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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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Image Credit: Giovanni Cancemi / Shutterstock.com Continue reading
For Dr. Hiroshi Ishiguro, one of the most interesting things about androids is the changing questions they pose us, their creators, as they evolve. Does it, for example, do something to the concept of being human if a human-made creation starts telling you about what kind of boys ‘she’ likes?
If you want to know the answer to the boys question, you need to ask ERICA, one of Dr. Ishiguro’s advanced androids. Beneath her plastic skull and silicone skin, wires connect to AI software systems that bring her to life. Her ability to respond goes far beyond standard inquiries. Spend a little time with her, and the feeling of a distinct personality starts to emerge. From time to time, she works as a receptionist at Dr. Ishiguro and his team’s Osaka University labs. One of her android sisters is an actor who has starred in plays and a film.
ERICA’s ‘brother’ is an android version of Dr. Ishiguro himself, which has represented its creator at various events while the biological Ishiguro can remain in his offices in Japan. Microphones and cameras capture Ishiguro’s voice and face movements, which are relayed to the android. Apart from mimicking its creator, the Geminoid™ android is also capable of lifelike blinking, fidgeting, and breathing movements.
Say hello to relaxation
As technological development continues to accelerate, so do the possibilities for androids. From a position as receptionist, ERICA may well branch out into many other professions in the coming years. Companion for the elderly, comic book storyteller (an ancient profession in Japan), pop star, conversational foreign language partner, and newscaster are some of the roles and responsibilities Dr. Ishiguro sees androids taking on in the near future.
“Androids are not uncanny anymore. Most people adapt to interacting with Erica very quickly. Actually, I think that in interacting with androids, which are still different from us, we get a better appreciation of interacting with other cultures. In both cases, we are talking with someone who is different from us and learn to overcome those differences,” he says.
A lot has been written about how robots will take our jobs. Dr. Ishiguro believes these fears are blown somewhat out of proportion.
“Robots and androids will take over many simple jobs. Initially there might be some job-related issues, but new schemes, like for example a robot tax similar to the one described by Bill Gates, should help,” he says.
“Androids will make it possible for humans to relax and keep evolving. If we compare the time we spend studying now compared to 100 years ago, it has grown a lot. I think it needs to keep growing if we are to keep expanding our scientific and technological knowledge. In the future, we might end up spending 20 percent of our lifetime on work and 80 percent of the time on education and growing our skills.”
Android asks who you are
For Dr. Ishiguro, another aspect of robotics in general, and androids in particular, is how they question what it means to be human.
“Identity is a very difficult concept for humans sometimes. For example, I think clothes are part of our identity, in a way that is similar to our faces and bodies. We don’t change those from one day to the next, and that is why I have ten matching black outfits,” he says.
This link between physical appearance and perceived identity is one of the aspects Dr. Ishiguro is exploring. Another closely linked concept is the connection between body and feeling of self. The Ishiguro avatar was once giving a presentation in Austria. Its creator recalls how he felt distinctly like he was in Austria, even capable of feeling sensation of touch on his own body when people laid their hands on the android. If he was distracted, he felt almost ‘sucked’ back into his body in Japan.
“I am constantly thinking about my life in this way, and I believe that androids are a unique mirror that helps us formulate questions about why we are here and why we have been so successful. I do not necessarily think I have found the answers to these questions, so if you have, please share,” he says with a laugh.
His work and these questions, while extremely interesting on their own, become extra poignant when considering the predicted melding of mind and machine in the near future.
The ability to be present in several locations through avatars—virtual or robotic—raises many questions of both philosophical and practical nature. Then add the hypotheticals, like why send a human out onto the hostile surface of Mars if you could send a remote-controlled android, capable of relaying everything it sees, hears and feels?
The two ways of robotics will meet
Dr. Ishiguro sees the world of AI-human interaction as currently roughly split into two. One is the chat-bot approach that companies like Amazon, Microsoft, Google, and recently Apple, employ using stationary objects like speakers. Androids like ERICA represent another approach.
“It is about more than the form factor. I think that the android approach is generally more story-based. We are integrating new conversation features based on assumptions about the situation and running different scenarios that expand the android’s vocabulary and interactions. Another aspect we are working on is giving androids desire and intention. Like with people, androids should have desires and intentions in order for you to want to interact with them over time,” Dr. Ishiguro explains.
This could be said to be part of a wider trend for Japan, where many companies are developing human-like robots that often have some Internet of Things capabilities, making them able to handle some of the same tasks as an Amazon Echo. The difference in approach could be summed up in the words ‘assistant’ (Apple, Amazon, etc.) and ‘companion’ (Japan).
Dr. Ishiguro sees this as partly linked to how Japanese as a language—and market—is somewhat limited. This has a direct impact on viability and practicality of ‘pure’ voice recognition systems. At the same time, Japanese people have had greater exposure to positive images of robots, and have a different cultural / religious view of objects having a ‘soul’. However, it may also mean Japanese companies and android scientists are both stealing a lap on their western counterparts.
“If you speak to an Amazon Echo, that is not a natural way to interact for humans. This is part of why we are making human-like robot systems. The human brain is set up to recognize and interact with humans. So, it makes sense to focus on developing the body for the AI mind, as well as the AI. I believe that the final goal for both Japanese and other companies and scientists is to create human-like interaction. Technology has to adapt to us, because we cannot adapt fast enough to it, as it develops so quickly,” he says.
Banner image courtesy of Hiroshi Ishiguro Laboratories, ATR all rights reserved.
Dr. Ishiguro’s team has collaborated with partners and developed a number of android systems:
Geminoid™ HI-2 has been developed by Hiroshi Ishiguro Laboratories and Advanced Telecommunications Research Institute International (ATR).
Geminoid™ F has been developed by Osaka University and Hiroshi Ishiguro Laboratories, Advanced Telecommunications Research Institute International (ATR).
ERICA has been developed by ERATO ISHIGURO Symbiotic Human-Robot Interaction Project Continue reading
Professor Hiroshi Ishiguro, creator of “Erica” – one of the most complex humanoid robots yet – thinks that desire and intention are the key prerequisites to humanizing Artificial Intelligence (AI) in the next 3 years. This entails the application of … Continue reading