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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.
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.
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.
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.
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?
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As artificial intelligence systems take on more tasks and solve more problems, it’s hard to say which is rising faster: our interest in them or our fear of them. Futurist Ray Kurzweil famously predicted that “By 2029, computers will have emotional intelligence and be convincing as people.”
We don’t know how accurate this prediction will turn out to be. Even if it takes more than 10 years, though, is it really possible for machines to become conscious? If the machines Kurzweil describes say they’re conscious, does that mean they actually are?
Perhaps a more relevant question at this juncture is: what is consciousness, and how do we replicate it if we don’t understand it?
In a panel discussion at South By Southwest titled “How AI Will Design the Human Future,” experts from academia and industry discussed these questions and more.
Wait, What Is AI?
Most of AI’s recent feats—diagnosing illnesses, participating in debate, writing realistic text—involve machine learning, which uses statistics to find patterns in large datasets then uses those patterns to make predictions. However, “AI” has been used to refer to everything from basic software automation and algorithms to advanced machine learning and deep learning.
“The term ‘artificial intelligence’ is thrown around constantly and often incorrectly,” said Jennifer Strong, a reporter at the Wall Street Journal and host of the podcast “The Future of Everything.” Indeed, one study found that 40 percent of European companies that claim to be working on or using AI don’t actually use it at all.
Dr. Peter Stone, associate chair of computer science at UT Austin, was the study panel chair on the 2016 One Hundred Year Study on Artificial Intelligence (or AI100) report. Based out of Stanford University, AI100 is studying and anticipating how AI will impact our work, our cities, and our lives.
“One of the first things we had to do was define AI,” Stone said. They defined it as a collection of different technologies inspired by the human brain to be able to perceive their surrounding environment and figure out what actions to take given these inputs.
Modeling on the Unknown
Here’s the crazy thing about that definition (and about AI itself): we’re essentially trying to re-create the abilities of the human brain without having anything close to a thorough understanding of how the human brain works.
“We’re starting to pair our brains with computers, but brains don’t understand computers and computers don’t understand brains,” Stone said. Dr. Heather Berlin, cognitive neuroscientist and professor of psychiatry at the Icahn School of Medicine at Mount Sinai, agreed. “It’s still one of the greatest mysteries how this three-pound piece of matter can give us all our subjective experiences, thoughts, and emotions,” she said.
This isn’t to say we’re not making progress; there have been significant neuroscience breakthroughs in recent years. “This has been the stuff of science fiction for a long time, but now there’s active work being done in this area,” said Amir Husain, CEO and founder of Austin-based AI company Spark Cognition.
Advances in brain-machine interfaces show just how much more we understand the brain now than we did even a few years ago. Neural implants are being used to restore communication or movement capabilities in people who’ve been impaired by injury or illness. Scientists have been able to transfer signals from the brain to prosthetic limbs and stimulate specific circuits in the brain to treat conditions like Parkinson’s, PTSD, and depression.
But much of the brain’s inner workings remain a deep, dark mystery—one that will have to be further solved if we’re ever to get from narrow AI, which refers to systems that can perform specific tasks and is where the technology stands today, to artificial general intelligence, or systems that possess the same intelligence level and learning capabilities as humans.
The biggest question that arises here, and one that’s become a popular theme across stories and films, is if machines achieve human-level general intelligence, does that also mean they’d be conscious?
Wait, What Is Consciousness?
As valuable as the knowledge we’ve accumulated about the brain is, it seems like nothing more than a collection of disparate facts when we try to put it all together to understand consciousness.
“If you can replace one neuron with a silicon chip that can do the same function, then replace another neuron, and another—at what point are you still you?” Berlin asked. “These systems will be able to pass the Turing test, so we’re going to need another concept of how to measure consciousness.”
Is consciousness a measurable phenomenon, though? Rather than progressing by degrees or moving through some gray area, isn’t it pretty black and white—a being is either conscious or it isn’t?
This may be an outmoded way of thinking, according to Berlin. “It used to be that only philosophers could study consciousness, but now we can study it from a scientific perspective,” she said. “We can measure changes in neural pathways. It’s subjective, but depends on reportability.”
