Tag Archives: engineer

#435172 DARPA’s New Project Is Investing ...

When Elon Musk and DARPA both hop aboard the cyborg hypetrain, you know brain-machine interfaces (BMIs) are about to achieve the impossible.

BMIs, already the stuff of science fiction, facilitate crosstalk between biological wetware with external computers, turning human users into literal cyborgs. Yet mind-controlled robotic arms, microelectrode “nerve patches”, or “memory Band-Aids” are still purely experimental medical treatments for those with nervous system impairments.

With the Next-Generation Nonsurgical Neurotechnology (N3) program, DARPA is looking to expand BMIs to the military. This month, the project tapped six academic teams to engineer radically different BMIs to hook up machines to the brains of able-bodied soldiers. The goal is to ditch surgery altogether—while minimizing any biological interventions—to link up brain and machine.

Rather than microelectrodes, which are currently surgically inserted into the brain to hijack neural communication, the project is looking to acoustic signals, electromagnetic waves, nanotechnology, genetically-enhanced neurons, and infrared beams for their next-gen BMIs.

It’s a radical departure from current protocol, with potentially thrilling—or devastating—impact. Wireless BMIs could dramatically boost bodily functions of veterans with neural damage or post-traumatic stress disorder (PTSD), or allow a single soldier to control swarms of AI-enabled drones with his or her mind. Or, similar to the Black Mirror episode Men Against Fire, it could cloud the perception of soldiers, distancing them from the emotional guilt of warfare.

When trickled down to civilian use, these new technologies are poised to revolutionize medical treatment. Or they could galvanize the transhumanist movement with an inconceivably powerful tool that fundamentally alters society—for better or worse.

Here’s what you need to know.

Radical Upgrades
The four-year N3 program focuses on two main aspects: noninvasive and “minutely” invasive neural interfaces to both read and write into the brain.

Because noninvasive technologies sit on the scalp, their sensors and stimulators will likely measure entire networks of neurons, such as those controlling movement. These systems could then allow soldiers to remotely pilot robots in the field—drones, rescue bots, or carriers like Boston Dynamics’ BigDog. The system could even boost multitasking prowess—mind-controlling multiple weapons at once—similar to how able-bodied humans can operate a third robotic arm in addition to their own two.

In contrast, minutely invasive technologies allow scientists to deliver nanotransducers without surgery: for example, an injection of a virus carrying light-sensitive sensors, or other chemical, biotech, or self-assembled nanobots that can reach individual neurons and control their activity independently without damaging sensitive tissue. The proposed use for these technologies isn’t yet well-specified, but as animal experiments have shown, controlling the activity of single neurons at multiple points is sufficient to program artificial memories of fear, desire, and experiences directly into the brain.

“A neural interface that enables fast, effective, and intuitive hands-free interaction with military systems by able-bodied warfighters is the ultimate program goal,” DARPA wrote in its funding brief, released early last year.

The only technologies that will be considered must have a viable path toward eventual use in healthy human subjects.

“Final N3 deliverables will include a complete integrated bidirectional brain-machine interface system,” the project description states. This doesn’t just include hardware, but also new algorithms tailored to these system, demonstrated in a “Department of Defense-relevant application.”

The Tools
Right off the bat, the usual tools of the BMI trade, including microelectrodes, MRI, or transcranial magnetic stimulation (TMS) are off the table. These popular technologies rely on surgery, heavy machinery, or personnel to sit very still—conditions unlikely in the real world.

The six teams will tap into three different kinds of natural phenomena for communication: magnetism, light beams, and acoustic waves.

Dr. Jacob Robinson at Rice University, for example, is combining genetic engineering, infrared laser beams, and nanomagnets for a bidirectional system. The $18 million project, MOANA (Magnetic, Optical and Acoustic Neural Access device) uses viruses to deliver two extra genes into the brain. One encodes a protein that sits on top of neurons and emits infrared light when the cell activates. Red and infrared light can penetrate through the skull. This lets a skull cap, embedded with light emitters and detectors, pick up these signals for subsequent decoding. Ultra-fast and utra-sensitvie photodetectors will further allow the cap to ignore scattered light and tease out relevant signals emanating from targeted portions of the brain, the team explained.

