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#435522 Harvard’s Smart Exo-Shorts Talk to the ...

Exosuits don’t generally scream “fashionable” or “svelte.” Take the mind-controlled robotic exoskeleton that allowed a paraplegic man to kick off the World Cup back in 2014. Is it cool? Hell yeah. Is it practical? Not so much.

Yapping about wearability might seem childish when the technology already helps people with impaired mobility move around dexterously. But the lesson of the ill-fated Google Glassholes, which includes an awkward dorky head tilt and an assuming voice command, clearly shows that wearable computer assistants can’t just work technologically—they have to look natural and allow the user to behave like as usual. They have to, in a sense, disappear.

To Dr. Jose Pons at the Legs + Walking Ability Lab in Chicago, exosuits need three main selling points to make it in the real world. One, they have to physically interact with their wearer and seamlessly deliver assistance when needed. Two, they should cognitively interact with the host to guide and control the robot at all times. Finally, they need to feel like a second skin—move with the user without adding too much extra mass or reducing mobility.

This week, a US-Korean collaboration delivered the whole shebang in a Lululemon-style skin-hugging package combined with a retro waist pack. The portable exosuit, weighing only 11 pounds, looks like a pair of spandex shorts but can support the wearer’s hip movement when needed. Unlike their predecessors, the shorts are embedded with sensors that let them know when the wearer is walking versus running by analyzing gait.

Switching between the two movement modes may not seem like much, but what naturally comes to our brains doesn’t translate directly to smart exosuits. “Walking and running have fundamentally different biomechanics, which makes developing devices that assist both gaits challenging,” the team said. Their algorithm, computed in the cloud, allows the wearer to easily switch between both, with the shorts providing appropriate hip support that makes the movement experience seamless.

To Pons, who was not involved in the research but wrote a perspective piece, the study is an exciting step towards future exosuits that will eventually disappear under the skin—that is, implanted neural interfaces to control robotic assistance or activate the user’s own muscles.

“It is realistic to think that we will witness, in the next several years…robust human-robot interfaces to command wearable robotics based on…the neural code of movement in humans,” he said.

A “Smart” Exosuit Hack
There are a few ways you can hack a human body to move with an exosuit. One is using implanted electrodes inside the brain or muscles to decipher movement intent. With heavy practice, a neural implant can help paralyzed people walk again or dexterously move external robotic arms. But because the technique requires surgery, it’s not an immediate sell for people who experience low mobility because of aging or low muscle tone.

The other approach is to look to biophysics. Rather than decoding neural signals that control movement, here the idea is to measure gait and other physical positions in space to decipher intent. As you can probably guess, accurately deciphering user intent isn’t easy, especially when the wearable tries to accommodate multiple gaits. But the gains are many: there’s no surgery involved, and the wearable is low in energy consumption.

Double Trouble
The authors decided to tackle an everyday situation. You’re walking to catch the train to work, realize you’re late, and immediately start sprinting.

That seemingly easy conversion hides a complex switch in biomechanics. When you walk, your legs act like an inverted pendulum that swing towards a dedicated center in a predictable way. When you run, however, the legs move more like a spring-loaded system, and the joints involved in the motion differ from a casual stroll. Engineering an assistive wearable for each is relatively simple; making one for both is exceedingly hard.

Led by Dr. Conor Walsh at Harvard University, the team started with an intuitive idea: assisted walking and running requires specialized “actuation” profiles tailored to both. When the user is moving in a way that doesn’t require assistance, the wearable needs to be out of the way so that it doesn’t restrict mobility. A quick analysis found that assisting hip extension has the largest impact, because it’s important to both gaits and doesn’t add mass to the lower legs.

Building on that insight, the team made a waist belt connected to two thigh wraps, similar to a climbing harness. Two electrical motors embedded inside the device connect the waist belt to other components through a pulley system to help the hip joints move. The whole contraption weighed about 11 lbs and didn’t obstruct natural movement.

Next, the team programmed two separate supporting profiles for walking and running. The goal was to reduce the “metabolic cost” for both movements, so that the wearer expends as little energy as needed. To switch between the two programs, they used a cloud-based classification algorithm to measure changes in energy fluctuation to figure out what mode—running or walking—the user is in.

Smart Booster
Initial trials on treadmills were highly positive. Six male volunteers with similar age and build donned the exosuit and either ran or walked on the treadmill at varying inclines. The algorithm performed perfectly at distinguishing between the two gaits in all conditions, even at steep angles.

