The future of silk

The invention of the hypodermic needle in 1844 brought major benefits ​to the practice of medicine, but ran headlong into an unexpected quirk of human nature. It turns out that millions of people feel an instinctive horror at the thought of receiving an injection – at least ten percent of the US adult population and 25 percent of children, according to one estimate. This common phobia partly explains the widespread reluctance to receive vaccinations against Covid-19, a reluctance which has led to tens of thousands of unnecessary deaths.

But a company in Cambridge, Massachusetts, called Vaxess Technologies plans to sidestep this common fear by abandoning stainless steel needles and switching to silk.

Vaxess is testing a skin patch covered in dozens of microneedles made of silk protein and infused with influenza vaccine. Each needle is barely visible to the naked eye and just long enough to pierce the outer layer of skin. A user sticks the patch on his arm, waits five minutes, then throws it away. Left behind are the silk microneedles, which painlessly dissolve over the next two weeks, releasing the vaccine all the while.

The silk protein acts as a preservative, so there’s no need to keep it on ice at a doctor’s office. ‘It’s similar to what happens when you freeze something,’ said Vaxess founder and chief executive Michael Schrader. ‘It’s room-temperature freezing.’ In testing, Vaxess found that flu vaccines stored in a silk patch at room temperature remained viable three years later.

No more need for a ‘cold chain’, the costly network of refrigerators ​between manufacturing plants and medical clinics required by so many vaccines. Indeed, there’d be no need to get vaccinated at a clinic at all. Patients could vaccinate themselves.

‘We would mail you a patch,’ said Schrader. ‘It looks like a nicotine patch, only much smaller. You wear the patch for five minutes, then take it off and throw it away.’

Having completed a successful phase one clinical trial of the silk patches in late 2022, Schrader hopes to bring them to market by 2028.

It’s hardly the sort of product we’d usually associate with silk, the tough, luxurious, and luminous fabric that has delighted people for at least 5,000 years. But silk is proving to be far more valuable than its early Chinese cultivators could have imagined.

Much of what we now understand about silk was discovered at Silklab, ​a branch of the department of engineering at Tufts University in Medford, a suburb of Boston. Here a visitor encounters silken lenses that project words and images when bathed in laser light; surgical gloves coated in silk that display a warning if they’ve been contaminated with pathogens; tiny silken screws that are strong enough to repair a broken bone, only to dissolve entirely once the injury is healed.

For Silklab director Fiorenzo Omenetto, silk is not a fashion statement. It’s a set of microscopic Lego blocks that he and his colleagues are pulling apart and reassembling into an array of unexpected products.

‘We make everything,’ said Omenetto. ‘We make plastics, we make edible electronics, we make coatings for food.’

Silk isn’t everything at Silklab. Omenetto and his colleagues experiment with a variety of similar molecules, known as structural proteins. They’re found all over the place, shaping and strengthening plant and animal ​tissues. There’s the keratin in hair, collagen that holds our organs together, and more.

But for Omenetto, silk comes first. And his team has found an array of new uses for a fiber that humans have been cultivating for millennia.

Legend has it that the wife of the Yellow Emperor, who reigned around 2700 BC, was sipping hot tea under a mulberry tree when the cocoon of a silkworm fell into her cup. The hot liquid dissolved the cocoon’s sticky coating and caused the silk underneath to unravel, revealing its extraordinary beauty and strength. Then again, Chinese archeologists in 2017 found traces of silk in the soil under bodies in tombs 8,500 years old. The traces could be wild silk, but they could also suggest that sericulture – silk farming – may have begun much earlier.

A gray moth called Bombyx mori is the source of the silk. Centuries of selective breeding have created moths that reproduce at an exceptional rate – up to eight generations per year, compared to just three for wild silk moths. Domestication has wrought other changes; their wings are so stubby that the moths can barely fly, and the female moths are born already fat with as many as 500 eggs ready for immediate fertilization by a male.

In about ten days, the eggs hatch into silkworms, tiny caterpillars that are only about two or three millimeters in size. They mature quickly; given proper care, the worms will grow to 10,000 times their birth weight in about a month.

