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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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The Demise of Rethink Robotics Shows How Hard It Is to Make Machines Truly Smart
Will Knight | MIT Technology Review
“There’s growing interest in using recent advances in AI to make industrial robots a lot smarter and more useful. …But look carefully and you’ll see that these technologies are at a very early stage, and that deploying them commercially could prove extremely challenging. The demise of Rethink doesn’t mean industrial robotics isn’t flourishing, or that AI-driven advances won’t come about. But it shows just how hard doing real innovation in robotics can be.”
The Human Cell Atlas Is Biologists’ Latest Grand Project
Megan Molteni | Wired
“Dubbed the Human Cell Atlas, the project intends to catalog all of the estimated 37 trillion cells that make up a human body. …By decoding the genes active in single cells, pegging different cell types to a specific address in the body, and tracing the molecular circuits between them, participating researchers plan to create a more comprehensive map of human biology than has ever existed before.”
US Will Rewrite Safety Rules to Permit Fully Driverless Cars on Public Roads
Andrew J. Hawkins | The Verge
“Under current US safety rules, a motor vehicle must have traditional controls, like a steering wheel, mirrors, and foot pedals, before it is allowed to operate on public roads. But that could all change under a new plan released on Thursday by the Department of Transportation that’s intended to open the floodgates for fully driverless cars.”
When an AI Goes Full Jack Kerouac
Brian Merchant | The Atlantic
“By the end of the four-day trip, receipts emblazoned with artificially intelligent prose would cover the floor of the car. …it is a hallucinatory, oddly illuminating account of a bot’s life on the interstate; the Electric Kool-Aid Acid Test meets Google Street View, narrated by Siri.”
FUTURE OF FOOD
New Autonomous Farm Wants to Produce Food Without Human Workers
Erin Winick | MIT Technology Review
“As the firm’s cofounder Brandon Alexander puts it: ‘We are a farm and will always be a farm.’ But it’s no ordinary farm. For starters, the company’s 15 human employees share their work space with robots who quietly go about the business of tending rows and rows of leafy greens.”
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“You really can’t justify tuna in Chicago as a source of sustenance.” That’s according to Dr. Sylvia Earle, a National Geographic Society Explorer who was the first female chief scientist at NOAA. She came to the Good Food Institute’s Good Food Conference to deliver a call to action around global food security, agriculture, environmental protection, and the future of consumer choice.
It seems like all options should be on the table to feed an exploding population threatened by climate change. But Dr. Earle, who is faculty at Singularity University, drew a sharp distinction between seafood for sustenance versus seafood as a choice. “There is this widespread claim that we must take large numbers of wildlife from the sea in order to have food security.”
A few minutes later, Dr. Earle directly addressed those of us in the audience. “We know the value of a dead fish,” she said. That’s market price. “But what is the value of a live fish in the ocean?”
That’s when my mind blew open. What is the value—or put another way, the cost—of using the ocean as a major source of protein for humans? How do you put a number on that? Are we talking about dollars and cents, or about something far larger?
Dr. Liz Specht of the Good Food Institute drew the audience’s attention to a strange imbalance. Currently, about half of the yearly global catch of seafood comes from aquaculture. That means that the other half is wild caught. It’s hard to imagine half of your meat coming directly from the forests and the plains, isn’t it? And yet half of the world’s seafood comes from direct harvesting of the oceans, by way of massive overfishing, a terrible toll from bycatch, a widespread lack of regulation and enforcement, and even human rights violations such as slavery.
The search for solutions is on, from both within the fishing industry and from external agencies such as governments and philanthropists. Could there be another way?
Makers of plant-based seafood and clean seafood think they know how to feed the global demand for seafood without harming the ocean. These companies are part of a larger movement harnessing technology to reduce our reliance on wild and domesticated animals—and all the environmental, economic, and ethical issues that come with it.
Producers of plant-based seafood (20 or so currently) are working to capture the taste, texture, and nutrition of conventional seafood without the limitations of geography or the health of a local marine population. Like with plant-based meat, makers of plant-based seafood are harnessing food science and advances in chemistry, biology, and engineering to make great food. The industry’s strategy? Start with what the consumer wants, and then figure out how to achieve that great taste through technology.
So how does plant-based seafood taste? Pretty good, as it turns out. (The biggest benefit of a food-oriented conference is that your mouth is always full!)
I sampled “tuna” salad made from Good Catch Food’s fish-free tuna, which is sourced from legumes; the texture was nearly indistinguishable from that of flaked albacore tuna, and there was no lingering fishy taste to overpower my next bite. In a blind taste test, I probably wouldn’t have known that I was eating a plant-based seafood alternative. Next I reached for Ocean Hugger Food’s Ahimi, a tomato-based alternative to raw tuna. I adore Hawaiian poke, so I was pleasantly surprised when my Ahimi-based poke captured the bite of ahi tuna. It wasn’t quite as delightfully fatty as raw tuna, but with wild tuna populations struggling to recover from a 97% decline in numbers from 40 years ago, Ahimi is a giant stride in the right direction.
