Tag Archives: death

#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

#434637 AI Is Rapidly Augmenting Healthcare and ...

When it comes to the future of healthcare, perhaps the only technology more powerful than CRISPR is artificial intelligence.

Over the past five years, healthcare AI startups around the globe raised over $4.3 billion across 576 deals, topping all other industries in AI deal activity.

During this same period, the FDA has given 70 AI healthcare tools and devices ‘fast-tracked approval’ because of their ability to save both lives and money.

The pace of AI-augmented healthcare innovation is only accelerating.

In Part 3 of this blog series on longevity and vitality, I cover the different ways in which AI is augmenting our healthcare system, enabling us to live longer and healthier lives.

In this blog, I’ll expand on:

Machine learning and drug design
Artificial intelligence and big data in medicine
Healthcare, AI & China

Let’s dive in.

Machine Learning in Drug Design
What if AI systems, specifically neural networks, could predict the design of novel molecules (i.e. medicines) capable of targeting and curing any disease?

Imagine leveraging cutting-edge artificial intelligence to accomplish with 50 people what the pharmaceutical industry can barely do with an army of 5,000.

And what if these molecules, accurately engineered by AIs, always worked? Such a feat would revolutionize our $1.3 trillion global pharmaceutical industry, which currently holds a dismal record of 1 in 10 target drugs ever reaching human trials.

It’s no wonder that drug development is massively expensive and slow. It takes over 10 years to bring a new drug to market, with costs ranging from $2.5 billion to $12 billion.

This inefficient, slow-to-innovate, and risk-averse industry is a sitting duck for disruption in the years ahead.

One of the hottest startups in digital drug discovery today is Insilico Medicine. Leveraging AI in its end-to-end drug discovery pipeline, Insilico Medicine aims to extend healthy longevity through drug discovery and aging research.

Their comprehensive drug discovery engine uses millions of samples and multiple data types to discover signatures of disease, identify the most promising protein targets, and generate perfect molecules for these targets. These molecules either already exist or can be generated de novo with the desired set of parameters.

In late 2018, Insilico’s CEO Dr. Alex Zhavoronkov announced the groundbreaking result of generating novel molecules for a challenging protein target with an unprecedented hit rate in under 46 days. This included both synthesis of the molecules and experimental validation in a biological test system—an impressive feat made possible by converging exponential technologies.

Underpinning Insilico’s drug discovery pipeline is a novel machine learning technique called Generative Adversarial Networks (GANs), used in combination with deep reinforcement learning.

Generating novel molecular structures for diseases both with and without known targets, Insilico is now pursuing drug discovery in aging, cancer, fibrosis, Parkinson’s disease, Alzheimer’s disease, ALS, diabetes, and many others. Once rolled out, the implications will be profound.

Dr. Zhavoronkov’s ultimate goal is to develop a fully-automated Health-as-a-Service (HaaS) and Longevity-as-a-Service (LaaS) engine.

Once plugged into the services of companies from Alibaba to Alphabet, such an engine would enable personalized solutions for online users, helping them prevent diseases and maintain optimal health.

Insilico, alongside other companies tackling AI-powered drug discovery, truly represents the application of the 6 D’s. What was once a prohibitively expensive and human-intensive process is now rapidly becoming digitized, dematerialized, demonetized and, perhaps most importantly, democratized.

Companies like Insilico can now do with a fraction of the cost and personnel what the pharmaceutical industry can barely accomplish with thousands of employees and a hefty bill to foot.

As I discussed in my blog on ‘The Next Hundred-Billion-Dollar Opportunity,’ Google’s DeepMind has now turned its neural networks to healthcare, entering the digitized drug discovery arena.

In 2017, DeepMind achieved a phenomenal feat by matching the fidelity of medical experts in correctly diagnosing over 50 eye disorders.

And just a year later, DeepMind announced a new deep learning tool called AlphaFold. By predicting the elusive ways in which various proteins fold on the basis of their amino acid sequences, AlphaFold may soon have a tremendous impact in aiding drug discovery and fighting some of today’s most intractable diseases.

Artificial Intelligence and Data Crunching
AI is especially powerful in analyzing massive quantities of data to uncover patterns and insights that can save lives. Take WAVE, for instance. Every year, over 400,000 patients die prematurely in US hospitals as a result of heart attack or respiratory failure.

Yet these patients don’t die without leaving plenty of clues. Given information overload, however, human physicians and nurses alone have no way of processing and analyzing all necessary data in time to save these patients’ lives.

Enter WAVE, an algorithm that can process enough data to offer a six-hour early warning of patient deterioration.

Just last year, the FDA approved WAVE as an AI-based predictive patient surveillance system to predict and thereby prevent sudden death.

