Tag Archives: brain
As a human you instinctively know that a leopard is closer to a cat than a motorbike, but the way we train most AI makes them oblivious to these kinds of relations. Building the concept of similarity into our algorithms could make them far more capable, writes the author of a new paper in Science Robotics.
Convolutional neural networks have revolutionized the field of computer vision to the point that machines are now outperforming humans on some of the most challenging visual tasks. But the way we train them to analyze images is very different from the way humans learn, says Atsuto Maki, an associate professor at KTH Royal Institute of Technology.
“Imagine that you are two years old and being quizzed on what you see in a photo of a leopard,” he writes. “You might answer ‘a cat’ and your parents might say, ‘yeah, not quite but similar’.”
In contrast, the way we train neural networks rarely gives that kind of partial credit. They are typically trained to have very high confidence in the correct label and consider all incorrect labels, whether ”cat” or “motorbike,” equally wrong. That’s a mistake, says Maki, because ignoring the fact that something can be “less wrong” means you’re not exploiting all of the information in the training data.
Even when models are trained this way, there will be small differences in the probabilities assigned to incorrect labels that can tell you a lot about how well the model can generalize what it has learned to unseen data.
If you show a model a picture of a leopard and it gives “cat” a probability of five percent and “motorbike” one percent, that suggests it picked up on the fact that a cat is closer to a leopard than a motorbike. In contrast, if the figures are the other way around it means the model hasn’t learned the broad features that make cats and leopards similar, something that could potentially be helpful when analyzing new data.
If we could boost this ability to identify similarities between classes we should be able to create more flexible models better able to generalize, says Maki. And recent research has demonstrated how variations of an approach called regularization might help us achieve that goal.
Neural networks are prone to a problem called “overfitting,” which refers to a tendency to pay too much attention to tiny details and noise specific to their training set. When that happens, models will perform excellently on their training data but poorly when applied to unseen test data without these particular quirks.
Regularization is used to circumvent this problem, typically by reducing the network’s capacity to learn all this unnecessary information and therefore boost its ability to generalize to new data. Techniques are varied, but generally involve modifying the network’s structure or the strength of the weights between artificial neurons.
More recently, though, researchers have suggested new regularization approaches that work by encouraging a broader spread of probabilities across all classes. This essentially helps them capture more of the class similarities, says Maki, and therefore boosts their ability to generalize.
One such approach was devised in 2017 by Google Brain researchers, led by deep learning pioneer Geoffrey Hinton. They introduced a penalty to their training process that directly punished overconfident predictions in the model’s outputs, and a technique called label smoothing that prevents the largest probability becoming much larger than all others. This meant the probabilities were lower for correct labels and higher for incorrect ones, which was found to boost performance of models on varied tasks from image classification to speech recognition.
Another came from Maki himself in 2017 and achieves the same goal, but by suppressing high values in the model’s feature vector—the mathematical construct that describes all of an object’s important characteristics. This has a knock-on effect on the spread of output probabilities and also helped boost performance on various image classification tasks.
While it’s still early days for the approach, the fact that humans are able to exploit these kinds of similarities to learn more efficiently suggests that models that incorporate them hold promise. Maki points out that it could be particularly useful in applications such as robotic grasping, where distinguishing various similar objects is important.
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A few years back, DeepMind’s Demis Hassabis famously prophesized that AI and neuroscience will positively feed into each other in a “virtuous circle.” If realized, this would fundamentally expand our insight into intelligence, both machine and human.
We’ve already seen some proofs of concept, at least in the brain-to-AI direction. For example, memory replay, a biological mechanism that fortifies our memories during sleep, also boosted AI learning when abstractly appropriated into deep learning models. Reinforcement learning, loosely based on our motivation circuits, is now behind some of AI’s most powerful tools.
Hassabis is about to be proven right again.
Last week, two studies independently tapped into the power of ANNs to solve a 70-year-old neuroscience mystery: how does our visual system perceive reality?
