
That enables the researchers to develop materials beyond fiber, including adhesives that “are better than an awful lot of the current commercial adhesives,” Lewis said, as well as coatings that could be used to dampen vibrations, for example.
“We’re making gels for various kinds of of tissue regeneration, as well as drug delivery, and things like that,” he added. “So we’ve expanded the use profile from something beyond fibers to something that is a much more extensive portfolio of possible kinds of materials.”
And, yes, there’s even designs at the Synthetic Spider Silk Lab for developing a Spider-Man web-slinger material. The US Navy is interested in non-destructive ways of disabling an enemy vessel, such as fouling its propeller. The project also includes producing synthetic proteins from the hagfish, an eel-like critter that exudes a gelatinous slime when threatened.
Lewis said that while the potential for spider silk is certainly headline-grabbing, he cautioned that much of the hype is not focused on the unique mechanical properties that could lead to advances in healthcare and other industries.
“We want to see spider silk out there because it’s a unique material, not because it’s got marketing appeal,” he said.
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Training a doctor takes years of grueling work in universities and hospitals. Building a doctor may be as easy as teaching an AI how to read.
Artificial intelligence has taken another step towards becoming an integral part of 21st-century medicine. New research out of Guangzhou, China, published February 11th in Nature Medicine Letters, has demonstrated a natural-language processing AI that is capable of out-performing rookie pediatricians in diagnosing common childhood ailments.
The massive study examined the electronic health records (EHR) from nearly 600,000 patients over an 18-month period at the Guangzhou Women and Children’s Medical Center and then compared AI-generated diagnoses against new assessments from physicians with a range of experience.
The verdict? On average, the AI was noticeably more accurate than junior physicians and nearly as reliable as the more senior ones. These results are the latest demonstration that artificial intelligence is on the cusp of becoming a healthcare staple on a global scale.
Less Like a Computer, More Like a Person
To outshine human doctors, the AI first had to become more human. Like IBM’s Watson, the pediatric AI leverages natural language processing, in essence “reading” written notes from EHRs not unlike how a human doctor would review those same records. But the similarities to human doctors don’t end there. The AI is a machine learning classifier (MLC), capable of placing the information learned from the EHRs into categories to improve performance.
Like traditionally-trained pediatricians, the AI broke cases down into major organ groups and infection areas (upper/lower respiratory, gastrointestinal, etc.) before breaking them down even further into subcategories. It could then develop associations between various symptoms and organ groups and use those associations to improve its diagnoses. This hierarchical approach mimics the deductive reasoning human doctors employ.
Another key strength of the AI developed for this study was the enormous size of the dataset collected to teach it: 1,362,559 outpatient visits from 567,498 patients yielded some 101.6 million data points for the MLC to devour on its quest for pediatric dominance. This allowed the AI the depth of learning needed to distinguish and accurately select from the 55 different diagnosis codes across the various organ groups and subcategories.
When comparing against the human doctors, the study used 11,926 records from an unrelated group of children, giving both the MLC and the 20 humans it was compared against an even playing field. The results were clear: while cohorts of senior pediatricians performed better than the AI, junior pediatricians (those with 3-15 years of experience) were outclassed.
Helping, Not Replacing
While the research used a competitive analysis to measure the success of the AI, the results should be seen as anything but hostile to human doctors. The near future of artificial intelligence in medicine will see these machine learning programs augment, not replace, human physicians. The authors of the study specifically call out augmentation as the key short-term application of their work. Triaging incoming patients via intake forms, performing massive metastudies using EHRs, providing rapid ‘second opinions’—the applications for an AI doctor that is better-but-not-the-best are as varied as the healthcare industry itself.
That’s only considering how artificial intelligence could make a positive impact immediately upon implementation. It’s easy to see how long-term use of a diagnostic assistant could reshape the way modern medical institutions approach their work.
Look at how the MLC results fit snugly between the junior and senior physician groups. Essentially, it took nearly 15 years before a physician could consistently out-diagnose the machine. That’s a decade and a half wherein an AI diagnostic assistant would be an invaluable partner—both as a training tool and a safety measure. Likewise, on the other side of the experience curve you have physicians whose performance could be continuously leveraged to improve the AI’s effectiveness. This is a clear opportunity for a symbiotic relationship, with humans and machines each assisting the other as they mature.
Closer to Us, But Still Dependent on Us
No matter the ultimate application, the AI doctors of the future are drawing nearer to us step by step. This latest research is a demonstration that artificial intelligence can mimic the results of human deductive reasoning even in some of the most complex and important decision-making processes. True, the MLC required input from humans to function; both the initial data points and the cases used to evaluate the AI depended on EHRs written by physicians. While every effort was made to design a test schema that removed any indication of the eventual diagnosis, some “data leakage” is bound to occur.
