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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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“You really can’t justify tuna in Chicago as a source of sustenance.” That’s according to Dr. Sylvia Earle, a National Geographic Society Explorer who was the first female chief scientist at NOAA. She came to the Good Food Institute’s Good Food Conference to deliver a call to action around global food security, agriculture, environmental protection, and the future of consumer choice.
It seems like all options should be on the table to feed an exploding population threatened by climate change. But Dr. Earle, who is faculty at Singularity University, drew a sharp distinction between seafood for sustenance versus seafood as a choice. “There is this widespread claim that we must take large numbers of wildlife from the sea in order to have food security.”
A few minutes later, Dr. Earle directly addressed those of us in the audience. “We know the value of a dead fish,” she said. That’s market price. “But what is the value of a live fish in the ocean?”
That’s when my mind blew open. What is the value—or put another way, the cost—of using the ocean as a major source of protein for humans? How do you put a number on that? Are we talking about dollars and cents, or about something far larger?
Dr. Liz Specht of the Good Food Institute drew the audience’s attention to a strange imbalance. Currently, about half of the yearly global catch of seafood comes from aquaculture. That means that the other half is wild caught. It’s hard to imagine half of your meat coming directly from the forests and the plains, isn’t it? And yet half of the world’s seafood comes from direct harvesting of the oceans, by way of massive overfishing, a terrible toll from bycatch, a widespread lack of regulation and enforcement, and even human rights violations such as slavery.
The search for solutions is on, from both within the fishing industry and from external agencies such as governments and philanthropists. Could there be another way?
Makers of plant-based seafood and clean seafood think they know how to feed the global demand for seafood without harming the ocean. These companies are part of a larger movement harnessing technology to reduce our reliance on wild and domesticated animals—and all the environmental, economic, and ethical issues that come with it.
Producers of plant-based seafood (20 or so currently) are working to capture the taste, texture, and nutrition of conventional seafood without the limitations of geography or the health of a local marine population. Like with plant-based meat, makers of plant-based seafood are harnessing food science and advances in chemistry, biology, and engineering to make great food. The industry’s strategy? Start with what the consumer wants, and then figure out how to achieve that great taste through technology.
So how does plant-based seafood taste? Pretty good, as it turns out. (The biggest benefit of a food-oriented conference is that your mouth is always full!)
I sampled “tuna” salad made from Good Catch Food’s fish-free tuna, which is sourced from legumes; the texture was nearly indistinguishable from that of flaked albacore tuna, and there was no lingering fishy taste to overpower my next bite. In a blind taste test, I probably wouldn’t have known that I was eating a plant-based seafood alternative. Next I reached for Ocean Hugger Food’s Ahimi, a tomato-based alternative to raw tuna. I adore Hawaiian poke, so I was pleasantly surprised when my Ahimi-based poke captured the bite of ahi tuna. It wasn’t quite as delightfully fatty as raw tuna, but with wild tuna populations struggling to recover from a 97% decline in numbers from 40 years ago, Ahimi is a giant stride in the right direction.
These plant-based alternatives aren’t the only game in town, however.
The clean meat industry, which has also been called “cultured meat” or “cellular agriculture,” isn’t seeking to lure consumers away from animal protein. Instead, cells are sampled from live animals and grown in bioreactors—meaning that no animal is slaughtered to produce real meat.
Clean seafood is poised to piggyback off platforms developed for clean meat; growing fish cells in the lab should rely on the same processes as growing meat cells. I know of four companies currently focusing on seafood (Finless Foods, Wild Type, BlueNalu, and Seafuture Sustainable Biotech), and a few more are likely to emerge from stealth mode soon.
Importantly, there’s likely not much difference between growing clean seafood from the top or the bottom of the food chain. Tuna, for example, are top predators that must grow for at least 10 years before they’re suitable as food. Each year, a tuna consumes thousands of pounds of other fish, shellfish, and plankton. That “long tail of groceries,” said Dr. Earle, “is a pretty expensive choice.” Excitingly, clean tuna would “level the trophic playing field,” as Dr. Specht pointed out.
