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I remember looking at this a while back. It is one of the reasons why I started looking into the E.coli producers with more scrutiny. From the PNAS article:
Thanks Mike!
I don't know much about these systems other than piggyBAC is one of the earliest systems, ZincFingr is newer, better, and more accurate, and CRISPR/Cas9 is even newer and also supposedly accurate.
Its always good to know more.
I saw in their presentation that they (Spiber Inc.) are attempting to achieve up to 1.6 gigapascals in the strength of their fibers at commercialization. Though their fiber is more coarse and uncomfortable and is likely more expensive to produce, it still worried me, TBH.
I am glad that KBLB has developed this new Dragon Silk as it now can compete with them in fiber properties as well. It might be a little longer to commercialization than MS, but with the experience already made, new equipment, and income (hopefully) made through sale of MS, he should be able to fast track it to the market.
I look forward to seeing how this plays out.
I was talking more about his comment “the gene is not as stable as we would like … after several generations the amount of spider protein starts to drop.”
I did not know about the issue with cytotoxins. I was under the impression that standard silkworm silk is perfectly compatible with humans since other companies such as Oxford Biomaterials and their offshoots have been working on using standard silk in medical applications. Does this only happen with worms that feed on mulberry or does it happen to the ones on the "silkworm chow mix" as well?
I don't know how it would be possible either, but Randy Lewis seems to be having an issue with it, so I am worried about it happening here as well. Hopefully, it is only an issue with using the CRISPR/CAS9 system.
Oh, good! That should also mean that it has been a few generations since he created it, so the traits are being passed down through the generations.
Thank you for that info!
I know you did not ask me, but I bleieve that it is not an issue with percentage of spider silk, but the quality of it.
I posted this earlier, but the 1.79 gigapascals value is indeed stronger than the Golden Orb Weaver dragline silk which is up to 1.2 gigapascals in strength and has been up to this point what we had been comparing Monsetr Silk to. That being said, it is within the range of the Darwin Bark Spider dragline silk strength which is 1.85 ±0.35 gigapascals.
This leads me to believe that they have developed a synthetic spider genetic insertion code utilizing Darwin Bark Spider DNA to use on the silkworms to develop this fiber.
Spider silk on cusp of storming textiles market
By Kamelia Kountcheva
19 June 2015
http://www.wtin.com/article/?articleID=4295000587&channelId=1120
Spider silk is definitely the new fibre to watch out for. It has been known for a while that spiders produce some of the most fascinating functional fibre: stronger than steel per unit wight, very lightweight, elastic (reportedly stretching up to 20 times its size), soft, water resistant – you name it.
However, news is suddenly erupting about companies on the brink of developing a means of commercialising this fibre or a close synthetic match, and beginning to explore its vast potential in textiles and apparel.
So far, spider silk has been unattainable on a large enough scale, due to the biology of the animals themselves. They produce the substance, but they are very difficult to rear and breed in a lab setting, as males usually die during the breeding process.
However, companies like AMSilk, Bolt Threads and Kraig Biocraft Laboratories have all recognised the enormous potential this fibre will have if it becomes commercially viable and are working tirelessly towards finding a method for its large-scale production.
The properties of spider and spider inspired silk could be put to good use in technical textiles, apparel, the fashion industry and potentially more. Spider silk producers believe that textiles produced with this fibre will offer better durability, lightness and flexibility than any synthetics currently on the market.
While Kraig is aiming to use genetically modified silkworms to produce spider silk as a natural fibre based on the same production process that has been proven effective for silk, Bolt Threads is working on a way to replicate the proteins that comprise spider silk and engineer a synthetic version which the company believes could be adapted to offer a number of different properties.
AMSilk is another company which has been developing a programme to manufacture a man-made fibre containing 100% spider silk, which it says would be of huge benefit to the technical textiles and medical textiles fields.
Other means of obtaining the protein which makes spider silk the incredible substance it is, include genetically modifying goats to produce it in their milk, which can then be extracted and spun into fibres. This was carried out in the US by Nexia Biotechnologies, and later by the Randy Lewis lab of the University of Wyoming and Utah State University. While they were successful in producing the substance without the use of spiders themselves, inability to produce in mass quantities has stunted the progression of the fibre onto the market. As well as transgenic goats, transgenic E. coli have also been developed to produce spider silk proteins.
This material is on the cusp of exploding into the textiles industry and it seems to have the potential to take the technical textiles market by storm. Recent news of Kraig Labs signing a memorandum of understanding with Vietnam, which outlines a framework for the creation and rearing of transgenic silkworms, means we are another step closer to mass-attaining this valuable substance.
I believe that it does refer to KBLB among others.
As FrankMD referenced in his Post #93346, Kim had chosen Lam Dong at the Provence that they would set up in. This is one of the provences referenced in the article he posted in his Post #93343.
