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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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#434297 How Can Leaders Ensure Humanity in a ...
It’s hard to avoid the prominence of AI in our lives, and there is a plethora of predictions about how it will influence our future. In their new book Solomon’s Code: Humanity in a World of Thinking Machines, co-authors Olaf Groth, Professor of Strategy, Innovation and Economics at HULT International Business School and CEO of advisory network Cambrian.ai, and Mark Nitzberg, Executive Director of UC Berkeley’s Center for Human-Compatible AI, believe that the shift in balance of power between intelligent machines and humans is already here.
I caught up with the authors about how the continued integration between technology and humans, and their call for a “Digital Magna Carta,” a broadly-accepted charter developed by a multi-stakeholder congress that would help guide the development of advanced technologies to harness their power for the benefit of all humanity.
Lisa Kay Solomon: Your new book, Solomon’s Code, explores artificial intelligence and its broader human, ethical, and societal implications that all leaders need to consider. AI is a technology that’s been in development for decades. Why is it so urgent to focus on these topics now?
Olaf Groth and Mark Nitzberg: Popular perception always thinks of AI in terms of game-changing narratives—for instance, Deep Blue beating Gary Kasparov at chess. But it’s the way these AI applications are “getting into our heads” and making decisions for us that really influences our lives. That’s not to say the big, headline-grabbing breakthroughs aren’t important; they are.
But it’s the proliferation of prosaic apps and bots that changes our lives the most, by either empowering or counteracting who we are and what we do. Today, we turn a rapidly growing number of our decisions over to these machines, often without knowing it—and even more often without understanding the second- and third-order effects of both the technologies and our decisions to rely on them.
There is genuine power in what we call a “symbio-intelligent” partnership between human, machine, and natural intelligences. These relationships can optimize not just economic interests, but help improve human well-being, create a more purposeful workplace, and bring more fulfillment to our lives.
However, mitigating the risks while taking advantage of the opportunities will require a serious, multidisciplinary consideration of how AI influences human values, trust, and power relationships. Whether or not we acknowledge their existence in our everyday life, these questions are no longer just thought exercises or fodder for science fiction.
In many ways, these technologies can challenge what it means to be human, and their ramifications already affect us in real and often subtle ways. We need to understand how
LKS: There is a lot of hype and misconceptions about AI. In your book, you provide a useful distinction between the cognitive capability that we often associate with AI processes, and the more human elements of consciousness and conscience. Why are these distinctions so important to understand?
OG & MN: Could machines take over consciousness some day as they become more powerful and complex? It’s hard to say. But there’s little doubt that, as machines become more capable, humans will start to think of them as something conscious—if for no other reason than our natural inclination to anthropomorphize.
Machines are already learning to recognize our emotional states and our physical health. Once they start talking that back to us and adjusting their behavior accordingly, we will be tempted to develop a certain rapport with them, potentially more trusting or more intimate because the machine recognizes us in our various states.
Consciousness is hard to define and may well be an emergent property, rather than something you can easily create or—in turn—deduce to its parts. So, could it happen as we put more and more elements together, from the realms of AI, quantum computing, or brain-computer interfaces? We can’t exclude that possibility.
Either way, we need to make sure we’re charting out a clear path and guardrails for this development through the Three Cs in machines: cognition (where AI is today); consciousness (where AI could go); and conscience (what we need to instill in AI before we get there). The real concern is that we reach machine consciousness—or what humans decide to grant as consciousness—without a conscience. If that happens, we will have created an artificial sociopath.
LKS: We have been seeing major developments in how AI is influencing product development and industry shifts. How is the rise of AI changing power at the global level?
OG & MN: Both in the public and private sectors, the data holder has the power. We’ve already seen the ascendance of about 10 “digital barons” in the US and China who sit on huge troves of data, massive computing power, and the resources and money to attract the world’s top AI talent. With these gaps already open between the haves and the have-nots on the technological and corporate side, we’re becoming increasingly aware that similar inequalities are forming at a societal level as well.
Economic power flows with data, leaving few options for socio-economically underprivileged populations and their corrupt, biased, or sparse digital footprints. By concentrating power and overlooking values, we fracture trust.
We can already see this tension emerging between the two dominant geopolitical models of AI. China and the US have emerged as the most powerful in both technological and economic terms, and both remain eager to drive that influence around the world. The EU countries are more contained on these economic and geopolitical measures, but they’ve leaped ahead on privacy and social concerns.
The problem is, no one has yet combined leadership on all three critical elements of values, trust, and power. The nations and organizations that foster all three of these elements in their AI systems and strategies will lead the future. Some are starting to recognize the need for the combination, but we found just 13 countries that have created significant AI strategies. Countries that wait too long to join them risk subjecting themselves to a new “data colonialism” that could change their economies and societies from the outside.
LKS: Solomon’s Code looks at AI from a variety of perspectives, considering both positive and potentially dangerous effects. You caution against the rising global threat and weaponization of AI and data, suggesting that “biased or dirty data is more threatening than nuclear arms or a pandemic.” For global leaders, entrepreneurs, technologists, policy makers and social change agents reading this, what specific strategies do you recommend to ensure ethical development and application of AI?
OG & MN: We’ve surrendered many of our most critical decisions to the Cult of Data. In most cases, that’s a great thing, as we rely more on scientific evidence to understand our world and our way through it. But we swing too far in other instances, assuming that datasets and algorithms produce a complete story that’s unsullied by human biases or intellectual shortcomings. We might choose to ignore it, but no one is blind to the dangers of nuclear war or pandemic disease. Yet, we willfully blind ourselves to the threat of dirty data, instead believing it to be pristine.
So, what do we do about it? On an individual level, it’s a matter of awareness, knowing who controls your data and how outsourcing of decisions to thinking machines can present opportunities and threats alike.
For business, government, and political leaders, we need to see a much broader expansion of ethics committees with transparent criteria with which to evaluate new products and services. We might consider something akin to clinical trials for pharmaceuticals—a sort of testing scheme that can transparently and independently measure the effects on humans of algorithms, bots, and the like. All of this needs to be multidisciplinary, bringing in expertise from across technology, social systems, ethics, anthropology, psychology, and so on.
Finally, on a global level, we need a new charter of rights—a Digital Magna Carta—that formalizes these protections and guides the development of new AI technologies toward all of humanity’s benefit. We’ve suggested the creation of a multi-stakeholder Cambrian Congress (harkening back to the explosion of life during the Cambrian period) that can not only begin to frame benefits for humanity, but build the global consensus around principles for a basic code-of-conduct, and ideas for evaluation and enforcement mechanisms, so we can get there without any large-scale failures or backlash in society. So, it’s not one or the other—it’s both.
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