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#434792 Extending Human Longevity With ...
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.
Organ Entrepreneurs
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.
Ambrosia
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.
Elevian
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.
Conclusion
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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#433474 How to Feed Global Demand for ...
“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.”
Widely available
Medium availability
Emerging
Gardein
Ahimi (Ocean Hugger)
New Wave Foods
Sophie’s Kitchen
Cedar Lake
To-funa Fish
Quorn
SoFine Foods
Seamore
Vegetarian Plus
Akua
Good Catch
Heritage
Hungry Planet
Odontella
Loma Linda
Heritage Health Food
Terramino Foods
The Vegetarian Butcher
May Wah
VBites
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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