Good Genes Magazine, Fall 2019, Volume 1 by Good Genes Magazine

OCTOBER 2019 www.GoodGenesMagazine.com

This Edition Features Bio Strategies For: Fashion This Ski Season, a Parka Brewed Like Spider’s Silk — Biotech Meets Fashion and Sports Performance Health Meet The Company Engineering Your Immune System — Your Skin: The New Frontier In Microbial Medicine

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Industry Gene Editing is Coming to the Fortune 500 — Why is Airbus Partnering With a Synthetic Biology Startup?

NOBEL PRIZE for synthetic biology Frances Arnold is nudging nature to make your world greener, one evolution at a time.

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Dear Readers, Few realize it, but biology is transforming almost every part of our daily lives -- from the beer we drink to the desks we work on to the clothes we wear. Nowhere is this more evident than at the frontier of biology and technology — a field we call synthetic biology — which views DNA as a programming language that is revolutionizing the way we farm, fuel, manufacture and heal in more sustainable ways. Imagine a smart medicine used to treat formerly incurable disease. Or even better, ones that can tailor themselves to the specific medical needs of each person. This is the future! I want to share with you my hope and excitement for this field, so I present to you Good Genes, the new quarterly magazine from SynBioBeta. We at SynBioBeta are a community of innovators, investors, engineers, and thinkers who share a passion for using synthetic biology to build a better, more sustainable universe. Good Genes aims to tell the stories of these amazing people. If you’ve never heard of “synthetic biology” before today, you are not alone — few outside of technology circles have. Whether or not synthetic biology is a household name yet, one thing is certain: it’s already starting to change your life. And in doing so, it’s creating a whole new bioeconomy, driven by growing consumer awareness around informed buying choices and the corresponding impact on our environment. Taken together, these trends highlight the influence that tech and biology are about to have on every person and business on the planet. With Good Genes, we will share our insights from the fast-growing field of synthetic biology and how it affects you. We’ll cover the people, companies, and ideas shaping the future with biology. We’ll also share how investors, business leaders, and consumers can best prepare themselves (and their portfolios) to thrive in the coming bio-economy.

CEO John Cumbers Editor

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Kevin A. Costa

Andriana Mendez

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Embriette Hyde

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Digital Media

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Marianna Limas

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Anissa Cooke

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Partnerships, Advertising,

Peter Bickerton

Get ready to be amazed by the incredible stories of the innovators and the companies leading the way to tomorrow. The future is here... and it belongs to biology!

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Kind regards, John

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Ian Haydon David Kirk Anna Marks Nicholas McCarty Stephanie Michelsen Fiona Mischel John Murray Calvin Schmidt Karl Schmieder Adeline Seah

John Cumbers, CEO and Founder of SynBioBeta

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John Hugh Snyder

-----------------------------------------------------------------------------------------------------------Five Reasons Jeff Bezos Should Bet Big on Synthetic Biology

Table of Contents

One of the most successful businessmen on Earth is trying to get off of it. Synthetic biology may hold the key.

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Strategic investment in biotechnology now would reinvigorate rural America and help secure our nation’s high-tech competitive advantage.

One company’s greenhouse gas is another company’s gold. Here’s how one company is taking the petroleum out of plastics.

The Bio-Belt: Growing the Future in Rural America p6

-----------------------------------------------------------------------------------------------------------Why the Future Will Be Written in DNA

The bad news: we’re running out of stuff to make hard drives. The good news: we can store all the world’s data in a teaspoon of DNA.

-----------------------------------------------------------------------------------------------------------Your Skin: The New Frontier in Microbial Medicine p12 Combining the power of the microbiome with genetic engineering to treat skin disease.

-----------------------------------------------------------------------------------------------------------Nobel Prize Winner, Frances Arnold, Feature p14

Turning Greenhouse Gas Into Renewable Biomaterials p39

-----------------------------------------------------------------------------------------------------------Synthetic Biology and You

How tech and bio are shaping the world around us.

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-----------------------------------------------------------------------------------------------------------Building the Future with Biology Why does synthetic biology matter to you?

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-----------------------------------------------------------------------------------------------------------Why is Global Aeronautics Leader Airbus Partnering With Synthetic Biology Startup? p47 Here’s a hint: synthetic spider silk is stronger, more sustainable, and more flexible than anything your plane is made of today.

Nudging nature to make your world greener, one molecule at a time.

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How Biomanufacturing Can Make Living on Mars a Reality

Your body is the world’s best drug maker. And now we have the tools to help your body heal itself.

-----------------------------------------------------------------------------------------------------------Getting to space is easy. The question is: how we will sustain ourselves once we get there?

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-----------------------------------------------------------------------------------------------------------Living Medicines, or How to Disrupt the Pharma Industry p18 Ginkgo Bioworks takes a bold step into the field of engineered, living biotherapeutics.

-----------------------------------------------------------------------------------------------------------Gene Editing is Coming to the Fortune 500

There isn’t a single industry that won’t be impacted by biotech. This company is making sure of that.

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-----------------------------------------------------------------------------------------------------------Art Meet Bio, Bio Meet Art Designing a sustainable future.

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-----------------------------------------------------------------------------------------------------------Sustainable Cities Via Synthetic Biology The next industrial revolution will be based on biology, fueled largely by what cities today throw away.

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-----------------------------------------------------------------------------------------------------------This Soluble Swatch Aims to Change Your Life, and Save the Planet p34 How Procter & Gamble is saving water, reducing carbon emissions, and eliminating plastic

This Company Is Engineering Your Immune System

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-----------------------------------------------------------------------------------------------------------Biotechnology Meets Fashion And Sports Performance p54 Biology isn’t just about sustainability in sports apparel. It’s also the way towards materials that athletes can only dream of now.

-----------------------------------------------------------------------------------------------------------New This Ski Season: A Jacket Brewed Like Spider’s Silk

At the intersection of fashion and biology, sustainability and high-performance are no longer just buzz words. They are the method of choice.

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---------------------------------------------------------------------SynBioBeta: Where Tech Meets Bio, and Bio Meets Tech

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---------------------------------------------------------------------What - And Who - Is Synthetic Biology? p60 ---------------------------------------------------------------------Synthetic Biology Data pp61-67 ---------------------------------------------------------------------The Synthetic Biology Landscape

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-----------------------------------------------------------------------------------------------------------How Synthetic Biology is Dyeing the Future of Fashion Few realize the environmental cost of our blue jeans and other dyed garments. Biology has a solution.

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Five Reasons Jeff Bezos Should Bet Big on Synthetic Biology

BY JOHN CUMBERS, AS SEEN IN FORBES.COM

The richest man on earth is trying to get off it. In a recent interview with CNBC news, Amazon CEO Jeff Bezos warned that humans are “in the process of destroying this planet.” We have to go to space, he added, “if we are going to continue to have a thriving civilization.” A stark warning, to be sure, and one that Bezos seems committed to. The entrepreneur has been pouring a billion dollars per year of cashed-out Amazon stock into his rocket company, Blue Origin, which is now working with the federal government to develop new rockets, landers, and spacefaring vehicles. To save the planet, Bezos wants to see manufacturing

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moved to space. In the same CNBC interview, he noted that by building microprocessors and other complex goods in orbit and then sending them back down to Earth, he believes humanity could dramatically cut back on the large factories and dirty industries that are currently driving climate change. There are others who want to make manufacturing more sustainable — both in space and here at home. The synthetic biology industry, which raised $3.8B in financing last year, is working to revolutionize how we build things by making biology easier to engineer. Here are five reasons why synthetic biology should be a major part of Bezos’ plan: 1. Meat without animals, fruit without dirt It costs $2,000 to ship a lemon to the space station. It’s

it, tissue from cows, chickens, tuna or even plants are made to grow in a lab, yielding the complex textures and rich tastes we are already accustomed to. Finless Foods, based in Emeryville, California, is working out how to manufacture fish and other seafood this way. Memphis Meats, headquartered in nearby Berkeley, California, is doing the same for beef and poultry. Limits on scale and high price points will need to be overcome before these products can take a bite out of terrestrial markets, but their economics may look different from space. 2. Materials grown in orbit Have you ever arrived at the beach only to discover that you forgot to pack a towel? Imagine that feeling, but in orbit. Thankfully, synthetic biologists are already working out how to grow textiles, building materials, and more using microbes. New York-based Ecovative is creating sustainable alternatives to plastics using mushrooms. Their dense root structures can be coaxed to form recyclable meshes, boards, and other advanced materials. Spiber, a biomaterials company based in Japan, is mass-producing spider silk using synthetic biology. It recently announced plans to build the largest structural protein production plant in the world. For long stints in space, having the ability to grow new textiles and recycle old ones would help ensure safety and comfort while cutting down on costs.

time we learned how to grow food after we get there. Two techniques from biology — one old, one new — could make this dream practical. Fermentation has been used for centuries to make bread and beer. Now terrestrial startups are pioneering ways of using it to produce animal proteins like whey and casein, with efficiencies that dwarf those seen when farming whole animals. With fermentors running in orbit, a simple mix of sugar and nitrogen could readily be converted into a laundry list of nutritious (and delicious) ingredients. Why bother estimating how many lemons your brave astronauts will need? Instead, ship simpler ingredients and let the crew brew the custom proteins, vitamins and flavors that they want. More advanced entrees could be grown in space using an emerging technique called cellular agriculture. With

3. Processing human waste On the International Space Station, all drinking water is sourced from urine. Synthetic biology control over microbial metabolism would allow products to be manufactured from waste materials in space. “The easy part of space flight is getting to space,” says Michael Flynn, a water recycling expert at NASA. Once you arrive, no natural biospheres, flowing rivers, or ecological niches will be waiting to sustain you. “Those functions need to be turned into devices,” notes Flynn, “then loaded into the spacecraft to operate to keep you alive in space.” Recycling urine into fresh drinking water is essential for any long stay in space, but current mechanical recycling systems—including those running on the International Space Station—are lacking. NASA is currently testing whether biological membranes can be used in orbit to help process urine, and how algae grown in porous plastic bags can be used to control humidity inside spacefaring vehicles. ...CONTINUED ON PAGE 74

The Bio-Belt: Growing the Future in Rural America BY JOHN CUMBERS, AS SEEN IN FORBES.COM

Strategic investment in biotechnology now would reinvigorate rural America and help secure our nation’s high-tech competitive advantage Cow-free burgers are now all the rage — after Beyond Meats’ recent IPO, shares rose 163% on the first day of trading. Shortly afterward, competitor Impossible Foods announced an additional $300M investment. That’s great for California, but rural America is stuck in a bind. Technology is wiping out traditional jobs, and high-tech training can be hard to come by in towns where livestock outnumber people. Young Americans know this. According to a recent report from the United States Department of Agriculture Economic Research Service, non-metropolitan communities are greying as they attract retirees and lose new members of the labor force. Although rural communities are home to 14 percent of the population, they have seen just 4 percent of the employment growth since 2013. Despite this economic pressure, rural America remains one of our nation’s most fertile regions, and recent advances in biotechnology are making it easier than

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ever to sustainably grow new kinds of valuable goods, from biopharmaceuticals to biomaterials. With the right strategic investments, rural America could see a biotech “bloom.” I propose a Bio-Belt stretching through middle America to bring new skills and high-paying jobs to communities that desperately need them. This initiative would bolster investment in biotechnology training, education, infrastructure and entrepreneurship in rural areas in order to develop new, sustainable sources of income. The Bio-Belt is about much more than biofuel. Fermentation is an increasingly powerful force for converting sugar and other forms of biomass into value-added goods—all through the rational design of cells that can be sustainably grown wherever land is abundant. Rural biotechnology, like all biotechnology, will require strategic partnerships between business and academia. Agriculture extension schools, which are often located in rural areas, should expand to deliver research and job training for rural communities. Success will also depend on partnerships between community colleges and local businesses to provide a pipeline of individuals with the skills needed to work in regional biotech clusters. The government should incentivize these partnerships.

National laboratories dedicated to biological manufacturing are also needed in rural areas. These could be standalone new labs or expansions of existing facilities. Biotechnology startups could use them as incubators to test their products without having to make a major investment in equipment themselves. At present, this vehicle for commercial success is mostly limited to the coasts. Likewise, access to existing fermentation capacity should expand to those outside of coastal cities. This could be one of the cheapest ways to spread the benefits of biotechnology to more entrepreneurs. Under the Bio-Belt initiative, innovation would grow in rural areas, and biomanufacturing could expand across the country, where land and feedstock are abundant. The New York-based company Ecovative is already producing sustainable alternatives to plastics and other modern materials using mushrooms. In Boston, Ginkgo Bioworks is fermenting perfumes with yeast. In Seattle, Arzeda is pioneering new enzymes that catalyze the formation of novel food products. In a recent House hearing on the impact of biotechnology on the national economy, representatives from both parties expressed a desire to see more of our nation’s future invested in their communities.

“We need more science and technology development in the Midwest, where I am proudly from,” said Rep. Anthony Gonzalez (R, OH-16). While the employment benefits of biotechnology have thus far been concentrated in coastal cities, “the needs and opportunities and brainpower are significant across our nation,” noted Rep. Haley Stevens (D, MI-11). A small number of pioneering biotech firms are already thriving outside major metropolitan areas, including Iowa’s Integrated DNA Technologies, which makes DNA for many different applications, and Illinois’ Sustainable Bioproducts, which is looking into exotic microbes that may one day be used to replace animal-based meats. With new ideas, creative policies, supportive infrastructure and sound investments in biotech research and development, these companies will be just the first of many to take root between the coasts of this great nation. As the country thinks about its future manufacturing competitiveness and infrastructure, let’s remember this: 21st-century infrastructure is not just roads and bridges. A critical component of our economic growth will be the bioeconomy.

