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#434528 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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#434518 NVIDIA Launches New Robotics Lab in ...

Dieter Fox tells us about his plans for NVIDIA's new robotics lab Continue reading

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

2018 was bonkers for science.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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#434492 Black Mirror’s ‘Bandersnatch’ ...

When was the last time you watched a movie where you could control the plot?

Bandersnatch is the first interactive film in the sci fi anthology series Black Mirror. Written by series creator Charlie Brooker and directed by David Slade, the film tells the story of young programmer Stefan Butler, who is adapting a fantasy choose-your-own-adventure novel called Bandersnatch into a video game. Throughout the film, viewers are given the power to influence Butler’s decisions, leading to diverging plots with different endings.

Like many Black Mirror episodes, this film is mind-bending, dark, and thought-provoking. In addition to innovating cinema as we know it, it is a fascinating rumination on free will, parallel realities, and emerging technologies.

Pick Your Own Adventure
With a non-linear script, Bandersnatch is a viewing experience like no other. Throughout the film viewers are given the option of making a decision for the protagonist. In these instances, they have 10 seconds to make a decision until a default decision is made. For example, in the early stage of the plot, Butler is given the choice of accepting or rejecting Tuckersoft’s offer to develop a video game and the viewer gets to decide what he does. The decision then shapes the plot accordingly.

The video game Butler is developing involves moving through a graphical maze of corridors while avoiding a creature called the Pax, and at times making choices through an on-screen instruction (sound familiar?). In other words, it’s a pick-your-own-adventure video game in a pick-your-own-adventure movie.

Many viewers have ended up spending hours exploring all the different branches of the narrative (though the average viewing is 90 minutes). One user on reddit has mapped out an entire flowchart, showing how all the different decisions (and pseudo-decisions) lead to various endings.

However, over time, Butler starts to question his own free will. It’s almost as if he’s beginning to realize that the audience is controlling him. In one branch of the narrative, he is confronted by this reality when the audience indicates to him that he is being controlled in a Netflix show: “I am watching you on Netflix. I make all the decisions for you”. Butler, as you can imagine, is horrified by this message.

But Butler isn’t the only one who has an illusion of choice. We, the seemingly powerful viewers, also appear to operate under the illusion of choice. Despite there being five main endings to the film, they are all more or less the same.

The Science Behind Bandersnatch
The premise of Bandersnatch isn’t based on fantasy, but hard science. Free will has always been a widely-debated issue in neuroscience, with reputable scientists and studies demonstrating that the whole concept may be an illusion.

In the 1970s, a psychologist named Benjamin Libet conducted a series of experiments that studied voluntary decision making in humans. He found that brain activity imitating an action, such as moving your wrist, preceded the conscious awareness of the action.

Psychologist Malcom Gladwell theorizes that while we like to believe we spend a lot of time thinking about our decisions, our mental processes actually work rapidly, automatically, and often subconsciously, from relatively little information. In addition to this, thinking and making decisions are usually a byproduct of several different brain systems, such as the hippocampus, amygdala, and prefrontal cortex working together. You are more conscious of some information processes in the brain than others.

As neuroscientist and philosopher Sam Harris points out in his book Free Will, “You did not pick your parents or the time and place of your birth. You didn’t choose your gender or most of your life experiences. You had no control whatsoever over your genome or the development of your brain. And now your brain is making choices on the basis of preferences and beliefs that have been hammered into it over a lifetime.” Like Butler, we may believe we are operating under full agency of our abilities, but we are at the mercy of many internal and external factors that influence our decisions.

Beyond free will, Bandersnatch also taps into the theory of parallel universes, a facet of the astronomical theory of the multiverse. In astrophysics, there is a theory that there are parallel universes other than our own, where all the choices you made are played out in alternate realities. For instance, if today you had the option of having cereal or eggs for breakfast, and you chose eggs, in a parallel universe, you chose cereal. Human history and our lives may have taken different paths in these parallel universes.

The Future of Cinema
In the future, the viewing experience will no longer be a passive one. Bandersnatch is just a glimpse into how technology is revolutionizing film as we know it and making it a more interactive and personalized experience. All the different scenarios and branches of the plot were scripted and filmed, but in the future, they may be adapted real-time via artificial intelligence.

Virtual reality may allow us to play an even more active role by making us participants or characters in the film. Data from your history of preferences and may be used to create a unique version of the plot that is optimized for your viewing experience.

Let’s also not underestimate the social purpose of advancing film and entertainment. Science fiction gives us the ability to create simulations of the future. Different narratives can allow us to explore how powerful technologies combined with human behavior can result in positive or negative scenarios. Perhaps in the future, science fiction will explore implications of technologies and observe human decision making in novel contexts, via AI-powered films in the virtual world.

Image Credit: andrey_l / Shutterstock.com

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#434336 These Smart Seafaring Robots Have a ...

Drones. Self-driving cars. Flying robo taxis. If the headlines of the last few years are to be believed, terrestrial transportation in the future will someday be filled with robotic conveyances and contraptions that will require little input from a human other than to download an app.

But what about the other 70 percent of the planet’s surface—the part that’s made up of water?

Sure, there are underwater drones that can capture 4K video for the next BBC documentary. Remotely operated vehicles (ROVs) are capable of diving down thousands of meters to investigate ocean vents or repair industrial infrastructure.

Yet most of the robots on or below the water today still lean heavily on the human element to operate. That’s not surprising given the unstructured environment of the seas and the poor communication capabilities for anything moving below the waves. Autonomous underwater vehicles (AUVs) are probably the closest thing today to smart cars in the ocean, but they generally follow pre-programmed instructions.