An outdoor test with eight volunteers also proved the algorithm nearly perfect. Even on uneven terrain, only two steps out of all test trials were misclassified. In an additional trial on mud or snow, the algorithm performed just as well.

“The system allows the wearer to use their preferred gait for each speed,” the team said.

Software excellence translated to performance. A test found that the exosuit reduced the energy for walking by over nine percent and running by four percent. It may not sound like much, but the range of improvement is meaningful in athletic performance. Putting things into perspective, the team said, the metabolic rate reduction during walking is similar to taking 16 pounds off at the waist.

The Wearable Exosuit Revolution
The study’s lightweight exoshorts are hardly the only players in town. Back in 2017, SRI International’s spin-off, Superflex, engineered an Aura suit to support mobility in the elderly. The Aura used a different mechanism: rather than a pulley system, it incorporated a type of smart material that contracts in a manner similar to human muscles when zapped with electricity.

Embedded with a myriad of sensors for motion, accelerometers and gyroscopes, Aura’s smartness came from mini-computers that measure how fast the wearer is moving and track the user’s posture. The data were integrated and processed locally inside hexagon-shaped computing pods near the thighs and upper back. The pods also acted as the control center for sending electrical zaps to give the wearer a boost when needed.

Around the same time, a collaboration between Harvard’s Wyss Institute and ReWalk Robotics introduced a fabric-based wearable robot to assist a wearer’s legs for balance and movement. Meanwhile, a Swiss team coated normal fabric with electroactive material to weave soft, pliable artificial “muscles” that move with the skin.

Although health support is the current goal, the military is obviously interested in similar technologies to enhance soldiers’ physicality. Superflex’s Aura, for example, was originally inspired by technology born from DARPA’s Warrior Web Program, which aimed to reduce a soldier’s mechanical load.

That said, military gear has had a long history of trickling down to consumer use. Similar to the way camouflage, cargo pants, and GORE-TEX trickled down into the consumer ecosphere, it’s not hard to imagine your local Target eventually stocking intelligent exowear.

Image and Video Credit: Wyss Institute at Harvard University. Continue reading

Posted in Human Robots

#435520 These Are the Meta-Trends Shaping the ...

Life is pretty different now than it was 20 years ago, or even 10 years ago. It’s sort of exciting, and sort of scary. And hold onto your hat, because it’s going to keep changing—even faster than it already has been.

The good news is, maybe there won’t be too many big surprises, because the future will be shaped by trends that have already been set in motion. According to Singularity University co-founder and XPRIZE founder Peter Diamandis, a lot of these trends are unstoppable—but they’re also pretty predictable.

At SU’s Global Summit, taking place this week in San Francisco, Diamandis outlined some of the meta-trends he believes are key to how we’ll live our lives and do business in the (not too distant) future.

Increasing Global Abundance
Resources are becoming more abundant all over the world, and fewer people are seeing their lives limited by scarcity. “It’s hard for us to realize this as we see crisis news, but what people have access to is more abundant than ever before,” Diamandis said. Products and services are becoming cheaper and thus available to more people, and having more resources then enables people to create more, thus producing even more resources—and so on.

Need evidence? The proportion of the world’s population living in extreme poverty is currently lower than it’s ever been. The average human life expectancy is longer than it’s ever been. The costs of day-to-day needs like food, energy, transportation, and communications are on a downward trend.

Take energy. In most of the world, though its costs are decreasing, it’s still a fairly precious commodity; we turn off our lights and our air conditioners when we don’t need them (ideally, both to save money and to avoid wastefulness). But the cost of solar energy has plummeted, and the storage capacity of batteries is improving, and solar technology is steadily getting more efficient. Bids for new solar power plants in the past few years have broken each other’s records for lowest cost per kilowatt hour.

“We’re not far from a penny per kilowatt hour for energy from the sun,” Diamandis said. “And if you’ve got energy, you’ve got water.” Desalination, for one, will be much more widely feasible once the cost of the energy needed for it drops.

Knowledge is perhaps the most crucial resource that’s going from scarce to abundant. All the world’s knowledge is now at the fingertips of anyone who has a mobile phone and an internet connection—and the number of people connected is only going to grow. “Everyone is being connected at gigabit connection speeds, and this will be transformative,” Diamandis said. “We’re heading towards a world where anyone can know anything at any time.”