Another highly valuable yet difficult-to-parse mountain of medical data comprises the 2.5 million medical papers published each year.

For some time, it has become physically impossible for a human physician to read—let alone remember—all of the relevant published data.

To counter this compounding conundrum, Johnson & Johnson is teaching IBM Watson to read and understand scientific papers that detail clinical trial outcomes.

Enriching Watson’s data sources, Apple is also partnering with IBM to provide access to health data from mobile apps.

One such Watson system contains 40 million documents, ingesting an average of 27,000 new documents per day, and providing insights for thousands of users.

After only one year, Watson’s successful diagnosis rate of lung cancer has reached 90 percent, compared to the 50 percent success rate of human doctors.

But what about the vast amount of unstructured medical patient data that populates today’s ancient medical system? This includes medical notes, prescriptions, audio interview transcripts, and pathology and radiology reports.

In late 2018, Amazon announced a new HIPAA-eligible machine learning service that digests and parses unstructured data into categories, such as patient diagnoses, treatments, dosages, symptoms and signs.

Taha Kass-Hout, Amazon’s senior leader in health care and artificial intelligence, told the Wall Street Journal that internal tests demonstrated that the software even performs as well as or better than other published efforts.

On the heels of this announcement, Amazon confirmed it was teaming up with the Fred Hutchinson Cancer Research Center to evaluate “millions of clinical notes to extract and index medical conditions.”

Having already driven extraordinary algorithmic success rates in other fields, data is the healthcare industry’s goldmine for future innovation.

Healthcare, AI & China
In 2017, the Chinese government published its ambitious national plan to become a global leader in AI research by 2030, with healthcare listed as one of four core research areas during the first wave of the plan.

Just a year earlier, China began centralizing healthcare data, tackling a major roadblock to developing longevity and healthcare technologies (particularly AI systems): scattered, dispersed, and unlabeled patient data.

Backed by the Chinese government, China’s largest tech companies—particularly Tencent—have now made strong entrances into healthcare.

Just recently, Tencent participated in a $154 million megaround for China-based healthcare AI unicorn iCarbonX.

Hoping to develop a complete digital representation of your biological self, iCarbonX has acquired numerous US personalized medicine startups.

Considering Tencent’s own Miying healthcare AI platform—aimed at assisting healthcare institutions in AI-driven cancer diagnostics—Tencent is quickly expanding into the drug discovery space, participating in two multimillion-dollar, US-based AI drug discovery deals just this year.

China’s biggest, second-order move into the healthtech space comes through Tencent’s WeChat. In the course of a mere few years, already 60 percent of the 38,000 medical institutions registered on WeChat allow patients to digitally book appointments through Tencent’s mobile platform. At the same time, 2,000 Chinese hospitals accept WeChat payments.

Tencent has additionally partnered with the U.K.’s Babylon Health, a virtual healthcare assistant startup whose app now allows Chinese WeChat users to message their symptoms and receive immediate medical feedback.

Similarly, Alibaba’s healthtech focus started in 2016 when it released its cloud-based AI medical platform, ET Medical Brain, to augment healthcare processes through everything from diagnostics to intelligent scheduling.

Conclusion
As Nvidia CEO Jensen Huang has stated, “Software ate the world, but AI is going to eat software.” Extrapolating this statement to a more immediate implication, AI will first eat healthcare, resulting in dramatic acceleration of longevity research and an amplification of the human healthspan.

Next week, I’ll continue to explore this concept of AI systems in healthcare.

Particularly, I’ll expand on how we’re acquiring and using the data for these doctor-augmenting AI systems: from ubiquitous biosensors, to the mobile healthcare revolution, and finally, to the transformative power of the health nucleus.

As AI and other exponential technologies increase our healthspan by 30 to 40 years, how will you leverage these same exponential technologies to take on your moonshots and live out your massively transformative purpose?

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Posted in Human Robots

#434616 What Games Are Humans Still Better at ...

Artificial intelligence (AI) systems’ rapid advances are continually crossing rows off the list of things humans do better than our computer compatriots.

AI has bested us at board games like chess and Go, and set astronomically high scores in classic computer games like Ms. Pacman. More complex games form part of AI’s next frontier.

While a team of AI bots developed by OpenAI, known as the OpenAI Five, ultimately lost to a team of professional players last year, they have since been running rampant against human opponents in Dota 2. Not to be outdone, Google’s DeepMind AI recently took on—and beat—several professional players at StarCraft II.

These victories beg the questions: what games are humans still better at than AI? And for how long?

The Making Of AlphaStar
DeepMind’s results provide a good starting point in a search for answers. The version of its AI for StarCraft II, dubbed AlphaStar, learned to play the games through supervised learning and reinforcement learning.