Why the Future will be Written in DNA BY KEVIN A. COSTA

How do we preserve our most important memories and how do we protect them from the ravages of war, nature, and time? Can we build everlasting stories of our shared human experience? What is the modern-day equivalent of the pyramids? A diverse group of historians, investors, and thinkers gathered in Switzerland this September to explore these questions. They were part of UNESCO’s Memory of the World Programme, an effort to safeguard our human heritage by preserving and making accessible the most valuable archives across the world. It helps protect documents, photos, paintings, and movies. A biotechnologist might seem an unlikely participant. But here was Bill Peck, PhD, co-founder and CTO of Twist Bioscience, who has spent most of his career upscaling complex biological manufacturing processes. What does he bring to this conversation? Dr. Peck believes that DNA is nature’s preferred storage medium. “There will be no new technology to replace DNA,” he says. “Nature already optimized the format.” Dr. Peck is part of a collaboration among Twist Bioscience, Microsoft, the University of Washington, EPFL, and the Montreux Jazz Digital Project to store two iconic musical pieces in DNA. The musical pieces will become part of UNESCO’s permanent archive. It’s the first time DNA has been used as a long-term, archival-quality storage medium. Twist’s blog tells the story behind the two songs selected for archiving and their Swiss debut. One can’t help but imagine a room of vaguely cool historians listening to the opening guitar riff on “Smoke on the Water,” Deep Purple’s account of the Casino Barrière burning to the ground during ‘71 Montreux Jazz Festival. Or

think of UNESCO archivists coolly considering the backand-forth between Miles Davis and his keytarist on Tutu from Montreux ‘86, transformed into an acoustic sea of As, Cs, Ts and Gs. I ask if our iPhones will be playing music directly from DNA anytime soon. “A music file would still be expensive to encode, write in DNA, decode, sequence, and convert back into a digital music file,” Dr. Peck says. As DNA reading and writing gets cheaper and cheaper, though, he speculates it may take just a matter of minutes to access huge amounts of data from DNA. For now, Twist is in the business of writing DNA. Peck feels that massive increases in DNA writing capacity matched by massive decreases in synthesis cost will be the catalyst for the DNA data storage market. Once the cost makes this technology accessible to the long-term digital storage market, other markets requiring less latency will follow. In a typical data center, there are several layers of storage. Flash memory is on top, which provides instantaneous access to information. Hard disks live underneath that. At the bottom are tape drives, which have high latency but store data cheaply with few errors for the longest time. These layers are joined together by machine intelligence that determines the best ways to allocate memory in the immediate, short, and mid- to long-term needs. Digital tapes are now the mainstay of long-term data storage. But as the world’s need for storage grows, a more stable, cost-effective, and long-term layer of storage will be needed, one that extends memory read-write systems into the biological realm. “Your ‘golden backup’ will be in DNA,” Dr. Peck thinks. Unlike flash memory and hard drives, DNA data storage is passive, meaning it doesn’t need a lot of electricity or love to keep it going for centuries, even millennia.

It might take a day or two to retrieve a complete restore, but it will always and forever be a lossless, failsafe backup. And if there is any doubt about the need to resort to DNA for storage, think about this: If we were to store all the world’s data in flash memory chips, at the current rate of growth we would run out of the elements needed to produce flash chips in under 25 years. Also consider how data is growing: The Sloan Digital Sky Survey produces about 73,000 GB of data every year, the CERN collider about 50 million GB per year. Life sciences research alone is expected to generate 40 billion GB worth of genomic data within a decade. These are staggering numbers, but DNA counters with similarly mind-boggling capabilities in terms of the amount of data it can store per area of space. DNA can theoretically store 455 exabytes per gram. That means all the world’s data (about 1.8 zettabytes) can fit on a DNA hard drive the size of a teaspoon (there are 1 billion gigabytes per exabyte, 1,000 exabytes per zettabyte). Not only could the world’s data be copied and backed up thousands of times over, but it could also stand the test of time much like mammoth DNA in the tundra. To get people thinking about this, researchers at the University of Washington (UW) collaborated with Twist to establish #MemoriesInDNA, a project that will encode 10,000 photos into DNA. Luis Ceze, a project leader and professor at UW, reports that about 3,000 images have been selected for synthesis so far. The images stored in DNA will live at UW and samples will be provided if other researchers want to work with the dataset. Everyone is welcome to upload a picture. Earthrise, as seen from Apollo 8 from the lunar surface, now a part of the #MemoriesInDNA project. Courtesy of NASA.

“My favorite photo,” Dr. Peck says, “and the one I submitted to #MemoriesInDNA, is Earthrise.” This is the iconic picture of the Earth rising over the Moon, taken in 1968 by the Apollo 8 astronauts. Dr. Peck remembers watching the landing as a kid: “For me, there was a beautiful metaphor in the astronauts’ readings from Genesis as they gazed out onto the whole of human history on a tiny blue spot.” Such elements of preciousness and perspective reverberate beyond the #MemoriesInDNA project, mingling with the whole concept of enshrining both our most cherished memories and the entirety of our human experience in spaces we can hold in the palm of our hand. It’s something that Dr. Peck identifies with personally. “One of my favorite books of all time is Histories by Herodotus, which begins: ‘Herodotus of Halicarnassus here presents his research, so that human achievements may not be forgotten in time,’” Peck says. “And I think that is what #MemoriesInDNA is partly about. We generate so much information, but it all fades with time. And digital data fades quicker than any other medium we’ve recorded human events on.” As DNA data storage makes its way into the mainstream, we might rest a little easier knowing our memories will soon be preserved in the time-tested building blocks of life.

Meet your new genome engineering

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tool.

Your Skin: the New Frontier in Microbial Medicine BY EMBRIETTE HYDE

I try not to laugh as Dr. Armpit carefully swipes — and tickles — my armpit with a large swab. I am a participant in his latest study to determine the factors that affect the microbes living on our skin — and how those microbes contribute to our body odor. Dr. Armpit is very clear: body odor is not a disease, it’s a problem with your microbiome. The gut microbiome has become a red hot topic in the last several years, and applications like probiotics and fecal microbial transplants have garnered much attention. But many people are less aware of how important a healthy microbiome is for your skin. Research groups across academia and industry are fervently studying how to leverage skin microbes to improve skin health. Armpit odor is just one example of how skin microbes can go haywire, and we’ll return to Dr. Armpit in a moment. But let’s first take look at how microbial engineering can help with one of the most prevalent skin disorders: eczema. Worldwide, about 10 percent of adults have some form of eczema, and it’s even more prevalent among children. If you or someone you know suffers from eczema, you know how challenging it can be. Scratchy, red skin that cracks and bleeds is not only painful, but can also leave you homebound, embarrassed to show your scarlet splotches in public. Hand and body lotions may offer some relief, while pharmaceuticals are pricey and come with an entourage of side effects.

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Skin is the largest organ of the human body, and is critical as a first line of defense against pathogens, the sun, wind, and water. Its function is crucial for human health, and it often holds important clues about our health. Skin breakouts can be a sign of a poor diet, food or environmental allergy, or early signs of an autoimmune disease. Blemishes can signal sun damage or cancer. We admire those whose skin “glows with health” and do anything we can to avoid wrinkles as we age. We feel sorry for those whose skin is ravaged by eczema. And, some skin diseases, such as Netherton Syndrome in infants, can be fatal or have life-long health consequences. Billions are poured into the cosmetics and skin pharmaceutical industries each year as we try to optimize the health of this critical organ. As we consider the health of our skin, we must take into account the thousands of microbes that call our skin home. These microscopic live-ins eat sweat and give us each our own body odor, attract or repel mosquitos (yes, mosquitos do prefer you to your brother on camping trips), and, most importantly, help keep our skin healthy. For example, Staphylococcus epidermidis helps promote wound healing by inhibiting inflammation and can protect against potential skin pathogens, such as Staphylococcus aureus. It has also been shown to help with moisture retention when applied topically. But it is likely too simplistic to view individual skin microbes as either good or bad. In most cases, the community as an entire ecosystem is the critical component for the well-being of our skin. More diverse microbial communities — those with a variety of species that contribute a wide array of metabolic functions — are associated with healthier skin. Conversely, unbalanced, or dysbiotic, microbial communities are observed in several skin conditions including acne and eczema, where Propionibacterium acnes and S. aureus, respectively, comprise abnormally large proportions of the skin microbial community. Chris Callewaert, known in the microbiome research community as “Dr. Armpit,” is one of the most active researchers seeking to apply skin microbes in practical ways. As a postdoctoral researcher at Ghent University in Belgium and the University of California, San Diego, Dr. Callewaert is particularly interested in tackling embarrassing body odor through skin microbiome “transplants.” He admits that body odor is not a disease, but emphasizes the psychological impacts it can have, especially on women, who, according to his research, tend to smell better than men but feel more ashamed ...CONTINUED ON PAGE 70

Meet Frances Arnold, the Synthetic Biology Nobel Prize Winner

“Would you call me a synthetic biologist?” Frances Arnold asks me. Yes, I reply. “Then I’m happy to be a synthetic biologist.”

Arnold’s work to modify the chemical pathways inside biological cells started before such “metabolic engineering” was recast by some as “synthetic biology.” In those days, synthetic biology was often described as putting biological parts together like Legos.

That’s how my conversation concluded with Frances Arnold, a Caltech professor who is a mechanical and aerospace engineer and a chemical engineer by training. Her success in engineering biology to create better enzymes for everything from sustainable biofuels to better ways of making drugs earned her the Nobel Prize in Chemistry in 2018. It led many people like me to wonder: Is this the first Nobel Prize in synthetic biology?

“It was pretty clear even back then when people were talking about standardized parts, that was a gross oversimplification of biological complexity,” Arnold says. That’s because a part might work one way in one kind of cell, but may not work at all in another cell. “There is no such thing as a standardized part. But the idea that you could engineer and become better at engineering biology — there we’ve clearly made a lot of progress.”

BY KEVIN A. COSTA

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Arnold’s work is clear evidence of that. And her approach to engineering biology relies on letting nature engineer itself. Let nature do what it does best: evolve “Life — the biological world — is the greatest chemist, and evolution is her design process,” explained Arnold in her Nobel Lecture. Through that process, Nature has come up with chemistry that no human has yet matched. Arnold pioneered a bioengineering method that lets biology evolve the best enzymes for a given task and condition. The process is called directed evolution of enzymes, and it works similar to the way dog breeders breed specific dogs to encourage desired traits. Arnold is sometimes asked: How can your research be used to help people? “Everything I’ve been working on for the last 30 years is my way of getting to a sustainable economy,” she says. “We have to be much more like nature in using renewable resources to make the materials and energy we need in our daily lives.” Arnold is an ardent environmentalist with a clear mission to make our human activities more sustainable. “I’ve spent my entire career putting in place the technologies that will make that happen. But those technologies won’t get used unless there’s support from the government, industry, and policymakers to make sure that the real costs of the way we’re currently behaving... get incorporated into the price of our products. I’m working on the technology side, and I hope to be working in concert with all of those other sectors to make this possible.” From academia to the real world Making truly useful products means getting her ideas out of the lab into the real world, and Arnold has started several companies to do just that. In 2004, she co-founded Gevo to make renewable fuels for jets, trucks, and cars. It is also using its technology to make renewable bioplastic bottles, flavors and fragrances, and bio-based industrial chemicals. Provivi is another company she started with a clever biological strategy to avoid pesticides. “Provivi makes insect pheromones that confuse males,” she explains. “This disrupts the mating of agricultural pests, leading to higher-quality crops with less use of pesticides.” Provivi recently expanded its Series B funding to $85 million to make these non-toxic replacements for pesticides.

“I think those are two excellent examples of where creativity in the synthetic biology and chemistry side of things can lead to big improvements in the way that we make fuels and the way that we look at agriculture.” Arnold’s latest company, Aralez Bio, makes direct use of engineered enzymes to expand the scope of valuable products that can be produced bio-renewably. Only 2% of the world’s chemicals are produced bio-renewably, according to its data. Aralez Bio aims to improve that figure by using biology to achieve the same versatility and efficiency of traditional chemistry — minus the usual energy, greenhouse gases, and waste. Bonding tech with bio In the ultimate expression of tech meeting bio, the Arnold lab has even been able to teach microbes how to stitch together carbon, the stuff of life, along with silicon, the stuff of computers. Nature has never before been able to do that. “We didn’t even have to nag the protein too hard to get it to do it,” said Jennifer Kan, a postdoctoral scholar in Dr. Arnold’s lab who performed the experiments, to the New York Times. The organosilicon industry is massive. Carbon and silicon bonds go into thousands of products that we use in our daily lives. “What I want to do is demonstrate that biology can learn how to make a vast array of molecules that people thought were outside the realm of biology,” says Arnold. “My feeling is that we can genetically encode almost any kind of chemistry. We just have to learn how to do that.” Arnold is the first woman to win the National Academy of Engineering’s flagship award, the Draper Prize, and only the fifth woman in 117 years to win the Nobel Prize in Chemistry. She views herself modestly as a role model for others. “For me, I was always the only woman in my cohort, first as a mechanical engineering undergraduate student, then as a chemical engineering graduate student. There were very few women getting degrees in those fields at the time,” she says. “My role models were men — great men role models.” “Doing science at the highest level is hard for anyone,” she elaborates. “It’s hard for women, and it’s hard for the men. And we need to have supportive mentors and role models we can look up to.”

BY FIONA MISCHEL

The wheels are in motion to send the first humans to Mars. For many, the first image that calls to mind may be of a spaceship touching down in a vast, red desert. But arriving on Mars is only half the picture. People also need to live there, something that can be difficult to imagine because there are so many unknowns. Martian habitation presents one of the greatest scientific challenges of the 21st century. And it is a challenge synthetic biology will be integral in solving. One of the most exciting ventures tackling this problem is CUBES, the Center for the Utilization of Biological Engineering in Space. SynBioBeta recently spoke with Adam Arkin, the director of CUBES and professor of bioengineering at UC Berkeley. Arkin, who will also speak at SynBioBeta 2019, described the goals of the CUBES project and how their work could enable human life on Mars.