Another point in the article suggesting this is where it states:
For those who do not want to register to read a single article:
Vietnam tie-up for spider silk venture
Published on Thursday, 18 June 2015
Written by Brett Mathews
MICHIGAN - US biotech firm Kraig Biocraft Laboratories, which develops genetically modified spider silk-based fibres, has signed a memorandum of understanding (MOU) with a provincial government in Vietnam which outlines a framework for the creation and rearing of transgenic silkworms in Vietnam. The company said the goal of the agreement is the commercialisation of its technology for the technical textile markets. Spider silk is antimicrobial, hypoallergenic, and completely biodegradable.
"The central and provincial government officials in Vietnam with whom we have held extensive meetings share our passion and vision for reinvigorating the silk industry," Kraig Biocraft CEO Kim Thompson said. "Vietnam offers specialised silk infrastructure which is ideal for expanding our operations and its tradition of quality silk production makes it an excellent fit for our transgenic silkworms."
Kraig Biocraft Laboratories, a fully reporting biotechnology company, is a leading developer of genetically engineered spider silk based fibre technologies and claims a series of scientific breakthroughs in the area of spider silk technology.
In 2013, the company announced plans to launch its first commercial production program with the hatching of its first batch of 'Monster Silk' silkworms, while last year the company announced that Warwick Mills had created the world's first textile utilising its genetically engineered spider silk, Monster Silk. The pilot scale production facility recently delivered a batch of finished material and continues to produce Monster Silk for use and evaluation; the company says it anticipates significant growth in the capacity and proficiency of its silk production operations moving forward.
The company also recently signed a new cooperative research and development agreement with the University of Notre Dame in a move aimed at accelerating the pace of development of transgenic silkworm technology and – it is hoped - producing stronger and more flexible fibres.
'Monster Silk' was initially developed in 2011 when Kraig mated its transgenic silkworms - which produce recombinant spider silk - with a physically larger commercial strain of the domesticated silkworm. The resulting hybrid silkworms are larger than Kraig's original transgenic silkworms and produce larger recombinant silk cocoons.
Heres a video of Bolt Threads CEO on Fox Business:
Cheryl Hayashi has worked pretty closely with Bolt Threads in the past. I would not be suprised if she speaks pretty heavily on them at this lecture.
I hope it gets recorded, I would love to watch it.
Thank you for confirming what I had suspected concerning your trip. I understand and respect that NDAs will prevent you from giving details. I just love to see where each company is and try to predict how they will do based on that. If I just had a bit more money lying around, I could be a part of it rather than just watching from the sidelines and being a minor investor in the only publicly traded company in the business. Maybe I can get in after the IPO of some of the companies, but I won’t be able to make nearly the amount from it then as I would at the current stage.
I do believe that KBLB still has a lot of potential and am not planning on getting out just yet, but I am keeping a very close eye on all potential competitors and try to assess and verify all information given from all sources, both positive and negative. After all, it is still a chunk of my retirement on the line. I agree and realize that there are some decisions made by Kim that I don’t fully understand the need for, bit I honestly believe that many of them are due to the CSC agreements or him wanting to maintain control of the direction of the company. I don’t believe that he is trying to outright lie or scam anyone, but I realize that he needs to maintain a share price to minimize dilution and maximize the income from the financing agreements, so I think he is purposely vague when speaking about the setbacks to prevent the drop of the share price that may happen if he comes right out and bluntly states any bad news.
Good luck with your charity and your future investments!
Thank you for your continuous DD on the subject of synthetic and recombinant spider silks. I am very interested in the science behind this, hence the reason why I invested in KBLB in the first place. Honestly, if I had the money to invest in some of these other companies, I would do so as well. You do make some very valid points concerning the cost structure of KBLB and where they are currently in fiber production as well as the future of silk proteins and spinning them into fibers. I also agree with you that DD and similar companies are more likely to be interested in processes that can be contained in a more stable setting such as a vat, as they are already used to with some of their other products.
You mention that the cost of the fibers spun from proteins will continue to drop, likely to even lower than silk (similar to rayon and polyester). I agree that this will eventually be the case, but I don’t believe that they are at that point yet. While this window of opportunity for KBLB to enter the market is getting smaller by the day, I still believe that they have some time to enter as the lower cost provider of spider silk fibers. You also have to keep in mind that the research into the transgenic silkworms has not stopped, so it is possible that there are applications for the silkworm silk that the bacterial or yeast silk cannot mimic. For example, I mentioned in a previous post that Spiber’s QMONOS fibers, while they may have similar properties to Monster Silk™, they are much more coarse and uncomfortable unlike Monster Silk’s much more comfortable silk. These proteins and fibers would be much better suited for other industrial applications, which seem to be where they are focusing with their agreement with Kojma. I am not saying that this coarseness issue cannot be overcome, but I just haven’t seen it yet.