All this is only the beginning of what might be possible.
Combining synthetic biology with clean meat and seafood means that future products could be personalized for individual taste preferences or health needs, by reprogramming the DNA of the cells in the lab. Industries such as bioremediation and biofuels likely have a lot to teach us about sourcing new ingredients and flavors from algae and marine plants. By harnessing rapid advances in automation, robotics, sensors, machine vision, and other big-data analytics, the manufacturing and supply chains for clean seafood could be remarkably safe and robust. Clean seafood would be just that: clean, without pathogens, parasites, or the plastic threatening to fill our oceans, meaning that you could enjoy it raw.
What about price? Dr. Mark Post, a pioneer in clean meat who is also faculty at Singularity University, estimated that 80% of clean-meat production costs come from the expensive medium in which cells are grown—and some ingredients in the medium are themselves sourced from animals, which misses the point of clean meat. Plus, to grow a whole cut of food, like a fish fillet, the cells need to be coaxed into a complex 3D structure with various cell types like muscle cells and fat cells. These two technical challenges must be solved before clean meat and seafood give consumers the experience they want, at the price they want.
In this respect clean seafood has an unusual edge. Most of what we know about growing animal cells in the lab comes from the research and biomedical industries (from tissue engineering, for example)—but growing cells to replace an organ has different constraints than growing cells for food. The link between clean seafood and biomedicine is less direct, empowering innovators to throw out dogma and find novel reagents, protocols, and equipment to grow seafood that captures the tastes, textures, smells, and overall experience of dining by the ocean.
Asked to predict when we’ll be seeing clean seafood in the grocery store, Lou Cooperhouse the CEO of BlueNalu, explained that the challenges aren’t only in the lab: marketing, sales, distribution, and communication with consumers are all critical. As Niya Gupta, the founder of Fork & Goode, said, “The question isn’t ‘can we do it’, but ‘can we sell it’?”
The good news is that the clean meat and seafood industry is highly collaborative; there are at least two dozen companies in the space, and they’re all talking to each other. “This is an ecosystem,” said Dr. Uma Valeti, the co-founder of Memphis Meats. “We’re not competing with each other.” It will likely be at least a decade before science, business, and regulation enable clean meat and seafood to routinely appear on restaurant menus, let alone market shelves.
Until then, think carefully about your food choices. Meditate on Dr. Earle’s question: “What is the real cost of that piece of halibut?” Or chew on this from Dr. Ricardo San Martin, of the Sutardja Center at the University of California, Berkeley: “Food is a system of meanings, not an object.” What are you saying when you choose your food, about your priorities and your values and how you want the future to look? Do you think about animal welfare? Most ethical regulations don’t extend to marine life, and if you don’t think that ocean creatures feel pain, consider the lobster.
Seafood is largely an acquired taste, since most of us don’t live near the water. Imagine a future in which children grow up loving the taste of delicious seafood but without hurting a living animal, the ocean, or the global environment.
Do more than imagine. As Dr. Earle urged us, “Convince the public at large that this is a really cool idea.”
Ahimi (Ocean Hugger)
New Wave Foods
Heritage Health Food
The Vegetarian Butcher
Table based on Figure 5 of the report “An Ocean of Opportunity: Plant-based and clean seafood for sustainable oceans without sacrifice,” from The Good Food Institute.
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Once upon a time, a powerful Sumerian king named Gilgamesh went on a quest, as such characters often do in these stories of myth and legend. Gilgamesh had witnessed the death of his best friend, Enkidu, and, fearing a similar fate, went in search of immortality. The great king failed to find the secret of eternal life but took solace that his deeds would live well beyond his mortal years.
Fast-forward four thousand years, give or take a century, and Gilgamesh (as famous as any B-list celebrity today, despite the passage of time) would probably be heartened to learn that many others have taken up his search for longevity. Today, though, instead of battling epic monsters and the machinations of fickle gods, those seeking to enhance and extend life are cutting-edge scientists and visionary entrepreneurs who are helping unlock the secrets of human biology.