The other new gene helps write commands into the brain. This protein tethers iron nanoparticles to the neurons’ activation mechanism. Using magnetic coils on the headset, the team can then remotely stimulate magnetic super-neurons to fire while leaving others alone. Although the team plans to start in cell cultures and animals, their goal is to eventually transmit a visual image from one person to another. “In four years we hope to demonstrate direct, brain-to-brain communication at the speed of thought and without brain surgery,” said Robinson.

Other projects in N3 are just are ambitious.

The Carnegie Mellon team, for example, plans to use ultrasound waves to pinpoint light interaction in targeted brain regions, which can then be measured through a wearable “hat.” To write into the brain, they propose a flexible, wearable electrical mini-generator that counterbalances the noisy effect of the skull and scalp to target specific neural groups.

Similarly, a group at Johns Hopkins is also measuring light path changes in the brain to correlate them with regional brain activity to “read” wetware commands.

The Teledyne Scientific & Imaging group, in contrast, is turning to tiny light-powered “magnetometers” to detect small, localized magnetic fields that neurons generate when they fire, and match these signals to brain output.

The nonprofit Battelle team gets even fancier with their ”BrainSTORMS” nanotransducers: magnetic nanoparticles wrapped in a piezoelectric shell. The shell can convert electrical signals from neurons into magnetic ones and vice-versa. This allows external transceivers to wirelessly pick up the transformed signals and stimulate the brain through a bidirectional highway.

The magnetometers can be delivered into the brain through a nasal spray or other non-invasive methods, and magnetically guided towards targeted brain regions. When no longer needed, they can once again be steered out of the brain and into the bloodstream, where the body can excrete them without harm.

Four-Year Miracle
Mind-blown? Yeah, same. However, the challenges facing the teams are enormous.

DARPA’s stated goal is to hook up at least 16 sites in the brain with the BMI, with a lag of less than 50 milliseconds—on the scale of average human visual perception. That’s crazy high resolution for devices sitting outside the brain, both in space and time. Brain tissue, blood vessels, and the scalp and skull are all barriers that scatter and dissipate neural signals. All six teams will need to figure out the least computationally-intensive ways to fish out relevant brain signals from background noise, and triangulate them to the appropriate brain region to decipher intent.

In the long run, four years and an average $20 million per project isn’t much to potentially transform our relationship with machines—for better or worse. DARPA, to its credit, is keenly aware of potential misuse of remote brain control. The program is under the guidance of a panel of external advisors with expertise in bioethical issues. And although DARPA’s focus is on enabling able-bodied soldiers to better tackle combat challenges, it’s hard to argue that wireless, non-invasive BMIs will also benefit those most in need: veterans and other people with debilitating nerve damage. To this end, the program is heavily engaging the FDA to ensure it meets safety and efficacy regulations for human use.

Will we be there in just four years? I’m skeptical. But these electrical, optical, acoustic, magnetic, and genetic BMIs, as crazy as they sound, seem inevitable.

“DARPA is preparing for a future in which a combination of unmanned systems, AI, and cyber operations may cause conflicts to play out on timelines that are too short for humans to effectively manage with current technology alone,” said Al Emondi, the N3 program manager.

The question is, now that we know what’s in store, how should the rest of us prepare?

Image Credit: With permission from DARPA N3 project. Continue reading

Posted in Human Robots

#435056 How Researchers Used AI to Better ...

A few years back, DeepMind’s Demis Hassabis famously prophesized that AI and neuroscience will positively feed into each other in a “virtuous circle.” If realized, this would fundamentally expand our insight into intelligence, both machine and human.

We’ve already seen some proofs of concept, at least in the brain-to-AI direction. For example, memory replay, a biological mechanism that fortifies our memories during sleep, also boosted AI learning when abstractly appropriated into deep learning models. Reinforcement learning, loosely based on our motivation circuits, is now behind some of AI’s most powerful tools.