The first, published in Cell, used generative networks to evolve DeepDream-like images that hyper-activate complex visual neurons in monkeys. These machine artworks are pure nightmare fuel to the human eye; but together, they revealed a fundamental “visual hieroglyph” that may form a basic rule for how we piece together visual stimuli to process sight into perception.
In the second study, a team used a deep ANN model—one thought to mimic biological vision—to synthesize new patterns tailored to control certain networks of visual neurons in the monkey brain. When directly shown to monkeys, the team found that the machine-generated artworks could reliably activate predicted populations of neurons. Future improved ANN models could allow even better control, giving neuroscientists a powerful noninvasive tool to study the brain. The work was published in Science.
The individual results, though fascinating, aren’t necessarily the point. Rather, they illustrate how scientists are now striving to complete the virtuous circle: tapping AI to probe natural intelligence. Vision is only the beginning—the tools can potentially be expanded into other sensory domains. And the more we understand about natural brains, the better we can engineer artificial ones.
It’s a “great example of leveraging artificial intelligence to study organic intelligence,” commented Dr. Roman Sandler at Kernel.co on Twitter.
ANNs and biological vision have quite the history.
In the late 1950s, the legendary neuroscientist duo David Hubel and Torsten Wiesel became some of the first to use mathematical equations to understand how neurons in the brain work together.
In a series of experiments—many using cats—the team carefully dissected the structure and function of the visual cortex. Using myriads of images, they revealed that vision is processed in a hierarchy: neurons in “earlier” brain regions, those closer to the eyes, tend to activate when they “see” simple patterns such as lines. As we move deeper into the brain, from the early V1 to a nub located slightly behind our ears, the IT cortex, neurons increasingly respond to more complex or abstract patterns, including faces, animals, and objects. The discovery led some scientists to call certain IT neurons “Jennifer Aniston cells,” which fire in response to pictures of the actress regardless of lighting, angle, or haircut. That is, IT neurons somehow extract visual information into the “gist” of things.
That’s not trivial. The complex neural connections that lead to increasing abstraction of what we see into what we think we see—what we perceive—is a central question in machine vision: how can we teach machines to transform numbers encoding stimuli into dots, lines, and angles that eventually form “perceptions” and “gists”? The answer could transform self-driving cars, facial recognition, and other computer vision applications as they learn to better generalize.
Hubel and Wiesel’s Nobel-prize-winning studies heavily influenced the birth of ANNs and deep learning. Much of earlier ANN “feed-forward” model structures are based on our visual system; even today, the idea of increasing layers of abstraction—for perception or reasoning—guide computer scientists to build AI that can better generalize. The early romance between vision and deep learning is perhaps the bond that kicked off our current AI revolution.
It only seems fair that AI would feed back into vision neuroscience.
Hieroglyphs and Controllers
In the Cell study, a team led by Dr. Margaret Livingstone at Harvard Medical School tapped into generative networks to unravel IT neurons’ complex visual alphabet.
Scientists have long known that neurons in earlier visual regions (V1) tend to fire in response to “grating patches” oriented in certain ways. Using a limited set of these patches like letters, V1 neurons can “express a visual sentence” and represent any image, said Dr. Arash Afraz at the National Institute of Health, who was not involved in the study.
But how IT neurons operate remained a mystery. Here, the team used a combination of genetic algorithms and deep generative networks to “evolve” computer art for every studied neuron. In seven monkeys, the team implanted electrodes into various parts of the visual IT region so that they could monitor the activity of a single neuron.
The team showed each monkey an initial set of 40 images. They then picked the top 10 images that stimulated the highest neural activity, and married them to 30 new images to “evolve” the next generation of images. After 250 generations, the technique, XDREAM, generated a slew of images that mashed up contorted face-like shapes with lines, gratings, and abstract shapes.
This image shows the evolution of an optimum image for stimulating a visual neuron in a monkey. Image Credit: Ponce, Xiao, and Schade et al. – Cell.
“The evolved images look quite counter-intuitive,” explained Afraz. Some clearly show detailed structures that resemble natural images, while others show complex structures that can’t be characterized by our puny human brains.