Increasing Capital Abundance
It’s not just goods, services, and knowledge that are becoming more plentiful. Money is, too—particularly money for business. “There’s more and more capital available to invest in companies,” Diamandis said. As a result, more people are getting the chance to bring their world-changing ideas to life.

Venture capital investments reached a new record of $130 billion in 2018, up from $84 billion in 2017—and that’s just in the US. Globally, VC funding grew 21 percent from 2017 to a total of $207 billion in 2018.

Through crowdfunding, any person in any part of the world can present their idea and ask for funding. That funding can come in the form of a loan, an equity investment, a reward, or an advanced purchase of the proposed product or service. “Crowdfunding means it doesn’t matter where you live, if you have a great idea you can get it funded by people from all over the world,” Diamandis said.

All this is making a difference; the number of unicorns—privately-held startups valued at over $1 billion—currently stands at an astounding 360.

One of the reasons why the world is getting better, Diamandis believes, is because entrepreneurs are trying more crazy ideas—not ideas that are reasonable or predictable or linear, but ideas that seem absurd at first, then eventually end up changing the world.

Everyone and Everything, Connected
As already noted, knowledge is becoming abundant thanks to the proliferation of mobile phones and wireless internet; everyone’s getting connected. In the next decade or sooner, connectivity will reach every person in the world. 5G is being tested and offered for the first time this year, and companies like Google, SpaceX, OneWeb, and Amazon are racing to develop global satellite internet constellations, whether by launching 12,000 satellites, as SpaceX’s Starlink is doing, or by floating giant balloons into the stratosphere like Google’s Project Loon.

“We’re about to reach a period of time in the next four to six years where we’re going from half the world’s people being connected to the whole world being connected,” Diamandis said. “What happens when 4.2 billion new minds come online? They’re all going to want to create, discover, consume, and invent.”

And it doesn’t stop at connecting people. Things are becoming more connected too. “By 2020 there will be over 20 billion connected devices and more than one trillion sensors,” Diamandis said. By 2030, those projections go up to 500 billion and 100 trillion. Think about it: there’s home devices like refrigerators, TVs, dishwashers, digital assistants, and even toasters. There’s city infrastructure, from stoplights to cameras to public transportation like buses or bike sharing. It’s all getting smart and connected.

Soon we’ll be adding autonomous cars to the mix, and an unimaginable glut of data to go with them. Every turn, every stop, every acceleration will be a data point. Some cars already collect over 25 gigabytes of data per hour, Diamandis said, and car data is projected to generate $750 billion of revenue by 2030.

“You’re going to start asking questions that were never askable before, because the data is now there to be mined,” he said.

Increasing Human Intelligence
Indeed, we’ll have data on everything we could possibly want data on. We’ll also soon have what Diamandis calls just-in-time education, where 5G combined with artificial intelligence and augmented reality will allow you to learn something in the moment you need it. “It’s not going and studying, it’s where your AR glasses show you how to do an emergency surgery, or fix something, or program something,” he said.

We’re also at the beginning of massive investments in research working towards connecting our brains to the cloud. “Right now, everything we think, feel, hear, or learn is confined in our synaptic connections,” Diamandis said. What will it look like when that’s no longer the case? Companies like Kernel, Neuralink, Open Water, Facebook, Google, and IBM are all investing billions of dollars into brain-machine interface research.

Increasing Human Longevity
One of the most important problems we’ll use our newfound intelligence to solve is that of our own health and mortality, making 100 years old the new 60—then eventually, 120 or 150.

“Our bodies were never evolved to live past age 30,” Diamandis said. “You’d go into puberty at age 13 and have a baby, and by the time you were 26 your baby was having a baby.”

Seeing how drastically our lifespans have changed over time makes you wonder what aging even is; is it natural, or is it a disease? Many companies are treating it as one, and using technologies like senolytics, CRISPR, and stem cell therapy to try to cure it. Scaffolds of human organs can now be 3D printed then populated with the recipient’s own stem cells so that their bodies won’t reject the transplant. Companies are testing small-molecule pharmaceuticals that can stop various forms of cancer.

“We don’t truly know what’s going on inside our bodies—but we can,” Diamandis said. “We’re going to be able to track our bodies and find disease at stage zero.”

Chins Up
The world is far from perfect—that’s not hard to see. What’s less obvious but just as true is that we’re living in an amazing time. More people are coming together, and they have more access to information, and that information moves faster, than ever before.

