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According to some scientists, humans really do have a sixth sense. There’s nothing supernatural about it: the sense of proprioception tells you about the relative positions of your limbs and the rest of your body. Close your eyes, block out all sound, and you can still use this internal “map” of your external body to locate your muscles and body parts – you have an innate sense of the distances between them, and the perception of how they’re moving, above and beyond your sense of touch.
This sense is invaluable for allowing us to coordinate our movements. In humans, the brain integrates senses including touch, heat, and the tension in muscle spindles to allow us to build up this map.
Replicating this complex sense has posed a great challenge for roboticists. We can imagine simulating the sense of sight with cameras, sound with microphones, or touch with pressure-pads. Robots with chemical sensors could be far more accurate than us in smell and taste, but building in proprioception, the robot’s sense of itself and its body, is far more difficult, and is a large part of why humanoid robots are so tricky to get right.
Simultaneous localization and mapping (SLAM) software allows robots to use their own senses to build up a picture of their surroundings and environment, but they’d need a keen sense of the position of their own bodies to interact with it. If something unexpected happens, or in dark environments where primary senses are not available, robots can struggle to keep track of their own position and orientation. For human-robot interaction, wearable robotics, and delicate applications like surgery, tiny differences can be extremely important.
In the case of hard robotics, this is generally solved by using a series of strain and pressure sensors in each joint, which allow the robot to determine how its limbs are positioned. That works fine for rigid robots with a limited number of joints, but for softer, more flexible robots, this information is limited. Roboticists are faced with a dilemma: a vast, complex array of sensors for every degree of freedom in the robot’s movement, or limited skill in proprioception?
New techniques, often involving new arrays of sensory material and machine-learning algorithms to fill in the gaps, are starting to tackle this problem. Take the work of Thomas George Thuruthel and colleagues in Pisa and San Diego, who draw inspiration from the proprioception of humans. In a new paper in Science Robotics, they describe the use of soft sensors distributed through a robotic finger at random. This placement is much like the constant adaptation of sensors in humans and animals, rather than relying on feedback from a limited number of positions.
The sensors allow the soft robot to react to touch and pressure in many different locations, forming a map of itself as it contorts into complicated positions. The machine-learning algorithm serves to interpret the signals from the randomly-distributed sensors: as the finger moves around, it’s observed by a motion capture system. After training the robot’s neural network, it can associate the feedback from the sensors with the position of the finger detected in the motion-capture system, which can then be discarded. The robot observes its own motions to understand the shapes that its soft body can take, and translate them into the language of these soft sensors.
“The advantages of our approach are the ability to predict complex motions and forces that the soft robot experiences (which is difficult with traditional methods) and the fact that it can be applied to multiple types of actuators and sensors,” said Michael Tolley of the University of California San Diego. “Our method also includes redundant sensors, which improves the overall robustness of our predictions.”
The use of machine learning lets the roboticists come up with a reliable model for this complex, non-linear system of motions for the actuators, something difficult to do by directly calculating the expected motion of the soft-bot. It also resembles the human system of proprioception, built on redundant sensors that change and shift in position as we age.
In Search of a Perfect Arm
Another approach to training robots in using their bodies comes from Robert Kwiatkowski and Hod Lipson of Columbia University in New York. In their paper “Task-agnostic self-modeling machines,” also recently published in Science Robotics, they describe a new type of robotic arm.
Robotic arms and hands are getting increasingly dexterous, but training them to grasp a large array of objects and perform many different tasks can be an arduous process. It’s also an extremely valuable skill to get right: Amazon is highly interested in the perfect robot arm. Google hooked together an array of over a dozen robot arms so that they could share information about grasping new objects, in part to cut down on training time.
Individually training a robot arm to perform every individual task takes time and reduces the adaptability of your robot: either you need an ML algorithm with a huge dataset of experiences, or, even worse, you need to hard-code thousands of different motions. Kwiatkowski and Lipson attempt to overcome this by developing a robotic system that has a “strong sense of self”: a model of its own size, shape, and motions.
They do this using deep machine learning. The robot begins with no prior knowledge of its own shape or the underlying physics of its motion. It then repeats a series of a thousand random trajectories, recording the motion of its arm. Kwiatkowski and Lipson compare this to a baby in the first year of life observing the motions of its own hands and limbs, fascinated by picking up and manipulating objects.
Again, once the robot has trained itself to interpret these signals and build up a robust model of its own body, it’s ready for the next stage. Using that deep-learning algorithm, the researchers then ask the robot to design strategies to accomplish simple pick-up and place and handwriting tasks. Rather than laboriously and narrowly training itself for each individual task, limiting its abilities to a very narrow set of circumstances, the robot can now strategize how to use its arm for a much wider range of situations, with no additional task-specific training.
In a further experiment, the researchers replaced part of the arm with a “deformed” component, intended to simulate what might happen if the robot was damaged. The robot can then detect that something’s up and “reconfigure” itself, reconstructing its self-model by going through the training exercises once again; it was then able to perform the same tasks with only a small reduction in accuracy.
Machine learning techniques are opening up the field of robotics in ways we’ve never seen before. Combining them with our understanding of how humans and other animals are able to sense and interact with the world around us is bringing robotics closer and closer to becoming truly flexible and adaptable, and, eventually, omnipresent.
But before they can get out and shape the world, as these studies show, they will need to understand themselves.
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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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