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#434823 The Tangled Web of Turning Spider Silk ...
Spider-Man is one of the most popular superheroes of all time. It’s a bit surprising given that one of the more common phobias is arachnophobia—a debilitating fear of spiders.
Perhaps more fantastical is that young Peter Parker, a brainy high school science nerd, seemingly developed overnight the famous web-shooters and the synthetic spider silk that he uses to swing across the cityscape like Tarzan through the jungle.
That’s because scientists have been trying for decades to replicate spider silk, a material that is five times stronger than steel, among its many superpowers. In recent years, researchers have been untangling the protein-based fiber’s structure down to the molecular level, leading to new insights and new potential for eventual commercial uses.
The applications for such a material seem near endless. There’s the more futuristic visions, like enabling robotic “muscles” for human-like movement or ensnaring real-life villains with a Spider-Man-like web. Near-term applications could include the biomedical industry, such as bandages and adhesives, and as a replacement textile for everything from rope to seat belts to parachutes.
Spinning Synthetic Spider Silk
Randy Lewis has been studying the properties of spider silk and developing methods for producing it synthetically for more than three decades. In the 1990s, his research team was behind cloning the first spider silk gene, as well as the first to identify and sequence the proteins that make up the six different silks that web slingers make. Each has different mechanical properties.
“So our thought process was that you could take that information and begin to to understand what made them strong and what makes them stretchy, and why some are are very stretchy and some are not stretchy at all, and some are stronger and some are weaker,” explained Lewis, a biology professor at Utah State University and director of the Synthetic Spider Silk Lab, in an interview with Singularity Hub.
Spiders are naturally territorial and cannibalistic, so any intention to farm silk naturally would likely end in an orgy of arachnid violence. Instead, Lewis and company have genetically modified different organisms to produce spider silk synthetically, including inserting a couple of web-making genes into the genetic code of goats. The goats’ milk contains spider silk proteins.
The lab also produces synthetic spider silk through a fermentation process not entirely dissimilar to brewing beer, but using genetically modified bacteria to make the desired spider silk proteins. A similar technique has been used for years to make a key enzyme in cheese production. More recently, companies are using transgenic bacteria to make meat and milk proteins, entirely bypassing animals in the process.
The same fermentation technology is used by a chic startup called Bolt Threads outside of San Francisco that has raised more than $200 million for fashionable fibers made out of synthetic spider silk it calls Microsilk. (The company is also developing a second leather-like material, Mylo, using the underground root structure of mushrooms known as mycelium.)
Lewis’ lab also uses transgenic silkworms to produce a kind of composite material made up of the domesticated insect’s own silk proteins and those of spider silk. “Those have some fairly impressive properties,” Lewis said.
The researchers are even experimenting with genetically modified alfalfa. One of the big advantages there is that once the spider silk protein has been extracted, the remaining protein could be sold as livestock feed. “That would bring the cost of spider silk protein production down significantly,” Lewis said.
Building a Better Web
Producing synthetic spider silk isn’t the problem, according to Lewis, but the ability to do it at scale commercially remains a sticking point.
Another challenge is “weaving” the synthetic spider silk into usable products that can take advantage of the material’s marvelous properties.
“It is possible to make silk proteins synthetically, but it is very hard to assemble the individual proteins into a fiber or other material forms,” said Markus Buehler, head of the Department of Civil and Environmental Engineering at MIT, in an email to Singularity Hub. “The spider has a complex spinning duct in which silk proteins are exposed to physical forces, chemical gradients, the combination of which generates the assembly of molecules that leads to silk fibers.”
Buehler recently co-authored a paper in the journal Science Advances that found dragline spider silk exhibits different properties in response to changes in humidity that could eventually have applications in robotics.
Specifically, spider silk suddenly contracts and twists above a certain level of relative humidity, exerting enough force to “potentially be competitive with other materials being explored as actuators—devices that move to perform some activity such as controlling a valve,” according to a press release.
Studying Spider Silk Up Close
Recent studies at the molecular level are helping scientists learn more about the unique properties of spider silk, which may help researchers develop materials with extraordinary capabilities.
For example, scientists at Arizona State University used magnetic resonance tools and other instruments to image the abdomen of a black widow spider. They produced what they called the first molecular-level model of spider silk protein fiber formation, providing insights on the nanoparticle structure. The research was published last October in Proceedings of the National Academy of Sciences.
A cross section of the abdomen of a black widow (Latrodectus Hesperus) spider used in this study at Arizona State University. Image Credit: Samrat Amin.
