Space & Regenerative Medicine

Home , Spire Global, Tom Mueller

“Tough Tech means tackling the problems of of the problems tackling means Tech “Tough to resource-intensive |“It’s today.” tomorrow, bring worthwhile to market but pursuing for its tech and “It’s | to humanity.” value transformative thinking about “It’s | ambitious.” their most VC at about |“It’s second.” and profits first, problems rather be met, must that addressing the challenges it harder, “It’s | are easy to solve.” than those that |“It’s are higher.” the payoffs but can take longer, desire to design solutions to seemingly an insatiable |“Unapologetic persistence. impossible problems.” deep societal need.” a moonshot based in It’s yielding significant, fundamental innovation, |“It’s + | “Technology game-changing breakthroughs.” “Changing the vector untraditional thinking.”| it initially |“Something so far off that of society.” the where at a café, paper napkin at on a lives |“When you time the sketch seems absurd.” not it’s the world, start-up can change your say world- high risk, |“High tech, an exaggeration.” often technologies, |“Tangible changing rewards.” long- to solve steeped in material science innovations, the estimated |“Take term problems.” real-world and commercialize time and money to develop Pi.” by the technology and multiply them both We asked attendees of the inaugural Tough Tech Summit what Summit Tough Tech the inaugural of attendees We asked responses. their some of These are them. means to Tech” “Tough

Tech We invest in founders who are working on scientific breakthroughs and converging technologies that founders. hold the potential to change the future. TOUGH TECH SUMMIT | 9 |

Katie Rae CEO & Managing Partner, The Engine CEO & Managing Partner, Jake Belcher Jake

Photos by We’ve seen, first hand, the desire for Tough Tech. We’ve seen, first hand, the desire for our job to help Collectively, as an ecosystem, it’s To help them founders in any way we can. To say yes. we all win. learn and thrive. Because if we do, We have a portfolio of 14 founder-led companies and We have a portfolio of 14 founder-led startups. a network including 23 other Tough Tech We are seeing industry, academia, investors, in—recognizing entrepreneurs, and government leaning these founders. that our collective future rests with Today, both are happening. When we founded The Engine, we had two goals. The When we founded The in and work with founders first was to invest breakthroughs and converging creating the scientific hold the potential to change the technologies that was to convene those who wanted to future. The second these founders solve society’s collaborate in helping most important problems.

Movement Movement to Tough Tech Tech to Tough Moment Moment Tough Tech Tech Tough From From

TOUGH TECH 02 | 8 | Why

It was Rafael Reif, the President of MIT, who, in 2015, first suggested Hans Peter Brøndmo continued the conversation with stories, data, and the idea of an innovation orchard to provide “physical space, lessons focused on a Tough Tech company’s human element, reminding Tough Tech mentorship, and bridge-funding for entrepreneurs”—the seed of which the audience that intentionally creating a culture of audacity helps would become The Engine. He, along with Katie Rae, The Engine’s inspire the novel thinking that can solve our toughest problems. CEO & Managing Director, kicked off the Summit, reflecting Sue Siegel concluded the keynote session with perspectives on how Matters upon the intersections between academia, venture capital, strategic one of the world’s largest corporations can help foster Tough Tech corporate partners, and government. innovation at scale using lessons from its past. TOUGH TECH SUMMIT | 11 TOUGH TECH 02 | 10

THE ROLE OF INVESTORS THE ROLE OF ACADEMIA THE ROLE OF TALENT THE ROLE OF CORPORATES Katie Rae L. Rafael Reif Hans Peter Brøndmo Sue Siegel

CEO and Managing Partner, The Engine President of Massachusetts Institute of Technology Robotics Project Lead, X, Chief Innovation Officer, The Moonshot Factory (formerly Google [x]) GE and CEO of Business Innovations

“The Engine follows the lead of “Research universities bring together “New ways of thinking about old “The pace of change will never be as our founders. Their vision of the talented people from around the world. problems—that’s what Tough Tech is slow as it is today.” future is born out of deep research And they empower them by providing the all about.” and knowledge about how the world expertise, experience, and resources “I’ve learned that [Tough Tech] is one should look. They’ve spent years if they need to innovate … and deliver “Start with just a vague inkling of the most inspiring things that you not decades to bring the technology their solutions to society. That is that it may be possible.” can do.” to the point that it is ready the role of academia in the Tough to commercialize, and they are Tech movement.” “Fall in love with the problem, “Tough Tech is not about financing and dedicated and motivated to face the not the technology.” technology alone, it’s the ecosystem challenges to make it a reality. “We believe in the tremendous that has to be developed.” They are on a mission.” potential that Tough Tech has to do “Take it to the real world early.” good in the world.” “Stay curious and humble.” “Working in partnerships does not come easy to those that could before, to those that didn’t have to before.” TOUGH TECH SUMMIT | 13 | Beers Bottles of wine 1 Column Sculpture

25 37 The Engine Network Tough Tech Startups 28 Wireless Microphones 160 Drinks 135 15 Palm Trees Prosciutto sanwiches Salads Turkey sanwiches 9 75¨LCD Monitors 130 6 CatchBox mics

4 10,000 Lumen laser projectors 22 Tabletop Succulents 325 Lunches 130 65 3 The Engine Network Strategic Corporate Members 20 Leaders Academic

450 Paddles 3 27 Leaders Confirm & Complicate Corporate AFTERNOON TRACKS IN PARALLEL AFTERNOON TRACKS IN PARALLEL 29 Speakers 1 31 Breakthrough Tough Tech Lunch Session Energy Ventures 29 Startups Posters Investors 3 Tough Tech Summit Sponsors

135 Founders

3 Keynote Speakers

MORNING TRACKS IN PARALLEL MORNING TRACKS IN PARALLEL

366

Attendees

Tough Tech Summit Partner 1

Tough Tech Summit Summit Tech Tough by the Numbers the by

TOUGH TECH 02 | 12 | TOUGH TECH SUMMIT | 15 |

Transforming Academic Leaders Leaders Academic Transforming in Business Leaders into Ilan Gur | Moderator Cyclotron Road Director, Executive & Founder Nabiha Saklayen Cellino & CEO, Co-Founder Bilal Zuberi Lux Capital Partner, Weitekamp Raymond polySpectra CEO, & Founder Chiang Yet-Ming of Materials Professor Science and Kyocera Energy Form Co-Founder, MIT, Engineering, Takeaways There is usually a “crisis moment” that catalyzes the transition of an academic into a business leader. A certain level of self-awareness helps navigate what can be a humbling transition. Founders should be dreamers, not realists. They should sell their vision. After all, most startups fail due to reasons other than their technology. “Why are you the right person to tackle this problem? The answer can’t be ‘because I was the grad student that invented this.’ The answer has to be ‘because I’m the right person to pull together all the resources.’” “It’s about problem definition before technology definition.”