There is also the fact that, despite how much of the general textile market has been taken over by rayon and other artificial fibers, there is still a demand for silk. This means that while these fibers may not be as revolutionary as was once believed once the synthetic spider silk creators can match the price, there is still a market for them and still an opportunity to make a good amount of money. Of course, the sooner KBLB enters the market, the more money they can make from other applications before these other fiber companies can match their costs.
By the way, I have been thinking about something you mentioned previously and I do have a question for you if you are able to answer. You mention in your Post #91981 that you have a potential business interest regarding silkworms. You then mention later in your Post #92570 that you plan on visiting Charlotte, NC in the near future. This just happens to be the city that houses the headquarters of Entogenetics Inc. My question is: Are you planning on meeting with David Brigham or any other representative of Entogenetics Inc.? If so, would you be willing to share any info that you learn there (not covered by a NDA, or course)? As I mentioned before, I am interested in the technology and am curious to know what they have accomplished recently.
There is a connection to the recent news alert.
The news alert: News Alert: Aqua V Micellization Technology Vital to Future Success and Brief Reports
This links to the site http://stocksimpossible.com/?p=463 which has at the bottom of the page “Stocks Impossible © Copyright 2015.”
In Cee-it’s link, it states:
KBLB Report from the News Alert:
http://bit.ly/_KBLB_AnalystReport
Companies you may have Overlooked in Your High Growth Portfolio
The following brief reports is provided to inform the investing public. We have not been compensated in any form for the following reports.
Published June 9, 2015
Kraig Biocraft Laboratories, Inc. (OTCQB: KBLB) FULL REPORT
It has long been known that certain fibers produced in nature possess remarkable mechanical properties in terms of strength, resilience and flexibility. These protein based fibers, exemplified by spider silk, have been the subject of much interest due to spider silk’s incredible toughness. While the superior properties of spider silks are well known, there was no known way to produce spider silk in commercial quantities. Since spiders are cannibalistic, they cannot be raised in concentrated colonies to produce silk.
Yet the production of spider silk in commercial quantities holds the potential of a life-saving ballistic resistant material, which is lighter, thinner, more flexible, and tougher than steel. Other applications of spider silk include use as structural material and for any application in which light weight and high strength are required. Kraig Biocraft Laboratories’ believes that in the near future, genetically engineered spider silk will make significant inroads into the market for high-strength fibers.
Golden Orb Weaver Spider Silk:
While scientists have been able to replicate the proteins that are the building blocks of spider silk, two technological barriers that have stymied production (until now) are the incapacity to form these proteins into a spider silk fiber with the desired mechanical characteristics and to do so on a cost-effective basis.
To solve these problems, Kraig acquired the exclusive right to use the patented genetic sequences for numerous fundamental spider silk proteins. We have placed ourselves in an advanced position by working collaboratively with the leading universities which developed some of the most relevant genetic engineering technologies. In fact, most of our genetic engineering work takes place inside university laboratories.
Kraig is the world leader in genetically engineered spider silk technologies. We earned that place by applying our proprietary genetic engineering spider silk technology to an organism which is already one of the most efficient commercial producers of silk: The domesticated silkworm.
Kraig’s spider silk technology builds upon the unique advantages of the domesticated silkworm for this application. The silkworm is ideally suited to produce genetically engineered spider silk because it is already an efficient commercial and industrial producer of silk. Forty percent (40%) of the caterpillars’ weight is devoted to the silk glands. The silk glands produce large volumes of protein, called fibroin, which are then spun into a composite protein thread (silk). [1]
We have used genetic engineering technology to create spider silk. A part of Kraig’s intellectual property portfolio is the exclusive right to use the patented spider silk gene sequences in silkworm. [2]
Spider Silk Strength: Stronger Than Steel:
Kraig envisions that this genetically engineered spider silk, with its superior mechanical characteristics, will surpass the current generation of high-performance fiber. We believe that spider silk is in some ways so superior to the materials currently available in the marketplace, that an expansion of demand and market opportunities will follow spider silk’s commercial introduction. For example, the ability of this natural silk to absorb in excess of 100,000 joules of kinetic energy makes it the potentially ideal material for structural blast protection.
QUICK EDIT: I was trying to figure out where the "[1]" and "[2]" referred to as it was not in the report. It looks as if it was copied directly from the KBLB website and not deleted: http://www.kraiglabs.com/spider-silk/
I agree which is why I tried to get those close ups.
The presenter there had stated that she had felt the dress herself and commented that it felt very coarse, similar to hemp fiber. This fiber might be decent when used in heavy body armor, but not as casual clothing.
I do not know if they can improve the feel of the fiber, but just based on the fiber on display, they would not be able to compete in the "mundane" textile market with this fiber.