“I don’t think any of us understand how fast the world is changing,” Diamandis said. “Most people are fearful about the future. But we should be excited about the tools we now have to solve the world’s problems.”

Image Credit: spainter_vfx / Shutterstock.com Continue reading

Posted in Human Robots

#435308 Brain-Machine Interfaces Are Getting ...

Elon Musk grabbed a lot of attention with his July 16 announcement that his company Neuralink plans to implant electrodes into the brains of people with paralysis by next year. Their first goal is to create assistive technology to help people who can’t move or are unable to communicate.

If you haven’t been paying attention, brain-machine interfaces (BMIs) that allow people to control robotic arms with their thoughts might sound like science fiction. But science and engineering efforts have already turned it into reality.

In a few research labs around the world, scientists and physicians have been implanting devices into the brains of people who have lost the ability to control their arms or hands for over a decade. In our own research group at the University of Pittsburgh, we’ve enabled people with paralyzed arms and hands to control robotic arms that allow them to grasp and move objects with relative ease. They can even experience touch-like sensations from their own hand when the robot grasps objects.

At its core, a BMI is pretty straightforward. In your brain, microscopic cells called neurons are sending signals back and forth to each other all the time. Everything you think, do and feel as you interact with the world around you is the result of the activity of these 80 billion or so neurons.

If you implant a tiny wire very close to one of these neurons, you can record the electrical activity it generates and send it to a computer. Record enough of these signals from the right area of the brain and it becomes possible to control computers, robots, or anything else you might want, simply by thinking about moving. But doing this comes with tremendous technical challenges, especially if you want to record from hundreds or thousands of neurons.

What Neuralink Is Bringing to the Table
Elon Musk founded Neuralink in 2017, aiming to address these challenges and raise the bar for implanted neural interfaces.

Perhaps the most impressive aspect of Neuralink’s system is the breadth and depth of their approach. Building a BMI is inherently interdisciplinary, requiring expertise in electrode design and microfabrication, implantable materials, surgical methods, electronics, packaging, neuroscience, algorithms, medicine, regulatory issues, and more. Neuralink has created a team that spans most, if not all, of these areas.

With all of this expertise, Neuralink is undoubtedly moving the field forward, and improving their technology rapidly. Individually, many of the components of their system represent significant progress along predictable paths. For example, their electrodes, that they call threads, are very small and flexible; many researchers have tried to harness those properties to minimize the chance the brain’s immune response would reject the electrodes after insertion. Neuralink has also developed high-performance miniature electronics, another focus area for labs working on BMIs.

Often overlooked in academic settings, however, is how an entire system would be efficiently implanted in a brain.

Neuralink’s BMI requires brain surgery. This is because implanted electrodes that are in intimate contact with neurons will always outperform non-invasive electrodes where neurons are far away from the electrodes sitting outside the skull. So, a critical question becomes how to minimize the surgical challenges around getting the device into a brain.

Maybe the most impressive aspect of Neuralink’s announcement was that they created a 3,000-electrode neural interface where electrodes could be implanted at a rate of between 30 and 200 per minute. Each thread of electrodes is implanted by a sophisticated surgical robot that essentially acts like a sewing machine. This all happens while specifically avoiding blood vessels that blanket the surface of the brain. The robotics and imaging that enable this feat, with tight integration to the entire device, is striking.

Neuralink has thought through the challenge of developing a clinically viable BMI from beginning to end in a way that few groups have done, though they acknowledge that many challenges remain as they work towards getting this technology into human patients in the clinic.

Figuring Out What More Electrodes Gets You
The quest for implantable devices with thousands of electrodes is not only the domain of private companies. DARPA, the NIH BRAIN Initiative, and international consortiums are working on neurotechnologies for recording and stimulating in the brain with goals of tens of thousands of electrodes. But what might scientists do with the information from 1,000, 3,000, or maybe even 100,000 neurons?

At some level, devices with more electrodes might not actually be necessary to have a meaningful impact in people’s lives. Effective control of computers for access and communication, of robotic limbs to grasp and move objects as well as of paralyzed muscles is already happening—in people. And it has been for a number of years.

Since the 1990s, the Utah Array, which has just 100 electrodes and is manufactured by Blackrock Microsystems, has been a critical device in neuroscience and clinical research. This electrode array is FDA-cleared for temporary neural recording. Several research groups, including our own, have implanted Utah Arrays in people that lasted multiple years.