CUBES is a five-year NASA Science Technology Research Institute. Veteran researchers, postdocs, and undergraduates have come together across six universities to develop biomanufacturing systems for Mars missions. But, explains Arkin, “since there isn’t a specified reference mission architecture for a real mission to Mars, we don’t know precisely what our constraints are.” Over the next five years, CUBES will build increasingly realistic models of what it will take to make integrated bio-systems feasible in space. NASA was instrumental in establishing CUBES and the project is continuing forward in communication with the agency. Arkin says this close working relationship is a huge privilege for the CUBES team as they work to understand what a Mars mission plan will look like. Feeding and keeping humans on Mars healthy These systems will rely heavily on Mars’ scant in situ resources. “The idea is to be able to produce food, pharmaceuticals, and light building materials using

How Biomanufacturing Can Make Living on Mars a Reality

waste recycling and the resources that are already there,” says Arkin. Using on-planet resources addresses a two-fold problem. It reduces the amount of mass needed to be shipped from Earth and it decreases the risk that a surprisingly critical item gets left out. Some things always make the proverbial suitcase; you really can’t leave Earth without a spacesuit. But what about medicine? Mars is an extremely harsh environment. Humans will need a whole host of medications to stay healthy. Though we have a very good idea of what we will need, there is still plenty of room for the unexpected. If something goes wrong, the nearest pharmacy is an average 140 million miles away. CUBES is tackling this particular problem through functional food.

choice] in a fairly controlled way. Once the drugs come to maturity, they can be isolated from the plant or you could just eat the damn plant,” Arkin chuckles.

The concept of functional food is not new. It typically involves engineering food to provide the body with more benefits than just fuel. Any Mars mission must grow its own food no matter what (Indeed, one of CUBES’s projects is transforming Martian regolith into agricultural soil). So why not get plants to work two jobs at once and produce the meds that Mars residents will need?

Helping academics think — and work — holistically There are four divisions within CUBES: Microbial Media and Feedstocks, Biofuel and Biomaterial Manufacturing, Food and Pharmaceutical Synthesis, and Systems Design and Integration. To achieve closed-loop biomanufacturing, researchers must account for every watt of energy, gram of material, and hour of astronaut labor used between the divisions. This kind of holistic thinking does not come naturally to academics. As director, one of Arkin’s biggest challenges is fostering this mentality. “I think that, in general, academics have a hard time with this because this doesn’t get you the science papers,” says Arkin. CUBES isn’t about the big, individual breakthrough. Instead, he says, it’s about the nitty-gritty details hammered out through cooperation, collaboration, and communication. For Arkin, this kind of community build is inspiring. It’s an emblem of the work at NASA and now at CUBES ...CONTINUED ON PAGE 83

Arkin strongly credits Karen McDonald, chemical engineer at UC Davis and upcoming SynBioBeta 2019 speaker, for spearheading the effort to produce biopharmaceuticals in plants. As biofactories, plants have certain advantages over bacteria. For one, plants are better at making complex proteins. They can also grow drugs stably without a lot of specialized equipment. “You don’t need a big bioreactor with CHO cells,” says Arkin. “Just take a lettuce leaf and a gene gun, shoot the construct into the leaf and it’ll make [the drug of

Space travel is all about efficiency. Any system that goes into space needs to be low energy, essentially zero-waste, and easily run by just a few people. Nutrition, biofuels, 3D printed biopolymer—one system’s waste is another one’s energy source. “You’re taking input from one group and giving your output to the next,” explains Arkin. Achieving this kind of closed loop is difficult in its own right. But Arkin points out another challenge; getting academics to also function as an integrated whole.

Living Medicines, or How to Disrupt the Pharma Industry BY KEVIN A. COSTA

Business is good for Ginkgo Bioworks, but the quality of the work is even better. Just ask Ena Cratsenburg, Ginkgo’s Chief Business Officer, whose job it is to find new markets for the company’s organism engineering technology. One of her goals is to give innovators the tools to create a new class of drug — living medicines — to help patients with subpar or no treatment options. I spoke with Ena recently about Ginkgo’s interest in pharmaceuticals, its new mammalian foundry, and the power of biology to do good in the world. Here’s our conversation, edited for brevity and clarity. What’s it like at Ginkgo these days? It’s exciting to be a part of Ginkgo and this bigger movement to pioneer bio-based products for the world. We’re excited about the power of biology and the possibilities of bio-based products, and we see Ginkgo as a partner that provides a powerful enabling platform that can make that happen. Ginkgo is very committed to the mission of making biology easier to engineer, and there are certain aspects of the Ginkgo technology platform that are unique in the space today. I look around the synbio world today and I really believe Ginkgo has a one-of-a-kind toolkit that is head-and-shoulders above the rest.

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Ginkgo is moving into the living medicines arena. What are we talking about when we say “living medicines”? Living medicines, broadly speaking, are modified living biotherapeutics. The term “living” is very important because they’re designed to sense and respond to cues in the human body, then deliver optimal treatment to the specific needs of the patient. “Imagine a medicine that can treat untreatable diseases with minimal side effects. That’s the potential we see with living medicine, which is to take advantage of all the amazing things that living cells can do.” Living medicine to me is essentially a form of personalized medicine. It provides treatment at exactly the right dosage, time, and place. It is designed to be smart so it is potentially more powerful and effective than conventional drugs today. How is Ginkgo’s technology platform helping to realize living medicines? We have built state-of-the art labs that we call foundries, and these foundries combine the latest automation and high-throughput equipment so that we can rapidly prototype genetically modified organisms for a variety of applications, ranging from industrial uses to consumer products and [now to] pharmaceuticals. Our first three foundries (Bioworks 1, 2, and 3) have been focused primarily on microbial systems. In late 2018 we opened our latest foundry, Bioworks4, and with this new foundry we now have a total of about 100,000 square feet of space that is dedicated completely to designing and printing DNA and engineering living cells. Bioworks4 enables us to apply our automat-

Will pharmaceuticals become a major portion of Ginkgo’s business? It will certainly be an important area for us. As far as what percentage of our projects or revenues, I think it is too early to tell. As we progress through the various stages of growth, we’ll probably see some changes up and down in terms of how much our portfolio comprises of one market or another. But it is an important part of our portfolio, and Bioworks4 is specifically dedicated to mammalian work. We are fully committed to working on pharma-related projects.

ed and high-throughput process to the engineering of the mammalian cells. And these mammalian cells are essential for pharmaceutical research and manufacturing. The opening of Bioworks4 gives us the ability to target more opportunities in a variety of novel therapies, whether it is engineered microbes or engineered cells or gene therapy. We can now use the foundries to rapidly design and develop high-quality drug candidates. What does the living medicines portfolio look like at Ginkgo? We are having a number of conversations with potential partners about developing drug candidates. One that I can share with you is a discovery collaboration with Synlogic, Inc. Synlogic is a company that is developing drug candidates within a specific class of living medicines that are engineered probiotics. These engineered probiotics are programmed with specific genes and molecular components to perform critical metabolic conversions in the gut that either replace or supplement physiological activities that are missing or damaged in patients. These programmed medicines have the potential to treat a range of conditions, including rare diseases, metabolic conditions, autoimmune and inflammatory diseases, and cancers.

From an industry-wide standpoint, what specific enabling technologies is Ginkgo most excited about? There’s a bit related to hardware, there’s a bit related to software, and there’s a bit related to the actual techniques, like genetic engineering. It’s not one particular technology that we’re excited about, it’s the confluence of all these things. At Ginkgo, we believe automation and high-throughput approaches are critically important to harnessing the power of biology to enable us to bring new bio-based products to market. It gives us the ability to turn the crank and do more experiments with higher efficiency. When we do more, we learn more. And when we learn more, we have a better set of data that informs us about the next cycle of design. It’s that flywheel of design-build-test-learn that gives us the ability to harness the power of biology. Biology is an important and powerful technology, and we are just now beginning to scratch the surface on how to harness it. There’s still a lot we don’t know and so much biological diversity we have yet to explore. We need to be able to rapidly run through a lot of experiments, and explore the vast potential of the incredibly broad diversity of biological sequences for answers. How does the synthetic biology industry as a whole — and Ginkgo specifically — measure its performance in terms of the engineering cycle? It’s important for companies to understand how they are improving their own processes. For a company like Ginkgo, which is very much focused on improving our scale economies and experiment cost efficiency and speed, we do have developed metrics internally to track progress to allow us to continue to seek improvements. But I think it’ll be very challenging to find a standard set of metrics that works across the board for everybody. Efficiency and speed are important as they relate to the cost of generating output. ...cONTINUED ON PAGE 68

Gene Editing is Coming to the Fortune 500 BY KEVIN A. COSTA

Richard Fox might be the world’s ultimate power user in computational biology, and when he heard about Inscripta’s new gene-editing technology, he joined the company to get his hands on it. It was just seven years ago when a revolutionary new system called CRISPR was announced. Discovered by two pioneering female researchers, what makes CRISPR so revolutionary is that labs now have a cutand-paste system for DNA. And as biologists and health care providers understand the genetic basis of diabetes, cancer, that ability is key to taking health and industry into the 21st century. But CRISPR is stuck. “We’ve been tinkering up to now,” he told me. Media headlines are still shouting about how great CRISPR is, but it’s limited by the two kinds of gene editing tools now available: tools that can edit thousands of different DNA sites with very limited changes, or tools that can edit one specific location with precision down to the base pair. Both are great, Fox says, but Inscripta wants to enable labs to tackle bigger challenges. Inscripta’s platform — which will be unveiled at SynBioBeta 2019 on October 1— promises that researchers will not have to choose between depth and breadth of genome editing. It’s an ability that Fox and his colleagues in research have dreamed about for years. “It’s really about taking the technology and applying it to interesting problems to stimulate the field and fuel their imagination,” Fox says.

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As Inscripta’s Executive Director for Data Science, Fox brings his passion for applying technology to big, important problems. He says that Inscripta’s platform is not only better at editing genes, but it also avoids a potential pitfall: freedom to operate. UC Berkeley and MIT’s Broad Institute are locked in a legal battle over who owns the rights to CRISPR technology. Berkeley filed first, but The Broad paid extra for a fast review, and got the patent first. “Research has been stymied because of the onerous licensing terms that are out there for other nucleases,” Fox explains. Instead of CRISPR, Inscripta’s new device uses a similar system called MAD7, which the company is basically giving away for free. “People fully own the products of their research,” says Fox. “The MAD7 enzyme is already opening up many more applications that have been forbidden because people don’t want to get into the big IP minefield.” Inscripta’s leaders are world-class tool builders. CEO Kevin Ness previously launched QuantaLife and 10x Genomics, two companies widely recognized for breakthroughs in genome reading. Board Chairman John Stuelpnagel co-founded Illumina — the company that will one day decode your entire genome for $100. Inscripta’s investors include Venrock, the technology investment firm that helped start little companies like Apple, Intel, and Illumina. How will this change the way we engineer biology? “At the risk of being a little melodramatic,” Fox says, “a quote from Shakespeare’s Hamlet comes to mind: ‘There are more things in heaven and Earth, Horatio, Lysine is an amino acid used in animal feed and other applications, with a global market of around $7 billion. Inscripta used the lysine biosynthesis pathway in E. coli to demonstrate the power of its new platform. In a single experiment, the company not only validated decades of published results on lysine biosynthesis, but it also found numerous edits (amino acid changes, knockouts, and promoter insertions) across the genome that gave rise to greater productivity. Many of those discoveries have not been previously reported in the literature.

Richard Fox Executive Director of Data Science, Inscripta

than are dreamt of in your philosophy.’ There’s so much we don’t know about biology, and despite the best efforts, it’s very hard to engineer these biological systems from anything like first principles. So for the foreseeable future, we’re going to have to let nature be our guide.” In other words: we will design systems, build them, let nature tell us what works best, and keep reiterating our designs until we get something useful. One thing is for sure: this new system will allow us to test many more ideas than we currently even dream of. This will help us understand not only how biology works, but also how we can design better systems to treat illness and disease. “There is a great deal of dark matter in genome sequence space that we still don’t understand.” In fact, Inscripta’s platform is so good at generating massive amounts of data that companies who build testing equipment may have to work harder to keep up. “I think there will be a new golden age for the Agilents and others out there who are developing high-throughput test capabilities to match the output of our platform.” I asked Fox what excites you most about the ability to make 200,000 edits in a genome. He thinks it could generate the massive datasets computers need to give us good predictions about biology and health -- even if we don’t understand the “why” of such predictions. “If it works, and you can predict, but it is difficult to understand or interpret, is that okay? From a forward engineering standpoint, it’s perfectly okay. But it might lead to a different definition of what it means to know something.” The supreme ability to predict outcomes and prescribe ways to intervene that improve system performance, even in the absence of interpretive ability, is the holy grail of genome engineering. At least for gene editing, that is a grand vision and something to be excited about.