Building and Nurturing Strategic Successful Partnerships Ann DeWitt | Moderator Ann DeWitt The Engine Partner, COO & General Bob Mumgaard & CEO, Co-Founder Fusion Systems Commonwealth Mick Mountz Systems Kiva CEO, & Founder Charlie Purtell Science Danaher Life Ventures, VP New Center Innovation Russ Wilcox E Ink & CEO, Co-Founder Former Pillar; Partner, Khalil Iya & Chief Commercial Officer, Co-Founder GNS Healthcare Gammell Dave Partner, WilmerHale Takeaways “Your strategic partner most often ends up shaping the way you build your product and your company. Nurturing such a relationship at all levels is paramount.” “Ask why. Then shut up and listen.” On negotiations: set principles and goals internally, then look for alignment of business interests and those goals. A deal is a dynamic process, pace yourself and your concessions. Don’t be afraid to play the startup card. Moderator

GE Ventures GE

Managing Director, Takeaways Family offices and high-net-worth individuals have high alignment, in particular, with Tough Tech— entrepreneurs take note: these segments are critical components of the funding ecosystem. The presumed capital intensity of Tough Tech makes small investors uncomfortable. But it is important to note that not all deals require massive amounts of capital. It’s imperative that larger investors make the importance of smaller investors known. “The notion of chasing early returns in software is tired. There is massive opportunity in Tough Tech. The competitive sets are smaller, and markets are bigger. All venture capital firms need to lean in to Tough Tech.” “Paying attention to the consumer is important, even though that’s not always in the main corporation strategy. Every business ends with C, even if it is a B2B.” Funding Tough Tech Tech Tough Funding Stage Every At Carmichael Roberts | Member, Breakthrough Energy Ventures Ventures Breakthrough Energy Member, Rae Katie The Engine CEO & Managing Partner, Zahler James Technology-to-Market, Director for Associate ARPA-E Grayson Dayna New EnterpriseAssociates Partner, Daniel Hullah

strategic partnerships. including funding, leadership, and leadership, including funding, the complex transition to market, to market, transition the complex on sessions focused on managingon sessions focused Tough Tech leaders moderated hands- leaders moderated Tech Tough

Building Company

TOUGH TECH 02 | 14 | TOUGH TECH SUMMIT | 17 |

Stan Lapidus Lapidx Research Managing Director, Tribble Theresa EverlyWell Chief Business Officer, | Facilitator Ann DeWitt The Engine Partner, COO & General Takeaways Determining an appropriate if product / market fit is easy, speak you listen. Founders should to the consumers of their product without selling anything, just listen and ask questions. Start with data, make a hypothesis on early customers, define the product, make sure that fits the market. This can be a messy process. Define when to “kill”, “improve”, “launch”. If not, it’s too easy to convince yourself that the data is good enough. “Sometimes you think you have a product and you think you have a market, but you really don’t have either.” Strategies That Inform a Inform That Strategies Fit Product/Market Successful

David Bradwell David Ambri and CTO, Co-founder Michael Kearney MIT Sloan School of Management | Facilitator Sturtevant Reed The Engine Partner, General Takeaways In an effort to de risk the to market, founders often have make suboptimal choices related to technology development. Founders need to be aware of the intrinsic trade-offs and balance the relative value of de risking the market with the relative value of de risking the technology. Investors should be aware of these trade-offs, as well, and ensure that founders are not pursuing sub-optimal paths simply because of perceived pressure from the investment community. “Market choices don’t happen in a vacuum, your technology trajectory is fundamentally dependent on the market you select.” “So many technologists have to deal with the challenging question of at what size they should scale their technology.” Managing the Tension Between Between Tension Managing the Demands R&D and Market

Supply Chain Strategy and Its Strategy Supply Chain on Commercialization Effects Munnelly Kevin in Residence, Executive Biological Engineering Ventures Sean LeBlanc DNA Synthesis Operations, Director, Bioworks Ginkgo | Facilitator Wayman Libby Breakthrough Energy Ventures Takeaways Supply chain strategy must be a part of a founder’s business strategy as early as possible. Founders should not think of corporate partners as slow and predictable—many of these companies may be in flux. Such unpredictability can affect a partnership and operating behavior in unexpected ways. “Allocating the resources to fix an unsound supply chain strategy can run into the 10s of millions of dollars. Redoing this work could spell the end of the venture.” “Founders should seek out supply chain advisors with diverse opinions and different areas of expertise.”

operating a Tough Tech company. Tech operating a Tough challenges of building, scaling, and scaling, of building, challenges and productive dialogue about the dialogue and productive companies, fostering an honest companies, pivotal moments within their own their own moments within pivotal Founders presented case studies of presented Founders Case Studies Case Product Strategy Product Technology & & Technology TOUGH TECH SUMMIT | 19 |

Breakthrough Energy Breakthrough Lunch Session Breakthrough Energy shared its model of linking government-funded research with risk-tolerant capital to bring clean This faster. to market energy innovations by a discussion followed introduction was with providing associated of the challenges durable food, healthy reliable electricity, and convenient comfortable buildings, goods, transportation to everyone on the planet without contributing change. to climate

TOUGH TECH 02 | 18 | TOUGH TECH SUMMIT | 21 | Co-Founder, Applied Invention Co-Founder, Danny Hillis Danny “Anybody who undertakes one “Anybody who undertakes Tech problems of these Tough some sense, is really, in foolish. doing something There are much easier ways to make money. But it turns out that the things that really change the world are those tough things. Even though it’s kind of crazy, and even though you’re likely to fail, those are the only things worth trying for.” “I learn more from things that don’t work out.” “The time you’re least paying attention to cash, is the time you’re most vulnerable for it. The lesson: have more cash than you think you need, especially if business is growing rapidly.” “Tough problems attract great people, who continue to thrive and work together.” Jason Kelly Bioworks Ginkgo CEO, could be “Tough Tech that successful the basis for abundant. The corporations is Tough Tech challenge is that requires deep, specialized knowledge. The reality is, you’ve got to know what the hell is going on.” “To me, the only example of functioning early-stage hard tech capital is in pharmaceuticals.” “Don’t be afraid of government funding.” “How to solve the missing early capital in Tough Tech? Hustle. Enable non- specialists to invest before technical de-risking with other validation.” Co-Founder & CEO, Accion Systems & CEO, Co-Founder Natalya Bailey Natalya “Almost everything you do at“Almost everything company willan early-stage sale, orbe a negotiation, canskills you These are both. learn and get good at. And they will be relevant to your time as a startup executive.” “The theme that’s been true for me [as a founder], and perhaps for the technical folks coming from labs, is that people have been the hardest part. Not the technology itself.” “Whether you’re a PhD student or a startup founder, you have to believe that the world truly needs your solution, and if you’re not going to do it, than somebody else will because the need is so real and powerful.” “Every company is a hypothesis that requires capital to test. And by the way, that capital has an opinion.” “If you do what everyone else does, you shouldn’t expect any different outcome.” “At some point in the lifecycle of your company, this becomes true: market value ∑ good decisions dv - ∑ bad decisions dv.” Tillman Gerngross of BioengineeringProfessor at & Co-Founder Dartmouth College; Adimab CEO, Ric Fulop Metal Desktop CEO & Founder, “Businesses that have a single or small number of customers are not good for venture returns. You have the consolidation of pricing power in the hands of few people. You want to work on products that have lots of customers.” “It’s all about people and team building. My management team has built their own teams—try to build a team of people who can create outsized returns, then they hire like that.”

