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#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.
Rapamycin
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
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.
Conclusion
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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Posted in Human Robots
#434569 From Parkour to Surgery, Here Are the ...
The robot revolution may not be here quite yet, but our mechanical cousins have made some serious strides. And now some of the leading experts in the field have provided a rundown of what they see as the 10 most exciting recent developments.
Compiled by the editors of the journal Science Robotics, the list includes some of the most impressive original research and innovative commercial products to make a splash in 2018, as well as a couple from 2017 that really changed the game.
1. Boston Dynamics’ Atlas doing parkour
It seems like barely a few months go by without Boston Dynamics rewriting the book on what a robot can and can’t do. Last year they really outdid themselves when they got their Atlas humanoid robot to do parkour, leaping over logs and jumping between wooden crates.
Atlas’s creators have admitted that the videos we see are cherry-picked from multiple attempts, many of which don’t go so well. But they say they’re meant to be inspirational and aspirational rather than an accurate picture of where robotics is today. And combined with the company’s dog-like Spot robot, they are certainly pushing boundaries.
2. Intuitive Surgical’s da Vinci SP platform
Robotic surgery isn’t new, but the technology is improving rapidly. Market leader Intuitive’s da Vinci surgical robot was first cleared by the FDA in 2000, but since then it’s come a long way, with the company now producing three separate systems.
The latest addition is the da Vinci SP (single port) system, which is able to insert three instruments into the body through a single 2.5cm cannula (tube) bringing a whole new meaning to minimally invasive surgery. The system was granted FDA clearance for urological procedures last year, and the company has now started shipping the new system to customers.
3. Soft robot that navigates through growth
Roboticists have long borrowed principles from the animal kingdom, but a new robot design that mimics the way plant tendrils and fungi mycelium move by growing at the tip has really broken the mold on robot navigation.
The editors point out that this is the perfect example of bio-inspired design; the researchers didn’t simply copy nature, they took a general principle and expanded on it. The tube-like robot unfolds from the front as pneumatic pressure is applied, but unlike a plant, it can grow at the speed of an animal walking and can navigate using visual feedback from a camera.
4. 3D printed liquid crystal elastomers for soft robotics
Soft robotics is one of the fastest-growing sub-disciplines in the field, but powering these devices without rigid motors or pumps is an ongoing challenge. A variety of shape-shifting materials have been proposed as potential artificial muscles, including liquid crystal elastomeric actuators.
Harvard engineers have now demonstrated that these materials can be 3D printed using a special ink that allows the designer to easily program in all kinds of unusual shape-shifting abilities. What’s more, their technique produces actuators capable of lifting significantly more weight than previous approaches.
5. Muscle-mimetic, self-healing, and hydraulically amplified actuators
In another effort to find a way to power soft robots, last year researchers at the University of Colorado Boulder designed a series of super low-cost artificial muscles that can lift 200 times their own weight and even heal themselves.
The devices rely on pouches filled with a liquid that makes them contract with the force and speed of mammalian skeletal muscles when a voltage is applied. The most promising for robotics applications is the so-called Peano-HASEL, which features multiple rectangular pouches connected in series that contract linearly, just like real muscle.
6. Self-assembled nanoscale robot from DNA
While you may think of robots as hulking metallic machines, a substantial number of scientists are working on making nanoscale robots out of DNA. And last year German researchers built the first remote-controlled DNA robotic arm.
They created a length of tightly-bound DNA molecules to act as the arm and attached it to a DNA base plate via a flexible joint. Because DNA carries a charge, they were able to get the arm to swivel around like the hand of a clock by applying a voltage and switch direction by reversing that voltage. The hope is that this arm could eventually be used to build materials piece by piece at the nanoscale.
7. DelFly nimble bioinspired robotic flapper
Robotics doesn’t only borrow from biology—sometimes it gives back to it, too. And a new flapping-winged robot designed by Dutch engineers that mimics the humble fruit fly has done just that, by revealing how the animals that inspired it carry out predator-dodging maneuvers.