Aminopeptidase and Autophagy Selective Autophagy Cell Illustrated by David S. Goodsell, PhD RCSB PROTEIN DATA BANK

Art Meet Bio, Bio Meet Art Designing a sustainable future BY ANNA MARKS

Synthetic biology is becoming central to the complex jigsaw puzzle of tackling sustainability. Living systems’ compounds, enzymes, and other biological matter can now be used as tools for biotechnological innovation, making synthetic biology a prominent branch of industrial design. The relationship between human intervention in natural systems and design is not a new one; for thousands of years, humans have manipulated natural systems for their own purposes. Plants have been cultivated and animals have been bred to fit specific frameworks of what society deems attractive and beneficial at a specific time; their genetic makeup “designed” for optimum aesthetics and use. Design: the history book of human intervention in biology As a discipline framed on its own, design has been central in illustrating humanity’s role in biological manipulation; for example, throughout art history visual artists have — often unknowingly — illustrated the changing aesthetic of farm animals across time through selective breeding. Contemporary designers also depict humanity’s role in biological manipulation — take Berlin-based designer Uli Westphal’s The Cultivar Series, where Westphal presents a photographic selection of fruit and vegetables resulting from mutations and polymorphism — how artificial selection is entwined with culinary heritage. And Amsterdam-based designer Diana Scherer’s work manipulates plant roots into elaborate Art Nouveau-style textiles, using a template to direct the plant’s growth and movements. Synthetic biology: the modern embodiment of biodesign Within the current cultural zeitgeist, synthetic biology is taking society’s relationship with nature to another

level by not only changing how genes interact but by manipulating entire genetic frameworks and biological systems. By developing systems at the genetic level, synthetic biologists can design biological components for the invention of advanced materials and medicines among other products. From the food we eat, to the fuels we use and the textiles we wear, engineering biological matter involves a hybrid, interdisciplinary relationship between biological sciences, engineering principles and design. As various disciplines in design have illustrated the changes in the natural world brought about by human intervention, design as a discipline is becoming increasingly thought of as a central component in innovation in the biological sciences. This interdisciplinary relationship is illustrated by this year’s Biodesign Challenge winners from the Universidad de Los Andes, who designed “PSEUDOFREEZE,” a sustainable refrigeration system created by manipulating Pseudomonas syringae — a rod-shaped plant pathogen — usually spread by the weather or insects. At this year’s London-based SynbiTECH conference, one of the main topics of the program centered around the evolving relationship between synthetic biology and design, with a focus on how innovation in synthetic biology is leading to sustainable design practice. In particular, speakers’ topics focused on how biotechnology start-ups are engineering living organisms to offer a new means of synthesizing medicines and products that could revolutionize a multitude of industries, from construction to healthcare to fashion. One of the focal points was the industry’s influence on the fashion industry and how biologists are manipulating biological systems to create eco-friendly fabrics, dyes, and materials, ...CONTINUED ON PAGE 51

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Sustainable Cities Via Synthetic Biology BY JOHN CUMBERS, AS SEEN IN MEETINGOFTHEMINDS.ORG

Sustainability is in vogue, with businesses and cities jostling to improve their public image and produce goods and services using renewable sources. Yet cities exponentially swell and carbon emissions continue to increase. Global CO2 emissions rise nearly every year (about 37.1 billion tons in 2018), with the bulk of these derived from solid and liquid fuels. Scientific and economic solutions to curtail these emissions have been proposed for decades, with some success along the way. But 21st century problems necessitate modern solutions, and businesses — the major contributors to carbon emissions — are not typically willing to promote sustainability at the cost of profits. Fortunately, synthetic biology, a scientific discipline that aims to engineer living organisms with new capabilities, offers a means to implement sustainable manufacturing processes that can reduce costs while producing materials, fuels and chemicals that are superior to existing products on the market. The engineering — and adaptability — of genetically-modified organisms holds the solution. Synthetic biology: the next industrial revolution In 2000, two research letters appeared back-to-back in the journal Nature. Confined to the final pages of the January issue, they heralded a paradigm shift in biology.

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In these letters, scientists reported the first successful genetic circuits operating in living cells. Modeled on electrical circuits, the scientists constructed two different types of biological circuits in living organisms using entirely synthetic DNA, programming the cell to perform predefined behaviors not found in nature. An amalgamation of physicists, bioengineers and molecular biologists soon flocked to the discipline, eager to program cells that could perform untapped functions. In the years that followed, engineered cells were processing and recording information, executing complex behaviors (like counting and forming patterns), and converting cheap starting materials into valuable compounds and medicines.

In April, synthetic biology graced the cover of The Economist, broadly conveying both its promise and perils. While synthetic biology has come a long way in the last two decades, its greatest test â&#x20AC;&#x201D; industrial scale manufacturing towards a circular, sustainable economy â&#x20AC;&#x201D; is only just beginning.

methane, rather than sugar. By changing their food supply, the cells can still produce a repertoire of products, albeit with less waste and expense.

Feeding organisms for a profit â&#x20AC;&#x201C; on earth and beyond Microbes have been exploited by humans for thousands of years. By supplying bacteria and yeast with simple sugars, they have long produced tasty foods like bread, wine, beer and cheese.

Some industrial cities, mainly in Asia, are already taking carbon dioxide and methane waste from factories and using it as a feedstock to manufacture a milieu of commercial products. Bioplastics, including pesky PET, are being degraded by engineered organisms. Microbes that produce nitrogen are even being used as a synthetic fertilizer to reduce our dependence on ammonia, the production of which is energy intensive and wasteful.

But synthetic biologists are now rerouting the metabolic pathways of these very same organisms so that they consume carbon waste, like carbon dioxide and

As our ability to reliably and rapidly engineer organisms improves, living cells will increasingly be used to produce goods at industrial scales. Synthetic biology

solutions can be implemented in many sectors of cities and municipalities to address current challenges in sustainable fuel production, waste and carbon emissions recycling, improvement of crop yields, and for the production of high-nutrient foods. These applications will have broad benefits regardless of where human communities arise, and the same technologies that sustain us on earth will also support our journey to inhabit the stars. Aboard the International Space Station, orbiting earth at nearly five miles per second, engineered seeds are growing into plants that could soon manufacture specific proteins, including antiviral antibodies, on-demand. NASA is also exploring synthetic biology to convert carbon dioxide to valuable organic materials on Mars and in deep space, since crude oil and other carbon sources will not be readily available. Other scientists are actively exploring ways to leverage synthetic organisms to produce food in space or to help terraform Mars’ atmosphere. The realization of these seemingly far-flung dreams is made closer by the businesses engaged in synthetic biology R&D. More companies join the biological revolution every day, eager to improve their products while reducing cost and waste.

Industrial synthetic biology is already making a dent in the circular economy If cells can be engineered to convert carbon to fuels and medicine, so too can they be modified to convert waste products – such as those billions of tons produced annually – to do the same. But plausibility rarely translates to lasting results. Take the city of Chicago as an example. In 2015, residents and activities in Chicago generated 32 million metric tons of carbon dioxide. Reducing these exorbitant emissions is no small feat, and it is unlikely that a single remedy will provide a full solution. But synthetic biology can – and already is – making cities like Chicago more sustainable by converting carbon emissions to valuable materials. LanzaTech is an industrial-level synthetic biology company that harnesses carbon waste and converts it to transportation fuel using engineered organisms. They opened their first industrial facility outside of Beijing last year, which collects emissions from a steel factory and generates more than 16 million gallons of ethanol per year. Soon, the company will expand to four additional facilities, reducing emissions comparable to removing hundreds of thousands of cars from the road each year.

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The chemical giant DuPont is also actively shifting their R&D towards synthetic biology solutions that can mitigate pesky chemical manufacturing issues through their Industrial Biosciences division. They are already operating large, active research programs to reduce food waste, produce fuels renewably and manufacture biomaterials with market-driven solutions using genetically-engineered organisms. Earlier this year, DuPont began construction on a new European headquarters for their Industrial Biosciences division in the Netherlands, with the aim of expanding their global impact. Other companies are exploring synthetic biology as a means to reduce carbon emissions in agriculture, a sector that makes up nearly 10% of US greenhouse gas emissions. The results are incredibly promising. Pivot Bio, based out of Berkeley, California, announced their successful development of a nitrogen-producing microorganism that can replace synthetic fertilizers. The production of ammonia is energy-intensive and wasteful, contributing many millions of tons of carbon dioxide to the atmosphere every year. Pivot Bio’s engineered strain will reduce the agricultural industry’s reliance on synthetic fertilizers, without impacting crop yield — in the latest growth trial, the microbe outperformed synthetic fertilizer by 7.7 bushels per acre. The “meatless meat” industry has also been expanding in recent years, leveraging the capabilities of engineered organisms to recreate the taste of real meat without the cow. Impossible Foods, creators of the famous Impossible Burger, use engineered yeast to produce heme, the major protein found in blood, to give plant-based burgers the taste of red meat. Other companies, like Spiber and Checkerspot, have their sights locked on producing high-performance materials from rudimentary carbon sources. Spiber is a Japanese company that produces synthetic spider silks, foams and films by designing proteins that assemble into pre-defined patterns and structures at the molecular level. Farming silk from spiders is excruciatingly time consuming. Now, the company can modify natural silk fibers and design new material functions in a matter of days with synthetic biology. While normal silk contracts in water, for example, Spiber has created altered versions that are hydrophobic, expanding their utility for outdoor apparel. Since 2015, Spiber has partnered with The North Face Japan to develop the MOON PARKA® prototype, which utilizes bioengineered materials.

Pushing beyond textiles, Checkerspot, based out of Berkeley, California, engineers microalgae, a type of photosynthetic organism found in water, to produce oils that are difficult to manufacture using chemistry alone. These include oil and water-repellent coatings and even a palm oil replacement. Large areas of rainforest are cleared to produce palm oil currently, destroying ecosystems and exacerbating carbon emissions. In all of these examples, nature is the breadboard and scientists are only limited by their imagination. A nearly infinite array of chemicals and materials can be produced from living organisms, with CO2 and other carbon sources, like methane, as the fodder. But there are roadblocks ahead. Future outlooks for a bio-based solution Imagination is not implementation. Despite the remarkable progress of synthetic biology over the last two decades, widespread public acceptance remains elusive. Gene editing continuously dominates headlines; a trend that is not always positive. Opposition to genetically-modified crops remains especially fierce. Of those Americans that have heard “a lot” about GM foods, nearly half see them as health risks, despite the widespread adoption of GM foods in agriculture over the last several decades. While synthetic biology has had less media coverage than GM food specifically, accurate and timely dissemination of information will prove crucial in swaying public acceptance, particularly as engineered organisms manufacture medicines and other consumables in greater volumes. Engineered E. coli have been used to produce human insulin since 1978 amid little public backlash, but there is no certainty that future medicines, clothing lines and fuels produced using synthetic biology will be so readily accepted. While a circular economy has long been imagined, it has only recently become fully implementable. For this next stage of the fight, synthetic biology — along with economic incentives and political sway — will usher cities and economies, on earth and in space, towards their inexorable destinies. CONTRIBUTING AUTHOR: NIKO MCCARTY

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This Soluble Swatch Aims to Change Your Life, and Save the Planet BY EMBRIETTE HYDE

“Relaxed sophistication: Juicy pineapple, along with a blend of frozen citrus notes combine perfectly with masculine woods and icy florals. Modern fougere: Infused with hints of crisp mint, pink peppercorn, and Green galbanum. Rich amber, sandalwood, and elegant musks provide a warm undertone.” This sounds like an amazing Chardonnay that I’d love to get my hands on, but no, this is not a wine. It’s the fragrance profile of something even better: a new line of home and personal cleaning products currently being tested that uses 80% less water in manufacture, reduces carbon emissions by 75%, and replaces plastic bottles with biodegradable packaging. A decade in the making, P&G’s EC30 product line takes everyday cleaners — shampoo, laundry detergent, toilet bowl cleaner, for example — and removes all the water, fillers, and other inactive ingredients not used in the actual cleaning process. What’s left is a rectangular swatch that looks a bit like a miniaturized coaster and packs a powerful cleaning punch. The process to make the swatches — which are comprised of woven fibers — is similar to that used to make non-woven materials, but in this the chemicals comprising liquid products are spun into soluble fibers. “Think of them like cotton candy,” says Tom Dierking, Design Director of Transformational Platform Technologies at Procter & Gamble. What results from the spinning process are dry sheets that are not only highly soluble but extraordinarily flexible, easy to cut, and extremely accepting of additives like surfactants and the delectable Chardonnay fragrance touted on EC30’s website (actually called “Blue Mist,” it’s one of two fragrance options). The products, split into personal care and home care,

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mimic branded water-based product, says Dierking So, essentially, the consumer has shampoo in an innocuous, lightweight form rather than a bulky, heavy bottle. If it sounds revolutionary, it’s because it is. “We put ingredients together in a way that had never been done before, and, importantly, put incompatible things together because they’re in a solid state,” says Dierking. Until you add water, that is. Reducing water use, reducing carbon emissions The lack of water is the most obvious characteristic of the product, with the easiest to understand implications: no more shipping thousands of gallons of water in the form of laundry detergents, shampoos, and other cleaning products thousands of miles. But, says Dierking, it has also been a source of frustration when introducing EC30 to consumers. “The consumer would look at this and say, ‘what is this, do you rub it on your head?’” says Dierking, chuckling.

that the core of P&G’s new product line is sustainability. Even the name, EC30, adheres to the theme: EC stands for enlightened clean, and reflects the equity of the brand. “But once they experienced the transformation in their hand, every single consumer, the first word out of their mouth was ‘wow.’” Later on they realize other benefits of the product: softer silkier hair as a result of less fillers and other additives, for example. The small size and feather lightness of the swatches are also pretty hard not to notice. Some advantages are immediately obvious: space savings in the traveler’s suitcase or in small living spaces characteristic of our increasingly urban lifestyle. But Dierking likes to translate these implications all of the way through the supply chain.

P&G has been discussing sustainability at length for many years, and their efforts are showing. They are striving to increase the number of plants that have zero waste to landfill, for example. And the company doesn’t plan on stopping there — they’ve developed a list of sustainability goals for 2030 that include achievements like making 100% of their packaging recyclable (the EC30 packaging already fits that bill), using 100% renewable electricity, and creating solutions that mean absolutely none of their packaging ends up in the ocean. Dierking reveals that some have been quick to point out that the company still uses water in the production of EC30 products — which to me seems like a silly thing to focus on given the tremendous reduction in water usage that the product does achieve.