Tough Tech companies. Tech Tough journeys of as founders from their respective from their respective lessons, and perspectives and perspectives lessons, shared candid moments, shared candid moments, these five founders these five brightest rising stars, brightest rising stars, and two of Tough Tech’s and Tech’s two of Tough Three industry veterans Founders Five Tough Tech Tech Tough Five Perspectives from from Perspectives

TOUGH TECH 02 | 20 | TOUGH TECH SUMMIT | 23 |

science, technology, and impact. and impact. technology, science, mingle, meet the companies, and learn about their meet the companies, mingle, hallways of the Tough Tech Summit. Attendees could Attendees Summit. Tech Tough of the hallways within The Engine Network, were displayed in the displayed were The Engine Network, within These posters, featuring Tough Tech startups Tech Tough featuring These posters,

Tough Tech Startups Tech Tough Connecting with

TOUGH TECH 02 | 22 | TOUGH TECH 02 | 25 | Hyalex HyperLight Inkbit ISEE Kebotix Kytopen Landsdowne Labs LECT Lightmatter Metalenz NBD Nano Portal Instruments Radix Labs RISE Robotics Suono Bio Vaxess Vesper Via Separations Zapata Computing

Commonwealth Fusion Systems DOTS DropWise E25Bio FemtoDx Form Energy Formlabs Fortify Gelsight Accion Systems Ambri Analytical Space Asimov Boston Metal C2Sense Cambridge Crops Cambridge Electronics Cellino Tough Tech Strategic Corporate Members Members Corporate Strategic Tech Tough 2018) (as of November Startups Tech Tough 2018) (as of November The Engine Network is driven to build long- is driven The Engine Network between relationships term, mutually beneficial corporate startups and strategic Tech Tough a sustain and members, in turn helping create the region. throughout movement Tech Tough kickoff the formal October 28, 2018 marked at with a gathering Network The Engine of The Engine in Cambridge, MA. founders Both participated in roundtable and corporates exercise. / offer” discussions and an “ask with the evening left members Network insights, and productive relationships, new forward. actionable paths THE ENGINE NETWORK ENGINE THE

TOUGH TECH 02 | 24 | TOUGH TECH 02 | 27 | As with our first publication, the following sections tell storiesfollowing the As with our first publication, Tech Tough most dynamic of today’s from the front lines of some of NewSpace they explore the worlds In this case, industries. 02 concludes with a Publication medicine. and regenerative The Engine and companies within the on the founders feature Fund Portfolio.

Tough Tech Summit 02. October 24 & 25, 2019 the most exciting thing of all. As Hans Peter Brøndmo remarked in his As Hans Peter Brøndmo remarked in his keynote, “We have just a vague inkling of what may be possible.” And that’s intended to forge some tidy solution intended to forge problems. It was to solving the big To unite the designed to convene. most visionary brightest minds, the most experienced thinkers, and the they could hear entrepreneurs so that faces to names, from each other, put started. and get the conversation That it did. The Tough Tech Summit was never The Tough Tech Summit

TOUGH TECH 02 | 26 | NEW LEASE ON LIFE | 29 | Image courtesy of: Cellino courtesy of: Image Human induced pluripotent stem cell-derived skeletal muscle cells. The red and Human induced pluripotent stem cell-derived skeletal muscle cells. The Chain, respectively, and the nuclei are stained blue with DAPI. and green stains are for skeletal muscle-specific proteins MYOD1 and Myosin Heavy and green stains are for skeletal muscle-specific proteins MYOD1 and

Why Why medicine regenerative is finally poised to reach its potential. By Michael Blanding for The Engine by Danilo Agutoli Portraits

Life

Lease New

TOUGH TECH 02 | 28 | NEW LEASE ON LIFE | 31 | Jerel Davis Jerel Bob Nelsen, Bob Doug Melton Co-Director, Co-Director, David Scadden Versant Ventures Managing Director, Managing Director, ARCH Venture Partners Harvard Stem Cell Institute Harvard Stem Cell Institute Harvard Stem Cell In addition to the work in producing to the work In addition stem of today’s Despite the novelty The first bone marrow transplant fundamentally revolutionize how we we how revolutionize fundamentally therapeutics.” develop companies says, Davis new cell therapies, to mass-manu- new ways are developing and regulators are becom- facture them, putting them, ing more open to approving the cusp of a gold- science potentially on “Every medicine. en age of regenerative - body is a new plat cell type in the human While he says. form new therapeutics,” for making huge strides been scientists have in petri new stem cells in creating dishes, is to figure the challenge now however, bodies to get them into human out how “The part that where they heal patients. “is Nelsen, says happened yet,” hasn’t and to really understand to deliver how ” target all of these cells in vivo. known scientists have cell therapies, about the role of stem cells in animal 100 years. embryo for over development biologists had begun By the 1950s, types of stem exploring the role of two - hematopoi cells in human bone marrow: new which create etic stem cells (HSCs), stem cells and mesenchymal blood cells; and bone, which grow new fat, (MSCs), cartilage cells. suffering patients from blood to treat cancers in the such as leukemia began years afterwards, many For 1950s. late bone marrow transplants have however, since of last resort, remained a treatment existing im- it requires killing patients’ chemothera- mune system with intensive py or radiation before transplanting new py or radiation cells. healthy can create stem cells that 60 percent when only Survival were rates they first started, rising to 85 percent to- those who survive can ex- and even day, perience including stunted complications brought “We and infertility. development David says people to the edge of death,” Co-Director of the Harvard Scadden, Recently, however, scientists and however, Recently, The Magic ofThe Magic Cells Stem as a me- long been seen have Stem cells unlocking the potential dicinal cure-all, “In a heal itself. of the human body to pharmaceutical,” the ultimate it’s way Managing Director Nelsen, Bob says which has Partners, Venture ARCH at co-founded stem funded Semma and “You Therapeutics. Fate cell company or disease, or prevent disease, can treat Despite reverse aging through the cells.” regenerative the promise of so-called to has yet the reality however, medicine, Beset by the contro- up to the hype. live research embryonic stem cells, versy over lagged throughout the into treatments Artificial using organs created 1990s. Biologistsstem cells simply fell apart. to protect stem struggledways to find by the hosts cells from being attacked while timelines tryingthey were to heal, optimistically predicted a few years stretched into ten or more. hope for seen new entrepreneurs have emerged to as techniques have the field, Since stem cells without embryos. create expedited cell trans- scientists have 2013, formation using gene editing technology a technique to identify CRISPR/Cas9, and replace specific snippets of DNA which functions like using guide-RNA, little zip codes to find the place in right the DNA strand to precisely change the technology, Along with that genome. new high-throughput screening tech- biologists to rapidly allowed niques have test multiple molecular compounds to constantly try “We transform stem cells. to gaze into a crystal ball and understand is going to be the next frontier in what Managing Davis, Jerel says medicine,” Director which Ventures, of Versant BlueRock helped found the company put we “A few years ago, Therapeutics. medicine on our list as an regenerative is going to something that inevitability, “It’s not going to happen in a couple of to happen going not years, “It’s but if with modification genetic we can combine to make cells, the change it could the ability ofpractice medicine.” - Beta cells aren’t the only stem cell ther- Beta cells aren’t potential market for such a therapy is up to 40 million Currently, enormous. dia Type-1 suffer from people worldwide betes, spending some $17 billion a year spending some $17 billion a year betes, In order to achieve on insulin injections. will company Melton’s however, success, to not only produce viable human have also ensure they produce but beta cells, the right amount of insulin in the body, and protect the cells from being rejected they are tryingby the patient to help. are currently promise. apies that showing Other researchers—many in the Cam- bridge and Boston area—are using gene techniques to editing and other advanced turn stem cells into heart and neu- muscle damaged cells could regenerate rons that already used stem They have in the body. cure some rare diseases cells to effectively therapies Such regenerative of the blood. could produce new transplantable organs “I diseases incurable today. cure and even within this is achievable honestly believe not going “It’s Melton. says our lifetime,” if we but to happen in a couple of years, withcan combine genetic modification it could change the ability to make cells, the practice of medicine.”