In other words, when AIs use human-created data, they inherit human insight to some degree. Yet the progress made in machine imaging, chatbots, sensors, and other fields all suggest that this dependence on human input is more about where we are right now than where we could be in the near future.
Data, and More Data
That near future may also have some clear winners and losers. For now, those winners seem to be the institutions that can capture and apply the largest sets of data. With a rapidly digitized society gathering incredible amounts of data, China has a clear advantage. Combined with their relatively relaxed approach to privacy, they are likely to continue as one of the driving forces behind machine learning and its applications. So too will Google/Alphabet with their massive medical studies. Data is the uranium in this AI arms race, and everyone seems to be scrambling to collect more.
In a global community that seems increasingly aware of the potential problems arising from this need for and reliance on data, it’s nice to know there’ll be an upside as well. The technology behind AI medical assistants is looking more and more mature—even if we are still struggling to find exactly where, when, and how that technology should first become universal.
Yet wherever we see the next push to make AI a standard tool in a real-world medical setting, I have little doubt it will greatly improve the lives of human patients. Today Doctor AI is performing as well as a human colleague with more than 10 years of experience. By next year or so, it may take twice as long for humans to be competitive. And in a decade, the combined medical knowledge of all human history may be a tool as common as a stethoscope in your doctor’s hands.
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When it comes to the future of healthcare, perhaps the only technology more powerful than CRISPR is artificial intelligence.
Over the past five years, healthcare AI startups around the globe raised over $4.3 billion across 576 deals, topping all other industries in AI deal activity.
During this same period, the FDA has given 70 AI healthcare tools and devices ‘fast-tracked approval’ because of their ability to save both lives and money.
The pace of AI-augmented healthcare innovation is only accelerating.
In Part 3 of this blog series on longevity and vitality, I cover the different ways in which AI is augmenting our healthcare system, enabling us to live longer and healthier lives.
In this blog, I’ll expand on:
Machine learning and drug design
Artificial intelligence and big data in medicine
Healthcare, AI & China
Let’s dive in.
Machine Learning in Drug Design
What if AI systems, specifically neural networks, could predict the design of novel molecules (i.e. medicines) capable of targeting and curing any disease?
Imagine leveraging cutting-edge artificial intelligence to accomplish with 50 people what the pharmaceutical industry can barely do with an army of 5,000.
And what if these molecules, accurately engineered by AIs, always worked? Such a feat would revolutionize our $1.3 trillion global pharmaceutical industry, which currently holds a dismal record of 1 in 10 target drugs ever reaching human trials.
It’s no wonder that drug development is massively expensive and slow. It takes over 10 years to bring a new drug to market, with costs ranging from $2.5 billion to $12 billion.
This inefficient, slow-to-innovate, and risk-averse industry is a sitting duck for disruption in the years ahead.
One of the hottest startups in digital drug discovery today is Insilico Medicine. Leveraging AI in its end-to-end drug discovery pipeline, Insilico Medicine aims to extend healthy longevity through drug discovery and aging research.
Their comprehensive drug discovery engine uses millions of samples and multiple data types to discover signatures of disease, identify the most promising protein targets, and generate perfect molecules for these targets. These molecules either already exist or can be generated de novo with the desired set of parameters.
In late 2018, Insilico’s CEO Dr. Alex Zhavoronkov announced the groundbreaking result of generating novel molecules for a challenging protein target with an unprecedented hit rate in under 46 days. This included both synthesis of the molecules and experimental validation in a biological test system—an impressive feat made possible by converging exponential technologies.
Underpinning Insilico’s drug discovery pipeline is a novel machine learning technique called Generative Adversarial Networks (GANs), used in combination with deep reinforcement learning.
Generating novel molecular structures for diseases both with and without known targets, Insilico is now pursuing drug discovery in aging, cancer, fibrosis, Parkinson’s disease, Alzheimer’s disease, ALS, diabetes, and many others. Once rolled out, the implications will be profound.
Dr. Zhavoronkov’s ultimate goal is to develop a fully-automated Health-as-a-Service (HaaS) and Longevity-as-a-Service (LaaS) engine.
Once plugged into the services of companies from Alibaba to Alphabet, such an engine would enable personalized solutions for online users, helping them prevent diseases and maintain optimal health.
Insilico, alongside other companies tackling AI-powered drug discovery, truly represents the application of the 6 D’s. What was once a prohibitively expensive and human-intensive process is now rapidly becoming digitized, dematerialized, demonetized and, perhaps most importantly, democratized.
Companies like Insilico can now do with a fraction of the cost and personnel what the pharmaceutical industry can barely accomplish with thousands of employees and a hefty bill to foot.
As I discussed in my blog on ‘The Next Hundred-Billion-Dollar Opportunity,’ Google’s DeepMind has now turned its neural networks to healthcare, entering the digitized drug discovery arena.