The lab has been building flapping robots for years, but this time they ditched the airplane-like tail used to control previous incarnations. Instead, they used insect-inspired adjustments to the motions of its twin pairs of flapping wings to hover, pitch, and roll with the agility of a fruit fly. That has provided a useful platform for investigating insect flight dynamics, as well as more practical applications.
8. Soft exosuit wearable robot
Exoskeletons could prevent workplace injuries, help people walk again, and even boost soldiers’ endurance. Strapping on bulky equipment isn’t ideal, though, so researchers at Harvard are working on a soft exoskeleton that combines specially-designed textiles, sensors, and lightweight actuators.
And last year the team made an important breakthrough by combining their novel exoskeleton with a machine-learning algorithm that automatically tunes the device to the user’s particular walking style. Using physiological data, it is able to adjust when and where the device needs to deliver a boost to the user’s natural movements to improve walking efficiency.
9. Universal Robots (UR) e-Series Cobots
Robots in factories are nothing new. The enormous mechanical arms you see in car factories normally have to be kept in cages to prevent them from accidentally crushing people. In recent years there’s been growing interest in “co-bots,” collaborative robots designed to work side-by-side with their human colleagues and even learn from them.
Earlier this year saw the demise of ReThink robotics, the pioneer of the approach. But the simple single arm devices made by Danish firm Universal Robotics are becoming ubiquitous in workshops and warehouses around the world, accounting for about half of global co-bot sales. Last year they released their latest e-Series, with enhanced safety features and force/torque sensing.
10. Sony’s aibo
After a nearly 20-year hiatus, Sony’s robotic dog aibo is back, and it’s had some serious upgrades. As well as a revamp to its appearance, the new robotic pet takes advantage of advances in AI, with improved environmental and command awareness and the ability to develop a unique character based on interactions with its owner.
The editors note that this new context awareness mark the device out as a significant evolution in social robots, which many hope could aid in childhood learning or provide companionship for the elderly.
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Posted in Human Robots
#433939 The Promise—and Complications—of ...
Every year, for just a few days in a major city, a small team of roboticists get to live the dream: ordering around their own personal robot butlers. In carefully-constructed replicas of a restaurant scene or a domestic setting, these robots perform any number of simple algorithmic tasks. “Get the can of beans from the shelf. Greet the visitors to the museum. Help the humans with their shopping. Serve the customers at the restaurant.”
This is Robocup @ Home, the annual tournament where teams of roboticists put their autonomous service robots to the test for practical domestic applications. The tasks seem simple and mundane, but considering the technology required reveals that they’re really not.
The Robot Butler Contest
Say you want a robot to fetch items in the supermarket. In a crowded, noisy environment, the robot must understand your commands, ask for clarification, and map out and navigate an unfamiliar environment, avoiding obstacles and people as it does so. Then it must recognize the product you requested, perhaps in a cluttered environment, perhaps in an unfamiliar orientation. It has to grasp that product appropriately—recall that there are entire multi-million-dollar competitions just dedicated to developing robots that can grasp a range of objects—and then return it to you.
It’s a job so simple that a child could do it—and so complex that teams of smart roboticists can spend weeks programming and engineering, and still end up struggling to complete simplified versions of this task. Of course, the child has the advantage of millions of years of evolutionary research and development, while the first robots that could even begin these tasks were only developed in the 1970s.
Even bearing this in mind, Robocup @ Home can feel like a place where futurist expectations come crashing into technologist reality. You dream of a smooth-voiced, sardonic JARVIS who’s already made your favorite dinner when you come home late from work; you end up shouting “remember the biscuits” at a baffled, ungainly droid in aisle five.