Hassabis is about to be proven right again.

Last week, two studies independently tapped into the power of ANNs to solve a 70-year-old neuroscience mystery: how does our visual system perceive reality?

The first, published in Cell, used generative networks to evolve DeepDream-like images that hyper-activate complex visual neurons in monkeys. These machine artworks are pure nightmare fuel to the human eye; but together, they revealed a fundamental “visual hieroglyph” that may form a basic rule for how we piece together visual stimuli to process sight into perception.

In the second study, a team used a deep ANN model—one thought to mimic biological vision—to synthesize new patterns tailored to control certain networks of visual neurons in the monkey brain. When directly shown to monkeys, the team found that the machine-generated artworks could reliably activate predicted populations of neurons. Future improved ANN models could allow even better control, giving neuroscientists a powerful noninvasive tool to study the brain. The work was published in Science.

The individual results, though fascinating, aren’t necessarily the point. Rather, they illustrate how scientists are now striving to complete the virtuous circle: tapping AI to probe natural intelligence. Vision is only the beginning—the tools can potentially be expanded into other sensory domains. And the more we understand about natural brains, the better we can engineer artificial ones.

It’s a “great example of leveraging artificial intelligence to study organic intelligence,” commented Dr. Roman Sandler at Kernel.co on Twitter.

Why Vision?
ANNs and biological vision have quite the history.

In the late 1950s, the legendary neuroscientist duo David Hubel and Torsten Wiesel became some of the first to use mathematical equations to understand how neurons in the brain work together.

In a series of experiments—many using cats—the team carefully dissected the structure and function of the visual cortex. Using myriads of images, they revealed that vision is processed in a hierarchy: neurons in “earlier” brain regions, those closer to the eyes, tend to activate when they “see” simple patterns such as lines. As we move deeper into the brain, from the early V1 to a nub located slightly behind our ears, the IT cortex, neurons increasingly respond to more complex or abstract patterns, including faces, animals, and objects. The discovery led some scientists to call certain IT neurons “Jennifer Aniston cells,” which fire in response to pictures of the actress regardless of lighting, angle, or haircut. That is, IT neurons somehow extract visual information into the “gist” of things.

That’s not trivial. The complex neural connections that lead to increasing abstraction of what we see into what we think we see—what we perceive—is a central question in machine vision: how can we teach machines to transform numbers encoding stimuli into dots, lines, and angles that eventually form “perceptions” and “gists”? The answer could transform self-driving cars, facial recognition, and other computer vision applications as they learn to better generalize.

Hubel and Wiesel’s Nobel-prize-winning studies heavily influenced the birth of ANNs and deep learning. Much of earlier ANN “feed-forward” model structures are based on our visual system; even today, the idea of increasing layers of abstraction—for perception or reasoning—guide computer scientists to build AI that can better generalize. The early romance between vision and deep learning is perhaps the bond that kicked off our current AI revolution.

It only seems fair that AI would feed back into vision neuroscience.

Hieroglyphs and Controllers
In the Cell study, a team led by Dr. Margaret Livingstone at Harvard Medical School tapped into generative networks to unravel IT neurons’ complex visual alphabet.

Scientists have long known that neurons in earlier visual regions (V1) tend to fire in response to “grating patches” oriented in certain ways. Using a limited set of these patches like letters, V1 neurons can “express a visual sentence” and represent any image, said Dr. Arash Afraz at the National Institute of Health, who was not involved in the study.

But how IT neurons operate remained a mystery. Here, the team used a combination of genetic algorithms and deep generative networks to “evolve” computer art for every studied neuron. In seven monkeys, the team implanted electrodes into various parts of the visual IT region so that they could monitor the activity of a single neuron.

The team showed each monkey an initial set of 40 images. They then picked the top 10 images that stimulated the highest neural activity, and married them to 30 new images to “evolve” the next generation of images. After 250 generations, the technique, XDREAM, generated a slew of images that mashed up contorted face-like shapes with lines, gratings, and abstract shapes.