This figure shows natural images (right) and images evolved by neurons in the inferotemporal cortex of a monkey (left). Image Credit: Ponce, Xiao, and Schade et al. – Cell.
“What started to emerge during each experiment were pictures that were reminiscent of shapes in the world but were not actual objects in the world,” said study author Carlos Ponce. “We were seeing something that was more like the language cells use with each other.”
This image was evolved by a neuron in the inferotemporal cortex of a monkey using AI. Image Credit: Ponce, Xiao, and Schade et al. – Cell.
Although IT neurons don’t seem to use a simple letter alphabet, it does rely on a vast array of characters like hieroglyphs or Chinese characters, “each loaded with more information,” said Afraz.
The adaptive nature of XDREAM turns it into a powerful tool to probe the inner workings of our brains—particularly for revealing discrepancies between biology and models.
The Science study, led by Dr. James DiCarlo at MIT, takes a similar approach. Using ANNs to generate new patterns and images, the team was able to selectively predict and independently control neuron populations in a high-level visual region called V4.
“So far, what has been done with these models is predicting what the neural responses would be to other stimuli that they have not seen before,” said study author Dr. Pouya Bashivan. “The main difference here is that we are going one step further and using the models to drive the neurons into desired states.”
It suggests that our current ANN models for visual computation “implicitly capture a great deal of visual knowledge” which we can’t really describe, but which the brain uses to turn vision information into perception, the authors said. By testing AI-generated images on biological vision, however, the team concluded that today’s ANNs have a degree of understanding and generalization. The results could potentially help engineer even more accurate ANN models of biological vision, which in turn could feed back into machine vision.
“One thing is clear already: Improved ANN models … have led to control of a high-level neural population that was previously out of reach,” the authors said. “The results presented here have likely only scratched the surface of what is possible with such implemented characterizations of the brain’s neural networks.”
To Afraz, the power of AI here is to find cracks in human perception—both our computational models of sensory processes, as well as our evolved biological software itself. AI can be used “as a perfect adversarial tool to discover design cracks” of IT, said Afraz, such as finding computer art that “fools” a neuron into thinking the object is something else.
“As artificial intelligence researchers develop models that work as well as the brain does—or even better—we will still need to understand which networks are more likely to behave safely and further human goals,” said Ponce. “More efficient AI can be grounded by knowledge of how the brain works.”
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As technology continues to progress, the possibility of an abundant future seems more likely. Artificial intelligence is expected to drive down the cost of labor, infrastructure, and transport. Alternative energy systems are reducing the cost of a wide variety of goods. Poverty rates are falling around the world as more people are able to make a living, and resources that were once inaccessible to millions are becoming widely available.
But such a life presents fuel for the most common complaint against abundance: if robots take all the jobs, basic income provides us livable welfare for doing nothing, and healthcare is a guarantee free of charge, then what is the point of our lives? What would motivate us to work and excel if there are no real risks or rewards? If everything is simply given to us, how would we feel like we’ve ever earned anything?
Time has proven that humans inherently yearn to overcome challenges—in fact, this very desire likely exists as the root of most technological innovation. And the idea that struggling makes us stronger isn’t just anecdotal, it’s scientifically validated.
For instance, kids who use anti-bacterial soaps and sanitizers too often tend to develop weak immune systems, causing them to get sick more frequently and more severely. People who work out purposely suffer through torn muscles so that after a few days of healing their muscles are stronger. And when patients visit a psychologist to handle a fear that is derailing their lives, one of the most common treatments is exposure therapy: a slow increase of exposure to the suffering so that the patient gets stronger and braver each time, able to take on an incrementally more potent manifestation of their fears.
Different Kinds of Struggle
It’s not hard to understand why people might fear an abundant future as a terribly mundane one. But there is one crucial mistake made in this assumption, and it was well summarized by Indian mystic and author Sadhguru, who said during a recent talk at Google:
Stomach empty, only one problem. Stomach full—one hundred problems; because what we refer to as human really begins only after survival is taken care of.
