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The causes of aging are extremely complex and unclear. But with longevity clinical trials increasing, more answers—and questions—are emerging than ever before.
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 turn those answers into practical ways to extend our healthspan.
In this article, I’ll explore how genome sequencing and editing, along with new classes of anti-aging drugs, are augmenting our biology to further extend our healthy lives.
Genome Sequencing and 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 for 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 $1,500 in 2015.
Today, the cost of genome sequencing has dropped below $600, 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 article).
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 have used CRISPR to genetically engineer cocaine resistance into mice, reverse the gene defect causing Duchenne muscular dystrophy (DMD) in dogs, and reduce genetic deafness in mice.
Already this year, CRISPR-edited immune cells have been shown to successfully kill cancer cells in human patients. Researchers have discovered ways to activate CRISPR with light and use the gene-editing technology to better understand Alzheimer’s disease progression.
With great power comes great responsibility, and the opportunity for 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. Because Jiankui forged ethical review documents and misled doctors in the process, he was sentenced to three years in prison and fined $429,000 last December.
Coupled with significant ethical conversations necessary for progress, 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, and 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 Biotechnologies is pioneering a programmable gene therapy that can destroy cells based on their internal biochemistry.
SIWA Therapeutics is 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.
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 for 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 went public in 2018) 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, and a 30.6 percent decrease in respiratory tract infection.
Impressive, to say the least.
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.
(3) 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 first clinical study reports that Basis increases NAD+ levels consistently by a sustained 40 percent.
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 article 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 toward 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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If you’d like to learn more and consider joining our 2021 membership, apply here.
(2) Abundance-Digital Online Community: I’ve also created a Digital/Online community of bold, abundance-minded entrepreneurs called Abundance-Digital. Abundance-Digital is Singularity University’s ‘onramp’ for exponential entrepreneurs—those who want to get involved and play at a higher level. Click here to learn more.
(Both A360 and Abundance-Digital are part of Singularity University—your participation opens you to a global community.)
This article originally appeared on diamandis.com. Read the original article here.
Image Credit: Arek Socha from Pixabay Continue reading
Assuming that the emergence of consciousness in artificial minds is possible, those minds will feel the urge to create art. But will we be able to understand it? To answer this question, we need to consider two subquestions: when does the machine become an author of an artwork? And how can we form an understanding of the art that it makes?
Empathy, we argue, is the force behind our capacity to understand works of art. Think of what happens when you are confronted with an artwork. We maintain that, to understand the piece, you use your own conscious experience to ask what could possibly motivate you to make such an artwork yourself—and then you use that first-person perspective to try to come to a plausible explanation that allows you to relate to the artwork. Your interpretation of the work will be personal and could differ significantly from the artist’s own reasons, but if we share sufficient experiences and cultural references, it might be a plausible one, even for the artist. This is why we can relate so differently to a work of art after learning that it is a forgery or imitation: the artist’s intent to deceive or imitate is very different from the attempt to express something original. Gathering contextual information before jumping to conclusions about other people’s actions—in art, as in life—can enable us to relate better to their intentions.
But the artist and you share something far more important than cultural references: you share a similar kind of body and, with it, a similar kind of embodied perspective. Our subjective human experience stems, among many other things, from being born and slowly educated within a society of fellow humans, from fighting the inevitability of our own death, from cherishing memories, from the lonely curiosity of our own mind, from the omnipresence of the needs and quirks of our biological body, and from the way it dictates the space- and time-scales we can grasp. All conscious machines will have embodied experiences of their own, but in bodies that will be entirely alien to us.
We are able to empathize with nonhuman characters or intelligent machines in human-made fiction because they have been conceived by other human beings from the only subjective perspective accessible to us: “What would it be like for a human to behave as x?” In order to understand machinic art as such—and assuming that we stand a chance of even recognizing it in the first place—we would need a way to conceive a first-person experience of what it is like to be that machine. That is something we cannot do even for beings that are much closer to us. It might very well happen that we understand some actions or artifacts created by machines of their own volition as art, but in doing so we will inevitably anthropomorphize the machine’s intentions. Art made by a machine can be meaningfully interpreted in a way that is plausible only from the perspective of that machine, and any coherent anthropomorphized interpretation will be implausibly alien from the machine perspective. As such, it will be a misinterpretation of the artwork.
But what if we grant the machine privileged access to our ways of reasoning, to the peculiarities of our perception apparatus, to endless examples of human culture? Wouldn’t that enable the machine to make art that a human could understand? Our answer is yes, but this would also make the artworks human—not authentically machinic. All examples so far of “art made by machines” are actually just straightforward examples of human art made with computers, with the artists being the computer programmers. It might seem like a strange claim: how can the programmers be the authors of the artwork if, most of the time, they can’t control—or even anticipate—the actual materializations of the artwork? It turns out that this is a long-standing artistic practice.
Suppose that your local orchestra is playing Beethoven’s Symphony No 7 (1812). Even though Beethoven will not be directly responsible for any of the sounds produced there, you would still say that you are listening to Beethoven. Your experience might depend considerably on the interpretation of the performers, the acoustics of the room, the behavior of fellow audience members or your state of mind. Those and other aspects are the result of choices made by specific individuals or of accidents happening to them. But the author of the music? Ludwig van Beethoven. Let’s say that, as a somewhat odd choice for the program, John Cage’s Imaginary Landscape No 4 (March No 2) (1951) is also played, with 24 performers controlling 12 radios according to a musical score. In this case, the responsibility for the sounds being heard should be attributed to unsuspecting radio hosts, or even to electromagnetic fields. Yet, the shaping of sounds over time—the composition—should be credited to Cage. Each performance of this piece will vary immensely in its sonic materialization, but it will always be a performance of Imaginary Landscape No 4.
Why should we change these principles when artists use computers if, in these respects at least, computer art does not bring anything new to the table? The (human) artists might not be in direct control of the final materializations, or even be able to predict them but, despite that, they are the authors of the work. Various materializations of the same idea—in this case formalized as an algorithm—are instantiations of the same work manifesting different contextual conditions. In fact, a common use of computation in the arts is the production of variations of a process, and artists make extensive use of systems that are sensitive to initial conditions, external inputs, or pseudo-randomness to deliberately avoid repetition of outputs. Having a computer executing a procedure to build an artwork, even if using pseudo-random processes or machine-learning algorithms, is no different than throwing dice to arrange a piece of music, or to pursuing innumerable variations of the same formula. After all, the idea of machines that make art has an artistic tradition that long predates the current trend of artworks made by artificial intelligence.
Machinic art is a term that we believe should be reserved for art made by an artificial mind’s own volition, not for that based on (or directed towards) an anthropocentric view of art. From a human point of view, machinic artworks will still be procedural, algorithmic, and computational. They will be generative, because they will be autonomous from a human artist. And they might be interactive, with humans or other systems. But they will not be the result of a human deferring decisions to a machine, because the first of those—the decision to make art—needs to be the result of a machine’s volition, intentions, and decisions. Only then will we no longer have human art made with computers, but proper machinic art.
The problem is not whether machines will or will not develop a sense of self that leads to an eagerness to create art. The problem is that if—or when—they do, they will have such a different Umwelt that we will be completely unable to relate to it from our own subjective, embodied perspective. Machinic art will always lie beyond our ability to understand it because the boundaries of our comprehension—in art, as in life—are those of the human experience.
This article was originally published at Aeon and has been republished under Creative Commons.
Image Credit: Rene Böhmer / Unsplash Continue reading