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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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#434260 The Most Surprising Tech Breakthroughs ...
Development across the entire information technology landscape certainly didn’t slow down this year. From CRISPR babies, to the rapid decline of the crypto markets, to a new robot on Mars, and discovery of subatomic particles that could change modern physics as we know it, there was no shortage of headline-grabbing breakthroughs and discoveries.
As 2018 comes to a close, we can pause and reflect on some of the biggest technology breakthroughs and scientific discoveries that occurred this year.
I reached out to a few Singularity University speakers and faculty across the various technology domains we cover asking what they thought the biggest breakthrough was in their area of expertise. The question posed was:
“What, in your opinion, was the biggest development in your area of focus this year? Or, what was the breakthrough you were most surprised by in 2018?”
I can share that for me, hands down, the most surprising development I came across in 2018 was learning that a publicly-traded company that was briefly valued at over $1 billion, and has over 12,000 employees and contractors spread around the world, has no physical office space and the entire business is run and operated from inside an online virtual world. This is Ready Player One stuff happening now.
For the rest, here’s what our experts had to say.
DIGITAL BIOLOGY
Dr. Tiffany Vora | Faculty Director and Vice Chair, Digital Biology and Medicine, Singularity University
“That’s easy: CRISPR babies. I knew it was technically possible, and I’ve spent two years predicting it would happen first in China. I knew it was just a matter of time but I failed to predict the lack of oversight, the dubious consent process, the paucity of publicly-available data, and the targeting of a disease that we already know how to prevent and treat and that the children were at low risk of anyway.
I’m not convinced that this counts as a technical breakthrough, since one of the girls probably isn’t immune to HIV, but it sure was a surprise.”
For more, read Dr. Vora’s summary of this recent stunning news from China regarding CRISPR-editing human embryos.
QUANTUM COMPUTING
Andrew Fursman | Co-Founder/CEO 1Qbit, Faculty, Quantum Computing, Singularity University
“There were two last-minute holiday season surprise quantum computing funding and technology breakthroughs:
First, right before the government shutdown, one priority legislative accomplishment will provide $1.2 billion in quantum computing research over the next five years. Second, there’s the rise of ions as a truly viable, scalable quantum computing architecture.”
*Read this Gizmodo profile on an exciting startup in the space to learn more about this type of quantum computing
ENERGY
Ramez Naam | Chair, Energy and Environmental Systems, Singularity University
“2018 had plenty of energy surprises. In solar, we saw unsubsidized prices in the sunny parts of the world at just over two cents per kwh, or less than half the price of new coal or gas electricity. In the US southwest and Texas, new solar is also now cheaper than new coal or gas. But even more shockingly, in Germany, which is one of the least sunny countries on earth (it gets less sunlight than Canada) the average bid for new solar in a 2018 auction was less than 5 US cents per kwh. That’s as cheap as new natural gas in the US, and far cheaper than coal, gas, or any other new electricity source in most of Europe.
In fact, it’s now cheaper in some parts of the world to build new solar or wind than to run existing coal plants. Think tank Carbon Tracker calculates that, over the next 10 years, it will become cheaper to build new wind or solar than to operate coal power in most of the world, including specifically the US, most of Europe, and—most importantly—India and the world’s dominant burner of coal, China.
Here comes the sun.”
GLOBAL GRAND CHALLENGES
Darlene Damm | Vice Chair, Faculty, Global Grand Challenges, Singularity University
“In 2018 we saw a lot of areas in the Global Grand Challenges move forward—advancements in robotic farming technology and cultured meat, low-cost 3D printed housing, more sophisticated types of online education expanding to every corner of the world, and governments creating new policies to deal with the ethics of the digital world. These were the areas we were watching and had predicted there would be change.
What most surprised me was to see young people, especially teenagers, start to harness technology in powerful ways and use it as a platform to make their voices heard and drive meaningful change in the world. In 2018 we saw teenagers speak out on a number of issues related to their well-being and launch digital movements around issues such as gun and school safety, global warming and environmental issues. We often talk about the harm technology can cause to young people, but on the flip side, it can be a very powerful tool for youth to start changing the world today and something I hope we see more of in the future.”
BUSINESS STRATEGY
Pascal Finette | Chair, Entrepreneurship and Open Innovation, Singularity University
“Without a doubt the rapid and massive adoption of AI, specifically deep learning, across industries, sectors, and organizations. What was a curiosity for most companies at the beginning of the year has quickly made its way into the boardroom and leadership meetings, and all the way down into the innovation and IT department’s agenda. You are hard-pressed to find a mid- to large-sized company today that is not experimenting or implementing AI in various aspects of its business.
On the slightly snarkier side of answering this question: The very rapid decline in interest in blockchain (and cryptocurrencies). The blockchain party was short, ferocious, and ended earlier than most would have anticipated, with a huge hangover for some. The good news—with the hot air dissipated, we can now focus on exploring the unique use cases where blockchain does indeed offer real advantages over centralized approaches.”
*Author note: snark is welcome and appreciated
ROBOTICS
Hod Lipson | Director, Creative Machines Lab, Columbia University
“The biggest surprise for me this year in robotics was learning dexterity. For decades, roboticists have been trying to understand and imitate dexterous manipulation. We humans seem to be able to manipulate objects with our fingers with incredible ease—imagine sifting through a bunch of keys in the dark, or tossing and catching a cube. And while there has been much progress in machine perception, dexterous manipulation remained elusive.