This image shows the evolution of an optimum image for stimulating a visual neuron in a monkey. Image Credit: Ponce, Xiao, and Schade et al. – Cell.
“The evolved images look quite counter-intuitive,” explained Afraz. Some clearly show detailed structures that resemble natural images, while others show complex structures that can’t be characterized by our puny human brains.

This figure shows natural images (right) and images evolved by neurons in the inferotemporal cortex of a monkey (left). Image Credit: Ponce, Xiao, and Schade et al. – Cell.
“What started to emerge during each experiment were pictures that were reminiscent of shapes in the world but were not actual objects in the world,” said study author Carlos Ponce. “We were seeing something that was more like the language cells use with each other.”

This image was evolved by a neuron in the inferotemporal cortex of a monkey using AI. Image Credit: Ponce, Xiao, and Schade et al. – Cell.
Although IT neurons don’t seem to use a simple letter alphabet, it does rely on a vast array of characters like hieroglyphs or Chinese characters, “each loaded with more information,” said Afraz.

The adaptive nature of XDREAM turns it into a powerful tool to probe the inner workings of our brains—particularly for revealing discrepancies between biology and models.

The Science study, led by Dr. James DiCarlo at MIT, takes a similar approach. Using ANNs to generate new patterns and images, the team was able to selectively predict and independently control neuron populations in a high-level visual region called V4.

“So far, what has been done with these models is predicting what the neural responses would be to other stimuli that they have not seen before,” said study author Dr. Pouya Bashivan. “The main difference here is that we are going one step further and using the models to drive the neurons into desired states.”

It suggests that our current ANN models for visual computation “implicitly capture a great deal of visual knowledge” which we can’t really describe, but which the brain uses to turn vision information into perception, the authors said. By testing AI-generated images on biological vision, however, the team concluded that today’s ANNs have a degree of understanding and generalization. The results could potentially help engineer even more accurate ANN models of biological vision, which in turn could feed back into machine vision.

“One thing is clear already: Improved ANN models … have led to control of a high-level neural population that was previously out of reach,” the authors said. “The results presented here have likely only scratched the surface of what is possible with such implemented characterizations of the brain’s neural networks.”

To Afraz, the power of AI here is to find cracks in human perception—both our computational models of sensory processes, as well as our evolved biological software itself. AI can be used “as a perfect adversarial tool to discover design cracks” of IT, said Afraz, such as finding computer art that “fools” a neuron into thinking the object is something else.

“As artificial intelligence researchers develop models that work as well as the brain does—or even better—we will still need to understand which networks are more likely to behave safely and further human goals,” said Ponce. “More efficient AI can be grounded by knowledge of how the brain works.”

Image Credit: Sangoiri / Shutterstock.com Continue reading

Posted in Human Robots

#434854 New Lifelike Biomaterial Self-Reproduces ...

Life demands flux.

Every living organism is constantly changing: cells divide and die, proteins build and disintegrate, DNA breaks and heals. Life demands metabolism—the simultaneous builder and destroyer of living materials—to continuously upgrade our bodies. That’s how we heal and grow, how we propagate and survive.

What if we could endow cold, static, lifeless robots with the gift of metabolism?

In a study published this month in Science Robotics, an international team developed a DNA-based method that gives raw biomaterials an artificial metabolism. Dubbed DASH—DNA-based assembly and synthesis of hierarchical materials—the method automatically generates “slime”-like nanobots that dynamically move and navigate their environments.

Like humans, the artificial lifelike material used external energy to constantly change the nanobots’ bodies in pre-programmed ways, recycling their DNA-based parts as both waste and raw material for further use. Some “grew” into the shape of molecular double-helixes; others “wrote” the DNA letters inside micro-chips.

The artificial life forms were also rather “competitive”—in quotes, because these molecular machines are not conscious. Yet when pitted against each other, two DASH bots automatically raced forward, crawling in typical slime-mold fashion at a scale easily seen under the microscope—and with some iterations, with the naked human eye.