In 2015, Melton’s lab reported a Melton’s In 2015, Harvard Stem Cell Institute, Melton has Melton Harvard Stem Cell Institute, placed his hopes on a bold proposition: the beta using stem cells to regenerate cells within the body to produce more the hall from Melton’s Down insulin. lab technicians inside a beta-cell office, “foundry” take stem cells—cells which a spe- into differentiated not yet have cific tissue type—and subject them to a complex recipe of small molecules and After some 15 different growth factors. the solution resem- six weeks, steps over bles pink strawberry soda containing tiny each cluster holding flakes, snow-globe some 6,000 cells. of the first the creation breakthrough: when injected into functional beta cells, them to produce allowed diabetic mice, demonstrating insulin for six months, a cure for the disease might be that can we the question is, “Now possible. to put it into humans?” figure out how a company, He created Melton says. Therapeutics (named after this Semma children Sam and Emma) to test that $150 million in raising over question, with hopes to go into clinical funding, The years. trials within the next two

wenty-seven years ago, years ago, wenty-seven son Doug Melton’s up sick and Sam woke and he up, throwing and his wife rushed

T The next year, Melton completely The next year, changed his research practice to focus on a proj- finding a cure for the disease, became more urgent when his ect that a diagno- daughter Emma also received Co-Director of the Now age 14. sis at their six-month-old baby to the hospital. their six-month-old baby to the hospital. them a sober diagnosis: A doctor gave meaning his 1 diabetes, Type Sam had the beta cells in his attacking body was Without produced insulin. pancreas that survive. he wouldn’t regular injections, The pronouncement sent the family into a six-month-old son, have “You turmoil. stop coming to tell you, and they can’t me in the middle of the night and prick- Melton, says needle,” ing me with that then a Harvard biologist researching frog what to watch “They have development. measure their blood sugars, they eat, At what with insulin. inject themselves child the respon- your give age do you if that knowing on, sibility to take that they will die?” they don’t, N

TOUGH TECH 02 | 30 | NEW LEASE ON LIFE | 33 | photo by Doug Levy. Marinna Madrid, Co-Founder, Cellino & Nabiha Sakyalen, Co-Founder & CEO, Cellino Marinna Madrid, Co-Founder, Cellino & Nabiha Sakyalen, Co-Founder & Jaensich, now at MIT’s Whitehead MIT’s at now Jaensich, Researchers using all of are now Other clinical trials are currently patient’s own blood or skin cells, without cells, blood or skin own patient’s embryos all. any at the first was to use iPSCs Institute, in 2007 when, therapeutically in animals the University of Townes Tim along with able he was Birmingham, Alabama at of tail of a mouse to take cells from the and suffering sickle-cell anemia, from The stem cells. induce them to become researchers the cells differentiated then HSCs without the sickle-cell into healthy and inserted them into the mutation, new creating bone marrow, mouse’s red blood cells. healthy MSCs, these kinds of stem cells—HSCs, medicines and iPSCs—to develop ESCs, Donald diseases in humans. for treating has genet- for example, Kohn of UCLA, ically modified patients’ own HSCs to ically modified patients’ adenosine deaminase-deficient se- treat combined immunodeficiency (ADA- vere as bubble-baby also known SCID), inhibition of the disease due to its severe can make a com- immune system that he announced Last year, mon cold fatal. nine out of ten children in clinical that trials cured from the disease. were genetical- own to use patients’ underway other blood ly modified HSCs to treat disorders such as sickle-cell anemia and - beta thalassemia in the same way—re genetically stem cells, patients’ moving and then returning modifying them, them to the body where they will hope- red blood cells. fully produce healthy three companies—Intellia Currently, Therapeutics, CRISPR Therapeutics, and Editas Medicine—are using CRIS- PR technology to edit the DNA in HSCs The Switzerland- and diseases. to attack Cambridge-based CRISPR Therapeutics in a new clinical began enrolling patients HSCs of pa- trial in October to remove genetically tients with sickle-cell anemia, modify them to correct the mutation them from holding enough prevents that John Gurdon of the University of Gurdon of the University John and Kazu- Yamanaka Enter Shinya own DNA or cells, then the body would then the body would DNA or cells, own theoretically accept the cell as its own. Cambridge able to in the UK had been DNA transfer into stem cells that show by insert- decades earlier, possible was ing the DNA into an embryonic stem into which successfully developed cell, By the 1998, a clone of an adult frog. embryonicscientists had isolated stem At the time, cells (ESCs) in humans. the use of over controversy however, human embryonic stem cells threatened medicine research, to halt regenerative and others began searching and Jaenisch stem cells that to create for a new way using human embryos. involve not would experiments that had shown Gurdon’s the body had within it all of cell in any the genetic material necessary to create cell. other any As in the early 2000s. Takahashi toshi in Japan, University researchers Kyoto at genes that they identified just four active cell pluripotent, could together make any of an the equivalent essentially creating embryonic stem cell from an adult cell. the firstThey created induced pluripotent stem cells (iPSCs) from both mice - Ya (Gurdon and and humans in 2006. manaka shared the Nobel Prize for these just invention That in 2012.) discoveries a decade ago opened the floodgates over that showing medicine, in regenerative stem cells from a scientists could create Jaenisch and Beatrice- Mintz succeed Jaenisch a retrovirused in using a to substitute of mouse DNA in the nuclei sequence of permanentlystem cells in order to alter “knock-in” first This their genome. possibilities for mouse opened up new one of its overcome stem cell therapy to primary the fact new that challenges: cells inserted could be into the body leading system, rejected by the immune as graft-to a serious known complication If stem versus-host disease (GVHD). a patient’s from cells could be created If stem cells could be created from a patient’s own own If cells could be created stem a patient’s from would theoretically cells, the body then or DNA the cell as its own.accept Scadden is now examining ways to ways examining Scadden is now Like Melton, Scadden was motivated motivated Scadden was Like Melton, Cellular Transformations Cellular therapies have Other regenerative focused not on injecting stem cells into on transforming but stem cells the body, into other cell types to repair damaged Rudolph In 1974, cells within the body. treat cancer cells—not by killing them, cancer cells—not by killing them, treat them as stem cells that treating by but If been stuck in their development. have “change the neighborhood” doctors can with drugs to alter the chemical makeup cancer treating “maybe niche, of a cell’s pounding it into oblivion with about isn’t by releasing “but he says, a hammer,” has caused it to be stuck. the brake that a cancer cell is not a rogue cell, Maybe has some normal a cell that but features, has been corruptedbut in its differenti- has caused that programation in a way By way.” it to grow in an unregulated exposing them to the right environment maybe—they maybe—just of chemicals, can be reformed to become healthy Through a contributors to the body. he co-founded named Magenta company to he has been working Therapeutics, medicines. develop to study stem cells through a personalto study stem cells through the pain his mother un- connection: He strugglingderwent with leukemia. currently much of his time in the spends and better safer lab focused on creating marrowtechniques for bone transplants Scadden is focusing on cancer. to treat unique chemical the “niche,” the HSC within the bone marrow environment Based on stem cells to thrive. allows that the analysis of high-throughput chemi- his lab is trying cal and genetic screens, in a dish environment that to recreate in order to make more stem cells that a a long time it was “For function better. in the field whether cells had their debate internal their own logic and followed that’s “But Scadden says. program,” own they that able to show were We not true. they listen to themselves; govern don’t If a neighbor- the signals around them. it can corrupthood goes bad, a cell.” Stem Cell Institute, whose office is one whose office Institute, Stem Cell almost was “It Melton’s. from floor down But ethical. was what the bounds of at miraculous.” it was when it worked