“When you load jugs onto a truck, a certain amount of energy is expended to get that load of liquid product to the market. If we did the equivalent [with the swatches], first of all, we wouldn’t need a semi truck, so right away, you see tremendous value,” he says. “I can pick up “I am very proud to say that I feel like we are taking the by myself, virtually an entire year’s supply of laundry strides necessary [to become more sustainable]. We’re detergent in this form; obviously I can’t do that in liquid trying to do it in a responsible way, both to the planet form. And I can pack more on a truck, which means and to our stakeholders. EC30 came as a result of fewer trucks on the road, which means less emissions.” doing better... and the beginning of even more.” A culture of sustainability So, less water, less carbon emissions — it’s easy to see

Things like replacing the current ingredients with bio-derived ones.

How Synthetic Biology is Dyeing the Future of Fashion BY NIKO MCCARTY

Your favorite pair of jeans began as strings of cotton yarn, bobbing and weaving through scalding hot water and vats of indigo dye. The cotton runs through the dyeing cycle nearly a dozen times; the cotton fibers first take a yellow, then green, and finally a rich, blue color. This process has remained pretty much the same for over a hundred years. But it’s about to change. Producing indigo relies on toxic chemicals and reducing agents. Tinctorium Bio, currently in the eighth Indie Bio Accelerator class, have created a method to produce indigo by leveraging synthetic biology – not chemicals. “In the [denim] industry, the widely accepted standard is to use indigo powder to dye denim, which is heavily petroleum based…On top of that, you also need other toxic chemicals, like formaldehyde and cyanide, to make this indigo powder,” says Michelle Zhu, co-founder and CEO of Tinctorium. Historically, indigo was harvested in India from specific plants, which store the chemical in their leaves. A recent study from the Joint BioEnergy Institute at UC Berkeley also demonstrated that indigoidine, another blue pigment, can be produced from engineered fungi. But the production of indigo and its derivatives

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via biology only addresses part of the issue. The toxic chemical compounds that make indigo water soluble are still required regardless of where the indigo comes from. “Part of the problem currently is that indigo crystallizes really quickly and it’s not water-soluble, so you have to apply equal parts of a water-polluting chemical reducing agent to actually use indigo and apply it as a dye,” says Zhu. “Our solution basically tackles both pieces of the problem and provides this holistic solution where we are biosynthesizing the dye precursor and, since we’re controlling the pathway to form the indigo, we bypass the need for any reducing agents.” Specifically, Tinctorium uses E. coli to produce indican, the chemical precursor to indigo, in large bioreactors (a process first reported in Nature Chemical Biology). To make the indican water-soluble, an enzyme called β-glucosidase is added, which produces leucoindigo, the actual chemical used to dye cotton yarn. The traditional process relies on sodium dithionite, a cheap but toxic reducing agent, to convert the indigo extracted from plants into leucoindigo. Tinctorium’s process, though different from the canonical approach, provides a completely equivalent result. Jeans look the same, but their dyeing requires far less chemicals. The leucoindigo that Tinctorium produces can even be dropped into existing dyeing facilities, without the need for new machines or equipment. But while the denim industry seems ripe for change, and a synthetic biology-based solution for indigo production seems like a natural progression, the route to form Tinctorium was completely unexpected. Despite the unexpected start, the team has ambitious plans. After completing the Indie Bio program, they will raise a Seed Round to help develop a first line product launch – high-end, designer blue jeans dyed with bio-based indigo (you can even add your name to the waitlist here). To reach their goal, the team has partnered with notable industry experts like David Breslauer, the CSO and co-founder of Bolt Threads, and the internationally-renowned denim designer, Adriano Goldschmied. While Tinctorium has opted to provide solutions to specific problems – namely, indigo production and denim dyeing – other companies have been inspired by the brilliant colors found in nature, aiming to recreate them in the laboratory, offer a broader palette of dyes, and reduce waste in the process.

Turning Greenhouse Gas Into Renewable Biomaterials BY EMBRIETTE HYDE

With today’s social and political climate, it can be hard to believe that irresponsible dumping of plastics and polymer-based materials still happens on a daily basis. Even the most environmentally conscious may be unknowingly polluting waterways and landfills when their persistent polymer-based fabrics break down in the laundry or they wash their faces with microdermabrasion cleansers containing microplastics. The unfortunate truth is this: we still have a long way to go when it comes to caring for our environment, and until substantial mindset and policy changes occur, our waterways and land ecosystems will continue to be polluted. Until we reach that moment, it may be better to face this truth and reduce the collateral damage associated with materials dumping as much as possible. Enter biodegradable materials. Averting environmental injury through biodegradable polymers Molly Morse has dedicated the better part of a decade of her life to studying and optimizing biodegradable materials. As a graduate student at Stanford University, she became extremely interested in the biodegradability of materials used for disaster housing. An engineer at heart, Morse focused on PHA (polyhydroxyalkanoate), an important component of biocomposites — and an incredibly biodegradable polymer. But back then it was difficult to acquire PHAs: they were expensive, not a trivial fact for an academic research lab — even one at Stanford.

Aerial view over biogas plant and farm in green fields. Renewable energy from biomass. Modern agriculture in Czech Republic and European Union.

Fortunately for Morse, a group at Stanford pioneered a way to make PHAs from bacterial fermentation of methane. Her resource supply issues solved, Morse was able to focus on studying how PHA degrades naturally. And though she was ...CONTINUED ON PAGE 80

Synthetic Biology and You How tech and bio are shaping the world around us

Agriculture, Food, & Consumer Goods To feed more people on an already straining planet, agriculture must become greener, more innovative and more bountiful. Biotechnology is already boosting crop yields, lab-grown meat and fish will further reduce greenhouse gas emissions, and gene editing can help agriculturalists modify traits without adding foreign DNA. But will the public get on board with these novel approaches? What regulatory challenges will be faced by companies in this space?

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Environment & Energy Maximizing the bioeconomy will help minimize the use of non-renewable resources by producing sustainable bioproducts, renewable fuels, and more — after all, nothing is greener than biology. Synthetic biology is an environmental boon. Compared to conventional manufacturing, biofabrication requires fewer harsh chemicals, less energy input and can even yield carbon-neutral liquid fuels. By synthesizing complex bioproducts in factories, we eliminate the need to extract them from the wild, leaving fragile ecosystems intact. From converting methane to edible protein to identifying novel approaches to carbon recycling, synthetic biologists are leading the way toward greener, more sustainable energy. These approaches can curb further damage to — and perhaps even begin to heal — our wounded environment.

Biopharma & Health Through continued breakthroughs in engineered biology, we are entering a new era of medicine. Engineered biomolecules are hitting ‘undruggable’ targets, the immune system is being optimized to fight cancer, CRISPR is being used for lightning-fast diagnostics, and the microbes within us are being harnessed and modified to target skin, gastrointestinal, and autoimmune conditions. With these breakthroughs — and more in the works — it is more important than ever to ensure that we are pursuing the right goals. Biopharmaceuticals must be affordable for those who need them, and we must not lose sight of global disease burden. And, as data sharing becomes more critical for democratizing clinical applications such as diagnostics, we must ensure that in our efforts toward the global good we don’t harm the individual. Synthetic biology is tackling the biopharma and health stage, and the ethical implications that we should all be considering.

DNA Data Storage The future is written in DNA. Biology has already provided us with the perfect information storage molecule; we just need to learn how to leverage it to store the terabytes of data our technology-based society is producing. We’ve already written the information for short film clips and songs in DNA, but to be able to fully realize the potential of DNA data storage and create the next-generation tape drive, the price of DNA synthesis must continue to drop — and we must efficiently tackle the other side of the equation: reading from DNA.

The Green New Deal It is rare for a piece of proposed legislation to go viral, but that is exactly what happened with the Green New Deal when the proposal went out earlier this year. New York representative Alexandria Ocasio-Cortez championed a version that would see the US transition to 100 percent renewable energy in only 10 years even as members of the synthetic biology community took part in active discussions around how synthetic biology could help the Green New Deal — and vice versa. While details are still being fleshed out, one thing is certain: the Green New Deal stands to affect the change the public wants to see, with an emphasis on economic, social, and environmental justice.

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Emerging Technology Platforms One of the most difficult challenges facing synthetic biology is measuring what matters. How do we know which experimental data are important? How do we identify the best amino acid sequence to create our desired protein? What parameters do we measure â&#x20AC;&#x201D; and seek to control â&#x20AC;&#x201D; in the laboratory? Automation, AI, and the Internet of Things are just a few examples of technology platforms being leveraged by industry and research groups to measure what really matters.

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BY EMBRIETTE HYDE

“When spider webs unite, they can tie up a lion.” – African Proverb For the nearly five decades, industries from the automotive to sporting goods to aerospace have been utilizing carbon fiber as a means to produce faster, lighter, and stronger products. If you’ve ever traveled on a commercial airliner, you’ve benefited from carbon fiber, which has reduced maintenance costs due to its increased strength and resistance to corrosion and weakening. And, carbon fiber, which comprises 53% of Airbus’ A350 XWB commercial airliner, had reduced operating costs, fuel burn, and CO2 emissions by 25% compared to the previous generation of aircraft. But air travel continues to rise, and a more durable, more sustainable solution to larger, lighter, more fuel-efficient planes is needed. Fortunately, nature has already provided us with the answer: the spiderweb. Or, more specifically, the silk fibers that spiders use to construct their intricate death traps. Spider silk has long been recognized for its strength, flexibility, and lightweight structure. It is the strongest naturally occurring fiber known, with a tensile strength comparable to that of high-grade steel. Compared to Kevlar, it is seven times more elastic and takes three times the energy to break it. It is also biodegradable and has been used in a variety of products, including bullet-proof clothing, ropes, parachutes, and even prostheses. Industrial biotech company AMSilk GmbH is capitalizing on and perfecting nature’s gift of spider silk. Based out of Planegg, Germany, the company, founded in 2008, produces high performance synthetic spider silk biopolymers — and is the world’s first industrial supplier of synthetic silk. Notably, the process used to create the biopolymers is a closed-loop system with no petroleum inputs, making the product extremely sustainable. The company’s high performance, organic biopolymers are already in use across industries from medical devices to personal care products – over 30 cosmetics products are currently available for purchase internationally. AMSilk’s bio-

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polymers can also be spun into fibers, called Biosteel®, which have been introduced in a prototype running shoe launched with Adidas. Today’s announcement takes Biosteel® fibers beyond fashion and sport applications for the first time – yes, all the way to airplanes. In a press release out today, AMSilk announced a new partnership with aerospace giant Airbus to develop the next generation of lightweight, high performance planes. This collaboration will realize the creation of the first composite material made of AMSilk’s Biosteel® fiber. Why would an aerospace company be interested in synthetic spider silk? The answer is simple. Biosteel® fiber is not only strong and sustainable, but it also has superior flexibility compared to carbon fiber, permitting new design and construction techniques that don’t lead to compromises in strength — an important consideration when dealing with winged tubes hurtling people hundreds of miles per hour through the skies at 37,000 feet. Airbus has long been committed to being at the forefront of aerospace innovation. As they seek to design the next generation of larger, more durable, and more flexible airplanes, exploring AMSilk’s novel biopolymers seems a natural move — and they are the first in the aerospace industry to experiment with Biosteel® fiber. “We are excited to be working with Airbus, the world leader in performance airplanes, to create a funda-

Why is Airbus Partnering with a Synthetic Biology Startup?

mentally new material,” said Jens Klein, CEO of AMSilk. “At AMSilk, we are committed to producing materials that are both high-performing and sustainable, and the current partnership with Airbus is an opportunity to set a new, stronger and more sustainable course for the entire aerospace industry.” It’s not likely that any commercial flight you step onto anytime soon will be on a vessel sporting AMSilk’s Biosteel® fiber. Today’s announcement by the two companies marks the start of a substantial R&D process – the first prototype is expected in 2019, with the material not expected to become commercially available until further in the future.

In aerospace, the potential applications of the new material are numerous, ranging from lightweight interior elements to new structural components for planes’ exteriors. This partnership could also help advance materials to support a new era of transportation in general, with further applications possible in sectors such as e-mobility, autonomous driving, drones and air taxis. With the help of synthetic biology and partnerships between global industrial leaders, the humble spider web is no longer tying up lions. Instead, it is conquering the skies — and beyond.