Also in 2018, a study presented in Nature Communications described a sort of molecular clamp that binds the silk protein building blocks, which are called spidroins. The researchers observed for the first time that the clamp self-assembles in a two-step process, contributing to the extensibility, or stretchiness, of spider silk.
Another team put the spider silk of a brown recluse under an atomic force microscope, discovering that each strand, already 1,000 times thinner than a human hair, is made up of thousands of nanostrands. That helps explain its extraordinary tensile strength, though technique is also a factor, as the brown recluse uses a special looping method to reinforce its silk strands. The study also appeared last year in the journal ACS Macro Letters.
Making Spider Silk Stick
Buehler said his team is now trying to develop better and faster predictive methods to design silk proteins using artificial intelligence.
“These new methods allow us to generate new protein designs that do not naturally exist and which can be explored to optimize certain desirable properties like torsional actuation, strength, bioactivity—for example, tissue engineering—and others,” he said.
Meanwhile, Lewis’ lab has discovered a method that allows it to solubilize spider silk protein in what is essentially a water-based solution, eschewing acids or other toxic compounds that are normally used in the process.
That enables the researchers to develop materials beyond fiber, including adhesives that “are better than an awful lot of the current commercial adhesives,” Lewis said, as well as coatings that could be used to dampen vibrations, for example.
“We’re making gels for various kinds of of tissue regeneration, as well as drug delivery, and things like that,” he added. “So we’ve expanded the use profile from something beyond fibers to something that is a much more extensive portfolio of possible kinds of materials.”
And, yes, there’s even designs at the Synthetic Spider Silk Lab for developing a Spider-Man web-slinger material. The US Navy is interested in non-destructive ways of disabling an enemy vessel, such as fouling its propeller. The project also includes producing synthetic proteins from the hagfish, an eel-like critter that exudes a gelatinous slime when threatened.
Lewis said that while the potential for spider silk is certainly headline-grabbing, he cautioned that much of the hype is not focused on the unique mechanical properties that could lead to advances in healthcare and other industries.
“We want to see spider silk out there because it’s a unique material, not because it’s got marketing appeal,” he said.
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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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#434701 3 Practical Solutions to Offset ...
In recent years, the media has sounded the alarm about mass job loss to automation and robotics—some studies predict that up to 50 percent of current jobs or tasks could be automated in coming decades. While this topic has received significant attention, much of the press focuses on potential problems without proposing realistic solutions or considering new opportunities.
The economic impacts of AI, robotics, and automation are complex topics that require a more comprehensive perspective to understand. Is universal basic income, for example, the answer? Many believe so, and there are a number of experiments in progress. But it’s only one strategy, and without a sustainable funding source, universal basic income may not be practical.
As automation continues to accelerate, we’ll need a multi-pronged approach to ease the transition. In short, we need to update broad socioeconomic strategies for a new century of rapid progress. How, then, do we plan practical solutions to support these new strategies?
Take history as a rough guide to the future. Looking back, technology revolutions have three themes in common.
First, past revolutions each produced profound benefits to productivity, increasing human welfare. Second, technological innovation and technology diffusion have accelerated over time, each iteration placing more strain on the human ability to adapt. And third, machines have gradually replaced more elements of human work, with human societies adapting by moving into new forms of work—from agriculture to manufacturing to service, for example.
Public and private solutions, therefore, need to be developed to address each of these three components of change. Let’s explore some practical solutions for each in turn.
Figure 1. Technology’s structural impacts in the 21st century. Refer to Appendix I for quantitative charts and technological examples corresponding to the numbers (1-22) in each slice.
Solution 1: Capture New Opportunities Through Aggressive Investment
The rapid emergence of new technology promises a bounty of opportunity for the twenty-first century’s economic winners. This technological arms race is shaping up to be a global affair, and the winners will be determined in part by who is able to build the future economy fastest and most effectively. Both the private and public sectors have a role to play in stimulating growth.
At the country level, several nations have created competitive strategies to promote research and development investments as automation technologies become more mature.
Germany and China have two of the most notable growth strategies. Germany’s Industrie 4.0 plan targets a 50 percent increase in manufacturing productivity via digital initiatives, while halving the resources required. China’s Made in China 2025 national strategy sets ambitious targets and provides subsidies for domestic innovation and production. It also includes building new concept cities, investing in robotics capabilities, and subsidizing high-tech acquisitions abroad to become the leader in certain high-tech industries. For China, specifically, tech innovation is driven partially by a fear that technology will disrupt social structures and government control.