Chief among them is Aubrey de Grey, a biomedical gerontologist who founded the SENS Research Foundation, a Silicon Valley-based research organization that seeks to advance the application of regenerative medicine to age-related diseases. SENS stands for Strategies for Engineered Negligible Senescence, a term coined by de Grey to describe a broad array (seven, to be precise) of medical interventions that attempt to repair or prevent different types of molecular and cellular damage that eventually lead to age-related diseases like cancer and Alzheimer’s.
Many of the strategies focus on senescent cells, which accumulate in tissues and organs as people age. Not quite dead, senescent cells stop dividing but are still metabolically active, spewing out all sorts of proteins and other molecules that can cause inflammation and other problems. In a young body, that’s usually not a problem (and probably part of general biological maintenance), as a healthy immune system can go to work to put out most fires.
However, as we age, senescent cells continue to accumulate, and at some point the immune system retires from fire watch. Welcome to old age.
Of Mice and Men
Researchers like de Grey believe that treating the cellular underpinnings of aging could not only prevent disease but significantly extend human lifespans. How long? Well, if you’re talking to de Grey, Biblical proportions—on the order of centuries.
De Grey says that science has made great strides toward that end in the last 15 years, such as the ability to copy mitochondrial DNA to the nucleus. Mitochondria serve as the power plant of the cell but are highly susceptible to mutations that lead to cellular degeneration. Copying the mitochondrial DNA into the nucleus would help protect it from damage.
Another achievement occurred about six years ago when scientists first figured out how to kill senescent cells. That discovery led to a spate of new experiments in mice indicating that removing these ticking-time-bomb cells prevented disease and even extended their lifespans. Now the anti-aging therapy is about to be tested in humans.
“As for the next few years, I think the stream of advances is likely to become a flood—once the first steps are made, things get progressively easier and faster,” de Grey tells Singularity Hub. “I think there’s a good chance that we will achieve really dramatic rejuvenation of mice within only six to eight years: maybe taking middle-aged mice and doubling their remaining lifespan, which is an order of magnitude more than can be done today.”
Not Horsing Around
Richard G.A. Faragher, a professor of biogerontology at the University of Brighton in the United Kingdom, recently made discoveries in the lab regarding the rejuvenation of senescent cells with chemical compounds found in foods like chocolate and red wine. He hopes to apply his findings to an animal model in the future—in this case,horses.
“We have been very fortunate in receiving some funding from an animal welfare charity to look at potential treatments for older horses,” he explains to Singularity Hub in an email. “I think this is a great idea. Many aspects of the physiology we are studying are common between horses and humans.”
What Faragher and his colleagues demonstrated in a paper published in BMC Cell Biology last year was that resveralogues, chemicals based on resveratrol, were able to reactivate a protein called a splicing factor that is involved in gene regulation. Within hours, the chemicals caused the cells to rejuvenate and start dividing like younger cells.
“If treatments work in our old pony systems, then I am sure they could be translated into clinical trials in humans,” Faragher says. “How long is purely a matter of money. Given suitable funding, I would hope to see a trial within five years.”
Show Them the Money
Faragher argues that the recent breakthroughs aren’t because a result of emerging technologies like artificial intelligence or the gene-editing tool CRISPR, but a paradigm shift in how scientists understand the underpinnings of cellular aging. Solving the “aging problem” isn’t a question of technology but of money, he says.
“Frankly, when AI and CRISPR have removed cystic fibrosis, Duchenne muscular dystrophy or Gaucher syndrome, I’ll be much more willing to hear tales of amazing progress. Go fix a single, highly penetrant genetic disease in the population using this flashy stuff and then we’ll talk,” he says. “My faith resides in the most potent technological development of all: money.”
De Grey is less flippant about the role that technology will play in the quest to defeat aging. AI, CRISPR, protein engineering, advances in stem cell therapies, and immune system engineering—all will have a part.
