National Geographic

Genetically engineered silkworms with spider genes spin super-strong silk

In a lab at the University of Wyoming, some silkworms are spinning cocoons of silk, just as every silkworm has done for millions of years. But these insects are special. They have been genetically engineered to spin a hybrid material that’s partly their own silk, and partly that of a spider. With spider DNA at their disposal, they can weave fibres that are unusually strong and tough. It’s the latest step in a decades-long quest to produce artificial spider silk.

Spider silk is a remarkable material, wonderfully adapted for trapping, crushing, climbing and more. It is extraordinarily strong and tough, while still being elastic enough to stretch several times its original length. Indeed, the toughest biological material ever found is the record-breaking silk of the Darwin’s bark spider. It’s 10 times tougher than Kevlar, and the basis of webs that can span rivers.

Because of its enticing properties, spider silk has enormous potential. It could be put to all sorts of uses, from strong sutures to artificial ligaments to body armour. That is, if only we could make enough of the stuff. Farming spiders is out of the question. They are territorial animals with a penchant for eating each other. It took 82 people, 4 years and 1 million large spiders to make a piece of cloth just 11 feet by 4 feet.

The alternative is to synthesise spider silk artificially. That hasn’t been easy. Scientists have long since managed to reconstruct the proteins in the silk, using everything from bacteria to potatoes to goats. But these systems only provided small amounts of silk proteins, and would be expensive to scale up. Making silk proteins is just part of the far harder challenge of turning proteins into silk fibres, with their complex microscopic structures. To get around these problems, Donald Jarvis, Malcolm Fraser and Randolph Lewis had a simple idea: why not use another animal that also spins silk?

As a large industry and centuries of history can attest to, silkworms are easy to farm in large numbers. And they’re silk-spinning machines, with massive glands that turn silk proteins into fibres. Their own silk is no mechanical slouch, and it’s already used to make sutures. But spider silk has many advantages. Not only is it stronger and tougher, but we understand how specific tweaks to a spider’s genes can produce silks with different properties. It should be possible to customise unique silks that are tailor-made for specific purposes.

Fraser had just the right tool for the job. In the 1980s, he identified pieces of DNA that can hop around insect genomes, cutting themselves out of one location and pasting themselves in somewhere else. He named them PiggyBac, and he has turned them into tools for genetic engineering. You can load PIggyBac elements with the genes of your choice, and use them to insert those genes into a given genome. In this case, Florence Teulé and Yun-Gen Miao used PiggyBac to shove spider silk genes into the silk-making glands of silkworms.

To identify the silkworms that had incorporated the spider genes, Teulé and Miao added another passenger to their PiggyBac vehicle – a gene for a glowing protein. The insects that had been successfully engineered all had glowing red eyes.

These engineered silkworms produced composite fibres that were mostly their own silk, with just 2 to 5 percent spider silk woven among it. This tiny fraction was enough to transform the fibres. They were stronger, more elastic, and twice as tough as normal silkworm fibres. And even though they didn’t approach the strength and elasticity of true spider silk, they were almost just as tough.

One other team has tried to do something similar, but their fibres didn’t show the same physical improvements. They also produced fibres where the spider silk merely coated the silkworm strands. When silkworm cocoons are harvested, these outer coats are usually removed. By contrast, Teulé and Miao’s engineered their spider genes so that the resulting silk would be woven throughout the silkworms’ own fibres.

Many spider silk proteins are extremely large and most attempts to create them artificially (including this one) use smaller versions that are around a quarter of the size.  When Sang Yup Lee engineered bacteria to produce spider silk, he found that the small proteins led to inferior fibres, and only the very large ones produced fibres comparable to actual spider silk. Given that Teulé and Miao have already produced reasonably strong composite fibres using the smaller version, it will be interesting to see what the larger proteins can do.

The team are also planning to refine their technique to take the silkworms’ own proteins out of the equation. “The next step will be to produce silkworms that produce silk fibres consisting entirely of spider silk proteins,” says Jarvis. Perhaps they could even use the genes from the best of the silk-producers, like Darwin’s bark spider.

