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#434823 The Tangled Web of Turning Spider Silk ...

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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Posted in Human Robots

#434818 Watch These Robots Do Tasks You Thought ...

Robots have been masters of manufacturing at speed and precision for decades, but give them a seemingly simple task like stacking shelves, and they quickly get stuck. That’s changing, though, as engineers build systems that can take on the deceptively tricky tasks most humans can do with their eyes closed.

Boston Dynamics is famous for dramatic reveals of robots performing mind-blowing feats that also leave you scratching your head as to what the market is—think the bipedal Atlas doing backflips or Spot the galloping robot dog.

Last week, the company released a video of a robot called Handle that looks like an ostrich on wheels carrying out the seemingly mundane task of stacking boxes in a warehouse.

It might seem like a step backward, but this is exactly the kind of practical task robots have long struggled with. While the speed and precision of industrial robots has seen them take over many functions in modern factories, they’re generally limited to highly prescribed tasks carried out in meticulously-controlled environments.

That’s because despite their mechanical sophistication, most are still surprisingly dumb. They can carry out precision welding on a car or rapidly assemble electronics, but only by rigidly following a prescribed set of motions. Moving cardboard boxes around a warehouse might seem simple to a human, but it actually involves a variety of tasks machines still find pretty difficult—perceiving your surroundings, navigating, and interacting with objects in a dynamic environment.

But the release of this video suggests Boston Dynamics thinks these kinds of applications are close to prime time. Last week the company doubled down by announcing the acquisition of start-up Kinema Systems, which builds computer vision systems for robots working in warehouses.

It’s not the only company making strides in this area. On the same day the video went live, Google unveiled a robot arm called TossingBot that can pick random objects from a box and quickly toss them into another container beyond its reach, which could prove very useful for sorting items in a warehouse. The machine can train on new objects in just an hour or two, and can pick and toss up to 500 items an hour with better accuracy than any of the humans who tried the task.

And an apple-picking robot built by Abundant Robotics is currently on New Zealand farms navigating between rows of apple trees using LIDAR and computer vision to single out ripe apples before using a vacuum tube to suck them off the tree.

In most cases, advances in machine learning and computer vision brought about by the recent AI boom are the keys to these rapidly improving capabilities. Robots have historically had to be painstakingly programmed by humans to solve each new task, but deep learning is making it possible for them to quickly train themselves on a variety of perception, navigation, and dexterity tasks.

It’s not been simple, though, and the application of deep learning in robotics has lagged behind other areas. A major limitation is that the process typically requires huge amounts of training data. That’s fine when you’re dealing with image classification, but when that data needs to be generated by real-world robots it can make the approach impractical. Simulations offer the possibility to run this training faster than real time, but it’s proved difficult to translate policies learned in virtual environments into the real world.

Recent years have seen significant progress on these fronts, though, and the increasing integration of modern machine learning with robotics. In October, OpenAI imbued a robotic hand with human-level dexterity by training an algorithm in a simulation using reinforcement learning before transferring it to the real-world device. The key to ensuring the translation went smoothly was injecting random noise into the simulation to mimic some of the unpredictability of the real world.

And just a couple of weeks ago, MIT researchers demonstrated a new technique that let a robot arm learn to manipulate new objects with far less training data than is usually required. By getting the algorithm to focus on a few key points on the object necessary for picking it up, the system could learn to pick up a previously unseen object after seeing only a few dozen examples (rather than the hundreds or thousands typically required).

How quickly these innovations will trickle down to practical applications remains to be seen, but a number of startups as well as logistics behemoth Amazon are developing robots designed to flexibly pick and place the wide variety of items found in your average warehouse.

Whether the economics of using robots to replace humans at these kinds of menial tasks makes sense yet is still unclear. The collapse of collaborative robotics pioneer Rethink Robotics last year suggests there are still plenty of challenges.

But at the same time, the number of robotic warehouses is expected to leap from 4,000 today to 50,000 by 2025. It may not be long until robots are muscling in on tasks we’ve long assumed only humans could do.

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Posted in Human Robots

#434767 7 Non-Obvious Trends Shaping the Future

When you think of trends that might be shaping the future, the first things that come to mind probably have something to do with technology: Robots taking over jobs. Artificial intelligence advancing and proliferating. 5G making everything faster, connected cities making everything easier, data making everything more targeted.