Looks like Bolt Threads is starting to come out of their self imposed quiet period:
http://www.bloomberg.com/news/articles/2015-06-03/a-bay-area-startup-spins-lab-grown-silk
http://www.forbes.com/sites/aarontilley/2015/06/04/bolt-threads-32-million/
http://techcrunch.com/2015/06/04/spiderpants/
http://www.businesswire.com/news/home/20150604005318/en/Bolt-Threads-Raises-40-Million-Bring-Generation#.VXA8mcvn_qA
http://www.wsj.com/articles/BL-VCDB-17132
http://m.fastcompany.com/3046999/this-startup-is-making-a-stronger-stretchier-softer-silk-and-its-all-done-in-a-lab
Dou ittashimashite
I recently got the opportunity to stop by the Spiber Inc. QMONOS display at TEPIA in Aoyama, Japan and here are some pictures: http://imgur.com/a/qqmpi#0
I am still in Japan, so i will not be able to reply in any timely manner, but I thought you guys would be interested in what I learned from the presenter there:
- They are using DNA from the Darwin's Bark Spider among others.
- They would not state exactly what bacteria(s) they are using.
- The fibers are ~7 times stronger than Kevlar, though they did not differentiate the difference between strength and toughness nor did they give numbers. I could not ask very easily due to my Japanese not being all that great.
- They are still in the process of improving the fibers' properties
- They did not let me touch it, though they did state that the feel of the fibers is very coarse, similar to hemp fibers. It would not make very comfortable clothing despite a dress being made from it.
- The production of the protein powder and fibers is still very expensive, though they are working on reducing the cost. They would not give a ballpark figure.
- They just completed their second prototype factory as of last week that will be able to produce up to 20 metric tons annually at full capacity. They will be making samples of the fibers available in 2017 for the first commercial applications and hope to be fully commercial by 2025.
Yeah, someone. I dont remember who or the post number nor do I have the ability to search for it. You could ask Ben yourself to verify, but you don't trust him anyway, so it likely would not really matter to you. Maybe try Jon, Kim, or Susie directly?
Either way, I don't know if they have or have not reached that arbitrary milestone of metric tons by now, but I don't feel that that would be enough production capacity to warrent being "commercial". I personally feel that we would need a full sericulture facility before we could reach that level which i havent seen any evidence of yet. At the very least for small scale production with WM, I think there would be a patent application filed which i haven't seen yet. My guess is that they are still working with it, however much of it there may be. Hopefully it is coming soon, though.
I communicated with the student a month ago.
He did not tell me anything about the 2016 date (I just got that from the article posted before I mentioned him). The only info that he was able to give me was the fact that he is a student of Dr. Sam Hudson, an NC State professor who worked with Nexia Biotechnologies back in the day and is now on the Bolt Threads Scientific Advisory Board. He apparently mentions Bolt Threads in class quite a bit and that is how he knew that they were using transgenic Yeast and a controlled drawing technique to give the silk better mechanical properties. He did state that he thinks that they will eventually have properties equivalent to natural dragline silk, but made it seem like they are not quite there yet.
I don’t deny that there may have been delays in their production, but I haven’t found anything that states anything either way other than a website that has not changed other than the job postings. I do know that they recently inaugurated their “completed space” as of April 30, but what that means, I am unsure.
Concerning Bolt Threads, I have been able to corroborate the 2016 target date from an article written last year when they were still called Refactored Materials: http://dev.synbiobeta.com/company/refactored-materials/
That is the address of the new factory they are building. I guess it is complete enough to move into, though i have not heard any official news about them starting production from it yet.
I had contacted Ben a while back about these sites and he was aware of them. I looked further into Michelle Wilson and did discover that she is the "Danish Dragon" that banana referred to in Post #91117.
I have never personally met her and am unsure if she posts on this board, but due to her apparent past enthusiasm for KBLB, I don't think that she intends any harm toward the company.
The info I contacted Ben about had nothing to do with the transgenic silkworms, it is completely irrelevant to this discussion other than it shows evidence that old info is carried forward.
The wording concerning the transgenic silkworm was never changed. I looked all the way back to 2010 and the wording for the sentences that are in the S-1 that refer to not yet having transgenic silkworms are the same as the ones in the recent one.
Click Here for the June 2010 S-1/A.
2010's 1st statement:
Sorry for the late reply, i have not been keeping up with this message board as much as I should. It seems like this board exploded over the last couple days that i have not been following it.
It was pretty obvious to me that Kim had already achieved a transgenic silkworm due to the old UND sponsored press release and the PNAS report. I don't think Kim would blatantly lie just due to the huge potential reprocussions of doing so. Because of this, I had assumed that the not achieving the transgenic silkworm was regarding one that produces pure spider silk. This recent facebook post shows that it was simply a mistake of carrying over old info.
I know that Kim has not been the most diligent with updating the S-1 info, seemingly preferring to copy & paste everything. I know this because I had contacted Ben last year with a similar question over different old info being carried forward in the past and he made sure it was corrected in the next filing.
