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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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Posted in Human Robots

#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?

Join Me
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#434658 The Next Data-Driven Healthtech ...

Increasing your healthspan (i.e. making 100 years old the new 60) will depend to a large degree on artificial intelligence. And, as we saw in last week’s blog, healthcare AI systems are extremely data-hungry.

Fortunately, a slew of new sensors and data acquisition methods—including over 122 million wearables shipped in 2018—are bursting onto the scene to meet the massive demand for medical data.

From ubiquitous biosensors, to the mobile healthcare revolution, to the transformative power of the Health Nucleus, converging exponential technologies are fundamentally transforming our approach to healthcare.

In Part 4 of this blog series on Longevity & Vitality, I expand on how we’re acquiring the data to fuel today’s AI healthcare revolution.

In this blog, I’ll explore:

How the Health Nucleus is transforming “sick care” to healthcare
Sensors, wearables, and nanobots
The advent of mobile health

Let’s dive in.

Health Nucleus: Transforming ‘Sick Care’ to Healthcare
Much of today’s healthcare system is actually sick care. Most of us assume that we’re perfectly healthy, with nothing going on inside our bodies, until the day we travel to the hospital writhing in pain only to discover a serious or life-threatening condition.

Chances are that your ailment didn’t materialize that morning; rather, it’s been growing or developing for some time. You simply weren’t aware of it. At that point, once you’re diagnosed as “sick,” our medical system engages to take care of you.

What if, instead of this retrospective and reactive approach, you were constantly monitored, so that you could know the moment anything was out of whack?

Better yet, what if you more closely monitored those aspects of your body that your gene sequence predicted might cause you difficulty? Think: your heart, your kidneys, your breasts. Such a system becomes personalized, predictive, and possibly preventative.

This is the mission of the Health Nucleus platform built by Human Longevity, Inc. (HLI). While not continuous—that will come later, with the next generation of wearable and implantable sensors—the Health Nucleus was designed to ‘digitize’ you once per year to help you determine whether anything is going on inside your body that requires immediate attention.

The Health Nucleus visit provides you with the following tests during a half-day visit:

Whole genome sequencing (30x coverage)
Whole body (non-contrast) MRI
Brain magnetic resonance imaging/angiography (MRI/MRA)
CT (computed tomography) of the heart and lungs
Coronary artery calcium scoring
Electrocardiogram
Echocardiogram
Continuous cardiac monitoring
Clinical laboratory tests and metabolomics

In late 2018, HLI published the results of the first 1,190 clients through the Health Nucleus. The results were eye-opening—especially since these patients were all financially well-off, and already had access to the best doctors.

Following are the physiological and genomic findings in these clients who self-selected to undergo evaluation at HLI’s Health Nucleus.

Physiological Findings [TG]

Two percent had previously unknown tumors detected by MRI
2.5 percent had previously undetected aneurysms detected by MRI
Eight percent had cardiac arrhythmia found on cardiac rhythm monitoring, not previously known
Nine percent had moderate-severe coronary artery disease risk, not previously known
16 percent discovered previously unknown cardiac structure/function abnormalities
30 percent had elevated liver fat, not previously known

Genomic Findings [TG]

24 percent of clients uncovered a rare (unknown) genetic mutation found on WGS
63 percent of clients had a rare genetic mutation with a corresponding phenotypic finding

In summary, HLI’s published results found that 14.4 percent of clients had significant findings that are actionable, requiring immediate or near-term follow-up and intervention.

Long-term value findings were found in 40 percent of the clients we screened. Long-term clinical findings include discoveries that require medical attention or monitoring but are not immediately life-threatening.

The bottom line: most people truly don’t know their actual state of health. The ability to take a fully digital deep dive into your health status at least once per year will enable you to detect disease at stage zero or stage one, when it is most curable.

Sensors, Wearables, and Nanobots
Wearables, connected devices, and quantified self apps will allow us to continuously collect enormous amounts of useful health information.

Wearables like the Quanttus wristband and Vital Connect can transmit your electrocardiogram data, vital signs, posture, and stress levels anywhere on the planet.

In April 2017, we were proud to grant $2.5 million in prize money to the winning team in the Qualcomm Tricorder XPRIZE, Final Frontier Medical Devices.

Using a group of noninvasive sensors that collect data on vital signs, body chemistry, and biological functions, Final Frontier integrates this data in their powerful, AI-based DxtER diagnostic engine for rapid, high-precision assessments.

Their engine combines learnings from clinical emergency medicine and data analysis from actual patients.

Google is developing a full range of internal and external sensors (e.g. smart contact lenses) that can monitor the wearer’s vitals, ranging from blood sugar levels to blood chemistry.

In September 2018, Apple announced its Series 4 Apple Watch, including an FDA-approved mobile, on-the-fly ECG. Granted its first FDA approval, Apple appears to be moving deeper into the sensing healthcare market.

Further, Apple is reportedly now developing sensors that can non-invasively monitor blood sugar levels in real time for diabetic treatment. IoT-connected sensors are also entering the world of prescription drugs.