These plant-based alternatives aren’t the only game in town, however.
The clean meat industry, which has also been called “cultured meat” or “cellular agriculture,” isn’t seeking to lure consumers away from animal protein. Instead, cells are sampled from live animals and grown in bioreactors—meaning that no animal is slaughtered to produce real meat.
Clean seafood is poised to piggyback off platforms developed for clean meat; growing fish cells in the lab should rely on the same processes as growing meat cells. I know of four companies currently focusing on seafood (Finless Foods, Wild Type, BlueNalu, and Seafuture Sustainable Biotech), and a few more are likely to emerge from stealth mode soon.
Importantly, there’s likely not much difference between growing clean seafood from the top or the bottom of the food chain. Tuna, for example, are top predators that must grow for at least 10 years before they’re suitable as food. Each year, a tuna consumes thousands of pounds of other fish, shellfish, and plankton. That “long tail of groceries,” said Dr. Earle, “is a pretty expensive choice.” Excitingly, clean tuna would “level the trophic playing field,” as Dr. Specht pointed out.
All this is only the beginning of what might be possible.
Combining synthetic biology with clean meat and seafood means that future products could be personalized for individual taste preferences or health needs, by reprogramming the DNA of the cells in the lab. Industries such as bioremediation and biofuels likely have a lot to teach us about sourcing new ingredients and flavors from algae and marine plants. By harnessing rapid advances in automation, robotics, sensors, machine vision, and other big-data analytics, the manufacturing and supply chains for clean seafood could be remarkably safe and robust. Clean seafood would be just that: clean, without pathogens, parasites, or the plastic threatening to fill our oceans, meaning that you could enjoy it raw.
What about price? Dr. Mark Post, a pioneer in clean meat who is also faculty at Singularity University, estimated that 80% of clean-meat production costs come from the expensive medium in which cells are grown—and some ingredients in the medium are themselves sourced from animals, which misses the point of clean meat. Plus, to grow a whole cut of food, like a fish fillet, the cells need to be coaxed into a complex 3D structure with various cell types like muscle cells and fat cells. These two technical challenges must be solved before clean meat and seafood give consumers the experience they want, at the price they want.
In this respect clean seafood has an unusual edge. Most of what we know about growing animal cells in the lab comes from the research and biomedical industries (from tissue engineering, for example)—but growing cells to replace an organ has different constraints than growing cells for food. The link between clean seafood and biomedicine is less direct, empowering innovators to throw out dogma and find novel reagents, protocols, and equipment to grow seafood that captures the tastes, textures, smells, and overall experience of dining by the ocean.
Asked to predict when we’ll be seeing clean seafood in the grocery store, Lou Cooperhouse the CEO of BlueNalu, explained that the challenges aren’t only in the lab: marketing, sales, distribution, and communication with consumers are all critical. As Niya Gupta, the founder of Fork & Goode, said, “The question isn’t ‘can we do it’, but ‘can we sell it’?”
The good news is that the clean meat and seafood industry is highly collaborative; there are at least two dozen companies in the space, and they’re all talking to each other. “This is an ecosystem,” said Dr. Uma Valeti, the co-founder of Memphis Meats. “We’re not competing with each other.” It will likely be at least a decade before science, business, and regulation enable clean meat and seafood to routinely appear on restaurant menus, let alone market shelves.
Until then, think carefully about your food choices. Meditate on Dr. Earle’s question: “What is the real cost of that piece of halibut?” Or chew on this from Dr. Ricardo San Martin, of the Sutardja Center at the University of California, Berkeley: “Food is a system of meanings, not an object.” What are you saying when you choose your food, about your priorities and your values and how you want the future to look? Do you think about animal welfare? Most ethical regulations don’t extend to marine life, and if you don’t think that ocean creatures feel pain, consider the lobster.
Seafood is largely an acquired taste, since most of us don’t live near the water. Imagine a future in which children grow up loving the taste of delicious seafood but without hurting a living animal, the ocean, or the global environment.
Do more than imagine. As Dr. Earle urged us, “Convince the public at large that this is a really cool idea.”
Ahimi (Ocean Hugger)
New Wave Foods
Heritage Health Food
The Vegetarian Butcher
Table based on Figure 5 of the report “An Ocean of Opportunity: Plant-based and clean seafood for sustainable oceans without sacrifice,” from The Good Food Institute.
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