What happened to those GM spider goats with the silky milk?

This really was an extraordinarily wacky and perhaps controversially ‘Homo Deus’ news story — GM goats who had been transplanted with a spider’s silk-making genes to transform their milk into something much less drinkable and much more silky. Yet this was all years ago now. So did that research ever lead anywhere? And what happened to those goats?

Well, all went a bit quiet. Partly because the Montreal-based company leading the way, Nexia Biotechnologies, a company spun out of McGill University, swiftly went bust and sold its two GM goats — Sugar and Spice — to the Canada Agriculture Museum in Ottawa, which in 2013 removed its genetically-engineered goats from display amid public pressure.

Quiet momentum continues, however, under Dr Randy Lewis of Utah State University and his team. Though he is unaware of the whereabouts of Sugar and Spice today, his lab looks after over twenty goats capable of producing silky milk. This is not just kidding around with mind-bending science experiments for its own sake; dozens of potential applications exist for spider silk, like new ligaments or bullet-proof vests. Yet attempts at farming silk spiders have failed on any scale, mostly because spiders kept in close proximity can turn to in-fighting and cannibalism.

Dr Lewis explained some of these applications by email when contacted by AFN during his trip last week to the International Symposium on Biomedicine and Biomaterials in Xi’an, China — as apt a place as any to discuss the ancient science of sericulture.

“Clearly for quantity the silkworms will always win but for material properties, we are very close or superior in most cases,” Dr Lewis writes. Though he expresses some skepticism about making smart outfits with it, at least for now. “I actually think clothing will be a later product as we can use these proteins to make adhesives, coatings, gels as well as fibers. Those products will be much higher value and thus better to move into for markets.”

Naval Goats

The properties of spider silk are mind boggling — its elasticity, of course, but also its bio-compatibility; its combined strength is several times that of steel on a per millimeter basis; and it’s resistant to extreme temperature variations. Little wonder that the US Navy is a consistent backer of Dr Lewis and his lab in Utah; in one of various grants announced last June, the US Navy backed research into an underwater spider silk web that could effectively ensnare hostile ship propellers. Another use for the grant was to apply Dr Lewis’s knowledge in the area of synthetic slime from hagfish proteins, the sort of stuff these eel-like hagfish produce and deploy to ward off predators.

Those hagfish proteins are probably cause for another article. But as for the well-being of those goats, Dr Lewis says: “In over 15 years of breeding these goats, we have no indications of any abnormal health risks …We have simply transferred a gene for spider silk protein into the goat genome and have put it under the same cell regulation system as the other milk proteins. So it is only made during lactation and only in the udder.”

All is compliant with regulations, he says: “Right now both the USDA and the FDA are regulating the transgenic animals and since we are not beyond the research stage, they have not required anything beyond their standard transgenic animal regulations.”

And there are signs of its application emerging: “We have been working with a company that has licensed the technology but they are still working on getting full funding to move ahead,” he says, not mentioning the company by name.

At least one company in the Netherlands has been openly inspired by the work of Dr Lewis. Inspidere, which is founded by the artist and entrepreneur Jalila Essaïdi, has been trying to create bullet-proof silk skin after reacting to talk of silky bullet proof vests with the question, “why not bullet proof humans?” She tested her concept last year at the Forensic Genomics Consortium Netherlands. Inspidere also works on a product called Mestic — manure-derived bio-plastic.

Gene Editing With CRISPR

Goats might, however, be more of a sideshow as advances in gene editing mean there could be even better ways to potentially farm and refine silk. Under the direction of Lewis, researchers at USU have pioneered initial, lab-scale production of synthetic spider silk through the use not only of transgenic goats, but also bacteria, alfalfa and silkworms. Now, the researchers are using emerging CRISPR technology to harness the spinning power and efficiency of silkworms. Their results demonstrate promise for using transgenic silkworms as natural spider silk spinners for industrial production of high-performance fibers.

Lewis and team members Xiaoli Zhang, Linjin Xia, Breton Day, Thomas Harris, Paula Oliveira and Justin Jones, along with colleagues at Pennsylvania’s Drexel University and China’s Soochow University, published their findings in May this year the American Chemical Society’s Biomacromolecules journal.