Also, concerning your Post #90762, I did a side by side comparison between the two S-1 statements and found that the two statements that you are referring to are seperate statements and both were carried over as legacy info.
Sorry I am a little late reviewing the newest S-1/A myself, but I finally got a little time to do so.
I agree with what you stated that changed, but there is one additional thing interesting that I caught in it that may be significant:
On page 4 and 7, they have removed the statement that they are a "development stage company".
Perhaps the reason that the SEC is now requiring more info is due to the FASB Accounting Standards Update No. 2014-10 concerning Development Stage Entities (Topic 915). The new S-1/A also added:
Researchers grow cardiac tissue on 'spider silk' substrate
(Click HERE For Article)
(Nanowerk News) Genetically engineered fibers of the protein spidroin, which is the construction material for spider webs, has proven to be a perfect substrate for cultivating heart tissue cells, MIPT researchers found. They discuss their findings in an article that has recently come out in the journal PLOS ONE ("Functional Analysis of the Engineered Cardiac Tissue Grown on Recombinant Spidroin Fiber Meshes").
The cultivation of organs and tissues from a patient's cells is the bleeding edge of medical research - regenerative methods can solve the problem of transplant rejection. However,it's quite a challenge to find a suitable frame, or substrate, to grow cells on. The material should be non-toxic and elastic andshould not be rejected by the body or impede cell growth.
A group of researchers led by Professor Konstantin Agladze, who heads the Laboratory of the Biophysics of Excitable Systems at MIPT, works on cardiac tissue engineering. The group has been cultivating fully functional cardiac tissues, able to contract and conduct excitation waves, from cells called cardiomyocytes. Previously, the group used synthetic polymeric nanofibers but recently decided to assay another material - electrospunfibers of spidroin, the cobweb protein. Cobweb strands are incredibly lightand durable. They're five times stronger than steel, twice more elastic than nylon, and are capable of stretching a third of their length. The structure of spidroin molecules that make up cobweb drag lines is similar to that of the silk protein, fibroin, but is much more durable.
Researchers would normally use artificial spidroin fiber matrices as a substrate to grow implants like bones, tendons and cartilages, as well as dressings. Professor Agladze's team decided to find out whether a spidroin substrate derived from genetically modified yeast cells can serve to grow cardiac cells.
For this purpose, they seeded isolated neonatal rat cardiomyocytes on fiber matrices. During the experiment, the researchers monitored the growth of the cells and tested their contractibility and the ability to conduct electric impulses, which are the main features of normal cardiac tissue.
The monitoring, carried out with the help of a microscope and fluorescent markers, showed that within three to five days a layer of cells formed on the substrate that were able to contract synchronously and conduct electrical impulses just like the tissue of a living heart would.
"We can answer positively all questions we put at the beginning of this research project," Professor Agladze says. "Cardiac tissue cells successfully adhere to the substrate of recombinant spidroin; they grow forming layers and are fully functional, which means they can contract coordinately."
Source: Moscow Institute of Physics and Technology
Proteins: The next generation of industrial materials
By: Kenji Higashi & Junichi Sugahara
(Click Here for Link to Article)
The development of synthetic protein materials that mimic naturally occurring proteins such as spider silks and insect tendons will offer solutions to the limitations and environmental impact made by the petrochemical plastics that revolutionized the manufacturing industry in the previous century. Spiber Inc. has demonstrated capabilities to create products with synthetic spider silk, and is poised to redefine 21st-century manufacturing with technologies that will enable industrial-scale production of high-performance industrial materials.
In the natural world, proteins are the building blocks of life. Some of these proteins are enzymes that enable chemical reactions, and some are used as structural components of cells and organisms, forming organs such as skin. When we look around the natural world, we see proteins that have evolved over 3.8 billion years to possess astounding functions. A good example is a spider’s dragline silk, which is made mainly of a protein called fibroin. Spiders use their dragline silk as a lifeline when they move through the air. Dragline silks spun by Caerostris darwini spiders have exhibited1 tensile strength (the maximum force that can be applied before rupture) of 1.6 GPa and toughness (a value indicating the amount of energy absorbed before rupture) of 354 MJ/m3. This is 14 times the toughness of carbon fibre — the strongest fibre to have been developed by mankind. If a spider’s lifeline were to break, the probability of the spider dying would increase. But thicker thread would waste the spider’s limited resources. The dragline silks that have evolved are those that have allowed the synthesis of the strongest, toughest threads while using a spider’s resources efficiently.
