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#435046 The Challenge of Abundance: Boredom, ...
As technology continues to progress, the possibility of an abundant future seems more likely. Artificial intelligence is expected to drive down the cost of labor, infrastructure, and transport. Alternative energy systems are reducing the cost of a wide variety of goods. Poverty rates are falling around the world as more people are able to make a living, and resources that were once inaccessible to millions are becoming widely available.
But such a life presents fuel for the most common complaint against abundance: if robots take all the jobs, basic income provides us livable welfare for doing nothing, and healthcare is a guarantee free of charge, then what is the point of our lives? What would motivate us to work and excel if there are no real risks or rewards? If everything is simply given to us, how would we feel like we’ve ever earned anything?
Time has proven that humans inherently yearn to overcome challenges—in fact, this very desire likely exists as the root of most technological innovation. And the idea that struggling makes us stronger isn’t just anecdotal, it’s scientifically validated.
For instance, kids who use anti-bacterial soaps and sanitizers too often tend to develop weak immune systems, causing them to get sick more frequently and more severely. People who work out purposely suffer through torn muscles so that after a few days of healing their muscles are stronger. And when patients visit a psychologist to handle a fear that is derailing their lives, one of the most common treatments is exposure therapy: a slow increase of exposure to the suffering so that the patient gets stronger and braver each time, able to take on an incrementally more potent manifestation of their fears.
Different Kinds of Struggle
It’s not hard to understand why people might fear an abundant future as a terribly mundane one. But there is one crucial mistake made in this assumption, and it was well summarized by Indian mystic and author Sadhguru, who said during a recent talk at Google:
Stomach empty, only one problem. Stomach full—one hundred problems; because what we refer to as human really begins only after survival is taken care of.
This idea is backed up by Maslow’s hierarchy of needs, which was first presented in his 1943 paper “A Theory of Human Motivation.” Maslow shows the steps required to build to higher and higher levels of the human experience. Not surprisingly, the first two levels deal with physiological needs and the need for safety—in other words, with the body. You need to have food, water, and sleep, or you die. After that, you need to be protected from threats, from the elements, from dangerous people, and from disease and pain.
Maslow’s Hierarchy of Needs. Photo by Wikimedia User:Factoryjoe / CC BY-SA 3.0
The beauty of these first two levels is that they’re clear-cut problems with clear-cut solutions: if you’re hungry, then you eat; if you’re thirsty, then you drink; if you’re tired, then you sleep.
But what about the next tiers of the hierarchy? What of love and belonging, of self-esteem and self-actualization? If we’re lonely, can we just summon up an authentic friend or lover? If we feel neglected by society, can we demand it validate us? If we feel discouraged and disappointed in ourselves, can we simply dial up some confidence and self-esteem?
Of course not, and that’s because these psychological needs are nebulous; they don’t contain clear problems with clear solutions. They involve the external world and other people, and are complicated by the infinite flavors of nuance and compromise that are required to navigate human relationships and personal meaning.
These psychological difficulties are where we grow our personalities, outlooks, and beliefs. The truly defining characteristics of a person are dictated not by the physical situations they were forced into—like birth, socioeconomic class, or physical ailment—but instead by the things they choose. So a future of abundance helps to free us from the physical limitations so that we can truly commit to a life of purpose and meaning, rather than just feel like survival is our purpose.
The Greatest Challenge
And that’s the plot twist. This challenge to come to grips with our own individuality and freedom could actually be the greatest challenge our species has ever faced. Can you imagine waking up every day with infinite possibility? Every choice you make says no to the rest of reality, and so every decision carries with it truly life-defining purpose and meaning. That sounds overwhelming. And that’s probably because in our current socio-economic systems, it is.
Studies have shown that people in wealthier nations tend to experience more anxiety and depression. Ron Kessler, professor of health care policy at Harvard and World Health Organization (WHO) researcher, summarized his findings of global mental health by saying, “When you’re literally trying to survive, who has time for depression? Americans, on the other hand, many of whom lead relatively comfortable lives, blow other nations away in the depression factor, leading some to suggest that depression is a ‘luxury disorder.’”
This might explain why America scores in the top rankings for the most depressed and anxious country on the planet. We surpassed our survival needs, and instead became depressed because our jobs and relationships don’t fulfill our expectations for the next three levels of Maslow’s hierarchy (belonging, esteem, and self-actualization).
But a future of abundance would mean we’d have to deal with these levels. This is the challenge for the future; this is what keeps things from being mundane.
As a society, we would be forced to come to grips with our emotional intelligence, to reckon with philosophy rather than simply contemplate it. Nearly every person you meet will be passionately on their own customized life journey, not following a routine simply because of financial limitations. Such a world seems far more vibrant and interesting than one where most wander sleep-deprived and numb while attempting to survive the rat race.
We can already see the forceful hand of this paradigm shift as self-driving cars become ubiquitous. For example, consider the famous psychological and philosophical “trolley problem.” In this thought experiment, a person sees a trolley car heading towards five people on the train tracks; they see a lever that will allow them to switch the trolley car to a track that instead only has one person on it. Do you switch the lever and have a hand in killing one person, or do you let fate continue and kill five people instead?
For the longest time, this was just an interesting quandary to consider. But now, massive corporations have to have an answer, so they can program their self-driving cars with the ability to choose between hitting a kid who runs into the road or swerving into an oncoming car carrying a family of five. When companies need philosophers to make business decisions, it’s a good sign of what’s to come.
Luckily, it’s possible this forceful reckoning with philosophy and our own consciousness may be exactly what humanity needs. Perhaps our great failure as a species has been a result of advanced cognition still trapped in the first two levels of Maslow’s hierarchy due to a long history of scarcity.
As suggested in the opening scenes in 2001: A Space Odyssey, our ape-like proclivity for violence has long stayed the same while the technology we fight with and live amongst has progressed. So while well-off Americans may have comfortable lives, they still know they live in a system where there is no safety net, where a single tragic failure could still mean hunger and homelessness. And because of this, that evolutionarily hard-wired neurotic part of our brain that fears for our survival has never been able to fully relax, and so that anxiety and depression that come with too much freedom but not enough security stays ever present.
Not only might this shift in consciousness help liberate humanity, but it may be vital if we’re to survive our future creations as well. Whatever values we hold dear as a species are the ones we will imbue into the sentient robots we create. If machine learning is going to take its guidance from humanity, we need to level up humanity’s emotional maturity.
While the physical struggles of the future may indeed fall to the wayside amongst abundance, it’s unlikely to become a mundane world; instead, it will become a vibrant culture where each individual is striving against the most important struggle that affects all of us: the challenge to find inner peace, to find fulfillment, to build meaningful relationships, and ultimately, the challenge to find ourselves.
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#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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