Technology is undoubtedly changing the way we live, and will continue to do so—probably at an accelerating rate—in the near and far future. But there are other trends impacting the course of our lives and societies, too. They’re less obvious, and some have nothing to do with technology.

For the past nine years, entrepreneur and author Rohit Bhargava has read hundreds of articles across all types of publications, tagged and categorized them by topic, funneled frequent topics into broader trends, analyzed those trends, narrowed them down to the most significant ones, and published a book about them as part of his ‘Non-Obvious’ series. He defines a trend as “a unique curated observation of the accelerating present.”

In an encore session at South by Southwest last week (his initial talk couldn’t fit hundreds of people who wanted to attend, so a re-do was scheduled), Bhargava shared details of his creative process, why it’s hard to think non-obviously, the most important trends of this year, and how to make sure they don’t get the best of you.

Thinking Differently
“Non-obvious thinking is seeing the world in a way other people don’t see it,” Bhargava said. “The secret is curating your ideas.” Curation collects ideas and presents them in a meaningful way; museum curators, for example, decide which works of art to include in an exhibit and how to present them.

For his own curation process, Bhargava uses what he calls the haystack method. Rather than searching for a needle in a haystack, he gathers ‘hay’ (ideas and stories) then uses them to locate and define a ‘needle’ (a trend). “If you spend enough time gathering information, you can put the needle into the middle of the haystack,” he said.

A big part of gathering information is looking for it in places you wouldn’t normally think to look. In his case, that means that on top of reading what everyone else reads—the New York Times, the Washington Post, the Economist—he also buys publications like Modern Farmer, Teen Vogue, and Ink magazine. “It’s like stepping into someone else’s world who’s not like me,” he said. “That’s impossible to do online because everything is personalized.”

Three common barriers make non-obvious thinking hard.

The first is unquestioned assumptions, which are facts or habits we think will never change. When James Dyson first invented the bagless vacuum, he wanted to sell the license to it, but no one believed people would want to spend more money up front on a vacuum then not have to buy bags. The success of Dyson’s business today shows how mistaken that assumption—that people wouldn’t adapt to a product that, at the end of the day, was far more sensible—turned out to be. “Making the wrong basic assumptions can doom you,” Bhargava said.

The second barrier to thinking differently is constant disruption. “Everything is changing as industries blend together,” Bhargava said. “The speed of change makes everyone want everything, all the time, and people expect the impossible.” We’ve come to expect every alternative to be presented to us in every moment, but in many cases this doesn’t serve us well; we’re surrounded by noise and have trouble discerning what’s valuable and authentic.

This ties into the third barrier, which Bhargava calls the believability crisis. “Constant sensationalism makes people skeptical about everything,” he said. With the advent of fake news and technology like deepfakes, we’re in a post-truth, post-fact era, and are in a constant battle to discern what’s real from what’s not.

2019 Trends
Bhargava’s efforts to see past these barriers and curate information yielded 15 trends he believes are currently shaping the future. He shared seven of them, along with thoughts on how to stay ahead of the curve.

Retro Trust
We tend to trust things we have a history with. “People like nostalgic experiences,” Bhargava said. With tech moving as fast as it is, old things are quickly getting replaced by shinier, newer, often more complex things. But not everyone’s jumping on board—and some who’ve been on board are choosing to jump off in favor of what worked for them in the past.

“We’re turning back to vinyl records and film cameras, deliberately downgrading to phones that only text and call,” Bhargava said. In a period of too much change too fast, people are craving familiarity and dependability. To capitalize on that sentiment, entrepreneurs should seek out opportunities for collaboration—how can you build a product that’s new, but feels reliable and familiar?

Muddled Masculinity
Women have increasingly taken on more leadership roles, advanced in the workplace, now own more homes than men, and have higher college graduation rates. That’s all great for us ladies—but not so great for men or, perhaps more generally, for the concept of masculinity.

“Female empowerment is causing confusion about what it means to be a man today,” Bhargava said. “Men don’t know what to do—should they say something? Would that make them an asshole? Should they keep quiet? Would that make them an asshole?”

By encouraging the non-conforming, we can help take some weight off the traditional gender roles, and their corresponding divisions and pressures.