In 2017, DeepMind achieved a phenomenal feat by matching the fidelity of medical experts in correctly diagnosing over 50 eye disorders.
And just a year later, DeepMind announced a new deep learning tool called AlphaFold. 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.
Artificial Intelligence and Data Crunching
AI is especially powerful in analyzing massive quantities of data to uncover patterns and insights that can save lives. Take WAVE, for instance. Every year, over 400,000 patients die prematurely in US hospitals as a result of heart attack or respiratory failure.
Yet these patients don’t die without leaving plenty of clues. Given information overload, however, human physicians and nurses alone have no way of processing and analyzing all necessary data in time to save these patients’ lives.
Enter WAVE, an algorithm that can process enough data to offer a six-hour early warning of patient deterioration.
Just last year, the FDA approved WAVE as an AI-based predictive patient surveillance system to predict and thereby prevent sudden death.
Another highly valuable yet difficult-to-parse mountain of medical data comprises the 2.5 million medical papers published each year.
For some time, it has become physically impossible for a human physician to read—let alone remember—all of the relevant published data.
To counter this compounding conundrum, Johnson & Johnson is teaching IBM Watson to read and understand scientific papers that detail clinical trial outcomes.
Enriching Watson’s data sources, Apple is also partnering with IBM to provide access to health data from mobile apps.
One such Watson system contains 40 million documents, ingesting an average of 27,000 new documents per day, and providing insights for thousands of users.
After only one year, Watson’s successful diagnosis rate of lung cancer has reached 90 percent, compared to the 50 percent success rate of human doctors.
But what about the vast amount of unstructured medical patient data that populates today’s ancient medical system? This includes medical notes, prescriptions, audio interview transcripts, and pathology and radiology reports.
In late 2018, Amazon announced a new HIPAA-eligible machine learning service that digests and parses unstructured data into categories, such as patient diagnoses, treatments, dosages, symptoms and signs.
Taha Kass-Hout, Amazon’s senior leader in health care and artificial intelligence, told the Wall Street Journal that internal tests demonstrated that the software even performs as well as or better than other published efforts.
On the heels of this announcement, Amazon confirmed it was teaming up with the Fred Hutchinson Cancer Research Center to evaluate “millions of clinical notes to extract and index medical conditions.”
Having already driven extraordinary algorithmic success rates in other fields, data is the healthcare industry’s goldmine for future innovation.
Healthcare, AI & China
In 2017, the Chinese government published its ambitious national plan to become a global leader in AI research by 2030, with healthcare listed as one of four core research areas during the first wave of the plan.
Just a year earlier, China began centralizing healthcare data, tackling a major roadblock to developing longevity and healthcare technologies (particularly AI systems): scattered, dispersed, and unlabeled patient data.
Backed by the Chinese government, China’s largest tech companies—particularly Tencent—have now made strong entrances into healthcare.
Just recently, Tencent participated in a $154 million megaround for China-based healthcare AI unicorn iCarbonX.
Hoping to develop a complete digital representation of your biological self, iCarbonX has acquired numerous US personalized medicine startups.
Considering Tencent’s own Miying healthcare AI platform—aimed at assisting healthcare institutions in AI-driven cancer diagnostics—Tencent is quickly expanding into the drug discovery space, participating in two multimillion-dollar, US-based AI drug discovery deals just this year.
China’s biggest, second-order move into the healthtech space comes through Tencent’s WeChat. In the course of a mere few years, already 60 percent of the 38,000 medical institutions registered on WeChat allow patients to digitally book appointments through Tencent’s mobile platform. At the same time, 2,000 Chinese hospitals accept WeChat payments.
Tencent has additionally partnered with the U.K.’s Babylon Health, a virtual healthcare assistant startup whose app now allows Chinese WeChat users to message their symptoms and receive immediate medical feedback.
Similarly, Alibaba’s healthtech focus started in 2016 when it released its cloud-based AI medical platform, ET Medical Brain, to augment healthcare processes through everything from diagnostics to intelligent scheduling.
As Nvidia CEO Jensen Huang has stated, “Software ate the world, but AI is going to eat software.” Extrapolating this statement to a more immediate implication, AI will first eat healthcare, resulting in dramatic acceleration of longevity research and an amplification of the human healthspan.
Next week, I’ll continue to explore this concept of AI systems in healthcare.
Particularly, I’ll expand on how we’re acquiring and using the data for these doctor-augmenting AI systems: from ubiquitous biosensors, to the mobile healthcare revolution, and finally, to the transformative power of the health nucleus.
As AI and other exponential technologies increase our healthspan by 30 to 40 years, how will you leverage these same exponential technologies to take on your moonshots and live out your massively transformative purpose?
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