First, AI agents were trained by analyzing and copying human players, learning basic strategies. The initial agents then played each other in a sort of virtual death match where the strongest agents stayed on. New iterations of the agents were developed and entered the competition. Over time, the agents became better and better at the game, learning new strategies and tactics along the way.

One of the advantages of AI is that it can go through this kind of process at superspeed and quickly develop better agents. DeepMind researchers estimate that the AlphaStar agents went through the equivalent of roughly 200 years of game time in about 14 days.

Cheating or One Hand Behind the Back?
The AlphaStar AI agents faced off against human professional players in a series of games streamed on YouTube and Twitch. The AIs trounced their human opponents, winning ten games on the trot, before pro player Grzegorz “MaNa” Komincz managed to salvage some pride for humanity by winning the final game. Experts commenting on AlphaStar’s performance used words like “phenomenal” and “superhuman”—which was, to a degree, where things got a bit problematic.

AlphaStar proved particularly skilled at controlling and directing units in battle, known as micromanagement. One reason was that it viewed the whole game map at once—something a human player is not able to do—which made it seemingly able to control units in different areas at the same time. DeepMind researchers said the AIs only focused on a single part of the map at any given time, but interestingly, AlphaStar’s AI agent was limited to a more restricted camera view during the match “MaNA” won.

Potentially offsetting some of this advantage was the fact that AlphaStar was also restricted in certain ways. For example, it was prevented from performing more clicks per minute than a human player would be able to.

Where AIs Struggle
Games like StarCraft II and Dota 2 throw a lot of challenges at AIs. Complex game theory/ strategies, operating with imperfect/incomplete information, undertaking multi-variable and long-term planning, real-time decision-making, navigating a large action space, and making a multitude of possible decisions at every point in time are just the tip of the iceberg. The AIs’ performance in both games was impressive, but also highlighted some of the areas where they could be said to struggle.

In Dota 2 and StarCraft II, AI bots have seemed more vulnerable in longer games, or when confronted with surprising, unfamiliar strategies. They seem to struggle with complexity over time and improvisation/adapting to quick changes. This could be tied to how AIs learn. Even within the first few hours of performing a task, humans tend to gain a sense of familiarity and skill that takes an AI much longer. We are also better at transferring skill from one area to another. In other words, experience playing Dota 2 can help us become good at StarCraft II relatively quickly. This is not the case for AI—yet.

Dwindling Superiority
While the battle between AI and humans for absolute superiority is still on in Dota 2 and StarCraft II, it looks likely that AI will soon reign supreme. Similar things are happening to other types of games.

In 2017, a team from Carnegie Mellon University pitted its Libratus AI against four professionals. After 20 days of No Limit Texas Hold’em, Libratus was up by $1.7 million. Another likely candidate is the destroyer of family harmony at Christmas: Monopoly.

Poker involves bluffing, while Monopoly involves negotiation—skills you might not think AI would be particularly suited to handle. However, an AI experiment at Facebook showed that AI bots are more than capable of undertaking such tasks. The bots proved skilled negotiators, and developed negotiating strategies like pretending interest in one object while they were interested in another altogether—bluffing.

So, what games are we still better at than AI? There is no precise answer, but the list is getting shorter at a rapid pace.

The Aim Of the Game
While AI’s mastery of games might at first glance seem an odd area to focus research on, the belief is that the way AI learn to master a game is transferrable to other areas.

For example, the Libratus poker-playing AI employed strategies that could work in financial trading or political negotiations. The same applies to AlphaStar. As Oriol Vinyals, co-leader of the AlphaStar project, told The Verge:

“First and foremost, the mission at DeepMind is to build an artificial general intelligence. […] To do so, it’s important to benchmark how our agents perform on a wide variety of tasks.”

A 2017 survey of more than 350 AI researchers predicts AI could be a better driver than humans within ten years. By the middle of the century, AI will be able to write a best-selling novel, and a few years later, it will be better than humans at surgery. By the year 2060, AI may do everything better than us.

Whether you think this is a good or a bad thing, it’s worth noting that AI has an often overlooked ability to help us see things differently. When DeepMind’s AlphaGo beat human Go champion Lee Sedol, the Go community learned from it, too. Lee himself went on a win streak after the match with AlphaGo. The same is now happening within the Dota 2 and StarCraft II communities that are studying the human vs. AI games intensely.

More than anything, AI’s recent gaming triumphs illustrate how quickly artificial intelligence is developing. In 1997, Dr. Piet Hut, an astrophysicist at the Institute for Advanced Study at Princeton and a GO enthusiast, told the New York Times that:

”It may be a hundred years before a computer beats humans at Go—maybe even longer.”

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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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