Last year, the FDA approved the first sensor-embedded pill, Abilify MyCite. This new class of digital pills can now communicate medication data to a user-controlled app, to which doctors may be granted access for remote monitoring.

Perhaps what is most impressive about the next generation of wearables and implantables is the density of sensors, processing, networking, and battery capability that we can now cheaply and compactly integrate.

Take the second-generation OURA ring, for example, which focuses on sleep measurement and management.

The OURA ring looks like a slightly thick wedding band, yet contains an impressive array of sensors and capabilities, including:

Two infrared LED
One infrared sensor
Three temperature sensors
One accelerometer
A six-axis gyro
A curved battery with a seven-day life
The memory, processing, and transmission capability required to connect with your smartphone

Disrupting Medical Imaging Hardware
In 2018, we saw lab breakthroughs that will drive the cost of an ultrasound sensor to below $100, in a packaging smaller than most bandages, powered by a smartphone. Dramatically disrupting ultrasound is just the beginning.

Nanobots and Nanonetworks
While wearables have long been able to track and transmit our steps, heart rate, and other health data, smart nanobots and ingestible sensors will soon be able to monitor countless new parameters and even help diagnose disease.

Some of the most exciting breakthroughs in smart nanotechnology from the past year include:

Researchers from the École Polytechnique Fédérale de Lausanne (EPFL) and the Swiss Federal Institute of Technology in Zurich (ETH Zurich) demonstrated artificial microrobots that can swim and navigate through different fluids, independent of additional sensors, electronics, or power transmission.

Researchers at the University of Chicago proposed specific arrangements of DNA-based molecular logic gates to capture the information contained in the temporal portion of our cells’ communication mechanisms. Accessing the otherwise-lost time-dependent information of these cellular signals is akin to knowing the tune of a song, rather than solely the lyrics.

MIT researchers built micron-scale robots able to sense, record, and store information about their environment. These tiny robots, about 100 micrometers in diameter (approximately the size of a human egg cell), can also carry out pre-programmed computational tasks.

Engineers at University of California, San Diego developed ultrasound-powered nanorobots that swim efficiently through your blood, removing harmful bacteria and the toxins they produce.

But it doesn’t stop there.

As nanosensor and nanonetworking capabilities develop, these tiny bots may soon communicate with each other, enabling the targeted delivery of drugs and autonomous corrective action.

Mobile Health
The OURA ring and the Series 4 Apple Watch are just the tip of the spear when it comes to our future of mobile health. This field, predicted to become a $102 billion market by 2022, puts an on-demand virtual doctor in your back pocket.

Step aside, WebMD.

In true exponential technology fashion, mobile device penetration has increased dramatically, while image recognition error rates and sensor costs have sharply declined.

As a result, AI-powered medical chatbots are flooding the market; diagnostic apps can identify anything from a rash to diabetic retinopathy; and with the advent of global connectivity, mHealth platforms enable real-time health data collection, transmission, and remote diagnosis by medical professionals.

Already available to residents across North London, Babylon Health offers immediate medical advice through AI-powered chatbots and video consultations with doctors via its app.

Babylon now aims to build up its AI for advanced diagnostics and even prescription. Others, like Woebot, take on mental health, using cognitive behavioral therapy in communications over Facebook messenger with patients suffering from depression.

In addition to phone apps and add-ons that test for fertility or autism, the now-FDA-approved Clarius L7 Linear Array Ultrasound Scanner can connect directly to iOS and Android devices and perform wireless ultrasounds at a moment’s notice.

Next, Healthy.io, an Israeli startup, uses your smartphone and computer vision to analyze traditional urine test strips—all you need to do is take a few photos.

With mHealth platforms like ClickMedix, which connects remotely-located patients to medical providers through real-time health data collection and transmission, what’s to stop us from delivering needed treatments through drone delivery or robotic telesurgery?

Welcome to the age of smartphone-as-a-medical-device.

Conclusion
With these DIY data collection and diagnostic tools, we save on transportation costs (time and money), and time bottlenecks.

No longer will you need to wait for your urine or blood results to go through the current information chain: samples will be sent to the lab, analyzed by a technician, results interpreted by your doctor, and only then relayed to you.

Just like the “sage-on-the-stage” issue with today’s education system, healthcare has a “doctor-on-the-dais” problem. Current medical procedures are too complicated and expensive for a layperson to perform and analyze on their own.

The coming abundance of healthcare data promises to transform how we approach healthcare, putting the power of exponential technologies in the patient’s hands and revolutionizing how we live.

Join Me
Abundance-Digital Online Community: I’ve created a Digital/Online community of bold, abundance-minded entrepreneurs called Abundance-Digital. Abundance-Digital is my ‘onramp’ for exponential entrepreneurs – those who want to get involved and play at a higher level. Click here to learn more.

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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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Posted in Human Robots

#434534 To Extend Our Longevity, First We Must ...

Healthcare today is reactive, retrospective, bureaucratic, and expensive. It’s sick care, not healthcare.