Meet the Synthetic Biology Company Engineering Your Immune System BY JOHN CUMBERS, AS SEEN IN FORBES.COM

For decades, the field of immunology was a black box. Leading experts in science and medicine had only a basic understanding of the powerful complexity of the human immune system. Everything changed in 1983 when a mysterious virus — later identified as HIV — swept through the world claiming the lives of otherwise healthy men and women. The hunt for a cure led to a more comprehensive understanding of the immune system. This altered the course of drug discovery and development. Antibodies became a household name, and the insights gained about their function and formation led pharmaceutical giants to invest in therapies that manipulated the body’s immune system to achieve a desired therapeutic goal. This led to safer and more potent therapeutics. Nearly forty years later, the fields of immunology and pharmacology are in the midst of another surge of scientific growth. Equipped with knowledge and tools acquired from various disciplines, biotechnology companies like Distributed Bio are redefining how pharmaceutical companies identify, design, and synthesize therapeutics. “We are now able to engineer antibodies in the lab faster than the body can do it,” says Jacob Glanville,

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a computational immuno-engineer and President of Distributed Bio. “It’s taken us 30 years to get there, but we’re in this golden age now in bioengineering where we’re really able to produce these molecules in unprecedented speed. And that’s what’s so exciting about today.” Glanville founded the company with two friends back in 2012. Unlike most other biotech startups, it didn’t seek traditional venture capital. Glanville and his team created a software platform on Amazon Cloud that let people around the world do computational immunology. They were profitable from the get-go. Distributed Bio then used its platform and cash to build a powerful antibody discovery and optimization lab. “We started licensing out not just on the data, but the ability to actually engineer new medicines,” says Glanville. “That’s when our company really started growing much faster because that was worth a lot more. That bootstrapped us to the point where we’re producing therapeutics, which is where we are now.” With these cool technologies, the company is now a provider for the likes of Pfizer, Boehringer Ingelheim, Gilead, Teva — a who’s who of pharma companies. And the future for antibody drugs is looking good. Today, 30% of prescription drugs in the market are antibody therapeutics. But Glanville points out that it’s taken 30 years for the pharmaceutical industry to discover how to manipulate antibodies. “If you can make an antibody, it’s an awesome drug,” he says, “but it’s really hard and time consuming. It can take over a year to do the engineering. It used to take longer.” And Glanville is assembling the tools and technologies to shorten that even further. Some of his favorite projects demonstrate just how relevant antibody engineering is to the real world: Universal vaccine. Distributed Bio was recently awarded a large grant to develop its broad-spectrum vaccine that can protect against not just one flu, but many versions. Snake bite vaccine. The company found a guy who spent 17 years being immunized with snake venom, building up an incredible immunity. Jake and his team screened his blood, found a bunch of these antibodies for snake venom, and made a broad-spectrum antivenom vaccine. The NIH is now supporting this project so that it can eventually come to market. ...CONTINUED ON PAGE 79

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CONTINUED FROM “ART MEET BIO, BIO MEET ART”: redesigning

the future of our clothes and challenging the culture surrounding fashion. Synthetic biology principles have also enabled the creation of sustainable dyes for the fashion industry such as Pili’s biotech dyes, and London-based designer Natsai Audrey Chieza’s use of bacteria to dye fabrics without water. Synthetic biologically crafted garments are predicted to soon enter mainstream fashion: Bolt Threads have partnered with Nike and Stella McCartney to construct clothing from synthetically engineered spiders’ silk.

As a co-founder of SynbiTECH and one of the most prominent thinkers and researchers in the synthetic biology field, Professor Paul Freemont, Head of structural biology at Imperial College London, recently received an honorary fellowship from the Royal College of Art (RCA). Freemont’s research at Imperial focuses around investigating molecular mechanisms of disease, designing drug therapies, and the development of synthetic biosensors and technologies. Freemont’s honorary award in design showcases how the discipline has become central to biological innovation and the culture and discourse surrounding it.

experimental studio space featuring a biomaterial lab, opened in London in 2018 to foster the development of biology, design, and technology. Additionally, the Science Gallery London, which also opened in 2018, further presents the collaboration between science and design to their public audience through their exhibitions and public program. Such developments in research, conferences, and public-centered programs within both the scientific and design fields illustrates the ongoing importance of collaborations between designers, artists, and biotechnologists for innovations in bio-based design. As this SynbiTECH program and Freemont’s award suggest, the ever-expanding connection between synthetic biology and design has become vital for the development of systems for a sustainable future. ANNA IS A DESIGN WRITER BASED IN LONDON WHOSE WORK CENTERS AROUND DESIGN, ARCHITECTURE, AND SCIENCE. SHE’S BEEN FEATURED IN WIRED, VICE, AND COLOSSAL, AND HER WORKS CAN BE FOUND AT ANNAVMMARKS.COM.

Designing biology for a sustainable future The interconnectivity between design and synthetic biology is further illustrated by the rise of public programs aiming to raise awareness between the crossover of the biological science and creative arts. For example, Open Cell, a Shepherds Bush-based

WEâ&#x20AC;&#x2122;RE THE ORGANISM COMPANY. 52

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WEâ&#x20AC;&#x2122;RE MAKING BIOLOGY EASIER TO ENGINEER. 53

Biotechnology Meets Fashion and Sports Performance Trends in the apparel industry BY NIKO MCCARTY

Organisms are the great designers of our planet, producing materials in distinct patterns to serve a specific function. Bees produce hexagonal honeycombs to store honey, spiders weave symmetrical webs to capture prey, and nautiluses form a logarithmic spiral shell to protect their insides. Synthetic biologists, ever inspired by nature, are leveraging these unique abilities, harnessing nature’s potential to revolutionize apparel by guiding structural assemblies at the molecular level. Here are three examples of innovative companies — in Tokyo, New York, and Berkeley — that are letting nature show the way to better, more sustainable materials in a quest to alter the fashion and apparel industries forever. Protein engineering to build materials stronger than steel Synthetic biologists have long “tweaked” genetic

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information to produce specific chemicals from living cells, but engineering the blueprints that specify higher-order structures may hold even greater potential. Nowhere is this more apparent than in spider silk, a material five times stronger than steel by weight and is increasingly being produced by microbes through fermentation, rather than actual spiders. “In the case of spider silk specifically, using bioengineered silks is the only real option for mass production. Spiders don’t like to be farmed — they prefer to eat each other when put into small spaces together — and harvesting threads from individual spiders is incredibly time consuming and inefficient,” says David Lips, Researcher at Spiber Inc., a biomaterials company headquartered in Japan that has generated a wide range of protein-based materials with functions that far outshine natural variants. For example, while natural silk contracts when in contact with water, Spiber has developed “an altered silk protein material that is hydrophobic and does not contract when wet or in

humid environments,” they explain. “We believe this achievement will be a game-changer for many outdoor applications.” For the last 12 years, Spiber has undoubtedly pioneered the genetic manipulation of silk, which in silkworms is made from just two interlocking proteins, but they have also found success in developing other protein-based materials using their molecular design, fermentation, and prototyping pipeline. “As you can imagine, different applications have different specifications that the material needs to adhere to, such as a specific tolerance for heat or humidity, more flexibility, more stiffness, extreme toughness or the ability to stick to surfaces. All of these properties are governed by the physical interactions that occur at the molecular level of the material. Needless to say, changing the molecular composition of proteins by designing a different amino acid sequence can drastically alter the performance of a material. This question — figuring out the best possible molecular design for a specific material — is an iterative process that lies at the core of what Spiber does,” says Lips. This approach has enabled Spiber to develop unique, protein-based materials for stiff resins, flexible films, and soft foams. In 2015, Spiber partnered with The North Face to launch a high-performance ski jacket, called the Moon Parka, which is now being prototyped for a second-generation version. But the future of apparel is not limited to engineered protein-based materials. Synthetic biologists have also managed to produce patterned and structured materials by going directly to the source. Molecular assembly platforms for fashion At Ecovative Design, materials are grown, not synthesized. The company uses mycelium, the root structure of mushrooms, to assemble complex materials that often outperform industry leading materials while remaining eco-friendly. Eben Bayer, Co-Founder and CEO, started the company in 2007 to leverage mycelium’s remarkably fast growth rate, higher heat resistance compared to plastic, ...CONTINUED ON PAGE 76 Photo, top right: The second MOON PARKA® prototype undergoing field testing. Photo courtesy: Spiber Middle: A film made from structural protein materials. Photo courtesy: Spiber Bottom: Ecovative Design co-founders Gavin McIntyre (left) and Eben Bayer (right) holding structured materials made from mycelium. Photo courtesy: Ecovative Design

New This Ski Season: A Jacket Brewed Like Spiderâ&#x20AC;&#x2122;s Silk

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BY JOHN CUMBERS, AS SEEN ON FORBES.COM

Spider silk may be the holy grail of biomaterials. In nature, it can be tougher than Kevlar, lighter than carbon fiber, and warmer than the densest down, depending on how it’s made. Today, Japanese biomaterial company Spiber announced the world’s first outerwear jacket made from proteins designed to be similar to natural spider silk. But instead of spiders producing its silk, precisionengineered microbes make it. Spiber unveiled the jacket at a press conference in Tokyo with apparel company The North Face Japan. The high-performance ski jacket, called Moon Parka, will hit shelves for a limited release on December 12, 2019. While this jacket isn’t designed to deflect bullets, the Moon Parka definitely lives up to its name: it’s made with the same kind of performance biomaterials that might one day sheathe astronauts living on a lunar base. This year also marks the 50th anniversary of humans walking on the moon. The textile used in the jacket is waterproof and breathable, and it uses a high-performance filler that makes it very warm. But what makes this parka really special is that its biological fabric was produced through a renewable process that meets the demanding North Face performance requirements, which would usually require non-natural, petroleum-based materials to achieve. You wouldn’t even try to make this jacket with natural wool or silk. The parka fabric is one example of “grown materials,” which are receiving increasing attention as potential replacements for petroleum-based fabrics like polyester and nylon. Spiber uses synthetic biology — a scientific field that leverages DNA editing techniques to program microorganisms — to quite literally grow their silk-based materials. In this case, engineered bacteria are fed sugar, which during fermentation produces the silk-like proteins that Spiber calls Brewed Protein. The proteins are then purified, spun into threads, and woven into fabrics. The production of the Moon Parka is also built with sustainability in mind from the outset; the microbes can be fed sugar from agricultural waste products. And since the coat is made almost entirely of protein, it is inherently biodegradable.

The Moon Parka’s release falls in line with Spiber’s ongoing plans to scale synthetic protein production. At the end of last year, they announced the construction of a new production facility in Thailand on the back of a $44 million investment. Once completed around 2021, the new facility is expected to be the world’s largest structural protein fermentation facility, supplying more than enough raw material to produce several thousand jackets each year. This uptick in production capacity comes, in part, because the global demand for designer biomaterials is growing; researchers can now engineer incredible control over a material’s mechanical properties at a molecular level. Fabrics derived from synthetic biology also offer sustainability at a time when a shift away from petroleum-based goods is desperately needed. Most outdoor jackets are made using nylon or polyester, both of which are non-biodegradable, derived from petrochemicals, and pollute waterways. Now, Spiber is taking its bioengineered materials to the next level. The Moon Parka marks a paradigm shift in synthetic biology and the fashion industry, where sustainability and high-performance are no longer “buzz words,” but the method of choice. Sustainable, designer biomaterials are of superior quality and soon, for the first time, they will be available in stores — and seen on the ski slopes. This jacket is not Spiber’s first fashion statement, either. They have already manufactured dozens of different garments using similar approaches – just not at scale. Last fall, renowned Japanese designer Yuima Nakazato featured bioengineered fabrics from Spiber at Paris Fashion Week. The lineup, called BIRTH (perhaps giving a nod to the future of the fashion industry?), was made almost entirely from engineered bacteria. The collection featured bold silhouettes and playful knits in muted earthen tones inspired by nature. Every piece in the collection lends credence to the power and versatility of molecular designs and the promise of synthetic biology. CONTRIBUTING AUTHOR: NIKO MCCARTY

Photo, left: The North Face Moon Parka is made with silk proteins produced by engineered bacteria. It marks a shift at the intersection of fashion and biology, where sustainability and high-performance are no longer buzz words, but the method of choice. Photo courtesy: Spiber

SynBioBeta: Where Tech Meets Bio, and Bio Meets Tech SynBioBeta unites leading biological engineers, investors, innovators, and entrepreneurs in building a better world with biology. As the industryâ&#x20AC;&#x2122;s premier annual

event, SynBioBeta showcases how engineered biology will disrupt consumer products, food, agriculture, medicine, chemicals, materials, and more.

The Coming Bioeconomy

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The last 12 months have set a new record for the synthetic biology industry, with over 185 companies raising over $5 billion in combined public and private funding. While funding continues to be strong for companies making the tools & technologies of synthetic biology, the majority of funding went into synthetic biology-enabled companies in consumer products, food, agriculture, medicine, chemicals, materials, and other manufacturing sectors, signaling the impact tech and biology is poised to have on every industry imaginable.

SynBioBeta offers a weekly digest, a podcast, a quarterly magazine, and educational courses. We also offer our world-class industry partners with opportunities for advertising, partnership, trade show exhibition, strategic consultation, exclusive networking events, and more.

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For more information, visit us at: www.synbiobeta.com

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Insulin Action Cells Illustrated by David S. Goodsell, PhD RCSB PROTEIN DATA BANK

What — and who — is synthetic biology? BY KEVIN A. COSTA

If you ask three synthetic biologists, “What is synthetic biology?”, you are likely to get four, maybe five or more answers. So what is it? Simply put, synthetic biology is an engineering approach to biology. The goal is to create and use tools that allow us to design and build functions in cells. It’s really that simple, but there’s tremendous power in that idea. Why? First, if you give cells the right mix of food, they will divide and divide and divide. Imagine that you design a cell to make a substance, such as a food ingredient. One tiny cell isn’t going to produce much. But if your little food factories divide and fill a fermenter the size of a house, then your cells are going to produce a lot. Second, cells are like little computers. They sense many factors in their environment, add those factors together, and compute the best response to their situation. Synthetic biologists can use this ability to program smart cells. For example, we can teach immune cells to behave so that if they see a cancer, they not only latch on, but also call their friends and maybe even release a cancer drug that is made within the cell itself. In the future, it’s likely that we will design cells with the ability to make many different drugs and, depending on the health

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status of the person, produce the drug that the person needs in just the right quantity at just the right time. Who are synthetic biologists? In addition to “what” is synthetic biology, another important question is “who” is synthetic biology. What kinds of people are in this field, and what are their motivations? Synthetic biology is a kind of mixture of biology, engineering, computing, and many other fields. There’s a combination of scientists (who tend to look for answers to natural phenomena) and engineers (who tend to build things). There are computer experts and microbe experts. And there are people from universities as well as small and large companies. So the people who call themselves “synthetic biologists” tend to come from many different backgrounds and perspectives. Synthetic biology tends to attract people who are curious about other disciplines and naturally open to collaborating with others. At its best, the synthetic biology community focuses on the social impacts of this technology. That includes having honest conversations about emerging issues in areas like biosecurity and biosafety. It also includes ensuring that we as a community are focused on applying our abilities to the needs of society, whether it’s feeding everyone, making sustainable materials and energy sources, or treating disease. Synthetic biology is an aspirational field, both in terms of technology and social goals. That is the kind of community we aim to foster at SynBioBeta.