Innovation Envy
Innovation has become an over-used word, to the point that it’s thrown onto ideas and actions that aren’t really innovative at all. “We innovate by looking at someone else and doing the same,” Bhargava said. If an employee brings a radical idea to someone in a leadership role, in many companies the leadership will say they need a case study before implementing the radical idea—but if it’s already been done, it’s not innovative. “With most innovation what ends up happening is not spectacular failure, but irrelevance,” Bhargava said.

He suggests that rather than being on the defensive, companies should play offense with innovation, and when it doesn’t work “fail as if no one’s watching” (often, no one will be).

Artificial Influence
Thanks to social media and other technologies, there are a growing number of fabricated things that, despite not being real, influence how we think. “15 percent of all Twitter accounts may be fake, and there are 60 million fake Facebook accounts,” Bhargava said. There are virtual influencers and even virtual performers.

“Don’t hide the artificial ingredients,” Bhargava advised. “Some people are going to pretend it’s all real. We have to be ethical.” The creators of fabrications meant to influence the way people think, or the products they buy, or the decisions they make, should make it crystal-clear that there aren’t living, breathing people behind the avatars.

Enterprise Empathy
Another reaction to the fast pace of change these days—and the fast pace of life, for that matter—is that empathy is regaining value and even becoming a driver of innovation. Companies are searching for ways to give people a sense of reassurance. The Tesco grocery brand in the UK has a “relaxed lane” for those who don’t want to feel rushed as they check out. Starbucks opened a “signing store” in Washington DC, and most of its regular customers have learned some sign language.

“Use empathy as a principle to help yourself stand out,” Bhargava said. Besides being a good business strategy, “made with empathy” will ideally promote, well, more empathy, a quality there’s often a shortage of.

Robot Renaissance
From automating factory jobs to flipping burgers to cleaning our floors, robots have firmly taken their place in our day-to-day lives—and they’re not going away anytime soon. “There are more situations with robots than ever before,” Bhargava said. “They’re exploring underwater. They’re concierges at hotels.”

The robot revolution feels intimidating. But Bhargava suggests embracing robots with more curiosity than concern. While they may replace some tasks we don’t want replaced, they’ll also be hugely helpful in multiple contexts, from elderly care to dangerous manual tasks.

Similar to retro trust and enterprise empathy, organizations have started to tell their brand’s story to gain customer loyalty. “Stories give us meaning, and meaning is what we need in order to be able to put the pieces together,” Bhargava said. “Stories give us a way of understanding the world.”

Finding the story behind your business, brand, or even yourself, and sharing it openly, can help you connect with people, be they customers, coworkers, or friends.

Tech’s Ripple Effects
While it may not overtly sound like it, most of the trends Bhargava identified for 2019 are tied to technology, and are in fact a sort of backlash against it. Tech has made us question who to trust, how to innovate, what’s real and what’s fake, how to make the best decisions, and even what it is that makes us human.

By being aware of these trends, sharing them, and having conversations about them, we’ll help shape the way tech continues to be built, and thus the way it impacts us down the road.

Image Credit: Rohit Bhargava by Brian Smale Continue reading

Posted in Human Robots

#434673 The World’s Most Valuable AI ...

It recognizes our faces. It knows the videos we might like. And it can even, perhaps, recommend the best course of action to take to maximize our personal health.

Artificial intelligence and its subset of disciplines—such as machine learning, natural language processing, and computer vision—are seemingly becoming integrated into our daily lives whether we like it or not. What was once sci-fi is now ubiquitous research and development in company and university labs around the world.

Similarly, the startups working on many of these AI technologies have seen their proverbial stock rise. More than 30 of these companies are now valued at over a billion dollars, according to data research firm CB Insights, which itself employs algorithms to provide insights into the tech business world.

Private companies with a billion-dollar valuation were so uncommon not that long ago that they were dubbed unicorns. Now there are 325 of these once-rare creatures, with a combined valuation north of a trillion dollars, as CB Insights maintains a running count of this exclusive Unicorn Club.

The subset of AI startups accounts for about 10 percent of the total membership, growing rapidly in just 4 years from 0 to 32. Last year, an unprecedented 17 AI startups broke the billion-dollar barrier, with 2018 also a record year for venture capital into private US AI companies at $9.3 billion, CB Insights reported.

What exactly is all this money funding?

AI Keeps an Eye Out for You
Let’s start with the bad news first.