Currently, the biggest constraints are related to connectors, electronics, and system-level engineering, not the implanted electrode itself—although increasing the electrodes’ lifespan to more than five years would represent a significant advance. As those technical capabilities improve, it might turn out that the ability to accurately control computers and robots is limited more by scientists’ understanding of what the neurons are saying—that is, the neural code—than by the number of electrodes on the device.

Even the most capable implanted system, and maybe the most capable devices researchers can reasonably imagine, might fall short of the goal of actually augmenting skilled human performance. Nevertheless, Neuralink’s goal of creating better BMIs has the potential to improve the lives of people who can’t move or are unable to communicate. Right now, Musk’s vision of using BMIs to meld physical brains and intelligence with artificial ones is no more than a dream.

So, what does the future look like for Neuralink and other groups creating implantable BMIs? Devices with more electrodes that last longer and are connected to smaller and more powerful wireless electronics are essential. Better devices themselves, however, are insufficient. Continued public and private investment in companies and academic research labs, as well as innovative ways for these groups to work together to share technologies and data, will be necessary to truly advance scientists’ understanding of the brain and deliver on the promise of BMIs to improve peoples’ lives.

While researchers need to keep the future societal implications of advanced neurotechnologies in mind—there’s an essential role for ethicists and regulation—BMIs could be truly transformative as they help more people overcome limitations caused by injury or disease in the brain and body.

This article is republished from The Conversation under a Creative Commons license. Read the original article.

Image Credit: UPMC/Pitt Health Sciences, / CC BY-NC-ND Continue reading

Posted in Human Robots

#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

#434792 Extending Human Longevity With ...

Lizards can regrow entire limbs. Flatworms, starfish, and sea cucumbers regrow entire bodies. Sharks constantly replace lost teeth, often growing over 20,000 teeth throughout their lifetimes. How can we translate these near-superpowers to humans?

The answer: through the cutting-edge innovations of regenerative medicine.

While big data and artificial intelligence transform how we practice medicine and invent new treatments, regenerative medicine is about replenishing, replacing, and rejuvenating our physical bodies.

In Part 5 of this blog series on Longevity and Vitality, I detail three of the regenerative technologies working together to fully augment our vital human organs.

Replenish: Stem cells, the regenerative engine of the body
Replace: Organ regeneration and bioprinting
Rejuvenate: Young blood and parabiosis

Let’s dive in.

Replenish: Stem Cells – The Regenerative Engine of the Body
Stem cells are undifferentiated cells that can transform into specialized cells such as heart, neurons, liver, lung, skin and so on, and can also divide to produce more stem cells.

In a child or young adult, these stem cells are in large supply, acting as a built-in repair system. They are often summoned to the site of damage or inflammation to repair and restore normal function.

But as we age, our supply of stem cells begins to diminish as much as 100- to 10,000-fold in different tissues and organs. In addition, stem cells undergo genetic mutations, which reduce their quality and effectiveness at renovating and repairing your body.

Imagine your stem cells as a team of repairmen in your newly constructed mansion. When the mansion is new and the repairmen are young, they can fix everything perfectly. But as the repairmen age and reduce in number, your mansion eventually goes into disrepair and finally crumbles.

What if you could restore and rejuvenate your stem cell population?

One option to accomplish this restoration and rejuvenation is to extract and concentrate your own autologous adult stem cells from places like your adipose (or fat) tissue or bone marrow.

These stem cells, however, are fewer in number and have undergone mutations (depending on your age) from their original ‘software code.’ Many scientists and physicians now prefer an alternative source, obtaining stem cells from the placenta or umbilical cord, the leftovers of birth.

These stem cells, available in large supply and expressing the undamaged software of a newborn, can be injected into joints or administered intravenously to rejuvenate and revitalize.

Think of these stem cells as chemical factories generating vital growth factors that can help to reduce inflammation, fight autoimmune disease, increase muscle mass, repair joints, and even revitalize skin and grow hair.

Over the last decade, the number of publications per year on stem cell-related research has increased 40x, and the stem cell market is expected to increase to $297 billion by 2022.

Rising research and development initiatives to develop therapeutic options for chronic diseases and growing demand for regenerative treatment options are the most significant drivers of this budding industry.

Biologists led by Kohji Nishida at Osaka University in Japan have discovered a new way to nurture and grow the tissues that make up the human eyeball. The scientists are able to grow retinas, corneas, the eye’s lens, and more, using only a small sample of adult skin.