SynBioBeta Community 2019 EVENT ATTENDEES

Company Size New Synthetic Biology Companies Formed

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RecentFunding: Funding: 2019 Recent 2019 Q3 Q3 Synlogic Lanza Tech Demetrix Codexis Vestaron Corp. Benchling Benson Hill Biosystems Calysta Inovio Pharmaceuticals Global Bioenergies 3fbio RoosterBio BenchSci Agrivida Arcadia Biosciences Sphere Fluidics Pili ProtienQure Puraffinity Aromyx Plastomics Lygos NovoNutrients Boost Biomes 0M

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Raised Amount $USD 64

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50M

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Where are Investors Putting Their Money? The last 12 months have set a new record for the synthetic biology industry, with 185 companies raising over $5 billion in combined public and private funding. While funding continues to be strong for companies making the tools & technologies of synthetic biology,

the majority of funding went into synthetic biology-enabled companies in consumer products, food, agriculture, medicine, chemicals, materials, and other manufacturing sectors, signaling the impact tech and biology is poised to have on every industry imaginable.

Synlogic leverages the most advanced technology platform available for the creation of synthetically engineered, therapeutic microbes with the potential to make significant advancements in the treatment of disease. On June 12th, 2019 Synlogic announced an $80 million equity investment by Ginkgo Bioworks to use their cell programming platform to accelerate the development of Synlogic’s pipeline of Synthetic Biotic medicines.

LanzaTech recycles carbon emissions to make fuels and chemicals, improving air quality and promoting a circular economy. The company raised a Series E investment on August 6th, 2019 from biotechnology investor Novo Holdings with the intention to expand its own suite of products beyond ethanol manufacturing.

Demetrix brews natural medicines utilizing founder Jay Keasling’s research from U.C. Berkeley. Returning investor Horizon Ventures led Demtrix’s $50 million Series A funding round on July 11, 2019, to further the company’s focus in brewing cannabinoids.

Vestaron, a company dedicated to improving the safety, efficacy, and sustainability of crop protection through its development of peptide-based biopesticides, announced its $40 million Series B Financing on June 10, 2019, led by Novo Holdings. Novo Holdings joins continuing investors Anterra Capital, Cultivian Sandbox, Open Prairie Ventures, and Pangaea Ventures.

Codexis, Inc. is an industrial biotechnology company that specializes in engineering enzymes for pharmaceutical and chemical production through biocatalysis. New York-based Casdin Capital invested $50 million in Codexis on June 20, 2019, through the purchase of shares of Codexis’ common stock in a private placement.

Benchling is the first modern software platform purpose-built for life science R&D powering breakthrough research on biotherapeutics, biofuels, and biomaterials at leading life science companies and the world’s most renowned academic labs. Menlo Ventures led Benchling’s $34.5 million Series C funding round on July 24th, 2019 to help them grow internationally and develop new products and services.

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Synthetic Biology Funding Synthetic Biology Funding by Stage Stage 4.5B

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CONTINUED FROM “LIVING MEDICINES”: “But at the end of the day, it only matters that you have a good product out on the market that is addressing the needs of society.”

And so from our perspective, not only do we look at speed and efficiencies, but we also look at the quality of the output that we deliver. Can you tell us about Ginkgo’s approach to partnering? Partnerships exist because you’re trying to develop products that require expertise beyond what you or your company has. To leverage that, you really need to have an open dialogue and treat your partner as an extended member of your team. This open dialogue has to continue throughout the collaboration, not just during the honeymoon phase. It has to happen when times are tough, so that you can weather the storm. When deals are signed, there’s a defined set of objectives underpinned by a technical plan that would generally guide the partnership throughout the

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collaboration. But rarely do projects progress precisely in the manner that’s originally envisioned. A successful partnership recognizes that, and both parties have to be willing to make changes along the way to get to a good outcome. A good outcome may be different than the original outcome, but it could be better than what was originally envisioned. I’ve had that happen to me a number of times. So the types of partnerships that are most successful are those that recognize one plus one is greater than two, that each party has something to bring to the table, and that we’re willing to work collaboratively during the entire process to bring a product to market. How involved does Ginkgo become in partners’ product development? We get quite involved at every stage of product development. The types of involvement change, depending on the stage of the project and the specific targets that we’re going after. But this is where the open dialogue comes in. Even with the early stages of

designing the product, we really work collaboratively with our partner to understand the problem we’re trying to solve. Often, a company will engage us with a specific set of technical targets they want to hit based on an internal project goal in mind. Those technical targets may not incorporate other possibilities that we would think about. Given the broad range of projects Ginkgo has in different areas, we may look at things from different angles and see other possibilities that the partner doesn’t think of initially. We generally start with the design specs for the technical project, then ask questions like how we get to intermediate milestones that get us to the final desired outcome, what are the different steps we want to take, how do we work with one another to leverage each other’s technical capabilities, what we know about the market and product, what downstream processes need to be performed, what type of regulatory protocols you need to adhere to, and what deployment factors we need to consider. There’s input and feedback from both parties that would influence how the project plan will be designed. Again, open dialogue becomes a very important aspect of how we leverage each other’s complementary skill sets to bring forth the synergy to ultimately deliver a successful product. How do you think the synthetic biology industry compares to, say, the Silicon Valley tech industry? There are a lot of parallels between those two markets. A lot of venture money goes into early stage emerging technologies, and you don’t know if these companies are going to make it. But there is a community in the Silicon Valley tech industry that supports entrepreneurship, encourages innovative thinking, and provides the financial horsepower to create this ecosystem that enables entrepreneurs to thrive. And so a lot of what you see happening in software tech,, you also see happening in biotech, not just in Silicon Valley but also in Boston, San Diego, Seattle, and others. Can we de-risk technical failure in biotech, pharma, and living medicines? I think there is a paradigm shift that could happen in drug discovery and development, where early-stage development is much more rooted in high-quality design. Researchers today are really focusing on optimizing a small handful of targets because they simply don’t have the tools to explore a broader range of possibilities. The scale and efficiencies of Ginkgo foundries can change that and usher in a new paradigm for drug discovery and development because we actually can explore broad biological diversity and

bring higher-quality, built-for-purpose candidates to clinic. Going to clinical trials – that’s what’s expensive. Imagine making the entire industry more efficient by bringing a lot more, higher-quality drugs to clinic that can treat diseases, many of them with no effective treatments today. What that means is that life-saving drugs can potentially be developed faster and cheaper. Now, that’s really cool and something important we are very excited to contribute. Can you speak to Ginkgo’s leadership in promoting transparency and social values within our industry? I would say that for all of us in the synbio community, we’re really excited about the new opportunities that genetic engineering is creating for many different industries. To the extent that we can bring more awareness to the great things that the technology can do and the benefits of GMO products, we are glad to do that. And as far as social values such as promoting women leaders, being transparent in our communication, and supporting equal opportunities for everyone, those are things that are important to us and are part of our DNA. We are made up of a community of people who believe in these values, and we love to share what we think and support others who feel the same. That’s just who we are. Ultimately, what we want to do is to bring good products to market with innovative thinkers. We believe there’s a lot of potential and excitement around using biology as a foundation for innovation, and we want to do what we can to realize it.

Photo, left: Designed specifically for mammalian cell engineering, Bioworks4 is Ginkgo Bioworks’ fourth foundry and seeks to create new possibilities in pharmaceutical research and manufacturing. Photo courtesy: Ginkgo Bioworks

“We found a way to temporarily solve body odor by means of an underarm bacterial transplant from a family member that does not have body odor,” he tells me. “Treatments on 17 subjects showed that we could shift the underarm microbiome to a better smelling one, which was coupled to a significant improvement in underarm odor, for up to one month.” And Dr. Armpit is not the only one interested in solving the problem of body odor through microbes. There are some microbiome-based commercial products already on the market that claim to reduce body odor and clear up acne and other conditions by re-introducing microbes that purportedly have been eliminated by modern hygiene practices, though many are skeptical, claiming that the supporting science doesn’t yet exist.

design of a personalized probiotic skin cream to relieve the most common form of eczema, atopic dermatitis. Motivated by research revealing dysbiotic skin microbiomes favoring an overgrowth of Staph aureus on individuals with eczema, Dr. Gallo went one step further and found that the skin of healthy individuals contained higher amounts of two Staphylococcus species — Staphylococcus epidermidis and Staphylococcus hominis — than the skin of eczema patients. These two species not only inhibited the growth of Staph aureus but did so without harming other beneficial members of the skin microbial community. A phase 1 clinical trial in which these two Staphylococcus species were isolated from the skin of patients with eczema and then applied to their skin in the form of a personalized probiotic lotion showed that the lotion decreased Staph aureus on the arms of eczema sufferers. Larger clinical studies are now underway.

Others are focused on more clinically relevant applications. Richard Gallo and his UC San Diego laboratory team recently reported the successful

Bioengineered bacteria may be another way to tackle eczema and other skin conditions — as well as to maintain healthy skin and prevent the development

CONTINUED FROM “YOUR SKIN: THE NEW FRONTIER IN MICROBIAL MEDICINE”: about

their body odor than men.

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of disease in the first place. Azitra, Inc., founded by a group of Yale University scientists, has developed a strain of S. epidermidis that in addition to retaining its normal anti-Staph aureus effects also secretes filaggrin, a skin molecule essential for maintaining a healthy skin barrier and preventing loss of moisture in the skin. Azitra scientists envision their bioengineered S. epidermidis successfully treating eczema and other skin conditions, as well as simply supporting and maintaining healthy skin by promoting a healthy, balanced skin microbial community. “Millions of people worldwide suffer from skin diseases with few effective treatment options,” say Travis Whitfill, Azitra Founder and CSO, who will be speaking at SynBioBeta 2018. “We hope to bring forward a novel platform using S. epidermidis to deliver missing proteins as a viable therapeutic strategy for skin diseases.” Azitra is developing an approach to tackle diseases ranging from eczema to rare skin diseases. Their success demonstrates the versatility and importance of a microbe-based platform to treat

skin disorders. To meet this vision, Azitra is working with top scientists such as Jackson Lab’s Julia Oh to enhance their platform, with human studies starting soon. The microbes that live on our skin come into direct contact with myriad things from our environment — toxins, chemicals, other microbes — and they interact with molecules produced by our own cells to help maintain a healthy first line of defense against the outside world. Considering our skin microbes — and how to keep them healthy — as we develop new cosmetics and skin treatments is sure to become a major component of future healthcare. In a world focused on the gut microbiome and how to diagnose and treat disease by targeting the microbes that live in our intestinal tracts, it can be easy to forget just how important our skin and the microbes that live on it are. Researchers like Chris Callewaert, Rich Gallo, the scientists at Azitra, and many others are leading the way into a new frontier of skincare.

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CONTINUED FROM “FIVE REASONS JEFF BEZOS SHOULD BET BIG ON SYNTHETIC BIOLOGY”:

“The level of refinement that has occurred in biological processes is an order of magnitude better than what has occurred in mechanical processes, so if we can take the lessons learned from evolution and apply it to life support systems, we can achieve higher levels of sustainability,” says Flynn. Engineers have yet found little use for astronaut feces, which account for only a tiny fraction of all human waste by weight, but this precious organic matter could be fodder for the right engineered microbes. Synthetic control over the microbial metabolism would allow for fresh products to be manufactured from this forgotten resource. 4. CO2 manufacturing Humans generate waste outside the bathroom, too. A single adult can exhale a kilogram of CO2 per day. Capturing that gas and turning it into something more useful would help close the carbon loop on any space outpost. Lanzatech, based in Skokie, Illinois, has shown that microbes in a reactor can convert carbon dioxide into ethanol, a useful fuel in its own right, but the company is also researching ways to further transform that ethanol into precursors for plastics and more. The company, which just received a $72 million Series E investment, is scaling up its carbon-capture operations in hopes of making a dent on the climate crisis, but even smallscale reactors could make an impact in orbit. 5. Send a seed, grow a house mushroom house This tiny house was built with mushroom insulation. Biology can do just about anything. (ECOVATIVE) Synthetic biology’s ultimate aim is to achieve mastery over the building blocks of life. With that mastery, all manner of new self-organizing structures could be programmed from the ground up. While this dream is still a long way out, its technological foundation is being laid today. IKEA has partnered with Ecovative to use mushroom packing for shipping furniture. This petroleum-free styrofoam alternative can be composted and even remade into new forms, slashing the waste generated by the furniture giant. Ecovative’s customers also include Dell and Crate & Barrel.

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Small startups aren’t the only ones thinking up new ways to grow habitats. NASA’s Center for the Utilization of Biological Engineering in Space, or CUBES, is working through ways of building with biology on Mars, given the red planet’s scant resources. There will be many billion-dollar manufacturing opportunities in space, but each of these synthetic biology moonshots would also improve conditions here on Earth. Who doesn’t want distributed biomanufacturing to produce new materials anywhere and anytime? ACKNOWLEDGMENT: THANK YOU TO IAN HAYDON FOR ADDITIONAL REPORTING IN THIS STORY. IAN IS A SEATTLE-BASED SCIENTIST AND SCIENCE COMMUNICATOR WHOSE WRITING HAS APPEARED IN SCIENTIFIC AMERICAN, REAL CLEAR SCIENCE, SALON, THE INTERNATIONAL BUSINESS TIMES, AND MORE. HE HOLDS A MASTER’S DEGREE IN BIOLOGICAL DESIGN AND WAS A 2018 AAAS MASS MEDIA FELLOW.