Reference: Tuele, Miao, Sohn, Kim, Hull, Fraser, Lewis & Jarvis. 2011. Silkworms transformed with chimeric silkworm/spider silk genes spin composite silk fibers with improved mechanical properties. PNAS http://dx.doi.org/10.1073/pnas.1109420109

Conflict of interest: Jarvis, Fraser and Lewis are all paid advisors to Kraig BioCraft Laboratories, Inc, the company that is commercialising the artificial silk, and that provided some of the funding for the study. The discovery was originally announced in a press conference last year, but has finally been published after a lengthy review process.

There are 23 Comments. Add Yours.

  1. Mary
    January 3, 2012

    OMG–GMOs! And farms! What will we do when these inevitably escape??

    Ok, I’m kidding. But I don’t see this as any different from an ecological perspective than the farmed GMO salmon everyone is bent out of shape about.

  2. Leslie Brunetta
    January 3, 2012

    We still don’t fully understand the role that the passage of silk protein from silk gland through the spinneret and out into the air plays in the final structure of spider silk proteins. There are volume and chemical gradients along this passage that affect how the protein molecules fold. Silkworm glands, ducts, and spinnerets are different from spider glands, ducts, and spinnerets, which may mean that a spider silk protein traveling the silkworm route won’t emerge in the same shape as the same protein traveling the spider route . Also, silkworms and spiders spin differently. Silkworm spinnerets are located near their mouths, while spiders’ are on their abdomens. Silkworms spin by anchoring their silk and then moving their heads round and round in a figure-8 pattern to draw the silk, while spiders (at least the araneoid spiders researchers are trying to copy) use their legs to draw their silk out of their spinnerets. These different spinning methods must exert different forces on the silk as it is spun, which can also affect protein structure and, therefore, function.

    Figuring out the sequence of silkworm and spider silk genes and proteins and managing to manipulate them as these researchers have done is a big accomplishment. Whether silkworms will ever be able to spin true spider silks is still an open question. But this research should lead to more clues about the evolution of both silk systems.

    If you’re interested in spiders, silks, or evolution, please check out “Spider Silk: Evolution and 400 Million Years of Spinning, Waiting, Snagging, and Mating” (Yale University Press), by me and Catherine L. Craig: http://www.lesliebrunetta.com/spider_silk_br__evolution_and_400_million_years_of_spinning__waiting__snagging___94619.htm

  3. amphiox
    January 3, 2012

    It’s kind of a little surprising that people ended up trying the bacteria (well, maybe not so much the bacteria), potato and goats first, before doing the silkworms.

    You’d think that if you wanted to get spider silk, and were looking to a genetically engineered model, the silkworm would the be the first one you’d think of, and try….

  4. DennyMo
    January 3, 2012

    Has anybody done a calmly rational assessment of “What could go wrong with such genetic manipulations?” What really would happen if they escaped? I can see many upsides, and find them rather exciting. But the Law of Unintended Consequences is inviolable, it would be comforting to know that someone has done some serious thinking about this.

    Also, does this spider/silkworm composite have any of the adhesive properties of spider silk?

  5. Gary B
    January 3, 2012

    I’ve thought about this before, and came up with two other possibilities. 1) There is a spider (I think endemic to Texas) which works in large groups to make a huge mass of web – they don’t eat each other. I forget the species or name. and 2), would it not be possible, maybe even easier, to alter the genes of the spiders to be more docile? Even selective breeding might work (if one can figure out a method of selection) – look at the success of the Russians in breeding docile foxes, as ‘tame as a pussycat’, in just a few generations.

    With a little Googling (‘spiders work together to make huge web’) I found several instances of giant (200 foot long) webs built as a joint effort in Texas back in 2007 – I don’t think that is the example I was looking for. But also the river-crossing web of the Darwin’s Bark Spider cited in the article was apparently made by millions of that species working together. So it’s certainly possible for spiders to get along under the right conditions. Is anyone pursuing that direction of research?

  6. Joby Owens
    January 3, 2012

    To the comments regarding the dangers of such GMOs and the effects if they escaped in the wild – the bombyx mori silkworm has been domesticated for so many years that it is now incapable of survival in the wild. Any escapees would find their new found freedom short lived!!

  7. Joby Owens
    January 3, 2012

    To Gary and your suggestion about possibly genetically altering the spiders themselves in order to make them more suitable for silk farming. Don’t forget the silkworm is a silk making machine!( Excuse me if I make errors in my numbers but I am certain the order of magnitude is there or thereabouts). I believe the average silkworm will spin approximately 1km of silk in a convenient neat little package (the cocoon) whereas the average spider will spin approximately 10-50m in its lifetime.