“There is not really anything distinctive about the ways in which these technologies will contribute,” he says. “What’s distinctive is that we will need all of these technologies, because there are so many different types of damage to repair and they each require different tricks.”
It’s in the Blood
A startup in the San Francisco Bay Area believes machines can play a big role in discovering the right combination of factors that lead to longer and healthier lives—and then develop drugs that exploit those findings.
BioAge Labs raised nearly $11 million last year for its machine learning platform that crunches big data sets to find blood factors, such as proteins or metabolites, that are tied to a person’s underlying biological age. The startup claims that these factors can predict how long a person will live.
“Our interest in this comes out of research into parabiosis, where joining the circulatory systems of old and young mice—so that they share the same blood—has been demonstrated to make old mice healthier and more robust,” Dr. Eric Morgen, chief medical officer at BioAge, tells Singularity Hub.
Based on that idea, he explains, it should be possible to alter those good or bad factors to produce a rejuvenating effect.
“Our main focus at BioAge is to identify these types of factors in our human cohort data, characterize the important molecular pathways they are involved in, and then drug those pathways,” he says. “This is a really hard problem, and we use machine learning to mine these complex datasets to determine which individual factors and molecular pathways best reflect biological age.”
Saving for the Future
Of course, there’s no telling when any of these anti-aging therapies will come to market. That’s why Forever Labs, a biotechnology startup out of Ann Arbor, Michigan, wants your stem cells now. The company offers a service to cryogenically freeze stem cells taken from bone marrow.
The theory behind the procedure, according to Forever Labs CEO Steven Clausnitzer, is based on research showing that stem cells may be a key component for repairing cellular damage. That’s because stem cells can develop into many different cell types and can divide endlessly to replenish other cells. Clausnitzer notes that there are upwards of a thousand clinical studies looking at using stem cells to treat age-related conditions such as cardiovascular disease.
However, stem cells come with their own expiration date, which usually coincides with the age that most people start experiencing serious health problems. Stem cells harvested from bone marrow at a younger age can potentially provide a therapeutic resource in the future.
“We believe strongly that by having access to your own best possible selves, you’re going to be well positioned to lead healthier, longer lives,” he tells Singularity Hub.
“There’s a compelling argument to be made that if you started to maintain the bone marrow population, the amount of nuclear cells in your bone marrow, and to re-up them so that they aren’t declining with age, it stands to reason that you could absolutely mitigate things like cardiovascular disease and stroke and Alzheimer’s,” he adds.
Clausnitzer notes that the stored stem cells can be used today in developing therapies to treat chronic conditions such as osteoarthritis. However, the more exciting prospect—and the reason he put his own 38-year-old stem cells on ice—is that he believes future stem cell therapies can help stave off the ravages of age-related disease.
“I can start reintroducing them not to treat age-related disease but to treat the decline in the stem-cell niche itself, so that I don’t ever get an age-related disease,” he says. “I don’t think that it equates to immortality, but it certainly is a step in that direction.”
Indecisive on Immortality
The societal implications of a longer-living human species are a guessing game at this point. We do know that by mid-century, the global population of those aged 65 and older will reach 1.6 billion, while those older than 80 will hit nearly 450 million, according to the National Academies of Science. If many of those people could enjoy healthy lives in their twilight years, an enormous medical cost could be avoided.
Faragher is certainly working toward a future where human health is ubiquitous. Human immortality is another question entirely.
“The longer lifespans become, the more heavily we may need to control birth rates and thus we may have fewer new minds. This could have a heavy ‘opportunity cost’ in terms of progress,” he says.
And does anyone truly want to live forever?
“There have been happy moments in my life but I have also suffered some traumatic disappointments. No [drug] will wash those experiences out of me,” Faragher says. “I no longer view my future with unqualified enthusiasm, and I do not think I am the only middle-aged man to feel that way. I don’t think it is an accident that so many ‘immortalists’ are young.
“They should be careful what they wish for.”
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