Theirs is a monotonous diet – they eat only the leaves of mulberry trees, and quite a lot of them. The recipe for one pound of silk: start with about 3,000 worms, gradually add 220 pounds of clean, fresh mulberry leaves, and wait about a month.

That’s when the silkworms begin to spew forth the cocoons that will shield them from harm as they develop into moths. The silk emerges from two glands called spinnerets located near the worm’s jaws. The stuff is almost entirely made of a protein called fibroin. The worm emits two streams of fibroin, then coats them in a gooey protein called sericin.

For up to three days, the silkworm’s head weaves back and forth as it wraps itself in silk. The finished cocoon is no bigger than a chocolate-​covered almond, yet its silk forms a continuous thread a kilometer long.

To get at the silk, humans boil the cocoons, killing the worm inside and stripping away the sericin. Then the silk fiber is unspooled.

The stuff is stronger than a steel wire of equal thickness, stronger even than the Kevlar fibers found in bullet-resistant vests. In fact, one of the first such vests, developed by Chicago Catholic priest Casimer Zeglen in 1897, was woven of silk. It worked, too.

Spider silk is actually stronger than that produced by silkworms. But nobody’s been able to successfully domesticate spiders, which have an unfortunate habit of eating one another. Happily, silkworms have been getting along well with humans and one another for quite a few centuries.

Omenetto had no particular interest in sericulture as he studied engi­neering and applied physics at Italy’s University of Pavia. His specialty ​was optics, the control of light as it passes through lenses, fibers, and prisms. He spent six years in postdoctoral research at the US Los ​Alamos National Laboratory. In 2005, he joined the faculty at Tufts, where he took up teaching and research in biomedical engineering. Though he knew little about living systems, Omenetto was undeterred. ‘The engineering tools for medicine’, he said, ‘are, after all, ​engineering tools. Their roots are in chemical engineering, and biological, and electrical.’

So Omenetto went to work on better ways to conduct optical examinations of living systems. But his focus shifted after a 2007 hallway ​conversation with his colleague David Kaplan.

For 30 years, Kaplan has studied medical uses of structural proteins like cellulose, collagen, and especially silk. Surgeons have been stitching up wounds with silk sutures since the second century AD. But Kaplan wanted ​to use silk as a kind of scaffold that could be implanted in a patient to provide support to damaged tissue – a knee ligament, for instance, or a cornea.

These silk scaffolds are built from individual molecules of fibroin protein. The process requires water, as well as salts, which are easily removed from the solution for reuse. The fibroid can then be dried to produce a powder, or the fibroid-water blend can be spread onto a flat surface to dry, resulting in a thin, clear film of silk.

‘It’s pure protein,’ said Kaplan. ‘It’s very safe in the human body.’ As the patient’s tissues heal, the silk scaffold would slowly melt away, the salts in the patient’s bodily fluids breaking down the hydrogen bonds that hold the silk proteins together.

But as Kaplan tried to fabricate a corneal implant from the film, he found he’d need to poke tiny holes in the material to enable cells to regrow. ​He asked Omenetto if a laser beam could do the job.

‘I went to put the laser on the holes, and I lost the laser beam,’ Omenetto said. ‘It meant the surface was atomically smooth . . . It had properties that you hardly find in glass.’

At once, Omenetto realized that silk protein film could be formed into all manner of optical devices – lenses to focus light, waveguides to aim light, prisms to diffract light, and more.

Consider photopharmacology – the use of drugs that activate in the presence of light. Scientists are testing the technology as a superior approach to chemotherapy. They inject an anticancer drug into the affected organ – ​the colon, for instance. The drug has little effect on healthy tissue. But when physicians insert a needlelike optical fiber into the tumor, and turn on the correct frequency of light, the drug is activated, attacking only the nearby cancerous cells.

Omenetto realized that needles made of optically pure silk protein could illuminate tumors just as well as an optical fiber. Besides, these silken strands need never be extracted. Over time, they’d break down into harmless amino acids and be absorbed into the body once their work was done.