Facial recognition is probably one of the most ubiquitous applications of AI today. It’s actually a decades-old technology often credited to a man named Woodrow Bledsoe, who used an instrument called a RAND tablet that could semi-autonomously match faces from a database. That was in the 1960s.

Today, most of us are familiar with facial recognition as a way to unlock our smartphones. But the technology has gained notoriety as a surveillance tool of law enforcement, particularly in China.

It’s no secret that the facial recognition algorithms developed by several of the AI unicorns from China—SenseTime, CloudWalk, and Face++ (also known as Megvii)—are used to monitor the country’s 1.3 billion citizens. Police there are even equipped with AI-powered eyeglasses for such purposes.

A fourth billion-dollar Chinese startup, Yitu Technologies, also produces a platform for facial recognition in the security realm, and develops AI systems in healthcare on top of that. For example, its CARE.AITM Intelligent 4D Imaging System for Chest CT can reputedly identify in real time a variety of lesions for the possible early detection of cancer.

The AI Doctor Is In
As Peter Diamandis recently noted, AI is rapidly augmenting healthcare and longevity. He mentioned another AI unicorn from China in this regard—iCarbonX, which plans to use machines to develop personalized health plans for every individual.

A couple of AI unicorns on the hardware side of healthcare are OrCam Technologies and Butterfly. The former, an Israeli company, has developed a wearable device for the vision impaired called MyEye that attaches to one’s eyeglasses. The device can identify people and products, as well as read text, conveying the information through discrete audio.

Butterfly Network, out of Connecticut, has completely upended the healthcare market with a handheld ultrasound machine that works with a smartphone.

“Orcam and Butterfly are amazing examples of how machine learning can be integrated into solutions that provide a step-function improvement over state of the art in ultra-competitive markets,” noted Andrew Byrnes, investment director at Comet Labs, a venture capital firm focused on AI and robotics, in an email exchange with Singularity Hub.

AI in the Driver’s Seat
Comet Labs’ portfolio includes two AI unicorns, Megvii and Pony.ai.

The latter is one of three billion-dollar startups developing the AI technology behind self-driving cars, with the other two being Momenta.ai and Zoox.

Founded in 2016 near San Francisco (with another headquarters in China), Pony.ai debuted its latest self-driving system, called PonyAlpha, last year. The platform uses multiple sensors (LiDAR, cameras, and radar) to navigate its environment, but its “sensor fusion technology” makes things simple by choosing the most reliable sensor data for any given driving scenario.

Zoox is another San Francisco area startup founded a couple of years earlier. In late 2018, it got the green light from the state of California to be the first autonomous vehicle company to transport a passenger as part of a pilot program. Meanwhile, China-based Momenta.ai is testing level four autonomy for its self-driving system. Autonomous driving levels are ranked zero to five, with level five being equal to a human behind the wheel.

The hype around autonomous driving is currently in overdrive, and Byrnes thinks regulatory roadblocks will keep most self-driving cars in idle for the foreseeable future. The exception, he said, is China, which is adopting a “systems” approach to autonomy for passenger transport.

“If [autonomous mobility] solves bigger problems like traffic that can elicit government backing, then that has the potential to go big fast,” he said. “This is why we believe Pony.ai will be a winner in the space.”

AI in the Back Office
An AI-powered technology that perhaps only fans of the cult classic Office Space might appreciate has suddenly taken the business world by storm—robotic process automation (RPA).

RPA companies take the mundane back office work, such as filling out invoices or processing insurance claims, and turn it over to bots. The intelligent part comes into play because these bots can tackle unstructured data, such as text in an email or even video and pictures, in order to accomplish an increasing variety of tasks.

Both Automation Anywhere and UiPath are older companies, founded in 2003 and 2005, respectively. However, since just 2017, they have raised nearly a combined $1 billion in disclosed capital.

Cybersecurity Embraces AI
Cybersecurity is another industry where AI is driving investment into startups. Sporting imposing names like CrowdStrike, Darktrace, and Tanium, these cybersecurity companies employ different machine-learning techniques to protect computers and other IT assets beyond the latest software update or virus scan.

Darktrace, for instance, takes its inspiration from the human immune system. Its algorithms can purportedly “learn” the unique pattern of each device and user on a network, detecting emerging problems before things spin out of control.