A new generation of seafaring robots—leveraging artificial intelligence, machine vision, and advanced sensors, among other technologies—are beginning to plunge into the ocean depths. Here are some of the latest and most exciting ones.

The Transformer of the Sea
Nic Radford, chief technology officer of Houston Mechatronics Inc. (HMI), is hesitant about throwing around the word “autonomy” when talking about his startup’s star creation, Aquanaut. He prefers the term “shared control.”

Whatever you want to call it, Aquanaut seems like something out of the script of a Transformers movie. The underwater robot begins each mission in a submarine-like shape, capable of autonomously traveling up to 200 kilometers on battery power, depending on the assignment.

When Aquanaut reaches its destination—oil and gas is the primary industry HMI hopes to disrupt to start—its four specially-designed and built linear actuators go to work. Aquanaut then unfolds into a robot with a head, upper torso, and two manipulator arms, all while maintaining proper buoyancy to get its job done.

The lightbulb moment of how to engineer this transformation from submarine to robot came one day while Aquanaut’s engineers were watching the office’s stand-up desks bob up and down. The answer to the engineering challenge of the hull suddenly seemed obvious.

“We’re just gonna build a big, gigantic, underwater stand-up desk,” Radford told Singularity Hub.

Hardware wasn’t the only problem the team, comprised of veteran NASA roboticists like Radford, had to solve. In order to ditch the expensive support vessels and large teams of humans required to operate traditional ROVs, Aquanaut would have to be able to sense its environment in great detail and relay that information back to headquarters using an underwater acoustics communications system that harkens back to the days of dial-up internet connections.

To tackle that problem of low bandwidth, HMI equipped Aquanaut with a machine vision system comprised of acoustic, optical, and laser-based sensors. All of that dense data is compressed using in-house designed technology and transmitted to a single human operator who controls Aquanaut with a few clicks of a mouse. In other words, no joystick required.

“I don’t know of anyone trying to do this level of autonomy as it relates to interacting with the environment,” Radford said.

HMI got $20 million earlier this year in Series B funding co-led by Transocean, one of the world’s largest offshore drilling contractors. That should be enough money to finish the Aquanaut prototype, which Radford said is about 99.8 percent complete. Some “high-profile” demonstrations are planned for early next year, with commercial deployments as early as 2020.

“What just gives us an incredible advantage here is that we have been born and bred on doing robotic systems for remote locations,” Radford noted. “This is my life, and I’ve bet the farm on it, and it takes this kind of fortitude and passion to see these things through, because these are not easy problems to solve.”

On Cruise Control
Meanwhile, a Boston-based startup is trying to solve the problem of making ships at sea autonomous. Sea Machines is backed by about $12.5 million in capital venture funding, with Toyota AI joining the list of investors in a $10 million Series A earlier this month.

Sea Machines is looking to the self-driving industry for inspiration, developing what it calls “vessel intelligence” systems that can be retrofitted on existing commercial vessels or installed on newly-built working ships.

For instance, the startup announced a deal earlier this year with Maersk, the world’s largest container shipping company, to deploy a system of artificial intelligence, computer vision, and LiDAR on the Danish company’s new ice-class container ship. The technology works similar to advanced driver-assistance systems found in automobiles to avoid hazards. The proof of concept will lay the foundation for a future autonomous collision avoidance system.

It’s not just startups making a splash in autonomous shipping. Radford noted that Rolls Royce—yes, that Rolls Royce—is leading the way in the development of autonomous ships. Its Intelligence Awareness system pulls in nearly every type of hyped technology on the market today: neural networks, augmented reality, virtual reality, and LiDAR.

In augmented reality mode, for example, a live feed video from the ship’s sensors can detect both static and moving objects, overlaying the scene with details about the types of vessels in the area, as well as their distance, heading, and other pertinent data.

While safety is a primary motivation for vessel automation—more than 1,100 ships have been lost over the past decade—these new technologies could make ships more efficient and less expensive to operate, according to a story in Wired about the Rolls Royce Intelligence Awareness system.

Sea Hunt Meets Science
As Singularity Hub noted in a previous article, ocean robots can also play a critical role in saving the seas from environmental threats. One poster child that has emerged—or, invaded—is the spindly lionfish.

A venomous critter endemic to the Indo-Pacific region, the lionfish is now found up and down the east coast of North America and beyond. And it is voracious, eating up to 30 times its own stomach volume and reducing juvenile reef fish populations by nearly 90 percent in as little as five weeks, according to the Ocean Support Foundation.

That has made the colorful but deadly fish Public Enemy No. 1 for many marine conservationists. Both researchers and startups are developing autonomous robots to hunt down the invasive predator.

At the Worcester Polytechnic Institute, for example, students are building a spear-carrying robot that uses machine learning and computer vision to distinguish lionfish from other aquatic species. The students trained the algorithms on thousands of different images of lionfish. The result: a lionfish-killing machine that boasts an accuracy of greater than 95 percent.

Meanwhile, a small startup called the American Marine Research Corporation out of Pensacola, Florida is applying similar technology to seek and destroy lionfish. Rather than spearfishing, the AMRC drone would stun and capture the lionfish, turning a profit by selling the creatures to local seafood restaurants.

Lionfish: It’s what’s for dinner.

Water Bots
A new wave of smart, independent robots are diving, swimming, and cruising across the ocean and its deepest depths. These autonomous systems aren’t necessarily designed to replace humans, but to venture where we can’t go or to improve safety at sea. And, perhaps, these latest innovations may inspire the robots that will someday plumb the depths of watery planets far from Earth.

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