Caring for the Elderly
Famously, Japan is one of the most robo-enthusiastic nations in the world; they are the nation that stunned us all with ASIMO in 2000, and several studies have been conducted into the phenomenon. It’s no surprise, then, that humanoid robotics should be seriously considered as a solution to the crisis of the aging population. The Japanese government, as part of its robots strategy, has already invested $44 million in their development.
Toyota’s Human Support Robot (HSR-2) is a simple but programmable robot with a single arm; it can be remote-controlled to pick up objects and can monitor patients. HSR-2 has become the default robot for use in Robocup @ Home tournaments, at least in tasks that involve manipulating objects.
Alongside this, Toyota is working on exoskeletons to assist people in walking after strokes. It may surprise you to learn that nurses suffer back injuries more than any other occupation, at roughly three times the rate of construction workers, due to the day-to-day work of lifting patients. Toyota has a Care Assist robot/exoskeleton designed to fix precisely this problem by helping care workers with the heavy lifting.
The Home of the Future
The enthusiasm for domestic robotics is easy to understand and, in fact, many startups already sell robots marketed as domestic helpers in some form or another. In general, though, they skirt the immensely complicated task of building a fully capable humanoid robot—a task that even Google’s skunk-works department gave up on, at least until recently.
It’s plain to see why: far more research and development is needed before these domestic robots could be used reliably and at a reasonable price. Consumers with expectations inflated by years of science fiction saturation might find themselves frustrated as the robots fail to perform basic tasks.
Instead, domestic robotics efforts fall into one of two categories. There are robots specialized to perform a domestic task, like iRobot’s Roomba, which stuck to vacuuming and became the most successful domestic robot of all time by far.
The tasks need not necessarily be simple, either: the impressive but expensive automated kitchen uses the world’s most dexterous hands to cook meals, providing it can recognize the ingredients. Other robots focus on human-robot interaction, like Jibo: they essentially package the abilities of a voice assistant like Siri, Cortana, or Alexa to respond to simple questions and perform online tasks in a friendly, dynamic robot exterior.
In this way, the future of domestic automation starts to look a lot more like smart homes than a robot or domestic servant. General robotics is difficult in the same way that general artificial intelligence is difficult; competing with humans, the great all-rounders, is a challenge. Getting superhuman performance at a more specific task, however, is feasible and won’t cost the earth.
Individual startups without the financial might of a Google or an Amazon can develop specialized robots, like Seven Dreamers’ laundry robot, and hope that one day it will form part of a network of autonomous robots that each have a role to play in the household.
Domestic Bliss?
The Smart Home has been a staple of futurist expectations for a long time, to the extent that movies featuring smart homes out of control are already a cliché. But critics of the smart home idea—and of the internet of things more generally—tend to focus on the idea that, more often than not, software just adds an additional layer of things that can break (NSFW), in exchange for minimal added convenience. A toaster that can short-circuit is bad enough, but a toaster that can refuse to serve you toast because its firmware is updating is something else entirely.
That’s before you even get into the security vulnerabilities, which are all the more important when devices are installed in your home and capable of interacting with them. The idea of a smart watch that lets you keep an eye on your children might sound like something a security-conscious parent would like: a smart watch that can be hacked to track children, listen in on their surroundings, and even fool them into thinking a call is coming from their parents is the stuff of nightmares.
Key to many of these problems is the lack of standardization for security protocols, and even the products themselves. The idea of dozens of startups each developing a highly-specialized piece of robotics to perform a single domestic task sounds great in theory, until you realize the potential hazards and pitfalls of getting dozens of incompatible devices to work together on the same system.
It seems inevitable that there are yet more layers of domestic drudgery that can be automated away, decades after the first generation of time-saving domestic devices like the dishwasher and vacuum cleaner became mainstream. With projected market values into the billions and trillions of dollars, there is no shortage of industry interest in ironing out these kinks. But, for now at least, the answer to the question: “Where’s my robot butler?” is that it is gradually, painstakingly learning how to sort through groceries.
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Posted in Human Robots