TOUGH TECH 02 | 32 | NEW LEASE ON LIFE | 35 | Stan Wang Paul Laikind Paul CEO, ViaCyte CSO, ViaCyte Kevin D’Amour Kevin Co-Founder & CSO, Cellino Co-Founder & CSO, In the meantime, it started pursuingIn the meantime, Eduardo Cedar-Sinai’s In 2009, it works with W.L. Gore, the makers of Gore, W.L. with it works design a fabric to for resisting Gore-Tex, the foreign-body response. response. the foreign-body another clinical trial- with a dif last year will allow that ferently designed capsule the capsule to penetrate blood vessels contact with the and come into direct the should obviate While that beta cells. of the capsule, difficulties with rejection - it will also require immunosuppres from the body sion therapy to prevent so, Even the cells themselves. attacking it can achieve ViaCyte is hopeful that of insulin in the near therapeutic levels to hope it will be possible “We term. efficacydemonstrate in six to twelve - Not taking any Laikind. says months,” has also the company thing for granted, partnered with gene-editing company in order to tryTherapeutics CRISPR and genetically modify its precursor cells in order to protect them from the body’s immune response. Discoveries New in stem cell biology While developments from HSCs to embryonic stem cells to iPSCs has opened up new possibilities in one of the most medicine, regenerative is the discovery exciting developments the body has multiple types of stem that have which may cells specific to organs, if scientists can the capacity to self-heal, These switch them on. to figure out how so-called endogenous stem cells have lungs, in the liver, so far, been found, and possibly the heart, and intestine, their and hold promise for regenerating corresponding organs both inside and outside the body. Marban reported the results of the first such endogenous clinical trial involving from the taking cells derived stem cells, hearts cultur- of heart-attack patients, and infusing them back into ing them, published in The The results, the body. of regeneration showed Lancet in 2012, the first heart successful healthy muscle, One company that is already involved is already involved that One company ViaCyte has had to Because of that, Endogenous stem cells have been found, so far, in the liver, lungs, and lungs, and in the liver, been cells have stem Endogenous found, so far, regenerating and hold promise the heart, for possibly and intestine, and outside the body. inside both organs their corresponding pany is working with Michael Laflamme with Michael is working pany of Keller of the University and Gordon to direct managed who have Toronto, into heart the pathway iPSC cells down They are currently working muscle cells. on increasing the maturity of the cells likelihood of in order to reduce their arrhythmia (irregular heartbeat) before into humans. they are ready to implant clinical trialsBlueRock plans to enter end, on the dopaminergic cells by year’s to follow. with cardiomyocytes which, ViaCyte, in human clinical trials is is Therapeutics, Semma like Melton’s pursuing to a stem cell–based therapy has The company diabetes. Type-1 tackle embryonicused small molecules to drive stem cells into something called pan- in the hopes that precursorcreatic cells, the cells once implanted into the body, into endocrine will continue to evolve “They are will produce insulin. cells that the time of transplan- not functional at - they become so after devel but tation, Chief ViaCyte’s says ,” opment in vivo Unlike Science Officer Kevin D’Amour. in which researchers in most diseases, to worryhave about the body rejecting of the entire nature implanted cells, the body attacks diabetes is that Type-1 whether they come beta cells, its own from another donor or not. a capsule in which to hold to create work will separate the implanted cells that immune cells that them from the body’s Researchers often it. seek to destroy a semi-permeable “tea bag,” liken it to a can hold the cells and membrane that them to infuse the body without allow directly coming into contact with the After implanting them in patients blood. researchers however, starting in 2015, off the cap- the body walled found that a saw “We of skin cells. sule with a layer ViaCyte says response,” pretty aggressive “The body is really Laikind. CEO Paul The trying foreign body.” that to isolate trialhas suspended that while company To do that, the company plans to use the company do that, To plans the company heartFor cells, iPSCs, including dopaminergic cells to iPSCs, - and cardiomyo disease Parkinson’s treat cytes to repair muscle cells in the heart. an off-the-shelf to create wanted “We solution by identifying cell populations the deficiency what is,” know where we “In Parkinson’s, Davis. Versant’s says lose dopa- you know we for example, minergic leads to the neurons and that approach is to so BlueRock’s symptoms, exact cell type.” replace that of transcriptiona combination factors, in order to and small molecules, proteins, to becom- the path push the iPSCs down ing a specific cell type without directly dopaminergic For editing their DNA. it will use a protocol for example, cells, Direc- by Lorenz Studer, developed The Center for Stem Biology at tor of York Sloan-Kettering Memorial in New and scientific co-founder of the company. of three The process uses a combination molecules to trigger something called the “wingless-type MMTV integrationsite to turn iSPCs (WNT) signaling pathway” These cells into functioning nerve cells. will then be implanted into the brain in to restore lost motor function. an attempt on subjecting cells to a similar process in order to repair damaged tissue after a the com- process, that For heart attack. The technology can speed creation The technology can speed creation - a nanobub it creates energy is absorbed, temporarilyble that opens a hole in the in guide-RNA floating allowing cell, Within 20 to solution to enter the cells. the cell membrane closes 30 seconds, with the material inside. - Saklay other techniques, of cells over takes over “One cell type that en says. been able to we’ve in a dish, 90 days “It opens she says. in three days,” create According of possibilities.” up a world Wang, to Chief Science Officer Stan formerly of Harvard Medical School, is planning to use a the company high-throughput system to rapidly experiment with engineering different cell human disease to treating types relevant as early as next year. the Blood With Beginning the first no accident that stem-cell It’s blood. diseases of the therapies involve single cells in a liquid medium Having makes it easier to take cells in and out them function. of the body and still have has begun to however, New research, other types on regenerating concentrate Cambridge-based of cells and tissues. BlueRock Therapeutics—funded by - Ver $225 million partnership between AG—has sant and pharma giant Bayer from ESCs and focused on cells derived The company grew out of Harvard’s grew out of Harvard’s The company While CRISPR technology has ad- School of Engineering and the Wyss Wyss School of Engineering and the financed and based and is now Institute, Cellino’s by MIT. built The Engine, at technique uses a nanopattern surface in pyramids covered studded with tiny iPSC cells are cultured a metal coating. and a laser is directly onto the surface, laser As the pulsed across the surface. vanced in editing genetic material, it can in editing genetic material, vanced still be a challenge to get the guide-RNA into cells in order to make the necessary genetic engi- Traditional substitutions. neering using viruses and is expensive can potentially introduce unintended genomic changes into (and unwanted) which uses fat mole- lipofection, cells; only cell membranes, cules to penetrate and nanopar- certain with works cells, metal and polymer res- ticles can leave problem, address that To idues behind. Cambridge-based startup Cellino has technique using laser a novel developed pulses to get genetic material into cells. to precisely manage the you “It allows delivery of these zip codes into the cell says the rightat time in the right order,” CEO Nabiha Saklayen. hemoglobin, and then insert them back hemoglobin, It hopes to begin another into patients. trial in Europe targeting beta thalassemia end. by year’s Image courtesy of: Semma Therapeutics courtesy of: Image Semma Therapeutics proprietary Stem Cell-derived Stem Cell-derived proprietary Therapeutics Semma or “SC-Islets”. cells, Islet