This idea is backed up by Maslow’s hierarchy of needs, which was first presented in his 1943 paper “A Theory of Human Motivation.” Maslow shows the steps required to build to higher and higher levels of the human experience. Not surprisingly, the first two levels deal with physiological needs and the need for safety—in other words, with the body. You need to have food, water, and sleep, or you die. After that, you need to be protected from threats, from the elements, from dangerous people, and from disease and pain.
Maslow’s Hierarchy of Needs. Photo by Wikimedia User:Factoryjoe / CC BY-SA 3.0
The beauty of these first two levels is that they’re clear-cut problems with clear-cut solutions: if you’re hungry, then you eat; if you’re thirsty, then you drink; if you’re tired, then you sleep.
But what about the next tiers of the hierarchy? What of love and belonging, of self-esteem and self-actualization? If we’re lonely, can we just summon up an authentic friend or lover? If we feel neglected by society, can we demand it validate us? If we feel discouraged and disappointed in ourselves, can we simply dial up some confidence and self-esteem?
Of course not, and that’s because these psychological needs are nebulous; they don’t contain clear problems with clear solutions. They involve the external world and other people, and are complicated by the infinite flavors of nuance and compromise that are required to navigate human relationships and personal meaning.
These psychological difficulties are where we grow our personalities, outlooks, and beliefs. The truly defining characteristics of a person are dictated not by the physical situations they were forced into—like birth, socioeconomic class, or physical ailment—but instead by the things they choose. So a future of abundance helps to free us from the physical limitations so that we can truly commit to a life of purpose and meaning, rather than just feel like survival is our purpose.
The Greatest Challenge
And that’s the plot twist. This challenge to come to grips with our own individuality and freedom could actually be the greatest challenge our species has ever faced. Can you imagine waking up every day with infinite possibility? Every choice you make says no to the rest of reality, and so every decision carries with it truly life-defining purpose and meaning. That sounds overwhelming. And that’s probably because in our current socio-economic systems, it is.
Studies have shown that people in wealthier nations tend to experience more anxiety and depression. Ron Kessler, professor of health care policy at Harvard and World Health Organization (WHO) researcher, summarized his findings of global mental health by saying, “When you’re literally trying to survive, who has time for depression? Americans, on the other hand, many of whom lead relatively comfortable lives, blow other nations away in the depression factor, leading some to suggest that depression is a ‘luxury disorder.’”
This might explain why America scores in the top rankings for the most depressed and anxious country on the planet. We surpassed our survival needs, and instead became depressed because our jobs and relationships don’t fulfill our expectations for the next three levels of Maslow’s hierarchy (belonging, esteem, and self-actualization).
But a future of abundance would mean we’d have to deal with these levels. This is the challenge for the future; this is what keeps things from being mundane.
As a society, we would be forced to come to grips with our emotional intelligence, to reckon with philosophy rather than simply contemplate it. Nearly every person you meet will be passionately on their own customized life journey, not following a routine simply because of financial limitations. Such a world seems far more vibrant and interesting than one where most wander sleep-deprived and numb while attempting to survive the rat race.
We can already see the forceful hand of this paradigm shift as self-driving cars become ubiquitous. For example, consider the famous psychological and philosophical “trolley problem.” In this thought experiment, a person sees a trolley car heading towards five people on the train tracks; they see a lever that will allow them to switch the trolley car to a track that instead only has one person on it. Do you switch the lever and have a hand in killing one person, or do you let fate continue and kill five people instead?
For the longest time, this was just an interesting quandary to consider. But now, massive corporations have to have an answer, so they can program their self-driving cars with the ability to choose between hitting a kid who runs into the road or swerving into an oncoming car carrying a family of five. When companies need philosophers to make business decisions, it’s a good sign of what’s to come.
Luckily, it’s possible this forceful reckoning with philosophy and our own consciousness may be exactly what humanity needs. Perhaps our great failure as a species has been a result of advanced cognition still trapped in the first two levels of Maslow’s hierarchy due to a long history of scarcity.