It was the beginning of Silklab, and of Omenetto’s investigations into the exceptional properties of silk. Over the next 17 years, the Silklab team has continued to discover unconventional uses for silk protein.

For example, mixing fibroin with antibodies and dye produces those medical gloves that know when they’re contaminated. The silk protein preserves the chemicals, just as it does with vaccines. But it also lets them do their work. When the glove comes into contact with unhealthy microbes, the antibodies are activated and the treated area changes color, displaying the word contaminated.

Silklab researchers have also found a way to spin silk into leather, of a sort. A blend of silk protein, cellulose, and chitosan – a sugar found in the shells of shellfish – produces an all-natural substitute for leather. The stuff starts out as a liquid, making it possible to create leather goods with unique patterns and shapes by squirting it from 3D printers. In effect, leather items can be woven together, like silk scarves. Old shoes and purses ​made of leatherlike silk need never be thrown in the trash. Instead, they could be dissolved and recycled into new items.

These products seem impressive in the lab but have yet to make it to market. Neither have any of the silk-based optical devices Omenetto has been developing. Still, he said there are promising ideas in the pipeline, such as silk-based disposable contact lenses that would leave behind no trace of plastic waste.

But several of Silklab’s other breakthroughs have made it to market. ​It isn’t often that a university science lab, focused on obscure and esoteric research, ends up spawning this many real-world accomplishments. Partly it’s about the neighborhood. Boston hosts many world-class pharmaceutical companies like Vertex Pharmaceuticals and Moderna. The Boston area also has venture capital companies that are accustomed to making big bets on biotech startups, including MIT’s own Engine.

There are also so many excellent universities, and ample opportunities for the cross-fertilization of ideas. Vaxess, for instance, was born out of a 2011 class at the Harvard Business School, about the commercialization of scientific breakthroughs. Omenetto gave a lecture about his work at Silklab and the idea for a new business was born.

Getting this many companies off the ground ‘means finding the right people to work with that have the same dedication that we do’, said Omenetto. ​‘And of course, you have to have something that works.’

One Silklab spinoff, Boston-based Mori, has raised over $82 million in investment capital, and has begun signing contracts with food distributors for a product that turns silk into a food preservative.

Keeping meats and vegetables flavorful is largely a matter of keeping oxygen and bacteria out and moisture in. A plastic wrapper can accomplish this, but supermarkets aren’t going to wrap each apple or banana. Apart from the cost and inconvenience, it would generate vast amounts of plastic waste.

But in 2016, Omenetto and Kaplan joined with Benedetto Marelli, an associate professor at the Massachusetts Institute of Technology, to demonstrate that merely dipping the food in a solution of silk and water leaves behind a film that holds in moisture and keeps out air and bacteria. ​On average, fruit and vegetables coated in silk protein can remain fresh at room temperature for one week longer than unwrapped food. And unlike plastic wrap, there’s no waste. It’s not even necessary to wash off the silk coating; it’s flavorless, nontoxic, and biodegradable.

A cheap, clean, and safe food preservative could make quite an impact, in a world where about a third of all food – as much as 2.1 billion tons – ​presently goes to waste, according to Boston Consulting Group. ​It could also spare millions from the ill effects of eating spoiled food. ​That explains why this Silklab innovation has attracted considerable ​attention, and so much money.

Down the road in Framingham, Massachusetts, a company called ​Sofregen has devised an FDA-approved silk solution for treating a disorder of the vocal folds – or vocal cords if you’re old-school.

There are two of them that help us talk and prevent food from entering the larynx. In some people, one of the folds is too small or immobile to close properly, causing breathing problems and sometimes choking. When that happens, doctors can inject a substance to build up the weak fold, helping it to close properly.

Doctors have used materials such as collagen or even body fat for these injections. But with Sofregen, it’s silk, largely because it decomposes ​at a slow, predictable rate, giving the patient’s vocal folds time to repair themselves.