TOUGH TECH 02 | 34 | NEW LEASE ON LIFE | 37 | Gupta and Ryuji Morizane from Brigham and Women’s Hospital. Women’s Gupta and Ryuji Morizane from Brigham and green, proximal tubule-like cells in yellow, vasculature in red). from stem cells (all cell nuclei in blue, glomerular-like cells in Confocal light microscopy 3D rendering of a kidney organoid derived Kimberly Homan, Katharina Kroll, and Jennifer Lewis from Harvard and Jennifer University and Navin Katharina Kroll, courtesy of: Kimberly Homan, Image Fugitive ink printed in the shape of a convoluted proximal tubule in the kidney. kidney. in the tubule proximal convoluted of a in the shape printed ink Fugitive Harvard Lewis from Jennifer and and the University Kolesky, David Herrmann, Jessica Homan, Kimberly courtesy of: Image Institute for Biologically Inspired Engineering.Wyss - Thus far, there have been few success- been few there have Thus far, are however, All of these organs, “but it’s not necessarily surprising it it’s that “but a magic bullet.” wasn’t Growing Organs pursuing Ott began Starting a in 2005, a new scaffold approach to creating novel stripping but by using donor organs, them of their original might be cells that the while leaving rejected by a new host, theoret- Then, extracellular matrix intact. scaffold could be repopulated that ically, Ott tried many cells. own with a patient’s different techniques and chemicals in an to purge organs of their cells. attempt everyone in it worked, “Up until the day on our paper can put you we the lab said, a crazy It was out. work if yours doesn’t Ott hit paydirt Finally, high-risk project.” signed. While the process gave scientists the process gave While signed. it has cells operate, into how key insights a failure. been ultimately artificialful transplants of an organ cre- In 2006, through synthetic scaffold. ated of School Forest Wake Atala of Anthony able to grow artificialMedicine was blad ders transplant them and successfully has since also used the He into patients. techniques to construct artificialvaginas. Macchiarini at surgeon Paolo In 2011, implanted an the Karolinska University artificial trachea into a cancer patient. Macchiarini the procedure with repeated however, a half-dozen other patients; - and the universi nearly all of them died, ty suspended its efforts after an inquiry methods that questioning Macchiarini’s found him guilty of ethical breaches in he represented the treatment. the way in both structure simple and relatively no more complex organs, For function. in the developed polymer scaffold was able was 1990s and early 2000s that their fine-tuned structure, to replicate of millions especially the vasculature needed to keep them of blood vessels there was the time, “At and alive. healthy could generate no good scaffolding that Harald Ott, says a human-scale organ,” a heart surgeon and organ engineer at “The heart is not just a Mass General. to regrowAttempts heart muscle blob.” - how by infusing stem cells into patients, “It also seemed not to be working. ever, Ott says, been great if it did,” have would Growing tissues from such tiny organ- tissues from such tiny Growing Tesar and Adams have not only used Adams have and Tesar using such “organoids” since 2008, when since 2008, “organoids” using such a biologist the Japanese at Sasai, Yoshiki that showed research institute RIKEN, embryonic stem cells could be coaxed into a dish to self-assemble into 3-di- Since then, mensional tissue structures. produced organoids from scientists have both iPSCs and endogenous stem cells, brains, virtualcreating lungs, hearts, - The devel and intestines. livers, kidneys, opment could reduce the cost and ethical as concerns of using animals for research, researchers as allowing to experimentwell which might directly with human tissue, results earlier than produce more accurate Scientists or monkeys. rats, using mice, organ- patient-specific create could even them to personalize could allow oids that testing of potential treatments. might oids into full-fledged organs that be transferredone day into the human body to replace a damaged or faulty a much more has proved however, organ, Back in the 1990s, challenging endeavor. of Massachusetts General Vacanti Joseph Hospital and Robert Langer of MIT pi- organs oneered a technique for building using biodegradable polymer scaffolding, they Build it, seeded with stem cells. the rest, do and the cells would thought, the scaffolding and performpopulating - de- ing the functions for which they were re-myelination of nerves. They found that found that They of nerves. re-myelination a combi- these OPCs with by targeting they could molecules, of small nation inhibit their that block specific enzymes and trigger them to regenerate growth, With funding of $7.8 million myelin. is now the company donors, from private to test the drugsmoving inside the body. but stem cells in their nerve cell therapy, stem cells in the lab- also used they have oratory to construct human brain tissue than rather theories, on which to test their been Researchers have using mice or rats. - Derrick Rossi Derrick Therapeutics Co-Founder of Intellia Co-Founder of Intellia Therapeutics and Magenta Therapeutics and Convelo is based on science by Case Convelo A new direction in stem cell therapy A new direction in stem cell therapy organ transplants due to disease or injury. or due to disease transplants organ improve the chances ofimprove survival those needing for Despite such prom therapy of its kind. artificially, however, it could dramatically it could dramatically however, artificially, If scientists do succeed in creating organs If organs in creating do succeed scientists Western Reserve’s Paul Tesar and Drew Tesar Paul Reserve’s Western something called Adams who discovered oligodendrocyte progenitor cells (OPCs) which within the central nervous system, could grow into cells responsible for is in treating endogenous stem cells endogenous stem cells is in treating - rath while they are still inside the body, re-inserting them and er than removing endogenous “The premise is that them. stem cells already exist inside the body, them to do only stimulate can if we says normally they would what do,” Children’s Derrick a researcher at Rossi, Hospital in Boston and co-founder Therapeutics and Magenta of Intellia He recently became Therapeutics. President and CEO of a new company, Cleveland-based Therapeutics, Convelo to use endogenous which is attempting stem cells in the central nervous system disease That multiple sclerosis. to treat is caused by destruction of the myelin nerves wraps and insulates that sheath leading to a devastating inside the body, range of symptoms from impaired vision to loss of muscle function. ise, however, patients did not see signifi- patients however, ise, and in heart function, cant improvement studies by Marban and others later have results. mixed shown