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While mycelium materials already possess better properties than other materials used in the apparel industry — particularly enhanced insulation with their MycoFlex platform for technical wear — the company is also addressing a serious, unmet need in the apparel industry with their mission for renewable biomaterials. The apparel industry accounts for 10% of global carbon emissions — the second largest industrial polluter after oil — and yet few solutions are on the table to curb the $3 trillion industry.

Photo, below: A strain of microalgae with high lipid content that is used in the manufacturing of bio-derived oils. Photo courtesy: Checkerspot CONTINUED FROM “BIOTECHNOLOGY MEETS FASHION AND SPORTS PERFORMANCE”: enhanced

insulating capabilities, and its tunable porosity to address serious challenges in biomanufacturing. Today, Ecovative Design has delivered millions of pounds of mycelium-based products to broad industries from their world-leading Mycelium Foundry in New York. MycoFlex, which is Ecovative Design’s “high-performance, pure mycelium foam” that can be used for everything from textiles to footwear, can be grown in just 9 days, and its properties tuned to specification. “The mission at Ecovative is using mycelium technology, which we view as a molecular assembly platform … to address the biggest problems facing our planet,” says Bayer. “Our MycoFlex platform, which is being used in the apparel space as leather…grows in the open air, like a sheet. [The mycelium] produce a matrix with variable porosity, tensile strength and other properties. The strain, food, and environmental conditions can all be used to influence the bulk structure properties or the properties at the molecular level to create a fully formed matrix made by nature,” Bayer explains. Published data from the company also demonstrates some of the relevant properties of the mycelium, which is a porous structure composed of tubular hypha filaments made from interlocking networks of chitin, glucan, and proteins. These data indicate that mycelium structures have “considerable strain hardening before rupture under tension” and mechanical rigidity and strength, a property derived from the chitin microfibrils.

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“In fashion or apparel, we are continuing to develop several products, including foam, like soft cushioning foam for sneakers to replace EVA foam,” says Bayer, referring to the plastic-based foam used in everything from yoga mats to sneakers. “Sneakers typically don’t last more than a year and it makes a ton of sense to have a material that is either recyclable or compostable in your sneaker, and the way EVA is combined with other materials today in sneakers means you can’t even recycle it, whereas a shoe that had an Ecovative MycoFlex cushioning section could actually be composted for the first step in recycling,” touts Bayer. Algae: Material production powerhouses While some biomaterials are particularly amenable to genetic engineering — like spider silk and protein-based materials — and others can be grown into desired structures with tunable properties — like mycelium — other biomaterials are produced by coupling metabolic engineering capabilities of synthetic strains with organic chemistry. Checkerspot, in Berkeley, California, has mastered this approach, engineering microalgae to produce bio-based oils that can subsequently be used in downstream chemical modifications to synthesize products that would otherwise be difficult to manufacture. “We use a microalgae that has a high lipid content, about 70%, to produce oils that would be otherwise difficult to manufacture by chemical means,” says Dr. Scott Franklin, scientific co-founder and Chief Scientific Officer of Checkerspot. “The strains that we use are also very robust, so we can reliably scale up production from this organism to greater than 625 cubic meters.” The apparel industry has long been plagued by a tradeoff between performance and renewability, with properties like hydrophobicity or tensile strength often demanding the use of a dangerous — or damaging — ingredient. Most athletic wear with water-repellent properties, for example, uses coatings that contains perfluorinated compounds to render them hydropho-

-8-

bic. But perfluorinated coatings are often toxic, particularly the short-chain (C6 and C8) variants, despite their ubiquity in commercial products with synthetic coatings. Checkerspot is looking to address these challenges with synthetic biology and a bit of chemistry, producing a repertoire of better, bio-derived oils to make better materials with comparable, or superior, hydrophobic properties.

Checkerspot are the rising kings in applying synthetic biology approaches to usher in a new era of apparel, where high-performance and sustainability actually coexist.

“Fluorinated coatings are used in a lot of products – apparel, cookware, yoga pants — but they can often be toxic and lose performance over time as they shed into the environment. We are developing bio-based hydrophobic coatings that do not contain fluorine and are comparable or have better properties than the leading standards … we are also working on oleophobic, or oil-repelling, products, which is a much more difficult problem,” says Franklin. Checkerspot has also supplied algal oil to one of its partners, Beyond Surface Techa substitute for palm oil — another 13 nologies 5(BST), - 8 -as13 - 21 5 - 8 - 13 - 21 - 36 ubiquitous lipid — just as the EU labels palm oil-derived biofuels as “unsustainable”. Chemical companies were also quick to realize microalgae’s unique advantages for advanced materials. For nearly a year, Checkerspot has been working with DIC, a large Japanese chemical company, on the sustainable production of high performance polyols, which are used in everything from spray coatings to elastomeric resins. While Checkerspot has proven capabilities in applying synthetic biology and chemistry to manufacture enhanced materials, they have also developed numerous tools for microalgae engineering that are vastly expanding the utility of these organisms in bioproduction. “We are really focused on producing products that are sustainable, high-performing, and can be used as a scaffold for subsequent chemical reactions — but discovery comes first. Discovery is always first,” says Franklin. In a world where organisms can be engineered to manufacture human insulin, biofuels, and even cannabinoids, the logical advancement is to think bigger — to use non-model organisms to produce renewable, macromolecular structures with defined properties and programmable behaviors. Sometimes these structures can be produced from retrofitted organisms — like E. coli and yeast for the production of protein-based materials — but other times, the “bigger picture” demands building tools for underutilized organisms, like mycelium and microalgae. Spiber, Ecovative Design, and

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CONTINUED FROM “THIS COMPANY IS ENGINEERING YOUR

AI engineering of antibodies. The company is using machine learning to make a million versions of a starting antibody, then it’s using more machine learning to figure out how to optimize the best of those antibodies even more. A number of companies are now using Distributed Bio’s system.

IMMUNE SYSTEM”:

Despite the truly amazing advances in computation, automation, and gene reading/writing/editing that enable us to begin engineering the immune system, the drug maker that Glanville is perhaps most fond of is the human body. “Your own body is a drug generation engine,” he says. “For the last 462 million years, our bodies have evolved the ability to develop antibodies. [We get sick and] within a week or two we’ve already produced medicine. It’s able to make drugs faster and better than the entire pharmaceutical industry. That’s pretty remarkable.” With the ability to engineer the human immune system, the future for medicine — and the ‘new pharma’ industry — seems bright. CONTRIBUTING AUTHOR: RODALYN GUINTO

CONTINUED FROM “TURNING GREENHOUSE GAS INTO RENEWABLE BIOMATERIALS”: initially inspired by disaster relief housing, Morse soon began thinking about plastic and polymer-based materials more broadly. What if there were a way she could create materials optimized to break down in landfills or in oceans, so that if they found their way there, they wouldn’t add more insult to our already injured environment?

And that’s how Mango Materials was born. With first funding from a National Science Foundation grant in 2012, Mango Materials focuses on the production of PHAs from methane and biopolymer formulation. Typically, plastic pellets (also known as chips) are melted down to make something — film for plastic bags, or fiber for yoga pants, for example. At Mango, biodegradable PHA serves as the backbone for an alternative plastic pellet, which is optimized for biodegradability while preserving optimal mechanical characteristics. So, whether you’re using a plastic bag for your groceries or a case for eye-shadow, Mango Materials is developing a product you can use guiltand worry-free. The Mango team is always thinking about the “end-of-life” or the “design for next use” of their products — where they might ultimately end up; for example, a wastewater treatment plant or the ocean. “We spend a lot of our time looking at biodegradability in anaerobic environments, marine environments, backyard compost,” says Morse, “making sure that it’s completely digestible, making sure there’s no intermediate that could be persistent, or that you’re not inversely having something that’s toxic accumulating.” This all sounds fantastic for the environment, right? Indeed, Mango Materials is helping fill the need for greener materials that won’t pollute the Earth’s ecosystems — but they’re doing it in a way that also uses methane, a greenhouse gas, as a feedstock — a two-for-one punch as it were. Or, as Morse calls it, Mango’s “gift with purchase.” The case for methane Using microbes to ferment a gas instead of sugar is no easy task. You have to jam the gas into solution so that it can be taken up by microbes, and the microbes that Mango uses require both methane and oxygen — a potentially explosive mixture. Not just any bioreactor can handle gas fermentation, which is why the Mango team has their own fermenter design. So why all the trouble? Why not make PHAs using sugar fermentation instead?

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“If you look at the carbon conversion of using methane as a feedstock, it’s significantly favorable to be using methane — especially if you look at the price, dollar per gram of carbon and methane and you convert that to dollars of sales from the PHA,” says Morse. Specifically, two-to-three pounds of methane is needed to produce one pound of PHA. There is also no need to ensure a “clean” input — dirty gas can be pumped directly into the system without the need for pre-treatment like traditional feedstocks. And there is the capability to go big with methane — there is no shortage of it. For now, Mango Materials is partnered with Silicon Valley Clean Water, the wastewater treatment facility in Redwood City, CA (in fact, they are located adjacent to the anaerobic digester) — but that will quickly change once the company has scaled up their processes. “We have a lot of interest from methane producers, not just from anaerobic digesters, but also from landfills, abandoned coal mines … it’s an issue for these producers what to do with their methane,” says Morse. Which leads us to perhaps the most obvious advantage of all to using methane as a feedstock: when your feedstock is recycling a greenhouse gas that is 30 times more harmful than carbon dioxide, it seems like a no-brainer. Leading the way in clearing consumer confusion Morse is careful to emphasize that while the company is creating products optimized for the “what-if” scenario, that doesn’t mean that Mango Materials condones or encourages dumping of materials where they don’t belong. One of the reasons irresponsible dumping continues to happen is consumer confusion around what plastics and polymers even are — a confusion that is aided in no small part by deceptive advertising and flip-floppy legislation around terms. Morse has seen some companies advertise a product that’s compostable in the ocean — impossible, as compost is an environment, not a process per se. Instead, things are biodegradable in the ocean, biodegradable in compost environments — so such labeling, which contradicts other labels and terms consumers may see, only adds to the confusion. Some of the legislation that State of California has enacted around plastics and polymers also leads to confusion, with terms being used interchangeably (and incorrectly) depending on where the technologies are based from or what they’re targeting, says Morse. And she hopes to change all of this.

“This is something that we want Mango Materials as a brand to really be a leader of — it’s extremely important to us that Mango Materials is seen as the solution to biodegradable materials, or at least a trusted source of information.” This is not a chunk that most companies bite off, and indeed Morse has been advised not to engage in policy and public education. But to Morse, this isn’t an issue that is up for debate — she has seen the confusion surrounding GMOs and how that has harmed consumer acceptance of elegant food solutions to some of the world’s most pressing problems. “It’s not too late [for bioplastics],” says Morse, “we’re not to the point yet, that gene editing, GMO have [where] there’s this negative connotation.” And, if she meets her goals, perhaps we will never reach that point. One thing is for certain — if Mango Materials is to succeed both in ushering in the next generation of biodegradable materials and improving consumer understanding around bioplastics — it doesn’t stand a better chance than it does with Morse at the helm. The challenges she has faced to get Mango off the ground are many: she’s using a novel feedstock and a methanotrophic organism that isn’t heavily industrialized, a non-drop-in replacement polymer, a biological technology in Silicon Valley (“we’re not an iPhone app,” says Morse), and she’s a PhD trained engineer (which, she says, causes many investors to turn a deaf ear because you’re viewed as being “too nerdy”). Oh, and she’s a woman who’s managed to command the attention and respect of CEOs and entrepreneurs around the world — even those from countries where women don’t have the rights to lead companies. “For better or worse, people remember me,” says Morse. “Maybe I just have tough skin,” she adds, laughing. Or maybe, just maybe, she has a technology that will help save the planet.

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CONTINUED FROM “HOW BIOMANUFACTURING CAN MAKE LIVING ON MARS A REALITY”: CUBES

initially came to life when Amor Menezes, then a postdoc with Arkin and now at the University of Florida, brought Arkin’s attention to the potential impact of controlled cellular engineering in space. Menezes, who will also speak at SynBioBeta 2019, and Arkin, eventually teamed up with SynBioBeta CEO John Cumbers, among others, to explore how biology could benefit space travel. But as with many space-related innovations, astronauts don’t have to be the only ones who benefit. Many of CUBES’s projects could have tremendous impact on our home world. Space science: not just for space As Earth’s population climbs and resources dwindle, biopharmaceuticals, advanced hydroponics, and bioengineered crops are urgently needed in addressing our growing crisis. But the focus in developing these technologies is often aimed towards the stars. The dire needs of the present are often overlooked for the exciting opportunities of the future. Arkin points out, however, that the aspirational aspect of space travel is a strong force in driving innovation.

I think space travel has always been about overcoming the limitations humankind has. We want to go beyond where we have gone before, and it provides a necessity which breeds invention. The CUBES mission will be complete in five years. If all goes well, the result will be a fully integrated Martian bio-system. No, the system won’t be headed to Mars on the next flight out. But ideally, it could be tested on a lunar station. After all, with private companies in this new space age, “it may be that the moon is in an Amazon delivery neighborhood,” jokes Arkin. But there is more to CUBES than building practicable models or even developing novel technologies. At its heart, CUBES is also about inspiring the next generation. Many of the CUBES team are students, just beginning their scientific careers. “There are moments in time in human development when people can be really inspired,” says Arkin. “Some of the best moments are when people are just entering or just exiting college and they can see all that potential laid out in front of them.” For Arkin, it’s not just the science at CUBES that will build the future, it’s the integrated community of people who are making it possible.

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Good Genes Magazine, Fall 2019, Volume 1

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Why the Future will be Written in DNA