Silk entrepreneurs Greg Altman and Rebecca Lacouture have two companies to their credit. In 1997, Altman was a senior studying chemistry at Tufts, and captain of the football team, when he tore a knee ligament. ​As a graduate student he worked with David Kaplan during his early experiments on silk scaffolding for ligament repair. Having earned a ​doctorate in biotechnology engineering, Altman teamed up with fellow PhD Lacouture to launch Serica Technologies, which makes silk scaffolds to fill in areas of the body where damaged or diseased tissue has been removed, such as the abdomen or breast.

When Serica was acquired by California pharma company Allergan in 2010, Altman and Lacouture set out on a new venture. They’d spent 15 years getting their silk scaffolds out of the laboratory and past the regulators of the US Food and Drug Administration to produce a product that would be used by only a relative handful of people.

This time Altman and Lacouture wanted to choose a bigger target. ​‘How do we advance the health of billions of people, instead of hundreds of thousands?’ Altman said. They decided that silk protein – nontoxic, flexible, and smooth to the touch – would make an excellent ingredient for something nearly everybody uses – skin care products.

Today’s skin care ingredients are mostly synthetic compounds supplied by petrochemical companies. Not dangerous in themselves, the manufacture of these synthetics often involves the use of toxins like cyanide and heavy metals. Besides, many of these chemicals eventually end up in our food and water.

‘We don’t necessarily know if they’re biodegradable,’ Altman said. ‘We don’t know where they end up.’

Altman and Lacouture’s new company, Evolved by Nature, developed a version of silk protein that substitutes for claudin, a different protein that occurs naturally in human skin. Over time, claudin tends to erode, making our skin more vulnerable to moisture loss. Evolved by Nature’s skin barrier is designed to deliver a dose of silk protein to fill in the gaps.

Evolved by Nature sells the protein as a stand-alone skin treatment. ​It doesn’t come cheap: you’ll pay $85 for a one-ounce bottle. Happily, it’s applied just two drops at a time. The company is also bringing to market a line of skin care products bearing the brand of former NFL athlete and current TV host Michael Strahan.

Investors are taking Altman and Lacouture’s company seriously. The company has raised $200 million, and a minority stake is held by cosmetics giant Chanel.

But Altman said skin care is only the beginning. Silk protein, he said, makes an excellent substitute for petrochemical coatings used in a vast array of products.

The stuff’s everywhere, Altman said. ‘There’s a layer on your glasses. There’s a coating on a trillion dollars of textiles produced every year. In every house, architectural surfaces. In every car, on every piece of leather.’

His company’s future product road map includes custom silk protein for coating fabrics and leather. Because it’s not a medical application, these coatings needn’t be made of the finest silk. Altman said his company could thrive on silk producers’ leftover scraps. ‘Evolved by Nature could generate a billion dollars in revenue’, he said, ‘and never use anything but the trash of the sericulture industry.’

But global success for Evolved by Nature and other makers of silk protein products will pose a challenge for US policymakers working to decouple the nation’s economy from that of China. Just as it dominates the world market for refined lithium, China dominates silk production, producing about 60 percent of global output. As US car companies transition to battery-powered vehicles, they’re paying billions to Chinese companies for the lithium to make those batteries.

The same sort of dependence could befall US makers of silk protein products. It’s happened before; over a century ago, the US was the world leader in silk fabric production but relied on raw silk imported from China and Japan. When World War II cut off the supply, US textile makers switched to synthetics like nylon and never looked back.

As scientists discover new uses for the real thing, we might see efforts to make the US self-sufficient in silk. Something similar was attempted in the early nineteenth century. But American farmers never mastered the fine points of sericulture, and foreign fiber was plentiful and cheap, and so the effort fizzled.

But just as the rise of electric cars has set off a race to develop new domestic sources of lithium, David Kaplan believes that the large-scale use of silk proteins could resurrect American sericulture. ‘We think it’s a great opportunity to bring manufacturing back to the US’, he said, ‘both in production of the raw material and in producing all kinds of products.’

So if Silklab’s spinoff companies prosper, perhaps we’ll see groves of mulberry trees sprouting across the land.