Such opportunities are not limited to existing economic powers. Estonia’s progress after the breakup of the Soviet Union is a good case study in transitioning to a digital economy. The nation rapidly implemented capitalistic reforms and transformed itself into a technology-centric economy in preparation for a massive tech disruption. Internet access was declared a right in 2000, and the country’s classrooms were outfitted for a digital economy, with coding as a core educational requirement starting at kindergarten. Internet broadband speeds in Estonia are among the fastest in the world. Accordingly, the World Bank now ranks Estonia as a high-income country.
Solution 2: Address Increased Rate of Change With More Nimble Education Systems
Education and training are currently not set for the speed of change in the modern economy. Schools are still based on a one-time education model, with school providing the foundation for a single lifelong career. With content becoming obsolete faster and rapidly escalating costs, this system may be unsustainable in the future. To help workers more smoothly transition from one job into another, for example, we need to make education a more nimble, lifelong endeavor.
Primary and university education may still have a role in training foundational thinking and general education, but it will be necessary to curtail rising price of tuition and increase accessibility. Massive open online courses (MooCs) and open-enrollment platforms are early demonstrations of what the future of general education may look like: cheap, effective, and flexible.
Georgia Tech’s online Engineering Master’s program (a fraction of the cost of residential tuition) is an early example in making university education more broadly available. Similarly, nanodegrees or microcredentials provided by online education platforms such as Udacity and Coursera can be used for mid-career adjustments at low cost. AI itself may be deployed to supplement the learning process, with applications such as AI-enhanced tutorials or personalized content recommendations backed by machine learning. Recent developments in neuroscience research could optimize this experience by perfectly tailoring content and delivery to the learner’s brain to maximize retention.
Finally, companies looking for more customized skills may take a larger role in education, providing on-the-job training for specific capabilities. One potential model involves partnering with community colleges to create apprenticeship-style learning, where students work part-time in parallel with their education. Siemens has pioneered such a model in four states and is developing a playbook for other companies to do the same.
Solution 3: Enhance Social Safety Nets to Smooth Automation Impacts
If predicted job losses to automation come to fruition, modernizing existing social safety nets will increasingly become a priority. While the issue of safety nets can become quickly politicized, it is worth noting that each prior technological revolution has come with corresponding changes to the social contract (see below).
The evolving social contract (U.S. examples)
– 1842 | Right to strike
– 1924 | Abolish child labor
– 1935 | Right to unionize
– 1938 | 40-hour work week
– 1962, 1974 | Trade adjustment assistance
– 1964 | Pay discrimination prohibited
– 1970 | Health and safety laws
– 21st century | AI and automation adjustment assistance?
Figure 2. Labor laws have historically adjusted as technology and society progressed
Solutions like universal basic income (no-strings-attached monthly payout to all citizens) are appealing in concept, but somewhat difficult to implement as a first measure in countries such as the US or Japan that already have high debt. Additionally, universal basic income may create dis-incentives to stay in the labor force. A similar cautionary tale in program design was the Trade Adjustment Assistance (TAA), which was designed to protect industries and workers from import competition shocks from globalization, but is viewed as a missed opportunity due to insufficient coverage.
A near-term solution could come in the form of graduated wage insurance (compensation for those forced to take a lower-paying job), including health insurance subsidies to individuals directly impacted by automation, with incentives to return to the workforce quickly. Another topic to tackle is geographic mismatch between workers and jobs, which can be addressed by mobility assistance. Lastly, a training stipend can be issued to individuals as means to upskill.
Policymakers can intervene to reverse recent historical trends that have shifted incomes from labor to capital owners. The balance could be shifted back to labor by placing higher taxes on capital—an example is the recently proposed “robot tax” where the taxation would be on the work rather than the individual executing it. That is, if a self-driving car performs the task that formerly was done by a human, the rideshare company will still pay the tax as if a human was driving.
Other solutions may involve distribution of work. Some countries, such as France and Sweden, have experimented with redistributing working hours. The idea is to cap weekly hours, with the goal of having more people employed and work more evenly spread. So far these programs have had mixed results, with lower unemployment but high costs to taxpayers, but are potential models that can continue to be tested.
We cannot stop growth, nor should we. With the roles in response to this evolution shifting, so should the social contract between the stakeholders. Government will continue to play a critical role as a stabilizing “thumb” in the invisible hand of capitalism, regulating and cushioning against extreme volatility, particularly in labor markets.
However, we already see business leaders taking on some of the role traditionally played by government—thinking about measures to remedy risks of climate change or economic proposals to combat unemployment—in part because of greater agility in adapting to change. Cross-disciplinary collaboration and creative solutions from all parties will be critical in crafting the future economy.
Note: The full paper this article is based on is available here.
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