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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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#434673 The World’s Most Valuable AI ...
It recognizes our faces. It knows the videos we might like. And it can even, perhaps, recommend the best course of action to take to maximize our personal health.
Artificial intelligence and its subset of disciplines—such as machine learning, natural language processing, and computer vision—are seemingly becoming integrated into our daily lives whether we like it or not. What was once sci-fi is now ubiquitous research and development in company and university labs around the world.
Similarly, the startups working on many of these AI technologies have seen their proverbial stock rise. More than 30 of these companies are now valued at over a billion dollars, according to data research firm CB Insights, which itself employs algorithms to provide insights into the tech business world.
Private companies with a billion-dollar valuation were so uncommon not that long ago that they were dubbed unicorns. Now there are 325 of these once-rare creatures, with a combined valuation north of a trillion dollars, as CB Insights maintains a running count of this exclusive Unicorn Club.
The subset of AI startups accounts for about 10 percent of the total membership, growing rapidly in just 4 years from 0 to 32. Last year, an unprecedented 17 AI startups broke the billion-dollar barrier, with 2018 also a record year for venture capital into private US AI companies at $9.3 billion, CB Insights reported.
What exactly is all this money funding?
AI Keeps an Eye Out for You
Let’s start with the bad news first.
Facial recognition is probably one of the most ubiquitous applications of AI today. It’s actually a decades-old technology often credited to a man named Woodrow Bledsoe, who used an instrument called a RAND tablet that could semi-autonomously match faces from a database. That was in the 1960s.
Today, most of us are familiar with facial recognition as a way to unlock our smartphones. But the technology has gained notoriety as a surveillance tool of law enforcement, particularly in China.
It’s no secret that the facial recognition algorithms developed by several of the AI unicorns from China—SenseTime, CloudWalk, and Face++ (also known as Megvii)—are used to monitor the country’s 1.3 billion citizens. Police there are even equipped with AI-powered eyeglasses for such purposes.
A fourth billion-dollar Chinese startup, Yitu Technologies, also produces a platform for facial recognition in the security realm, and develops AI systems in healthcare on top of that. For example, its CARE.AITM Intelligent 4D Imaging System for Chest CT can reputedly identify in real time a variety of lesions for the possible early detection of cancer.
The AI Doctor Is In
As Peter Diamandis recently noted, AI is rapidly augmenting healthcare and longevity. He mentioned another AI unicorn from China in this regard—iCarbonX, which plans to use machines to develop personalized health plans for every individual.
A couple of AI unicorns on the hardware side of healthcare are OrCam Technologies and Butterfly. The former, an Israeli company, has developed a wearable device for the vision impaired called MyEye that attaches to one’s eyeglasses. The device can identify people and products, as well as read text, conveying the information through discrete audio.
Butterfly Network, out of Connecticut, has completely upended the healthcare market with a handheld ultrasound machine that works with a smartphone.
“Orcam and Butterfly are amazing examples of how machine learning can be integrated into solutions that provide a step-function improvement over state of the art in ultra-competitive markets,” noted Andrew Byrnes, investment director at Comet Labs, a venture capital firm focused on AI and robotics, in an email exchange with Singularity Hub.
AI in the Driver’s Seat
Comet Labs’ portfolio includes two AI unicorns, Megvii and Pony.ai.
The latter is one of three billion-dollar startups developing the AI technology behind self-driving cars, with the other two being Momenta.ai and Zoox.
Founded in 2016 near San Francisco (with another headquarters in China), Pony.ai debuted its latest self-driving system, called PonyAlpha, last year. The platform uses multiple sensors (LiDAR, cameras, and radar) to navigate its environment, but its “sensor fusion technology” makes things simple by choosing the most reliable sensor data for any given driving scenario.
Zoox is another San Francisco area startup founded a couple of years earlier. In late 2018, it got the green light from the state of California to be the first autonomous vehicle company to transport a passenger as part of a pilot program. Meanwhile, China-based Momenta.ai is testing level four autonomy for its self-driving system. Autonomous driving levels are ranked zero to five, with level five being equal to a human behind the wheel.
The hype around autonomous driving is currently in overdrive, and Byrnes thinks regulatory roadblocks will keep most self-driving cars in idle for the foreseeable future. The exception, he said, is China, which is adopting a “systems” approach to autonomy for passenger transport.
“If [autonomous mobility] solves bigger problems like traffic that can elicit government backing, then that has the potential to go big fast,” he said. “This is why we believe Pony.ai will be a winner in the space.”
AI in the Back Office
An AI-powered technology that perhaps only fans of the cult classic Office Space might appreciate has suddenly taken the business world by storm—robotic process automation (RPA).
RPA companies take the mundane back office work, such as filling out invoices or processing insurance claims, and turn it over to bots. The intelligent part comes into play because these bots can tackle unstructured data, such as text in an email or even video and pictures, in order to accomplish an increasing variety of tasks.
Both Automation Anywhere and UiPath are older companies, founded in 2003 and 2005, respectively. However, since just 2017, they have raised nearly a combined $1 billion in disclosed capital.
Cybersecurity Embraces AI
Cybersecurity is another industry where AI is driving investment into startups. Sporting imposing names like CrowdStrike, Darktrace, and Tanium, these cybersecurity companies employ different machine-learning techniques to protect computers and other IT assets beyond the latest software update or virus scan.
Darktrace, for instance, takes its inspiration from the human immune system. Its algorithms can purportedly “learn” the unique pattern of each device and user on a network, detecting emerging problems before things spin out of control.
All three companies are used by major corporations and governments around the world. CrowdStrike itself made headlines a few years ago when it linked the hacking of the Democratic National Committee email servers to the Russian government.
Looking Forward
I could go on, and introduce you to the world’s most valuable startup, a Chinese company called Bytedance that is valued at $75 billion for news curation and an app to create 15-second viral videos. But that’s probably not where VC firms like Comet Labs are generally putting their money.
Byrnes sees real value in startups that are taking “data-driven approaches to problems specific to unique industries.” Take the example of Chicago-based unicorn Uptake Technologies, which analyzes incoming data from machines, from wind turbines to tractors, to predict problems before they occur with the machinery. A not-yet unicorn called PingThings in the Comet Labs portfolio does similar predictive analytics for the energy utilities sector.
“One question we like asking is, ‘What does the state of the art look like in your industry in three to five years?’” Byrnes said. “We ask that a lot, then we go out and find the technology-focused teams building those things.”
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