In a Stanford study, seven of 18 stroke victims who agreed to stem cell treatments showed remarkable motor function improvements. This treatment could work for other neurodegenerative conditions such as Alzheimer’s, Parkinson’s, and ALS.

Doctors from the USC Neurorestoration Center and Keck Medicine of USC injected stem cells into the damaged cervical spine of a recently paralyzed 21-year-old man. Three months later, he showed dramatic improvement in sensation and movement of both arms.

In 2019, doctors in the U.K. cured a patient with HIV for the second time ever thanks to the efficacy of stem cells. After giving the cancer patient (who also had HIV) an allogeneic haematopoietic (e.g. blood) stem cell treatment for his Hodgkin’s lymphoma, the patient went into long-term HIV remission—18 months and counting at the time of the study’s publication.

Replace: Organ Regeneration and 3D Printing
Every 10 minutes, someone is added to the US organ transplant waiting list, totaling over 113,000 people waiting for replacement organs as of January 2019.

Countless more people in need of ‘spare parts’ never make it onto the waiting list. And on average, 20 people die each day while waiting for a transplant.

As a result, 35 percent of all US deaths (~900,000 people) could be prevented or delayed with access to organ replacements.

The excessive demand for donated organs will only intensify as technologies like self-driving cars make the world safer, given that many organ donors result from auto and motorcycle accidents. Safer vehicles mean less accidents and donations.

Clearly, replacement and regenerative medicine represent a massive opportunity.

Organ Entrepreneurs
Enter United Therapeutics CEO, Dr. Martine Rothblatt. A one-time aerospace entrepreneur (she was the founder of Sirius Satellite Radio), Rothblatt changed careers in the 1990s after her daughter developed a rare lung disease.

Her moonshot today is to create an industry of replacement organs. With an initial focus on diseases of the lung, Rothblatt set out to create replacement lungs. To accomplish this goal, her company United Therapeutics has pursued a number of technologies in parallel.

3D Printing Lungs
In 2017, United teamed up with one of the world’s largest 3D printing companies, 3D Systems, to build a collagen bioprinter and is paying another company, 3Scan, to slice up lungs and create detailed maps of their interior.

This 3D Systems bioprinter now operates according to a method called stereolithography. A UV laser flickers through a shallow pool of collagen doped with photosensitive molecules. Wherever the laser lingers, the collagen cures and becomes solid.

Gradually, the object being printed is lowered and new layers are added. The printer can currently lay down collagen at a resolution of around 20 micrometers, but will need to achieve resolution of a micrometer in size to make the lung functional.

Once a collagen lung scaffold has been printed, the next step is to infuse it with human cells, a process called recellularization.

The goal here is to use stem cells that grow on scaffolding and differentiate, ultimately providing the proper functionality. Early evidence indicates this approach can work.

In 2018, Harvard University experimental surgeon Harald Ott reported that he pumped billions of human cells (from umbilical cords and diced lungs) into a pig lung stripped of its own cells. When Ott’s team reconnected it to a pig’s circulation, the resulting organ showed rudimentary function.

Humanizing Pig Lungs
Another of Rothblatt’s organ manufacturing strategies is called xenotransplantation, the idea of transplanting an animal’s organs into humans who need a replacement.

Given the fact that adult pig organs are similar in size and shape to those of humans, United Therapeutics has focused on genetically engineering pigs to allow humans to use their organs. “It’s actually not rocket science,” said Rothblatt in her 2015 TED talk. “It’s editing one gene after another.”

To accomplish this goal, United Therapeutics made a series of investments in companies such as Revivicor Inc. and Synthetic Genomics Inc., and signed large funding agreements with the University of Maryland, University of Alabama, and New York Presbyterian/Columbia University Medical Center to create xenotransplantation programs for new hearts, kidneys, and lungs, respectively. Rothblatt hopes to see human translation in three to four years.

In preparation for that day, United Therapeutics owns a 132-acre property in Research Triangle Park and built a 275,000-square-foot medical laboratory that will ultimately have the capability to annually produce up to 1,000 sets of healthy pig lungs—known as xenolungs—from genetically engineered pigs.

Lung Ex Vivo Perfusion Systems
Beyond 3D printing and genetically engineering pig lungs, Rothblatt has already begun implementing a third near-term approach to improve the supply of lungs across the US.