There seemed to be something almost magical in how we humans can physically manipulate the physical world around us. Decades of research in grasping and manipulation, and millions of dollars spent on robot-hand hardware development, has brought us little progress. But in late 2018, the Berkley OpenAI group demonstrated that this hurdle may finally succumb to machine learning as well. Given 200 years worth of practice, machines learned to manipulate a physical object with amazing fluidity. This might be the beginning of a new age for dexterous robotics.”
MACHINE LEARNING
Jeremy Howard | Founding Researcher, fast.ai, Founder/CEO, Enlitic, Faculty Data Science, Singularity University
“The biggest development in machine learning this year has been the development of effective natural language processing (NLP).
The New York Times published an article last month titled “Finally, a Machine That Can Finish Your Sentence,” which argued that NLP neural networks have reached a significant milestone in capability and speed of development. The “finishing your sentence” capability mentioned in the title refers to a type of neural network called a “language model,” which is literally a model that learns how to finish your sentences.
Earlier this year, two systems (one, called ELMO, is from the Allen Institute for AI, and the other, called ULMFiT, was developed by me and Sebastian Ruder) showed that such a model could be fine-tuned to dramatically improve the state-of-the-art in nearly every NLP task that researchers study. This work was further developed by OpenAI, which in turn was greatly scaled up by Google Brain, who created a system called BERT which reached human-level performance on some of NLP’s toughest challenges.
Over the next year, expect to see fine-tuned language models used for everything from understanding medical texts to building disruptive social media troll armies.”
DIGITAL MANUFACTURING
Andre Wegner | Founder/CEO Authentise, Chair, Digital Manufacturing, Singularity University
“Most surprising to me was the extent and speed at which the industry finally opened up.
While previously, only few 3D printing suppliers had APIs and knew what to do with them, 2018 saw nearly every OEM (or original equipment manufacturer) enabling data access and, even more surprisingly, shying away from proprietary standards and adopting MTConnect, as stalwarts such as 3D Systems and Stratasys have been. This means that in two to three years, data access to machines will be easy, commonplace, and free. The value will be in what is being done with that data.
Another example of this openness are the seemingly endless announcements of integrated workflows: GE’s announcement with most major software players to enable integrated solutions, EOS’s announcement with Siemens, and many more. It’s clear that all actors in the additive ecosystem have taken a step forward in terms of openness. The result is a faster pace of innovation, particularly in the software and data domains that are crucial to enabling comprehensive digital workflow to drive agile and resilient manufacturing.
I’m more optimistic we’ll achieve that now than I was at the end of 2017.”
SCIENCE AND DISCOVERY
Paul Saffo | Chair, Future Studies, Singularity University, Distinguished Visiting Scholar, Stanford Media-X Research Network
“The most important development in technology this year isn’t a technology, but rather the astonishing science surprises made possible by recent technology innovations. My short list includes the discovery of the “neptmoon”, a Neptune-scale moon circling a Jupiter-scale planet 8,000 lightyears from us; the successful deployment of the Mars InSight Lander a month ago; and the tantalizing ANITA detection (what could be a new subatomic particle which would in turn blow the standard model wide open). The highest use of invention is to support science discovery, because those discoveries in turn lead us to the future innovations that will improve the state of the world—and fire up our imaginations.”
ROBOTICS
Pablos Holman | Inventor, Hacker, Faculty, Singularity University
“Just five or ten years ago, if you’d asked any of us technologists “What is harder for robots? Eyes, or fingers?” We’d have all said eyes. Robots have extraordinary eyes now, but even in a surgical robot, the fingers are numb and don’t feel anything. Stanford robotics researchers have invented fingertips that can feel, and this will be a kingpin that allows robots to go everywhere they haven’t been yet.”
BLOCKCHAIN
Nathana Sharma | Blockchain, Policy, Law, and Ethics, Faculty, Singularity University
“2017 was the year of peak blockchain hype. 2018 has been a year of resetting expectations and technological development, even as the broader cryptocurrency markets have faced a winter. It’s now about seeing adoption and applications that people want and need to use rise. An incredible piece of news from December 2018 is that Facebook is developing a cryptocurrency for users to make payments through Whatsapp. That’s surprisingly fast mainstream adoption of this new technology, and indicates how powerful it is.”
ARTIFICIAL INTELLIGENCE
Neil Jacobstein | Chair, Artificial Intelligence and Robotics, Singularity University
“I think one of the most visible improvements in AI was illustrated by the Boston Dynamics Parkour video. This was not due to an improvement in brushless motors, accelerometers, or gears. It was due to improvements in AI algorithms and training data. To be fair, the video released was cherry-picked from numerous attempts, many of which ended with a crash. However, the fact that it could be accomplished at all in 2018 was a real win for both AI and robotics.”
NEUROSCIENCE
Divya Chander | Chair, Neuroscience, Singularity University
“2018 ushered in a new era of exponential trends in non-invasive brain modulation. Changing behavior or restoring function takes on a new meaning when invasive interfaces are no longer needed to manipulate neural circuitry. The end of 2018 saw two amazing announcements: the ability to grow neural organoids (mini-brains) in a dish from neural stem cells that started expressing electrical activity, mimicking the brain function of premature babies, and the first (known) application of CRISPR to genetically alter two fetuses grown through IVF. Although this was ostensibly to provide genetic resilience against HIV infections, imagine what would happen if we started tinkering with neural circuitry and intelligence.”
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