As suggested in the opening scenes in 2001: A Space Odyssey, our ape-like proclivity for violence has long stayed the same while the technology we fight with and live amongst has progressed. So while well-off Americans may have comfortable lives, they still know they live in a system where there is no safety net, where a single tragic failure could still mean hunger and homelessness. And because of this, that evolutionarily hard-wired neurotic part of our brain that fears for our survival has never been able to fully relax, and so that anxiety and depression that come with too much freedom but not enough security stays ever present.
Not only might this shift in consciousness help liberate humanity, but it may be vital if we’re to survive our future creations as well. Whatever values we hold dear as a species are the ones we will imbue into the sentient robots we create. If machine learning is going to take its guidance from humanity, we need to level up humanity’s emotional maturity.
While the physical struggles of the future may indeed fall to the wayside amongst abundance, it’s unlikely to become a mundane world; instead, it will become a vibrant culture where each individual is striving against the most important struggle that affects all of us: the challenge to find inner peace, to find fulfillment, to build meaningful relationships, and ultimately, the challenge to find ourselves.
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Open AI’s Dota 2 AI Steamrolls World Champion e-Sports Team With Back-to-Back Victories
Nick Statt | The Verge
“…[OpenAI cofounder and CEO, Sam Altman] tells me there probably does not exist a video game out there right now that a system like OpenAI Five can’t eventually master at a level beyond human capability. For the broader AI industry, mastering video games may soon become passé, simple table stakes required to prove your system can learn fast and act in a way required to tackle tougher, real-world tasks with more meaningful benefits.”
Boston Dynamics Debuts the Production Version of SpotMini
Brian Heater, Catherine Shu | TechCrunch
“SpotMini is the first commercial robot Boston Dynamics is set to release, but as we learned earlier, it certainly won’t be the last. The company is looking to its wheeled Handle robot in an effort to push into the logistics space. It’s a super-hot category for robotics right now. Notably, Amazon recently acquired Colorado-based start up Canvas to add to its own arm of fulfillment center robots.”
Scientists Restore Some Brain Cell Functions in Pigs Four Hours After Death
Joel Achenbach | The Washington Post
“The ethicists say this research can blur the line between life and death, and could complicate the protocols for organ donation, which rely on a clear determination of when a person is dead and beyond resuscitation.”
How Scientists 3D Printed a Tiny Heart From Human Cells
Yasmin Saplakoglu | Live Science
“Though the heart is much smaller than a human’s (it’s only the size of a rabbit’s), and there’s still a long way to go until it functions like a normal heart, the proof-of-concept experiment could eventually lead to personalized organs or tissues that could be used in the human body…”
The Next Clash of Silicon Valley Titans Will Take Place in Space
Luke Dormehl | Digital Trends
“With bold plans that call for thousands of new satellites being put into orbit and astronomical costs, it’s going to be fascinating to observe the next phase of the tech platform battle being fought not on our desktops or mobile devices in our pockets, but outside of Earth’s atmosphere.”
The Images That Could Help Rebuild Notre-Dame Cathedral
Alexis C. Madrigal | The Atlantic
“…in 2010, [Andrew] Tallon, an art professor at Vassar, took a Leica ScanStation C10 to Notre-Dame and, with the assistance of Columbia’s Paul Blaer, began to painstakingly scan every piece of the structure, inside and out. …Over five days, they positioned the scanner again and again—50 times in all—to create an unmatched record of the reality of one of the world’s most awe-inspiring buildings, represented as a series of points in space.”
Mapping Our World in 3D Will Let Us Paint Streets With Augmented Reality
Charlotte Jee | MIT Technology Review
“Scape wants to use its location services to become the underlying infrastructure upon which driverless cars, robotics, and augmented-reality services sit. ‘Our end goal is a one-to-one map of the world covering everything,’ says Miller. ‘Our ambition is to be as invisible as GPS is today.’i”
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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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