“Fundamentally, we may be able to change how we create and use the materials with lifelike characteristics. Typically materials and objects we create in general are basically static… one day, we may be able to ‘grow’ objects like houses and maintain their forms and functions autonomously,” said study author Dr. Shogo Hamada to Singularity Hub.

“This is a great study that combines the versatility of DNA nanotechnology with the dynamics of living materials,” said Dr. Job Boekhoven at the Technical University of Munich, who was not involved in the work.

Dissipative Assembly
The study builds on previous ideas on how to make molecular Lego blocks that essentially assemble—and destroy—themselves.

Although the inspiration came from biological metabolism, scientists have long hoped to cut their reliance on nature. At its core, metabolism is just a bunch of well-coordinated chemical reactions, programmed by eons of evolution. So why build artificial lifelike materials still tethered by evolution when we can use chemistry to engineer completely new forms of artificial life?

Back in 2015, for example, a team led by Boekhoven described a way to mimic how our cells build their internal “structural beams,” aptly called the cytoskeleton. The key here, unlike many processes in nature, isn’t balance or equilibrium; rather, the team engineered an extremely unstable system that automatically builds—and sustains—assemblies from molecular building blocks when given an external source of chemical energy.

Sound familiar? The team basically built molecular devices that “die” without “food.” Thanks to the laws of thermodynamics (hey ya, Newton!), that energy eventually dissipates, and the shapes automatically begin to break down, completing an artificial “circle of life.”

The new study took the system one step further: rather than just mimicking synthesis, they completed the circle by coupling the building process with dissipative assembly.

Here, the “assembling units themselves are also autonomously created from scratch,” said Hamada.

DNA Nanobots
The process of building DNA nanobots starts on a microfluidic chip.

Decades of research have allowed researchers to optimize DNA assembly outside the body. With the help of catalysts, which help “bind” individual molecules together, the team found that they could easily alter the shape of the self-assembling DNA bots—which formed fiber-like shapes—by changing the structure of the microfluidic chambers.

Computer simulations played a role here too: through both digital simulations and observations under the microscope, the team was able to identify a few critical rules that helped them predict how their molecules self-assemble while navigating a maze of blocking “pillars” and channels carved onto the microchips.

This “enabled a general design strategy for the DASH patterns,” they said.

In particular, the whirling motion of the fluids as they coursed through—and bumped into—ridges in the chips seems to help the DNA molecules “entangle into networks,” the team explained.

These insights helped the team further develop the “destroying” part of metabolism. Similar to linking molecules into DNA chains, their destruction also relies on enzymes.

Once the team pumped both “generation” and “degeneration” enzymes into the microchips, along with raw building blocks, the process was completely autonomous. The simultaneous processes were so lifelike that the team used a metric commonly used in robotics, finite-state automation, to measure the behavior of their DNA nanobots from growth to eventual decay.

“The result is a synthetic structure with features associated with life. These behaviors include locomotion, self-regeneration, and spatiotemporal regulation,” said Boekhoven.

Molecular Slime Molds
Just witnessing lifelike molecules grow in place like the dance move running man wasn’t enough.

In their next experiments, the team took inspiration from slugs to program undulating movements into their DNA bots. Here, “movement” is actually a sort of illusion: the machines “moved” because their front ends kept regenerating, whereas their back ends degenerated. In essence, the molecular slime was built from linking multiple individual “DNA robot-like” units together: each unit receives a delayed “decay” signal from the head of the slime in a way that allowed the whole artificial “organism” to crawl forward, against the steam of fluid flow.

Here’s the fun part: the team eventually engineered two molecular slime bots and pitted them against each other, Mario Kart-style. In these experiments, the faster moving bot alters the state of its competitor to promote “decay.” This slows down the competitor, allowing the dominant DNA nanoslug to win in a race.

Of course, the end goal isn’t molecular podracing. Rather, the DNA-based bots could easily amplify a given DNA or RNA sequence, making them efficient nano-diagnosticians for viral and other infections.

The lifelike material can basically generate patterns that doctors can directly ‘see’ with their eyes, which makes DNA or RNA molecules from bacteria and viruses extremely easy to detect, the team said.