TOUGH TECH 02 | 36 | NEW LEASE ON LIFE | 39 | Her technique consists of three differ- Her next step is to print tissue that Short organs working of creating vascularization, however, Lewis and her Lewis however, vascularization, organs colleagues decided to just create to emu- have don’t we said, “We for real. she says. can do biology,” We biology. late “inks”—a sacrificial ink that ent types of a networks; vascular can help template a extracellular biopolymer ink to create and finally, matrix for the organ scaffold; - a cell-laden ink containing mesenchy or organoids to iSPCs, mal stem cells, The the living cells of the organ. replicate all three then coordinate machine would “The of these inks to print the organ. the is to replicate of course, challenge, architectural complexity and cellular den- do “If you Lewis says. sity of the organ,” means you then hopefully that all of that, not only looks like something that have also functions like one.” but an organ, are very “We could be used in animals. she much in the infancy in this process,” certainly we “but hope our work admits, basis for some foundational is providing around the world.” labs many - Both recellularization and xenotrans them like pigs,” Church says. Now, the Now, says. Church them like pigs,” project on a separate is working company using CRISPR to knock out pig genes a response in the human provoke that trick the human “You immune system. immune system into believing that cells are okay,” otherwise incompatible is that the hope Eventually, Church says. strains of pigs they can breed the two together to produce pigs safe enough their organs to humans in a to donate virtually endless supply. require some harvestingplantation of organs in order to transplant them into A third method for organ a new body. aims to literally engineering, however, Church’s produce them from scratch. Jennifer Institute, Wyss the colleague at has produced a 3D bioprinter that Lewis, she is using to artificially print organs be transplanted into could later that humans. The idea grew out of earlier humans. techniques to produce synthetic organs from polymers could replicate that trying In the midst of to human organs. synthetic analogues for tissues and create A pair of decellularized pig lungs in a bioreactor. A pair of decellularized pig lungs Lab / Massachusetts General Hospital The Ott courtesy of: Image Combined with techniques to create create with techniques to Combined Using pig organs poses its own vation timelines being investigated by investigated timelines being vation lab. Toner’s preservationartificial technology organs, could bring a us closer to Toner’s like “off-the- organs are available when day shelf” ready to be used at for patients, notice—whether they are a moment’s cells or created from their own generated need an aspirin, “When you from iPSCs. who makes it for call someone don’t you “For Toner. says CVS,” go to you you, easily usable, cell therapies to become them so need to be able to stabilize you they can be used when needed.” Printing and Organ Pig Hearts A more radical method to ensure we when we viable organs available have by George need them is being developed Harvard a geneticist at Medical Church, Institute for Wyss School and Harvard’s Biologically Inspired Engineering who Among other CRISPR. helped invent he and former graduate student projects, to develop are working Yang Luhan organs in pigs for transplanting into - as xenotrans a method known humans, scientists he says, Previously, plantation. explored the idea of using pig have decellularizing them organs as scaffolds, and replacing them with human stem that however, Yang, Church and To cells. are go- “You just requires an extra step. With ing to sacrifice the animal anyway. are pursuing, one animal the option we can produce dozens of useable compo- can and you nents for transplantation, synchronize it before and after so they he says. need them,” are ready when you One large concern however. challenges, is the presence of porcine endogenous could infect that retroviruses (PERVs) the other human cells and cause disease; worry the human body might is that reject the organ outright as a foreign formed a com- Yang Church and object. In to tackle these issues. eGenesis, pany, they succeeded in using CRISPR 2015, genes in more to knock out the PERV than 60 different places in the genome they are in the process of now, of a pig; pigs in breeding a strain of PERV-free fancy to do any have don’t “We China. breed can just we molecular biology; Another colleague at Mass Gener- Another colleague at - on tech His lab has been working temperature. “You put it into a perfusion put it into a “You temperature. device and perfuse it with media and can get nearly and you other goodies, If you rate. 100 percent transplantation - it out for 60 minutes without put leave get zero.” you ting it in a restore solution, on ways is working Toner, Mehmet al, to extend the life of organs for even if an organ Even longer periods of time. be stored it can’t he says, is kept cool, outside the body. for more than a day to cryogenicFreezing an organ down damages vital however, temperatures, on lab is working Toner’s tissue function. to preserveby cooling them organs ways cool to intermediatedown temperatures, metabolism long enough enough to slow or months to preserve them for weeks he’s Currently, without damaging them. for a been able to preserve liver a rat transplanting with no harm before week - important to note that It’s ful effects. alternative organ preservation techniques nutrient-rich flowing, blood, using warm, Organ Care System, Transmedics like the represent a fundamental step forward from traditional cold ischemic storage, do not address the longer preser- but removed from the body so that more more that from the body so removed surviveorgans can transplanted. to be from millions of cadavers, “There are are that motorcycle accidents and such, but human beings, perfect specimens of an organ will lose all of after 30 minutes, - the Found Yarmush, says its function,” for Engineering Director of the Center - ing in Medicine. been have that niques to perfuse organs so and nutrients, deprived of oxygen he has So far, they can be transplanted. has been that liver been able to take a rat room 60 minutes outside of the body at If scientists do succeed in creating If scientists do succeed in creating The next problem was to put new to put The next problem was Combined with techniques to create artificial artificial with techniques to create Combined could technology like Toner’s preservation organs, available are organs when to a day us closer bring “off-the-shelf” at a to be used patients, ready for they generated are notice—whether moment’s created iPSCs. their own cells or from from iPSCs to create hearts, kidneys, liver, and liver, kidneys, hearts, iPSCs to create and has be- and pigs, pancreases for rats Recently, on human organs. gun working intestine seeded with a rat he created able to absorb was human stem cells that and a rat-sized nutrients for four weeks, able to cure diabetes was pancreas that he Despite those successes, for weeks. a complicated is realistic about how still very “It’s road he still has to travel. hard “It’s Ott, says high-risk research,” for me to get the financial support to perform this kind of academic research research- and find the and development, ers who are willing to make this high-risk decision for their career.” it could dra- however, organs artificially, the chances of survival improve matically for those needing organ transplants due - According to gov to disease or injury. some 35,000 last year ernment statistics, performedorgan transplants were the in more than 100,000 people however U.S.; are currently list for an on the waiting 20 people die waiting Each day, organ. Mass colleague at Ott’s for a transplant. is working Yarmush, Martin General, of organs to extend the lives on ways - of detergents includ with a combination which ing sodium-dodecyl sulfate (SDS), while or break open, to lyse, caused cells matrixkeeping the extracellular and its sturdy protein core intact. Ott started matrix. with cells onto that heart seeding it with fetal a rat matrix, which are already cells, cardiomyocyte partially into heart differentiated muscle of maturation, After only eight days cells. they the cells had grown enough so that electrical with an could be stimulated lab Ott’s pulse to produce a heartbeat. has since used similar techniques using Harald Ott Harald University Mehmet Toner Mehmet George Church George Martin Yarmush Martin Mass General Hospital Mass General Hospital Mass General Hospital for Engineering in Medicine, Funding Director of The Center Founding Core Faculty Synthetic Heart Surgeon & Organ Engineer, Heart Surgeon & Organ Biology, Wyss Institute at Harvard Center for Engineering in Medicine,

