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#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
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

#434759 To Be Ethical, AI Must Become ...

As over-hyped as artificial intelligence is—everyone’s talking about it, few fully understand it, it might leave us all unemployed but also solve all the world’s problems—its list of accomplishments is growing. AI can now write realistic-sounding text, give a debating champ a run for his money, diagnose illnesses, and generate fake human faces—among much more.

After training these systems on massive datasets, their creators essentially just let them do their thing to arrive at certain conclusions or outcomes. The problem is that more often than not, even the creators don’t know exactly why they’ve arrived at those conclusions or outcomes. There’s no easy way to trace a machine learning system’s rationale, so to speak. The further we let AI go down this opaque path, the more likely we are to end up somewhere we don’t want to be—and may not be able to come back from.

In a panel at the South by Southwest interactive festival last week titled “Ethics and AI: How to plan for the unpredictable,” experts in the field shared their thoughts on building more transparent, explainable, and accountable AI systems.

Not New, but Different
Ryan Welsh, founder and director of explainable AI startup Kyndi, pointed out that having knowledge-based systems perform advanced tasks isn’t new; he cited logistical, scheduling, and tax software as examples. What’s new is the learning component, our inability to trace how that learning occurs, and the ethical implications that could result.

“Now we have these systems that are learning from data, and we’re trying to understand why they’re arriving at certain outcomes,” Welsh said. “We’ve never actually had this broad society discussion about ethics in those scenarios.”

Rather than continuing to build AIs with opaque inner workings, engineers must start focusing on explainability, which Welsh broke down into three subcategories. Transparency and interpretability come first, and refer to being able to find the units of high influence in a machine learning network, as well as the weights of those units and how they map to specific data and outputs.

Then there’s provenance: knowing where something comes from. In an ideal scenario, for example, Open AI’s new text generator would be able to generate citations in its text that reference academic (and human-created) papers or studies.

Explainability itself is the highest and final bar and refers to a system’s ability to explain itself in natural language to the average user by being able to say, “I generated this output because x, y, z.”

“Humans are unique in our ability and our desire to ask why,” said Josh Marcuse, executive director of the Defense Innovation Board, which advises Department of Defense senior leaders on innovation. “The reason we want explanations from people is so we can understand their belief system and see if we agree with it and want to continue to work with them.”

Similarly, we need to have the ability to interrogate AIs.

Two Types of Thinking
Welsh explained that one big barrier standing in the way of explainability is the tension between the deep learning community and the symbolic AI community, which see themselves as two different paradigms and historically haven’t collaborated much.

Symbolic or classical AI focuses on concepts and rules, while deep learning is centered around perceptions. In human thought this is the difference between, for example, deciding to pass a soccer ball to a teammate who is open (you make the decision because conceptually you know that only open players can receive passes), and registering that the ball is at your feet when someone else passes it to you (you’re taking in information without making a decision about it).

“Symbolic AI has abstractions and representation based on logic that’s more humanly comprehensible,” Welsh said. To truly mimic human thinking, AI needs to be able to both perceive information and conceptualize it. An example of perception (deep learning) in an AI is recognizing numbers within an image, while conceptualization (symbolic learning) would give those numbers a hierarchical order and extract rules from the hierachy (4 is greater than 3, and 5 is greater than 4, therefore 5 is also greater than 3).

Explainability comes in when the system can say, “I saw a, b, and c, and based on that decided x, y, or z.” DeepMind and others have recently published papers emphasizing the need to fuse the two paradigms together.

Implications Across Industries
One of the most prominent fields where AI ethics will come into play, and where the transparency and accountability of AI systems will be crucial, is defense. Marcuse said, “We’re accountable beings, and we’re responsible for the choices we make. Bringing in tech or AI to a battlefield doesn’t strip away that meaning and accountability.”

In fact, he added, rather than worrying about how AI might degrade human values, people should be asking how the tech could be used to help us make better moral choices.