All three companies are used by major corporations and governments around the world. CrowdStrike itself made headlines a few years ago when it linked the hacking of the Democratic National Committee email servers to the Russian government.

Looking Forward
I could go on, and introduce you to the world’s most valuable startup, a Chinese company called Bytedance that is valued at $75 billion for news curation and an app to create 15-second viral videos. But that’s probably not where VC firms like Comet Labs are generally putting their money.

Byrnes sees real value in startups that are taking “data-driven approaches to problems specific to unique industries.” Take the example of Chicago-based unicorn Uptake Technologies, which analyzes incoming data from machines, from wind turbines to tractors, to predict problems before they occur with the machinery. A not-yet unicorn called PingThings in the Comet Labs portfolio does similar predictive analytics for the energy utilities sector.

“One question we like asking is, ‘What does the state of the art look like in your industry in three to five years?’” Byrnes said. “We ask that a lot, then we go out and find the technology-focused teams building those things.”

Image Credit: Andrey Suslov / Shutterstock.com Continue reading

Posted in Human Robots

#434580 How Genome Sequencing and Senolytics Can ...

The causes of aging are extremely complex and unclear. With the dramatic demonetization of genome reading and editing over the past decade, and Big Pharma, startups, and the FDA starting to face aging as a disease, we are starting to find practical ways to extend our healthspan.

Here, in Part 2 of a series of blogs on longevity and vitality, I explore how genome sequencing and editing, along with new classes of anti-aging drugs, are augmenting our biology to further extend our healthy lives.

In this blog I’ll cover two classes of emerging technologies:

Genome Sequencing and Editing;
Senolytics, Nutraceuticals & Pharmaceuticals.

Let’s dive in.

Genome Sequencing & Editing
Your genome is the software that runs your body.

A sequence of 3.2 billion letters makes you “you.” These base pairs of A’s, T’s, C’s, and G’s determine your hair color, your height, your personality, your propensity to disease, your lifespan, and so on.

Until recently, it’s been very difficult to rapidly and cheaply “read” these letters—and even more difficult to understand what they mean.

Since 2001, the cost to sequence a whole human genome has plummeted exponentially, outpacing Moore’s Law threefold. From an initial cost of $3.7 billion, it dropped to $10 million in 2006, and to $5,000 in 2012.

Today, the cost of genome sequencing has dropped below $500, and according to Illumina, the world’s leading sequencing company, the process will soon cost about $100 and take about an hour to complete.

This represents one of the most powerful and transformative technology revolutions in healthcare.

When we understand your genome, we’ll be able to understand how to optimize “you.”

We’ll know the perfect foods, the perfect drugs, the perfect exercise regimen, and the perfect supplements, just for you.
We’ll understand what microbiome types, or gut flora, are ideal for you (more on this in a later blog).
We’ll accurately predict how specific sedatives and medicines will impact you.
We’ll learn which diseases and illnesses you’re most likely to develop and, more importantly, how to best prevent them from developing in the first place (rather than trying to cure them after the fact).

CRISPR Gene Editing
In addition to reading the human genome, scientists can now edit a genome using a naturally-occurring biological system discovered in 1987 called CRISPR/Cas9.

Short for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9, the editing system was adapted from a naturally-occurring defense system found in bacteria.

Here’s how it works:

The bacteria capture snippets of DNA from invading viruses (or bacteriophage) and use them to create DNA segments known as CRISPR arrays.
The CRISPR arrays allow the bacteria to “remember” the viruses (or closely related ones), and defend against future invasions.
If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA. The bacteria then use Cas9 to cut the DNA apart, which disables the virus.

Most importantly, CRISPR is cheap, quick, easy to use, and more accurate than all previous gene editing methods. As a result, CRISPR/Cas9 has swept through labs around the world as the way to edit a genome.

A short search in the literature will show an exponential rise in the number of CRISPR-related publications and patents.

2018: Filled With CRISPR Breakthroughs
Early results are impressive. Researchers from the University of Chicago recently used CRISPR to genetically engineer cocaine resistance into mice.

Researchers at the University of Texas Southwestern Medical Center used CRISPR to reverse the gene defect causing Duchenne muscular dystrophy (DMD) in dogs (DMD is the most common fatal genetic disease in children).

With great power comes great responsibility, and moral and ethical dilemmas.

In 2015, Chinese scientists sparked global controversy when they first edited human embryo cells in the lab with the goal of modifying genes that would make the child resistant to smallpox, HIV, and cholera.