  8. Joby Owens
    January 3, 2012

    One last point! This research was performed some time back but underwent lengthy review. The company that has helped fund (and has the commercial rights to the work) the work has since then (through their continued collaboration with the professors above) achieved much more. One important achievement has been using an alternative method (Zinc Fingers from Sigma Aldrich) in order to knock-out the relevant silkworm silk producing genes in order to prevent the worms from producing silkworm silk at all. These worms have been referred to as the ‘platform worm’ with the intention of adding in the genes responsible for producing the relevant spider silk proteins (or whatever proteins were desired). The obvious initial aim to have silkworms producing 100% (i.e no silkworm silk) spider silk. Other potential possibilities include adding an antibiotic such as hepcidin to the mix which would obviously have beneficial uses in sutures etc. The pace of their developments is astounding!

  9. Leslie Brunetta
    January 3, 2012

    Gary–There are a number of species of social spiders that live communally on large webs. They don’t eat each other. Still, I think raising such spiders in order to harvest their silk would probably be considered uneconomical. Silkworms are easy–they live together in giant trays, you toss lots of leaves in, and then each makes a cocoon out of a single, very long, continuous fiber that can be unspooled in bulk using technology that’s been improved over the course of thousands of years. Spiders eat insects and other arthropods (which would have to be provided somehow in large quantities). Communal webs are not the nice neat orb webs we think of when we think of spider webs: they’re huge tangles. I suspect that it would be extremely difficult to harvest long, continuous lengths of dragline silk (the desired kind) out of these tangles. The alternative, which both spider silk entrepreneurs and researchers use, is to “silk” the spider: you immobilize it, coax it into starting to produce silk, and then very, very, very carefully draw the silk out and onto a spool. Extremely labor intensive.

    The Darwin Bark Spider makes that giant orb web by itself.

    The more you find out about spiders, the more interesting they are. Believe me.

  10. Iain
    January 3, 2012

    Denny, spider silk isn’t sticky, the droplets of ‘glue’ they put/leave on it are. The spider doesn’t step on it’s own glue either, they manage to miss, maybe that’s part of why they have so many eyes.

  11. Eideard
    January 4, 2012

    There will be one or another flavor of organic, anti-GM dweeb, who will try to organize resistance to the enslavement of silkworms, No doubt.

  12. Justin
    January 4, 2012

    Ed, unfortunately the links to your other blog articles are all broken in the preview version of the article. They all work fine in the full view. They all appear to be missing the blog name part of the URL.

    Eg;

    Preview link (broken; missing your blog name):
    http://blogs.discovermagazine.com/2010/09/16/a-spider-web-that-spans-rivers-made-from-the-world%E2%80%99s-toughest-biological-material/

    Full version link:
    http://blogs.discovermagazine.com/notrocketscience/2010/09/16/a-spider-web-that-spans-rivers-made-from-the-world%E2%80%99s-toughest-biological-material/

    Is it just me? :)

    Feel free to delete this after reading it. Thanks as usual for the great science writing!

  13. Eleanor
    January 4, 2012

    Given some experts are on hand, can the ‘new’ silkworms still break out of their cocoons now it is super strong and stretchy? I can imagine it might be a struggle, poor beasties! I know the silk harvested before the silkworms leave the cocoon but was just curious. Presumably there is (was) a balance between cocoons strong enought to deter predators and so strong the caterpillars couldn’t escape themselves.

  14. Ed Yong
    January 4, 2012

    Silkworms break out of their cocoons by releasing enzymes that break it down. So the material properties wouldn’t matter too much. That’s why they… er… boil the cocoons when they harvest the silk.

  15. JimK
    January 4, 2012

    So, silkworms lie in a tray and eat leaves and produce silk – they are making rayon?

  16. Leslie Brunetta
    January 4, 2012

    Well, rayon used to be thought of as “artificial silk.” I’m no expert on rayon, but my understanding is that it’s reconstituted cellulose, which is a polysaccharide, whereas both silkworm and spider silk is protein. When people make artificial silks like rayon and nylon, the process usually involves lots of heat, pressure, and/or nasty solvents. Silkworms and spiders make silk at ambient temperatures and pressures and the raw materials are either leaves or bugs–that’s a big part of why industrialists have been chasing after how they do it. It’s just that proteins are devilishly complicated molecules, so it’s not easy.