In the early 20th century, scientists embarked on a new era of polymer material development with the invention of petrochemical plastics. Researchers have been synthesizing new polymers and developing materials ever since, so that today we are surrounded by synthetic fibres, resins, rubber and other materials born of the union between petroleum and chemistry. Carbon fibre-reinforced resins have begun to replace metal materials in vehicle and electronic appliance bodies to reduce their weight. A spider’s dragline silk has a specific gravity of 1.3, making it about 70% lighter than carbon fibre. If we could use spider silk as a structural material in cars, aeroplanes and appliance casings, not only could we expect even further reductions in weight, but also dramatic improvements in shock absorption performance, which would translate into more economical and durable products, and greater safety for users.
Other areas in which synthetic proteins promise to enable new levels of functionality include lighter-weight and more impact-resistant protective clothing, such as bulletproof vests, and supple, highly biocompatible material for medical applications, such as surgical sutures, artificial blood vessels, wound dressings and cell culture scaffolds.
Spider silk is not the only protein that offers amazing possibilities. Resilin, found at the base of insects’ limbs and wings, has incredible elastic properties. When it needs to escape from a predator, the tiny spittlebug (or froghopper) can jump as high as 70 times its own height2. Resilin, the protein that makes this possible, has been known to exhibit3 resilience of 99.2%. In other words, it rebounds with 99.2% of the force that is applied to it. No conventional general-purpose rubber material exhibits such a high-energy storage rate. Resilin is also very durable. The resilin found at the base of the wings of a fruit fly (Drosophila melanogaster) withstands repetitive wing flapping from the time the fly matures into adulthood until it dies, without ever being replaced, even though a fly’s wings are estimated4 to flap at 720,000 cycles h-1. Resilin appears promising as a new type of rubber material for use in industrial applications and in implanted medical devices such as artificial heart valves and artificial tendons.
Other high-performance natural proteins include the egg-sac silk spun by one type of spider that can be stretched more than spandex, with a rupture elongation of 750%5. And squid beak is made of a compound material consisting of polysaccharide and proteins, making it one of the hardest organic materials known to man. It has a stiffness that is approximately three times more than synthetic commodity resins such as polycarbonate or polyphenylene ether6.
Humans have long been aware of the outstanding properties of many natural proteins but have not yet been able to use spider silk, resilin or similar structural proteins as manufacturing materials because, unlike wool or silkworm silk, we have not been able to obtain them in sufficient quantities. However, as a result of remarkable developments in biotechnology, this is about to change. We now have the tools we need to decode the genetic information of natural proteins and mass-produce them using recombinant systems.
Setting up Spiber Inc.
Spiber Inc. was established in 2007 to achieve industrial commercialization of synthetic spider silk and other high-performance protein materials. So far Spiber Inc., whose roots are in research conducted at the Institute for Advanced Biosciences at Keio University, has been financed mainly by venture capitalists and grants from the Japanese government. Among the various technologies that Spiber Inc. has been researching and developing are technologies for mass-producing recombinant structural proteins using microbes, fibre spinning and other material processing technologies, and technologies for applying materials in the manufacture of final products.
Spiber Inc. has adopted a highly systematic approach to fibre development. Researchers start by designing new recombinant genes in line with hypotheses aimed at balancing the mechanical properties of fibres against fermentation productivity, and artificially synthesizing the genes using genetic engineering techniques. Next, the genes are introduced into host microbes and cultured under various fermentation conditions and using various nutrient mixtures for maximum protein production. The protein is then separated from the host microbes, refined into a purified polymer solution called dope, and spun into fibres by applying various spinning techniques and conditions. Each time a new recombinant protein is produced, its productivity and fibre properties are examined and recorded, resulting in a database of knowledge founded on hypothesis-driven trial and error. The insights gained from these iterations are incorporated into each ensuing generation of genetic design.
Producing spider silk protein using fermentation
It is impossible to obtain industrially significant amounts of spider silk by cultivating and ‘milking’ spiders. Spiders are highly territorial and aggressively cannibalistic. Moreover, they only eat live prey. In addition, a single spider produces several types of thread. So even if it were possible to successfully cultivate a large number of spiders, it would still not be possible to consistently harvest thread with identical quality.
Given these hurdles, scientists around the world have been searching for ways to mass-produce spider silk using genetic engineering by introducing fibroin genes into a variety of potential hosts, which include goats, tobacco, yeast and Escherichia coli. However, none of these attempts have yet achieved a level of productivity that is remotely sufficient for industrial application. Of all the methods tested, those using microbes were found to be the most efficient. Kazuhide Sekiyama and Junichi Sugahara, then undergraduate students who later co-founded Spiber Inc., began by extracting genes from Nephila clavata (Golden orb-web spiders) caught in the shrubbery around the campus of Keio University. They introduced these genes into host microbes in a university laboratory, but were initially only able to produce quantities of recombinant fibroin weighed in milligrams. It is extremely difficult to get microbes to efficiently produce a protein whose molecular structure is as large and complex as that of spider silk.
