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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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With the Thanksgiving holiday upon us, it’s a great time to reflect on the future of food. Over the last few years, we have seen a dramatic rise in exponential technologies transforming the food industry from seed to plate. Food is important in many ways—too little or too much of it can kill us, and it is often at the heart of family, culture, our daily routines, and our biggest celebrations. The agriculture and food industries are also two of the world’s biggest employers. Let’s take a look to see what is in store for the future.
Over the last few years, we have seen a number of new companies emerge in the robotic farming industry. This includes new types of farming equipment used in arable fields, as well as indoor robotic vertical farms. In November 2017, Hands Free Hectare became the first in the world to remotely grow an arable crop. They used autonomous tractors to sow and spray crops, small rovers to take soil samples, drones to monitor crop growth, and an unmanned combine harvester to collect the crops. Since then, they’ve also grown and harvested a field of winter wheat, and have been adding additional technologies and capabilities to their arsenal of robotic farming equipment.
Indoor vertical farming is also rapidly expanding. As Engadget reported in October 2018, a number of startups are now growing crops like leafy greens, tomatoes, flowers, and herbs. These farms can grow food in urban areas, reducing transport, water, and fertilizer costs, and often don’t need pesticides since they are indoors. IronOx, which is using robots to grow plants with navigation technology used by self-driving cars, can grow 30 times more food per acre of land using 90 percent less water than traditional farmers. Vertical farming company Plenty was recently funded by Softbank’s Vision Fund, Jeff Bezos, and others to build 300 vertical farms in China.
These startups are not only succeeding in wealthy countries. Hello Tractor, an “uberized” tractor, has worked with 250,000 smallholder farms in Africa, creating both food security and tech-infused agriculture jobs. The World Food Progam’s Innovation Accelerator (an impact partner of Singularity University) works with hundreds of startups aimed at creating zero hunger. One project is focused on supporting refugees in developing “food computers” in refugee camps—computerized devices that grow food while also adjusting to the conditions around them. As exponential trends drive down the costs of robotics, sensors, software, and energy, we should see robotic farming scaling around the world and becoming the main way farming takes place.
Exponential technologies are not only revolutionizing how we grow vegetables and grains, but also how we generate protein and meat. The new cultured meat industry is rapidly expanding, led by startups such as Memphis Meats, Mosa Meats, JUST Meat, Inc. and Finless Foods, and backed by heavyweight investors including DFJ, Bill Gates, Richard Branson, Cargill, and Tyson Foods.
Cultured meat is grown in a bioreactor using cells from an animal, a scaffold, and a culture. The process is humane and, potentially, scientists can make the meat healthier by adding vitamins, removing fat, or customizing it to an individual’s diet and health concerns. Another benefit is that cultured meats, if grown at scale, would dramatically reduce environmental destruction, pollution, and climate change caused by the livestock and fishing industries. Similar to vertical farms, cultured meat is produced using technology and can be grown anywhere, on-demand and in a decentralized way.
Similar to robotic farming equipment, bioreactors will also follow exponential trends, rapidly falling in cost. In fact, the first cultured meat hamburger (created by Singularity University faculty Member Mark Post of Mosa Meats in 2013) cost $350,000 dollars. In 2018, Fast Company reported the cost was now about $11 per burger, and the Israeli startup Future Meat Technologies predicted they will produce beef at about $2 per pound in 2020, which will be competitive with existing prices. For those who have turkey on their mind, one can read about New Harvest’s work (one of the leading think tanks and research centers for the cultured meat and cellular agriculture industry) in funding efforts to generate a nugget of cultured turkey meat.
One outstanding question is whether cultured meat is safe to eat and how it will interact with the overall food supply chain. In the US, regulators like the Food and Drug Administration (FDA) and the US Department of Agriculture (USDA) are working out their roles in this process, with the FDA overseeing the cellular process and the FDA overseeing production and labeling.
Tech companies are also making great headway in streamlining food processing. Norwegian company Tomra Foods was an early leader in using imaging recognition, sensors, artificial intelligence, and analytics to more efficiently sort food based on shape, composition of fat, protein, and moisture, and other food safety and quality indicators. Their technologies have improved food yield by 5-10 percent, which is significant given they own 25 percent of their market.
These advances are also not limited to large food companies. In 2016 Google reported how a small family farm in Japan built a world-class cucumber sorting device using their open-source machine learning tool TensorFlow. SU startup Impact Vision uses hyper-spectral imaging to analyze food quality, which increases revenues and reduces food waste and product recalls from contamination.
These examples point to a question many have on their mind: will we live in a future where a few large companies use advanced technologies to grow the majority of food on the planet, or will the falling costs of these technologies allow family farms, startups, and smaller players to take part in creating a decentralized system? Currently, the future could flow either way, but it is important for smaller companies to take advantage of the most cutting-edge technology in order to stay competitive.
Food Purchasing and Delivery
In the last year, we have also seen a number of new developments in technology improving access to food. Amazon Go is opening grocery stores in Seattle, San Francisco, and Chicago where customers use an app that allows them to pick up their products and pay without going through cashier lines. Sam’s Club is not far behind, with an app that also allows a customer to purchase goods in-store.
The market for food delivery is also growing. In 2017, Morgan Stanley estimated that the online food delivery market from restaurants could grow to $32 billion by 2021, from $12 billion in 2017. Companies like Zume are pioneering robot-powered pizza making and delivery. In addition to using robotics to create affordable high-end gourmet pizzas in their shop, they also have a pizza delivery truck that can assemble and cook pizzas while driving. Their system combines predictive analytics using past customer data to prepare pizzas for certain neighborhoods before the orders even come in. In early November 2018, the Wall Street Journal estimated that Zume is valued at up to $2.25 billion.
While each of these developments is promising on its own, it’s also important to note that since all these technologies are in some way digitized and connected to the internet, the various food tech players can collaborate. In theory, self-driving delivery restaurants could share data on what they are selling to their automated farm equipment, facilitating coordination of future crops. There is a tremendous opportunity to improve efficiency, lower costs, and create an abundance of healthy, sustainable food for all.
On the other hand, these technologies are also deeply disruptive. According to the Food and Agricultural Organization of the United Nations, in 2010 about one billion people, or a third of the world’s workforce, worked in the farming and agricultural industries. We need to ensure these farmers are linked to new job opportunities, as well as facilitate collaboration between existing farming companies and technologists so that the industries can continue to grow and lead rather than be displaced.
Just as importantly, each of us might think about how these changes in the food industry might impact our own ways of life and culture. Thanksgiving celebrates community and sharing of food during a time of scarcity. Technology will help create an abundance of food and less need for communities to depend on one another. What are the ways that you will create community, sharing, and culture in this new world?
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