In the short run, “the detection device with this self-generating material could be applied to many places and help people on site, from farmers to clinics, by providing an easy and accurate way to detect pathogens,” explained Hamaga.

A Futuristic Iron Man Nanosuit?
I’m letting my nerd flag fly here. In Avengers: Infinity Wars, the scientist-engineer-philanthropist-playboy Tony Stark unveiled a nanosuit that grew to his contours when needed and automatically healed when damaged.

DASH may one day realize that vision. For now, the team isn’t focused on using the technology for regenerating armor—rather, the dynamic materials could create new protein assemblies or chemical pathways inside living organisms, for example. The team also envisions adding simple sensing and computing mechanisms into the material, which can then easily be thought of as a robot.

Unlike synthetic biology, the goal isn’t to create artificial life. Rather, the team hopes to give lifelike properties to otherwise static materials.

“We are introducing a brand-new, lifelike material concept powered by its very own artificial metabolism. We are not making something that’s alive, but we are creating materials that are much more lifelike than have ever been seen before,” said lead author Dr. Dan Luo.

“Ultimately, our material may allow the construction of self-reproducing machines… artificial metabolism is an important step toward the creation of ‘artificial’ biological systems with dynamic, lifelike capabilities,” added Hamada. “It could open a new frontier in robotics.”

Image Credit: A timelapse image of DASH, by Jeff Tyson at Cornell University. 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.

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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Image Credit: ktsdesign / Shutterstock.com Continue reading

Posted in Human Robots

#434508 The Top Biotech and Medicine Advances to ...

2018 was bonkers for science.

From a woman who gave birth using a transplanted uterus, to the infamous CRISPR baby scandal, to forensics adopting consumer-based genealogy test kits to track down criminals, last year was a factory churning out scientific “whoa” stories with consequences for years to come.

With CRISPR still in the headlines, Britain ready to bid Europe au revoir, and multiple scientific endeavors taking off, 2019 is shaping up to be just as tumultuous.

Here are the science and health stories that may blow up in the new year. But first, a note of caveat: predicting the future is tough. Forecasting is the lovechild between statistics and (a good deal of) intuition, and entire disciplines have been dedicated to the endeavor. But January is the perfect time to gaze into the crystal ball for wisps of insight into the year to come. Last year we predicted the widespread approval of gene therapy products—on the most part, we nailed it. This year we’re hedging our bets with multiple predictions.

Gene Drives Used in the Wild
The concept of gene drives scares many, for good reason. Gene drives are a step up in severity (and consequences) from CRISPR and other gene-editing tools. Even with germline editing, in which the sperm, egg, or embryos are altered, gene editing affects just one genetic line—one family—at least at the beginning, before they reproduce with the general population.

Gene drives, on the other hand, have the power to wipe out entire species.

In a nutshell, they’re little bits of DNA code that help a gene transfer from parent to child with almost 100 percent perfect probability. The “half of your DNA comes from dad, the other comes from mom” dogma? Gene drives smash that to bits.

In other words, the only time one would consider using a gene drive is to change the genetic makeup of an entire population. It sounds like the plot of a supervillain movie, but scientists have been toying around with the idea of deploying the technology—first in mosquitoes, then (potentially) in rodents.

By releasing just a handful of mutant mosquitoes that carry gene drives for infertility, for example, scientists could potentially wipe out entire populations that carry infectious scourges like malaria, dengue, or Zika. The technology is so potent—and dangerous—the US Defense Advances Research Projects Agency is shelling out $65 million to suss out how to deploy, control, counter, or even reverse the effects of tampering with ecology.

Last year, the U.N. gave a cautious go-ahead for the technology to be deployed in the wild in limited terms. Now, the first release of a genetically modified mosquito is set for testing in Burkina Faso in Africa—the first-ever field experiment involving gene drives.

The experiment will only release mosquitoes in the Anopheles genus, which are the main culprits transferring disease. As a first step, over 10,000 male mosquitoes are set for release into the wild. These dudes are genetically sterile but do not cause infertility, and will help scientists examine how they survive and disperse as a preparation for deploying gene-drive-carrying mosquitoes.