    It’s worth remembering that spiders, unlike silkworms, make a number of different silks, the number depending on where a species is on the spider evolutionary tree. An orb web weaver can make more than 6 different silk proteins. Industrially focused research is usually interested in dragline silk and sometimes flagelliform silk, which is the silk found in the capture spiral of orb webs. Lately, there’s also interest in the aggregate silk protein glue that araneoid spiders deposit on their flagelliform lines.

    But thousands of spider species who can’t make flagelliform or aggregate silk proteins make cribellate silk, which also sticks to insects. And thousands of other species can’t make cribellate or flagelliform or aggregate silk proteins but still do fine. The evolutionary development of all this stuff is fascinating.

  17. Wendy Laubach
    January 6, 2012

    Mr. Yong, could you expound on this a little: “And even though they didn’t approach the strength and elasticity of true spider silk, they were almost just as tough.” I’m not catching the distinction you’re making among strength, elasticity, and toughness. Tensile strength vs. abrasion resistance, something like that?

  18. Texan99
    January 6, 2012

    Leslie Brunetta, thanks for the link to your book, “Spider Silk,” which I’ve downloaded on Kindle and am reading with pleasure this instant. Great stuff. I love the idea that spiders have maintained a fairly uniform body type over the eons by concentrating their genetic innovation in their silks, changes in which enable them to compete in a wide variety of new environments.

  19. PG
    January 6, 2012

    Leslie, wow. very cool stuff. What spider species was used for the source of genetic material in this study and why? due to the silk quality or the ability to effectively integrate the gene/genes into a the silk worm or something else? You said there is much variation in terms of spider silk proteins, I assume that corresponds to genetic variation as well. What is your view of potential genetic resources available for breeding for/ engineering new silks.

    Are people patenting these hybrid lines? My first thought would be obviously.

    Thanks, great stuff, I am going to check out your book as well.

  20. Leslie Brunetta
    January 7, 2012

    Texan99–Thank you! I’m glad you’re enjoying it.

    PG–The research team (which includes Randy Lewis, who was involved in the first deciphering of the structure of spider dragline silk protein in 1990) actually introduced a synthetic spider silk gene into the silkworms, rather than a natural one. They synthesized it by combining stretches of flagelliform silk gene (which dictates the super-stretchy silk protein orb weavers use to make the capture spiral in the orb) with stretches of major ampullate spidroin 2 gene, which dictates one of the components of dragline silk, which is very strong. It’s really clever research: they not only synthesized this gene, but also strategically introduced it into the silkworm silk gene at a position they thought most likely to promote good fiber formation. I don’t fully understand everything they did here (I’m the English major part of our writing team), but they’ve put together a multitude of genetic engineering techniques and I’m sure they’re learning just as much from what’s not working as from what is. Even if they never get real spider silk out of silkworms, getting enhanced silkworm silk may be good enough for many applications.

    It appears that the spider silk genes originated in Nephila clavipes, one of the golden orb weavers. They produce very strong major ampullate silk. They also produce it in large quantities (they’re big spiders) so they were favorites in the early days of silk research partly just because they provided large samples and they’re easier to dissect. As researchers understand more, and as it gets cheaper to conduct this kind of analysis (due to technology advances), more silk proteins and genes from more spider species are being studied. Different silks have different properties. None of them are going to be easy to reproduce.

  21. Leslie Brunetta
    January 8, 2012

    I realized I left all these comments without commenting on how much I appreciate Ed’s posts–always interesting, always in-depth. One of the best things on the Web.
    Leslie

  22. jerry irons
    January 12, 2012

    Perhaps if we genetically engineered the spiders to grow into larger ones, say the size of basketballs, we then could farm the silk in large quantities. We’ve done it in dairy animals except we’ve kept the body small and enlarged the bag and teats so that a good producer can produce 15 gallons or so of milk each day over less than a quarter of that amount in the past. More so with 2 or more milkings each day.

  23. Jocelyne
    September 6, 2012

    Please don’t make spiders any bigger than they already are! I have a job coping already, although I am getting less phobic with time but basketball size seems just over the top!

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