Researchers seeking to improve productivity when cultivating recombinant proteins will usually test microbes to find the most efficient hosts and fine-tune culturing conditions to optimize fermentation processes. The Spiber Inc. team succeeded in boosting productivity to extraordinary levels because it didn’t stop at finding highly efficient hosts and fermentation processes but also devel-oped methods of optimizing the genetic codes of recombinant proteins. Based on published reports, Spiber Inc. has been the only research team in the world to succeed using this approach.
As a result, Spiber Inc. has continued to gradually raise productivity. The company has synthesized almost 500 variations of designed fibroin genes, and has improved productivity by a factor of many thousands since it was founded.
Turning proteins into workable materials
Even the best technologies for producing spider silk protein would not be enough to make the industrial use of artificial spider silk a reality. Once produced, the protein must be dissolved in a safe and economical solvent and subjected to optimal spinning processes to produce high-performance fibre.
Just as a spider spins out thread from its abdomen using liquid protein secreted from its silk glands, protein obtained through fer-mentation is dissolved in liquid, extruded through tiny holes, and processed into fibres. Fibre-making processes entail the determina-tion of precise parameters for solvent blends, spinning mechanisms, solidification methods and drafting processes. Each choice has a critical impact on the physical properties and durability of the fibre produced. Spiber Inc. and its business partners have developed optimal equipment and processes for spinning their QMONOS™ brand synthetic fibres, which are made with spider silk-inspired recombinant protein polymers. By conducting trial-and-error experiments aimed at finding optimal spinning conditions, the company has succeeded in producing fibre that is equivalent to natural spider silk in toughness and far stronger than other synthetic spider-silk fibre reported to date.
In addition to developing fibre, Spiber Inc. is cultivating production technologies for a variety of materials including films, gels, sponge and nanofibre non-woven cloth made from protein polymers, and tough resin-fibre compounds made by post-processing fibre. These efforts include finding optimal molecular designs for each material format and optimizing processing conditions.
As it works to improve productivity and performance through iterative design — prototyping — feedback cycles, Spiber Inc.
is simultaneously building its knowledge of the mechanisms by which molecular design affects productivity and material perfor-mance. The company is close to being able to freely design proteins with specific characteristics based on molecular design. In other words, it will be able to supply tailor-made fibres to manufacturers’ requirements. Customers will be able to say, for example, “We want a fibre with x strength and y elasticity”, and Spiber Inc. will be able to oblige. Varying both molecular design and processing conditions should make it possible to produce a virtually infinite range of materials.
Application in industrial products
In May 2013, Spiber Inc. used its proprietary elemental technologies to create a dress using QMONOS™ fibres, proving its ability to make an industrial product from artificially synthesized protein material. In November 2013, Spiber Inc. and its partner, Kojima Industries Corporation, backed by funding from the Japanese government, built a prototyping studio with facilities for fermenting, refining and spinning. Spiber Inc.’s groundbreaking prototyping studio, with maximum annual production capacity of 1,000kg, is the world’s first facility in which protein is produced by microbial fermentation, processed into usable material, and developed into prototypes of final products under one roof. In spring 2015, Spiber Inc. plans to inaugurate a next-generation pilot line that will serve as a model for scaling up processes already developed in the lab and prototyping studio. Within a few years, the company plans to enable this facility to handle a wide range of production scales.
The benefits of sustainability
Using new synthetic versions of naturally occurring proteins promises other benefits to man in addition to the introduction of ultra high-performance consumer products. For centuries, man has used new materials to help trigger revolutionary industrial devel-opments that have shaped the structure of human society. The invention of ceramic technologies around 10,000 BC enabled people to produce a variety of containers by freely forming clay. Around 3,000 BC, people living in Mesopotamia learned to make bronze tools, leading to dramatic innovations in building, farming and hunting implements that took advantage of the strength of bronze. From around 300 BC the Romans began the widespread use of concrete, which for the first time enabled them to design buildings and infrastructure without limitations caused by the shapes of raw materials such as stone or brick. The 20th century saw the rise of petrochemical industries kicked off by Leo Baekeland’s invention of Bakelite, the first synthetic thermosetting plastic, and the invention of nylon by Wallace Carothers. A wide variety of petroleum-derived synthetic fibres, synthetic resins and synthetic rubbers — including polyester and vinyl — were developed in rapid succession. Low-cost sup-plies of these materials have come to support modern industrialized societies.
Most of the 4.2 billion tons of petroleum consumed worldwide each year is used for fuel. Some 230 million tons, or 5%, is used to produce petrochemical-derived polymer materials. It is clear that the existing social structure — dependent as it is on dwindling petroleum resources — is problematic for various reasons. One reason is that petroleum supplies will eventually run out. The 1.2 billion inhabitants of industrialized OECD countries consume 50% of the petroleum resources currently used by the world’s 7.3 billion people. The world population is still growing, and is expected to reach 9 billion in 2050. If people in developing countries begin to use petroleum the way it is currently used in industrialized countries, petroleum consumption will increase dramatically.