Three years later, in November 2018, researcher He Jiankui informed the world that the first set of CRISPR-engineered female twins had been delivered.

To accomplish his goal, Jiankui deleted a region of a receptor on the surface of white blood cells known as CCR5, introducing a rare, natural genetic variation that makes it more difficult for HIV to infect its favorite target, white blood cells.

Setting aside the significant ethical conversations, CRISPR will soon provide us the tools to eliminate diseases, create hardier offspring, produce new environmentally resistant crops, and even wipe out pathogens.

Senolytics, Nutraceuticals & Pharmaceuticals
Over the arc of your life, the cells in your body divide until they reach what is known as the Hayflick limit, or the number of times a normal human cell population will divide before cell division stops, which is typically about 50 divisions.

What normally follows next is programmed cell death or destruction by the immune system. A very small fraction of cells, however, become senescent cells and evade this fate to linger indefinitely.

These lingering cells secrete a potent mix of molecules that triggers chronic inflammation, damages the surrounding tissue structures, and changes the behavior of nearby cells for the worse.

Senescent cells appear to be one of the root causes of aging, causing everything from fibrosis and blood vessel calcification, to localized inflammatory conditions such as osteoarthritis, to diminished lung function.

Fortunately, both the scientific and entrepreneurial communities have begun to work on senolytic therapies, moving the technology for selectively destroying senescent cells out of the laboratory and into a half-dozen startup companies.

Prominent companies in the field include the following:

Unity Biotechnology is developing senolytic medicines to selectively eliminate senescent cells with an initial focus on delivering localized therapy in osteoarthritis, ophthalmology and pulmonary disease.
Oisin Biotechnologiesis pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.
SIWA Therapeuticsis working on an immunotherapy approach to the problem of senescent cells.

In recent years, researchers have identified or designed a handful of senolytic compounds that can curb aging by regulating senescent cells. Two of these drugs that have gained mainstay research traction are rapamycin and metformin.

Originally extracted from bacteria found on Easter Island, Rapamycin acts on the m-TOR (mechanistic target of rapamycin) pathway to selectively block a key protein that facilitates cell division.

Currently, rapamycin derivatives are widely used as immunosuppression in organ and bone marrow transplants. Research now suggests that use results in prolonged lifespan and enhanced cognitive and immune function.

PureTech Health subsidiary resTORbio (which started 2018 by going public) is working on a rapamycin-based drug intended to enhance immunity and reduce infection. Their clinical-stage RTB101 drug works by inhibiting part of the mTOR pathway.

Results of the drug’s recent clinical trial include:

Decreased incidence of infection
Improved influenza vaccination response
A 30.6 percent decrease in respiratory tract infections

Impressive, to say the least.

Metformin is a widely-used generic drug for mitigating liver sugar production in Type 2 diabetes patients.

Researchers have found that Metformin also reduces oxidative stress and inflammation, which otherwise increase as we age.

There is strong evidence that Metformin can augment cellular regeneration and dramatically mitigate cellular senescence by reducing both oxidative stress and inflammation.

Over 100 studies registered on ClinicalTrials.gov are currently following up on strong evidence of Metformin’s protective effect against cancer.

Nutraceuticals and NAD+
Beyond cellular senescence, certain critical nutrients and proteins tend to decline as a function of age. Nutraceuticals combat aging by supplementing and replenishing these declining nutrient levels.

NAD+ exists in every cell, participating in every process from DNA repair to creating the energy vital for cellular processes. It’s been shown that NAD+ levels decline as we age.

The Elysium Health Basis supplement aims to elevate NAD+ levels in the body to extend one’s lifespan. Elysium’s clinical study reports that Basis increases NAD+ levels consistently by a sustained 40 percent.

These are just a taste of the tremendous momentum that longevity and aging technology has right now. As artificial intelligence and quantum computing transform how we decode our DNA and how we discover drugs, genetics and pharmaceuticals will become truly personalized.

The next blog in this series will demonstrate how artificial intelligence is converging with genetics and pharmaceuticals to transform how we approach longevity, aging, and vitality.

We are edging closer to a dramatically extended healthspan—where 100 is the new 60. What will you create, where will you explore, and how will you spend your time if you are able to add an additional 40 healthy years to your life?

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