It’s also important not to conflate AI with autonomy—a worst-case scenario that springs to mind is an intelligent destructive machine on a rampage. But in fact, Marcuse said, in the defense space, “We have autonomous systems today that don’t rely on AI, and most of the AI systems we’re contemplating won’t be autonomous.”

The US Department of Defense released its 2018 artificial intelligence strategy last month. It includes developing a robust and transparent set of principles for defense AI, investing in research and development for AI that’s reliable and secure, continuing to fund research in explainability, advocating for a global set of military AI guidelines, and finding ways to use AI to reduce the risk of civilian casualties and other collateral damage.

Though these were designed with defense-specific aims in mind, Marcuse said, their implications extend across industries. “The defense community thinks of their problems as being unique, that no one deals with the stakes and complexity we deal with. That’s just wrong,” he said. Making high-stakes decisions with technology is widespread; safety-critical systems are key to aviation, medicine, and self-driving cars, to name a few.

Marcuse believes the Department of Defense can invest in AI safety in a way that has far-reaching benefits. “We all depend on technology to keep us alive and safe, and no one wants machines to harm us,” he said.

A Creation Superior to Its Creator
That said, we’ve come to expect technology to meet our needs in just the way we want, all the time—servers must never be down, GPS had better not take us on a longer route, Google must always produce the answer we’re looking for.

With AI, though, our expectations of perfection may be less reasonable.

“Right now we’re holding machines to superhuman standards,” Marcuse said. “We expect them to be perfect and infallible.” Take self-driving cars. They’re conceived of, built by, and programmed by people, and people as a whole generally aren’t great drivers—just look at traffic accident death rates to confirm that. But the few times self-driving cars have had fatal accidents, there’s been an ensuing uproar and backlash against the industry, as well as talk of implementing more restrictive regulations.

This can be extrapolated to ethics more generally. We as humans have the ability to explain our decisions, but many of us aren’t very good at doing so. As Marcuse put it, “People are emotional, they confabulate, they lie, they’re full of unconscious motivations. They don’t pass the explainability test.”

Why, then, should explainability be the standard for AI?

Even if humans aren’t good at explaining our choices, at least we can try, and we can answer questions that probe at our decision-making process. A deep learning system can’t do this yet, so working towards being able to identify which input data the systems are triggering on to make decisions—even if the decisions and the process aren’t perfect—is the direction we need to head.

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Posted in Human Robots

#434643 Sensors and Machine Learning Are Giving ...

According to some scientists, humans really do have a sixth sense. There’s nothing supernatural about it: the sense of proprioception tells you about the relative positions of your limbs and the rest of your body. Close your eyes, block out all sound, and you can still use this internal “map” of your external body to locate your muscles and body parts – you have an innate sense of the distances between them, and the perception of how they’re moving, above and beyond your sense of touch.

This sense is invaluable for allowing us to coordinate our movements. In humans, the brain integrates senses including touch, heat, and the tension in muscle spindles to allow us to build up this map.

Replicating this complex sense has posed a great challenge for roboticists. We can imagine simulating the sense of sight with cameras, sound with microphones, or touch with pressure-pads. Robots with chemical sensors could be far more accurate than us in smell and taste, but building in proprioception, the robot’s sense of itself and its body, is far more difficult, and is a large part of why humanoid robots are so tricky to get right.

Simultaneous localization and mapping (SLAM) software allows robots to use their own senses to build up a picture of their surroundings and environment, but they’d need a keen sense of the position of their own bodies to interact with it. If something unexpected happens, or in dark environments where primary senses are not available, robots can struggle to keep track of their own position and orientation. For human-robot interaction, wearable robotics, and delicate applications like surgery, tiny differences can be extremely important.

Piecemeal Solutions
In the case of hard robotics, this is generally solved by using a series of strain and pressure sensors in each joint, which allow the robot to determine how its limbs are positioned. That works fine for rigid robots with a limited number of joints, but for softer, more flexible robots, this information is limited. Roboticists are faced with a dilemma: a vast, complex array of sensors for every degree of freedom in the robot’s movement, or limited skill in proprioception?