But that is radically changing at an exponential rate.

Through this multi-part blog series on longevity, I’ll take a deep dive into aging, longevity, and healthcare technologies that are working together to dramatically extend the human lifespan, disrupting the $3 trillion healthcare system in the process.

I’ll begin the series by explaining the nine hallmarks of aging, as explained in this journal article. Next, I’ll break down the emerging technologies and initiatives working to combat these nine hallmarks. Finally, I’ll explore the transformative implications of dramatically extending the human health span.

In this blog I’ll cover:

Why the healthcare system is broken
Why, despite this, we live in the healthiest time in human history
The nine mechanisms of aging

Let’s dive in.

The System is Broken—Here’s the Data:

Doctors spend $210 billion per year on procedures that aren’t based on patient need, but fear of liability.
Americans spend, on average, $8,915 per person on healthcare—more than any other country on Earth.
Prescription drugs cost around 50 percent more in the US than in other industrialized countries.
At current rates, by 2025, nearly 25 percent of the US GDP will be spent on healthcare.
It takes 12 years and $359 million, on average, to take a new drug from the lab to a patient.
Only 5 in 5,000 of these new drugs proceed to human testing. From there, only 1 of those 5 is actually approved for human use.

And Yet, We Live in the Healthiest Time in Human History
Consider these insights, which I adapted from Max Roser’s excellent database Our World in Data:

Right now, the countries with the lowest life expectancy in the world still have higher life expectancies than the countries with the highest life expectancy did in 1800.
In 1841, a 5-year-old had a life expectancy of 55 years. Today, a 5-year-old can expect to live 82 years—an increase of 27 years.
We’re seeing a dramatic increase in healthspan. In 1845, a newborn would expect to live to 40 years old. For a 70-year-old, that number became 79. Now, people of all ages can expect to live to be 81 to 86 years old.
100 years ago, 1 of 3 children would die before the age of 5. As of 2015, the child mortality rate fell to just 4.3 percent.
The cancer mortality rate has declined 27 percent over the past 25 years.

Figure: Around the globe, life expectancy has doubled since the 1800s. | Image from Life Expectancy by Max Roser – Our World in Data / CC BY SA
Figure: A dramatic reduction in child mortality in 1800 vs. in 2015. | Image from Child Mortality by Max Roser – Our World in Data / CC BY SA
The 9 Mechanisms of Aging
*This section was adapted from CB INSIGHTS: The Future Of Aging.

Longevity, healthcare, and aging are intimately linked.

With better healthcare, we can better treat some of the leading causes of death, impacting how long we live.

By investigating how to treat diseases, we’ll inevitably better understand what causes these diseases in the first place, which directly correlates to why we age.

Following are the nine hallmarks of aging. I’ll share examples of health and longevity technologies addressing each of these later in this blog series.

Genomic instability: As we age, the environment and normal cellular processes cause damage to our genes. Activities like flying at high altitude, for example, expose us to increased radiation or free radicals. This damage compounds over the course of life and is known to accelerate aging.
Telomere attrition: Each strand of DNA in the body (known as chromosomes) is capped by telomeres. These short snippets of DNA repeated thousands of times are designed to protect the bulk of the chromosome. Telomeres shorten as our DNA replicates; if a telomere reaches a certain critical shortness, a cell will stop dividing, resulting in increased incidence of disease.
Epigenetic alterations: Over time, environmental factors will change how genes are expressed, i.e., how certain sequences of DNA are read and the instruction set implemented.
Loss of proteostasis: Over time, different proteins in our body will no longer fold and function as they are supposed to, resulting in diseases ranging from cancer to neurological disorders.
Deregulated nutrient-sensing: Nutrient levels in the body can influence various metabolic pathways. Among the affected parts of these pathways are proteins like IGF-1, mTOR, sirtuins, and AMPK. Changing levels of these proteins’ pathways has implications on longevity.
Mitochondrial dysfunction: Mitochondria (our cellular power plants) begin to decline in performance as we age. Decreased performance results in excess fatigue and other symptoms of chronic illnesses associated with aging.
Cellular senescence: As cells age, they stop dividing and cannot be removed from the body. They build up and typically cause increased inflammation.
Stem cell exhaustion: 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 the body.
Altered intercellular communication: The communication mechanisms that cells use are disrupted as cells age, resulting in decreased ability to transmit information between cells.

Conclusion
Over the past 200 years, we have seen an abundance of healthcare technologies enable a massive lifespan boom.

Now, exponential technologies like artificial intelligence, 3D printing and sensors, as well as tremendous advancements in genomics, stem cell research, chemistry, and many other fields, are beginning to tackle the fundamental issues of why we age.

In the next blog in this series, we will dive into how genome sequencing and editing, along with new classes of drugs, are augmenting our biology to further extend our healthy lives.

What will you be able to achieve with an extra 30 to 50 healthy years (or longer) in your lifespan? Personally, I’m excited for a near-infinite lifespan to take on moonshots.

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