She described three levels of consciousness: pure subjective experience (“Look, the sky is blue”), awareness of one’s own subjective experience (“Oh, it’s me that’s seeing the blue sky”), and relating one subjective experience to another (“The blue sky reminds me of a blue ocean”).
“These subjective states exist all the way down the animal kingdom. As humans we have a sense of self that gives us another depth to that experience, but it’s not necessary for pure sensation,” Berlin said.
Husain took this definition a few steps farther. “It’s this self-awareness, this idea that I exist separate from everything else and that I can model myself,” he said. “Human brains have a wonderful simulator. They can propose a course of action virtually, in their minds, and see how things play out. The ability to include yourself as an actor means you’re running a computation on the idea of yourself.”
Most of the decisions we make involve envisioning different outcomes, thinking about how each outcome would affect us, and choosing which outcome we’d most prefer.
“Complex tasks you want to achieve in the world are tied to your ability to foresee the future, at least based on some mental model,” Husain said. “With that view, I as an AI practitioner don’t see a problem implementing that type of consciousness.”
Moving Forward Cautiously (But Not too Cautiously)
To be clear, we’re nowhere near machines achieving artificial general intelligence or consciousness, and whether a “conscious machine” is possible—not to mention necessary or desirable—is still very much up for debate.
As machine intelligence continues to advance, though, we’ll need to walk the line between progress and risk management carefully.
Improving the transparency and explainability of AI systems is one crucial goal AI developers and researchers are zeroing in on. Especially in applications that could mean the difference between life and death, AI shouldn’t advance without people being able to trace how it’s making decisions and reaching conclusions.
Medicine is a prime example. “There are already advances that could save lives, but they’re not being used because they’re not trusted by doctors and nurses,” said Stone. “We need to make sure there’s transparency.” Demanding too much transparency would also be a mistake, though, because it will hinder the development of systems that could at best save lives and at worst improve efficiency and free up doctors to have more face time with patients.
Similarly, self-driving cars have great potential to reduce deaths from traffic fatalities. But even though humans cause thousands of deadly crashes every day, we’re terrified by the idea of self-driving cars that are anything less than perfect. “If we only accept autonomous cars when there’s zero probability of an accident, then we will never accept them,” Stone said. “Yet we give 16-year-olds the chance to take a road test with no idea what’s going on in their brains.”
This brings us back to the fact that, in building tech modeled after the human brain—which has evolved over millions of years—we’re working towards an end whose means we don’t fully comprehend, be it something as basic as choosing when to brake or accelerate or something as complex as measuring consciousness.
“We shouldn’t charge ahead and do things just because we can,” Stone said. “The technology can be very powerful, which is exciting, but we have to consider its implications.”
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More often than not, we fall into the trap of trying to predict and anticipate the future, forgetting that the future is up to us to envision and create. In the words of Buckminster Fuller, “We are called to be architects of the future, not its victims.”
But how, exactly, do we create a “good” future? What does such a future look like to begin with?
In Future Consciousness: The Path to Purposeful Evolution, Tom Lombardo analytically deconstructs how we can flourish in the flow of evolution and create a prosperous future for humanity. Scientifically informed, the books taps into themes that are constructive and profound, from both eastern and western philosophies.
As the executive director of the Center for Future Consciousness and an executive board member and fellow of the World Futures Studies Federation, Lombardo has dedicated his life and career to studying how we can create a “realistic, constructive, and ethical future.”
In a conversation with Singularity Hub, Lombardo discussed purposeful evolution, ethical use of technology, and the power of optimism.
Raya Bidshahri: Tell me more about the title of your book. What is future consciousness and what role does it play in what you call purposeful evolution?
Tom Lombardo: Humans have the unique capacity to purposefully evolve themselves because they possess future consciousness. Future consciousness contains all of the cognitive, motivational, and emotional aspects of the human mind that pertain to the future. It’s because we can imagine and think about the future that we can manipulate and direct our future evolution purposefully. Future consciousness empowers us to become self-responsible in our own evolutionary future. This is a jump in the process of evolution itself.
RB: In several places in the book, you discuss the importance of various eastern philosophies. What can we learn from the east that is often missing from western models?
TL: The key idea in the east that I have been intrigued by for decades is the Taoist Yin Yang, which is the idea that reality should be conceptualized as interdependent reciprocities.