Only about 30 percent of potential donor lungs meet transplant criteria in the first place; of those, only about 85 percent of those are usable once they arrive at the surgery center. As a result, nearly 75 percent of possible lungs never make it to the recipient in need.

What if these lungs could be rejuvenated? This concept informs Dr. Rothblatt’s next approach.

In 2016, United Therapeutics invested $41.8 million in TransMedics Inc., an Andover, Massachusetts company that develops ex vivo perfusion systems for donor lungs, hearts, and kidneys.

The XVIVO Perfusion System takes marginal-quality lungs that initially failed to meet transplantation standard-of-care criteria and perfuses and ventilates them at normothermic conditions, providing an opportunity for surgeons to reassess transplant suitability.

Rejuvenate Young Blood and Parabiosis
In HBO’s parody of the Bay Area tech community, Silicon Valley, one of the episodes (Season 4, Episode 5) is named “The Blood Boy.”

In this installment, tech billionaire Gavin Belson (Matt Ross) is meeting with Richard Hendricks (Thomas Middleditch) and his team, speaking about the future of the decentralized internet. A young, muscled twenty-something disrupts the meeting when he rolls in a transfusion stand and silently hooks an intravenous connection between himself and Belson.

Belson then introduces the newcomer as his “transfusion associate” and begins to explain the science of parabiosis: “Regular transfusions of the blood of a younger physically fit donor can significantly retard the aging process.”

While the sitcom is fiction, that science has merit, and the scenario portrayed in the episode is already happening today.

On the first point, research at Stanford and Harvard has demonstrated that older animals, when transfused with the blood of young animals, experience regeneration across many tissues and organs.

The opposite is also true: young animals, when transfused with the blood of older animals, experience accelerated aging. But capitalizing on this virtual fountain of youth has been tricky.

Ambrosia
One company, a San Francisco-based startup called Ambrosia, recently commenced one of the trials on parabiosis. Their protocol is simple: Healthy participants aged 35 and older get a transfusion of blood plasma from donors under 25, and researchers monitor their blood over the next two years for molecular indicators of health and aging.

Ambrosia’s founder Jesse Karmazin became interested in launching a company around parabiosis after seeing impressive data from animals and studies conducted abroad in humans: In one trial after another, subjects experience a reversal of aging symptoms across every major organ system. “The effects seem to be almost permanent,” he said. “It’s almost like there’s a resetting of gene expression.”

Infusing your own cord blood stem cells as you age may have tremendous longevity benefits. Following an FDA press release in February 2019, Ambrosia halted its consumer-facing treatment after several months of operation.

Understandably, the FDA raised concerns about the practice of parabiosis because to date, there is a marked lack of clinical data to support the treatment’s effectiveness.

Elevian
On the other end of the reputability spectrum is a startup called Elevian, spun out of Harvard University. Elevian is approaching longevity with a careful, scientifically validated strategy. (Full Disclosure: I am both an advisor to and investor in Elevian.)

CEO Mark Allen, MD, is joined by a dozen MDs and Ph.Ds out of Harvard. Elevian’s scientific founders started the company after identifying specific circulating factors that may be responsible for the “young blood” effect.

One example: A naturally occurring molecule known as “growth differentiation factor 11,” or GDF11, when injected into aged mice, reproduces many of the regenerative effects of young blood, regenerating heart, brain, muscles, lungs, and kidneys.

More specifically, GDF11 supplementation reduces age-related cardiac hypertrophy, accelerates skeletal muscle repair, improves exercise capacity, improves brain function and cerebral blood flow, and improves metabolism.

Elevian is developing a number of therapeutics that regulate GDF11 and other circulating factors. The goal is to restore our body’s natural regenerative capacity, which Elevian believes can address some of the root causes of age-associated disease with the promise of reversing or preventing many aging-related diseases and extending the healthy lifespan.

Conclusion
In 1992, futurist Leland Kaiser coined the term “regenerative medicine”:

“A new branch of medicine will develop that attempts to change the course of chronic disease and in many instances will regenerate tired and failing organ systems.”

Since then, the powerful regenerative medicine industry has grown exponentially, and this rapid growth is anticipated to continue.

A dramatic extension of the human healthspan is just over the horizon. Soon, we’ll all have the regenerative superpowers previously relegated to a handful of animals and comic books.

What new opportunities open up when anybody, anywhere, and at anytime can regenerate, replenish, and replace entire organs and metabolic systems on command?

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