Our planet’s oil reserves have been estimated at 240 billion tons. At the current pace of consumption, these reserves should remain available for several decades, and if we consider other reserves that are not currently available for exploitation due to technical or economic factors, petroleum resources may not be depleted for another several centuries. But in either case, it is clear that our descendants will need to find sustainable, alternative resources to replace petroleum. Another problem is that reliance on scarce resources has historically led to wars. As long as world economies depend on non-renewable resources, these violent conflicts cannot be fundamentally resolved.
A number of initiatives around the world aim to solve these global problems. In the field of energy production, a great deal of research aims to free humanity from the yoke of petroleum dependence by developing sustainable alternative fuels like biodiesel and bioethanol as well as cleaner methods of electric power generation using solar power, wind power, hydropower and geothermal power. No doubt the success of such efforts will lead to increasing replacement of fossil fuels. Similarly, there are a number of initiatives aimed at producing industrial materials such as polylactic acid, polyhydroxyalkanoate, biopolypropylane and bio-nylon from corn, sugar cane and other biomass feed stocks. Looking at the long-term future, it is likely that biomass-derived synthetic polymers will replace petroleum-derived synthetic polymers.
Spiber’s vision of the future
The potential design space for creating new synthetic protein materials is huge. Whereas conventional industrial polymers typically consist of chains of one or at the most two types of monomers, each link of a protein can draw from a group of 20 amino acids. This offers a tremendous degree of control over the final material’s structure and properties. Through the ages, the process of evolution has driven dynamic changes in the structures and functions of living beings. By designing new synthetic proteins, we will be able to create materials that are tailor-made at the molecular level to suit users’ specific needs for characteristics such as strength, elasticity, hydrophilic or hydrophobic properties, ultraviolet ray resistance, biocompatibility and resin compatibility. The range of properties that proteins can express are far broader than those of petrochemical polymers such as nylons or polyesters, and the range of poten-tial applications could touch every scene of our daily life and every area of industry.
Biomass-derived polymer materials that have been developed so far resemble petro-leum-derived polymers in the sense that they require polymerization by means of a chemical process. They also resemble existing materials in that they require dedicated production equipment designed specifically for each type of material produced. On the other hand, a single microbe-based fermentation process can be used to produce an enormous range of protein polymers by simply changing the genes that provide the code for each target protein. In a single fermentation plant, infinite varieties of materials could be manufactured through a biochemical process from a single type of biomass feed stock. This constitutes an epoch-making change. It means that the reductions in cost that can be achieved by making large quantities of a single type of material can be achieved when making small quantities of a variety of types of material as long as the overall volume is large. Once a large-scale production system for making structural protein materials has been constructed, it may be possible to introduce tens of thousands of tons of a new material to the market within a year of conceiving the molecular design for that new material. It is unlikely that there is any category of material other than proteins for which this could be true. This capability will have a dramatic impact on the life cycles of industrial materials. And this in turn will bring about a major paradigm shift in manufacturing. Instead of looking at a material and considering what can be made from it, people will be free to imagine a product they want to make and then design a material from which to make it.
In light of the industrial significance of structural proteins described above, structural proteins will constitute more than a small portion of the biomass-derived synthetic polymers that will be used in the future. Spiber Inc. aims to replace some 30% of worldwide synthetic polymer production with structural protein materials by the end of this century. Following stone, ceramics, bronze, iron, glass, concrete and plastics, proteins — natural materials that are now being developed in new ways — may be the next material to spark a revolution in industry.
References:
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4. Elvin, C.M., Carr, A.G., Huson, M.G., Maxwell, J.M., Pearson, R.D., Vuocolo, T., Liyou, N.E., Wong, D.C., Merritt, D.J. & Dixon, N.E. (2005) Synthesis and properties of crosslinked recombinant pro-resilin. Nature 437(7061): 999–1002.
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Here is something interesting that I have stumbled across. It looks like someone named Doo Kalmanson Aquino is trying to create a startup company for designer body armor (Click Here for more info). He mentiones KBLB along with other spider silk companies in his patent as a potential source for "Ballistic Materials". While it does not necessarily mean that KBLB is currently working with this person, it is good to see them at least being acknowledged.
Here is the patent itself:
https://www.google.com/patents/US20150059042
See the following KBLB press releases:
Kraig Biocraft Laboratories and Warwick Mills Sign Strategic Joint Development Agreement
Kraig Biocraft Laboratories’ Prepares for First Monster Silk™ Textiles
World’s First Monster Silk™ Textile Created by Warwick Mills and Kraig Biocraft Laboratories Collaborative Effort
I agree, I really don't see them commercializing anytime soon without some legal battle to do so or a lawsuit if they ignore the patent.
Ideally, Big Red should be out by then anyway and outshine whatever they have developed.