In the west we think dualistically, or we attempt to think in terms of one end of the duality to the exclusion of the other, such as whole versus parts or consciousness versus physical matter. Yin Yang thinking is seeing how both sides of a “duality,” even though they appear to be opposites, are interdependent; you can’t have one without the other. You can’t have order without chaos, consciousness without the physical world, individuals without the whole, humanity without technology, and vice versa for all these complementary pairs.
RB: You talk about the importance of chaos and destruction in the trajectory of human progress. In your own words, “Creativity frequently involves destruction as a prelude to the emergence of some new reality.” Why is this an important principle for readers to keep in mind, especially in the context of today’s world?
TL: In order for there to be progress, there often has to be a disintegration of aspects of the old. Although progress and evolution involve a process of building up, growth isn’t entirely cumulative; it’s also transformative. Things fall apart and come back together again.
Throughout history, we have seen a transformation of what are the most dominant human professions or vocations. At some point, almost everybody worked in agriculture, but most of those agricultural activities were replaced by machines, and a lot of people moved over to industry. Now we’re seeing that jobs and functions are increasingly automated in industry, and humans are being pushed into vocations that involve higher cognitive and artistic skills, services, information technology, and so on.
RB: You raise valid concerns about the dark side of technological progress, especially when it’s combined with mass consumerism, materialism, and anti-intellectualism. How do we counter these destructive forces as we shape the future of humanity?
TL: We can counter such forces by always thoughtfully considering how our technologies are affecting the ongoing purposeful evolution of our conscious minds, bodies, and societies. We should ask ourselves what are the ethical values that are being served by the development of various technologies.
For example, we often hear the criticism that technologies that are driven by pure capitalism degrade human life and only benefit the few people who invented and market them. So we need to also think about what good these new technologies can serve. It’s what I mean when I talk about the “wise cyborg.” A wise cyborg is somebody who uses technology to serve wisdom, or values connected with wisdom.
RB: Creating an ideal future isn’t just about progress in technology, but also progress in morality. How we do decide what a “good” future is? What are some philosophical tools we can use to determine a code of ethics that is as objective as possible?
TL: Let’s keep in mind that ethics will always have some level of subjectivity. That being said, the way to determine a good future is to base it on the best theory of reality that we have, which is that we are evolutionary beings in an evolutionary universe and we are interdependent with everything else in that universe. Our ethics should acknowledge that we are fluid and interactive.
Hence, the “good” can’t be something static, and it can’t be something that pertains to me and not everybody else. It can’t be something that only applies to humans and ignores all other life on Earth, and it must be a mode of change rather than something stable.
RB: You present a consciousness-centered approach to creating a good future for humanity. What are some of the values we should develop in order to create a prosperous future?
TL: A sense of self-responsibility for the future is critical. This means realizing that the “good future” is something we have to take upon ourselves to create; we can’t let something or somebody else do that. We need to feel responsible both for our own futures and for the future around us.
Another one is going to be an informed and hopeful optimism about the future, because both optimism and pessimism have self-fulfilling prophecy effects. If you hope for the best, you are more likely to look deeply into your reality and increase the chance of it coming out that way. In fact, all of the positive emotions that have to do with future consciousness actually make people more intelligent and creative.
Some other important character virtues are discipline and tenacity, deep purpose, the love of learning and thinking, and creativity.
RB: Are you optimistic about the future? If so, what informs your optimism?
I justify my optimism the same way that I have seen Ray Kurzweil, Peter Diamandis, Kevin Kelly, and Steven Pinker justify theirs. If we look at the history of human civilization and even the history of nature, we see a progressive motion forward toward greater complexity and even greater intelligence. There’s lots of ups and downs, and catastrophes along the way, but the facts of nature and human history support the long-term expectation of continued evolution into the future.
You don’t have to be unrealistic to be optimistic. It’s also, psychologically, the more empowering position. That’s the position we should take if we want to maximize the chances of our individual or collective reality turning out better.
A lot of pessimists are pessimistic because they’re afraid of the future. There are lots of reasons to be afraid, but all in all, fear disempowers, whereas hope empowers.
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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.
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 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.
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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