Hot on the project’s heels, the nonprofit consortium Target Malaria, backed by the Bill and Melinda Gates foundation, is engineering a gene drive called Mosq that will spread infertility across the population or kill out all female insects. Their attempt to hack the rules of inheritance—and save millions in the process—is slated for 2024.

A Universal Flu Vaccine
People often brush off flu as a mere annoyance, but the infection kills hundreds of thousands each year based on the CDC’s statistical estimates.

The flu virus is actually as difficult of a nemesis as HIV—it mutates at an extremely rapid rate, making effective vaccines almost impossible to engineer on time. Scientists currently use data to forecast the strains that will likely explode into an epidemic and urge the public to vaccinate against those predictions. That’s partly why, on average, flu vaccines only have a success rate of roughly 50 percent—not much better than a coin toss.

Tired of relying on educated guesses, scientists have been chipping away at a universal flu vaccine that targets all strains—perhaps even those we haven’t yet identified. Often referred to as the “holy grail” in epidemiology, these vaccines try to alert our immune systems to parts of a flu virus that are least variable from strain to strain.

Last November, a first universal flu vaccine developed by BiondVax entered Phase 3 clinical trials, which means it’s already been proven safe and effective in a small numbers and is now being tested in a broader population. The vaccine doesn’t rely on dead viruses, which is a common technique. Rather, it uses a small chain of amino acids—the chemical components that make up proteins—to stimulate the immune system into high alert.

With the government pouring $160 million into the research and several other universal candidates entering clinical trials, universal flu vaccines may finally experience a breakthrough this year.

In-Body Gene Editing Shows Further Promise
CRISPR and other gene editing tools headed the news last year, including both downers suggesting we already have immunity to the technology and hopeful news of it getting ready for treating inherited muscle-wasting diseases.

But what wasn’t widely broadcasted was the in-body gene editing experiments that have been rolling out with gusto. Last September, Sangamo Therapeutics in Richmond, California revealed that they had injected gene-editing enzymes into a patient in an effort to correct a genetic deficit that prevents him from breaking down complex sugars.

The effort is markedly different than the better-known CAR-T therapy, which extracts cells from the body for genetic engineering before returning them to the hosts. Rather, Sangamo’s treatment directly injects viruses carrying the edited genes into the body. So far, the procedure looks to be safe, though at the time of reporting it was too early to determine effectiveness.

This year the company hopes to finally answer whether it really worked.

If successful, it means that devastating genetic disorders could potentially be treated with just a few injections. With a gamut of new and more precise CRISPR and other gene-editing tools in the works, the list of treatable inherited diseases is likely to grow. And with the CRISPR baby scandal potentially dampening efforts at germline editing via regulations, in-body gene editing will likely receive more attention if Sangamo’s results return positive.

Neuralink and Other Brain-Machine Interfaces
Neuralink is the stuff of sci fi: tiny implanted particles into the brain could link up your biological wetware with silicon hardware and the internet.

But that’s exactly what Elon Musk’s company, founded in 2016, seeks to develop: brain-machine interfaces that could tinker with your neural circuits in an effort to treat diseases or even enhance your abilities.

Last November, Musk broke his silence on the secretive company, suggesting that he may announce something “interesting” in a few months, that’s “better than anyone thinks is possible.”

Musk’s aspiration for achieving symbiosis with artificial intelligence isn’t the driving force for all brain-machine interfaces (BMIs). In the clinics, the main push is to rehabilitate patients—those who suffer from paralysis, memory loss, or other nerve damage.

2019 may be the year that BMIs and neuromodulators cut the cord in the clinics. These devices may finally work autonomously within a malfunctioning brain, applying electrical stimulation only when necessary to reduce side effects without requiring external monitoring. Or they could allow scientists to control brains with light without needing bulky optical fibers.

Cutting the cord is just the first step to fine-tuning neurological treatments—or enhancements—to the tune of your own brain, and 2019 will keep on bringing the music.

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