New techniques, often involving new arrays of sensory material and machine-learning algorithms to fill in the gaps, are starting to tackle this problem. Take the work of Thomas George Thuruthel and colleagues in Pisa and San Diego, who draw inspiration from the proprioception of humans. In a new paper in Science Robotics, they describe the use of soft sensors distributed through a robotic finger at random. This placement is much like the constant adaptation of sensors in humans and animals, rather than relying on feedback from a limited number of positions.

The sensors allow the soft robot to react to touch and pressure in many different locations, forming a map of itself as it contorts into complicated positions. The machine-learning algorithm serves to interpret the signals from the randomly-distributed sensors: as the finger moves around, it’s observed by a motion capture system. After training the robot’s neural network, it can associate the feedback from the sensors with the position of the finger detected in the motion-capture system, which can then be discarded. The robot observes its own motions to understand the shapes that its soft body can take, and translate them into the language of these soft sensors.

“The advantages of our approach are the ability to predict complex motions and forces that the soft robot experiences (which is difficult with traditional methods) and the fact that it can be applied to multiple types of actuators and sensors,” said Michael Tolley of the University of California San Diego. “Our method also includes redundant sensors, which improves the overall robustness of our predictions.”

The use of machine learning lets the roboticists come up with a reliable model for this complex, non-linear system of motions for the actuators, something difficult to do by directly calculating the expected motion of the soft-bot. It also resembles the human system of proprioception, built on redundant sensors that change and shift in position as we age.

In Search of a Perfect Arm
Another approach to training robots in using their bodies comes from Robert Kwiatkowski and Hod Lipson of Columbia University in New York. In their paper “Task-agnostic self-modeling machines,” also recently published in Science Robotics, they describe a new type of robotic arm.

Robotic arms and hands are getting increasingly dexterous, but training them to grasp a large array of objects and perform many different tasks can be an arduous process. It’s also an extremely valuable skill to get right: Amazon is highly interested in the perfect robot arm. Google hooked together an array of over a dozen robot arms so that they could share information about grasping new objects, in part to cut down on training time.

Individually training a robot arm to perform every individual task takes time and reduces the adaptability of your robot: either you need an ML algorithm with a huge dataset of experiences, or, even worse, you need to hard-code thousands of different motions. Kwiatkowski and Lipson attempt to overcome this by developing a robotic system that has a “strong sense of self”: a model of its own size, shape, and motions.

They do this using deep machine learning. The robot begins with no prior knowledge of its own shape or the underlying physics of its motion. It then repeats a series of a thousand random trajectories, recording the motion of its arm. Kwiatkowski and Lipson compare this to a baby in the first year of life observing the motions of its own hands and limbs, fascinated by picking up and manipulating objects.

Again, once the robot has trained itself to interpret these signals and build up a robust model of its own body, it’s ready for the next stage. Using that deep-learning algorithm, the researchers then ask the robot to design strategies to accomplish simple pick-up and place and handwriting tasks. Rather than laboriously and narrowly training itself for each individual task, limiting its abilities to a very narrow set of circumstances, the robot can now strategize how to use its arm for a much wider range of situations, with no additional task-specific training.

Damage Control
In a further experiment, the researchers replaced part of the arm with a “deformed” component, intended to simulate what might happen if the robot was damaged. The robot can then detect that something’s up and “reconfigure” itself, reconstructing its self-model by going through the training exercises once again; it was then able to perform the same tasks with only a small reduction in accuracy.

Machine learning techniques are opening up the field of robotics in ways we’ve never seen before. Combining them with our understanding of how humans and other animals are able to sense and interact with the world around us is bringing robotics closer and closer to becoming truly flexible and adaptable, and, eventually, omnipresent.

But before they can get out and shape the world, as these studies show, they will need to understand themselves.

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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.

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

#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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