In a statement back in May, the team summarised the outlook: “Developing a way to spin synthetic spider silk fibers in a consistent, high quality, cost-efficient and environmentally-friendly way for commercial-scale production, has been a challenge,” says Zhang, lead author on the paper and postdoctoral fellow in USU’s Department of Biology.

The project is the team’s first attempt with CRISPR/Cas9 – short for “Clustered regularly interspaced short palindromic repeats and CRISPR-associated protein-9 nuclease” – a variation of a naturally occurring immune system found in bacteria. Like a pair of molecular scissors, CRISPR/Cas9 enables gene editing.

“Prior to using CRISPR, our attempts to insert spider protein DNA into transgenic hosts were somewhat random,” Lewis says. “CRISPR offers much more precision.”

And that precision is paying off. The researchers are reaping the spinning benefits of silkworms, organisms used for centuries by humans for silk fiber production. But they’re also discovering the offspring of CRISPR/Cas9-assisted transgenic silkworms, and subsequent generations of offspring, are retaining the spider silk protein genes.

If teams like these can start to produce quality, gene-edited silk at scale, it could assist likes of Germany’s AM Silk, which uses bacterial fermentation to make silk proteins as part of a biodegradable shoe from Adidas. IBolt Threads, another creator of synthetic clothing, could also gain from this.

For food tech startups, this might eventually prove a boost to the viability of companies like Boston’s Cambridge Crops, a startup seeking to reduce food waste by effectively cocooning sausages or steaks with an imperceptible and edible micro-layer of silk-based proteins. These keep all varieties of food from going to waste, the team claims, and reduces dependence on single use plastics.

Such a peculiar reimagining of sericulture won Cambridge Crops an AgFunder Innovation Award earlier this year in San Francisco. And in the months since, things have run smoothly. A few weeks ago, Cambridge Crops revealed its $4 million seed round led by The Engine, a venture capital firm launched by MIT in 2016 to invest in early-stage “tough tech” companies. Refactor Capital, Closed Loop Ventures, Bluestein & Associates, SOSV and Supply Chain Ventures also joined the round.

$4m Seed Funding For Cambridge Crops and Their Plans For Silky Sausages

In a statement, The Engine’s General Partner Ann DeWitt expressed enthusiasm for helping Cambridge Crops’ “efforts in building and bringing to market a technology that can reshape how the food system works.”Those efforts are based upon a silk protein extraction process that Cambridge Crops’ has developed, which involves boiling silkworm cocoons and then adding salt to free up silk fibroin, a biocompatible protein, according to a Medium post written by Michael Blanding for The Engine. Cambridge Crops then dissolves the protein it in water, so it can be lathered on food such as beef, poultry or fruit.

“Once dry, the solution reforms into something very much resembling the original cocoon that protected the silkworm during its metamorphosis,” the post states. The protective layer is edible, tasteless, and does not alter the food, the team claims, yet still delivers “drastically longer shelf life.” The solution can be “easily implemented at a wash or coating station in the supply chain, and has proven efficacy across a broad range of food products; from whole produce and cut produce to meat and fish and everything in between.” Cambridge Crops’ process was spun out of professor Fiorenzo Omenetto’s silk lab at Tufts University and was co-invented with MIT professor Benedetto Marelli.

“Typically, a membrane is either a good barrier for oxygen, or a good barrier for water. Given the structure of polymers, there is a mutual exclusivity between the two,” Marelli said in The Engine’s Medium post. “Silk somehow has both qualities.” The barrier around the food, the post continues, “prevents both dehydration, which can cause food to dry out and lose shape, and oxidation, which can change color and flavor. In addition, silk provides a natural barrier to microbes, which can cause food to spoil.

Marelli first started experimenting with silk for biomedical applications as an undergrad at the Polytechnic Institute of Milan. While at Tufts, he coated some strawberries in silk as part of a lab cooking competition, and serendipitously discovered its unique properties. “I left them on the bench — when I came back four or five days later, the ones [that] were not coated spoiled, while the other ones did not.”

In a note sent to AFN this August, Cambridge Crops CEO Adam Behrens was bullish about his team’s prospects after the funding round. “The technology we’ve developed has far-reaching impact, from minimizing our reliance on single-use plastics to expanding global access to safe and nutritious foods,” he wrote.

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Image: The reels contain “synthetic” spider silk fibers spun from the spider silk proteins produced by Saanen goats. Photo © Lewis Lab at Utah State University.