TOUGH TECH 02 | 38 | NEW LEASE ON LIFE | 41 | Don Ingber Don Wyss Institute Founding Director, Founding Director, three-dimensional cluster of cells that three-dimensional cluster of cells that Organoid: can serveversion as simplified of a specific organ in the lab. of living cells and combination Organ-on-a-chip: the can simulate mechanical components that response of an organ activities and physiological in the lab. type of into any able to differentiate Pluripotent: cell in the body. artificialversion scaffold: the extra- of Polymer with cellular matrix designed to be populated an organ in the lab. living cells to create cells process of populating Recellularization: onto extracellular matrix a in order to create functioning organ. molecular molecules of low molecules: Small which can such as sugars or amino acids, weight, a biologicalstimulate process. process of transplanting an Xenotransplantation: organ or tissue from one species into another. body before using them inside the body. body. the inside them using before body And given the strides regenerative that medicine has made within the last 50 within the next 50 its likely that years, once seemed like science fic- years what - tion could become a reality—a near-in exhaustible supply of replacement cells created to us, and organs available to repair cells or others, from our own part and replace any of the body that able to medicine is If regenerative fails. it will as seems possible, that, achieve / truly revolutionary. be That combination of therapies, in in of therapies, combination That change an organism’s DNA by adding, removing, removing, DNA by adding, change an organism’s or altering genetic material. potentially disease (GVHD): Graft-versus-host serious caused by rejection of cells complication or organs introduced into the body. protein or such as a molecule, factor: Growth cellular growth. can stimulate that hormone, (HSC): cell found within cell stem Hematopoietic into can develop blood and bone marrow that type of blood cell. any adult cell (iPSC): cell stem pluripotent Induced is transformedthat into a stem cell with the capability to turn cell of the body. into any multipotent (MSCs): cells stem Mesenchymal can stem cells found in bone marrow that and muscle, into a variety of bone, differentiate cartilage cells. into the ability of a cell to develop Multipotent: different cell types. not all, but many, can within tissues that microenvironment Niche: determine stem cells differentiate. how nique, but from a combination multiple from a combination but nique, edit using CRISPR to technologies: and growthgenes and small molecules factors- cer to drive stem cells towards as using stem as well tain cell lineages, and outside organs inside cells to build human of the body in order to improve of stem-cell bi- “In the early days health. thought it offered the opportu we - ology, nity to use things like blood stem cells as While Scadden. says replacement parts,” “That’s he says, is true, undoubtedly that regener- of looking at a very narrow way it can clear that it’s Now medicine. ative models for diseases, also help us create us medicine to triggerand also give the cells inside of our body to heal itself.” could fundamentally change the turn, medicine is practiced and life is way individual could have Patients lived. and tested for therapies developed them on artificial organs outside the three-dimensional network three-dimensional network Ingber is scientific founder of Em- Ingber is scientific founder medicine is The future of regenerative The of to future is likely medicine regenerative but technique, a one from not any come from multiple technologies. combination models don’t adequately predict what predict what adequately models don’t will happen in humans.” a to create working a company ulate, network would that “body-on-a-chip” artificialseveral with organs together channels to further explore the inter- In the future, organs. actions between those structures with a could be created stem cells in order to test own patient’s the efficacy and side effects of multiple to use before deciding on which drugs, of individual- Outside inside the body. a drug could company ized treatment, an organ- or body-on-a-chip cus- create tom-designed for a certain genetic sub- group efficacy to demonstrate for a drug otherwise be seen as a failure might that could be “That in typical animal models. a game-changer for drug development,” Ingber says. one tech- likely to come not from any cells in the body that produce insulin. cells in the body that cell: Beta 3D printing can technology that Bioprinting: produce living tissues. gene-editing technology that CRISPR-Cas9: uses an enzyme and guide RNA to replace “clustered regularly Short for DNA sequences. interspaced short and CRIS- palindromic repeats protein 9.” PR-associated of cells from an or- removal Decellularization: the extracellular matrix intact. while leaving gan, (ESC): cell from early-stage cell stem Embryonic cell type in the into any embryo can develop that body. a stem cell found within cell: stem Endogenous can regenerate specific tissues in the body that tissue. new cells of that matrix: Extracellular of molecules such as collagen and glycopro- structural provides support that for cells teins, of an organ. biologists allowing to editing: Technology Gene GLOSSARY tionality,” says Ingber. While traditional Ingber. says tionality,” testing on a single cell cell culture allows organs-on-a-chip can include layers type, printed on top of one of different cells, the complete organ to simulate another, could help drug in turn, That, function. conduct re- companies more accurately “Seventy-five search into new therapies. percent of drugs fail in clinical trials,” because animal “That’s Ingber says. - Ingber first participated in the cre- can mimic physiological breathing in breathing can mimic physiological peristaltic-like motions in the the lungs, says and pulses in the heart,” intestine, - Found Institute’s Wyss the Don Ingber, ing Director. alve recreating of a lung-on-a-chip, ation oli sac and alveolic-capillary interface on in silicone rubber. a metal chip covered of func- “It included incredible levels for transplantation, 3D bioprinting can for transplantation, also produce artificial organ structures “or- So-called for medical research. are like organoids in gans-on-a- chip” they can consist of actual human that tissue in vitro to test drugs as and toxins Using to animal testing. an alternative mechanical and electronic engineering, they can also be stimulated however, “We organ function as well. to recreate photo by Doug Levy. Jennifer Lewis, Core Faculty, Wyss Institute at Harvard University; Hansjörg University; Harvard at Wyss Institute Faculty, Core Lewis, Jennifer A. Paulson John Harvard Engineering, Inspired of Biologically Professor Wyss Applied Sciences Engineering and School of

TOUGH TECH 02 | 40 | THE NEW WORLD OF NEW SPACE | 43 | By Emily Calandrelli for The Engine by Camilo Zuñiga Illustrations

Space Revolution Companies Powering Today’s Today’s Companies Powering The Technology and and The Technology

World

New

The The NewSpace TOUGH TECH 02 | 42 | THE NEW WORLD OF NEW SPACE | 45 | SpaceX photo by PAZ mission launch. Today, a new generation of private space startups of private a new generation has Today, are living in the era of NewSpace. We Defined by its prioritization of commercially viable access NewSpace is an increasingly complex and nuanced ecosys- (1) Commercial Orbital Transportation Services, A New Era in Spaceflight; 2014 in 2004; and, perhaps most importantly, Commercial Orbital perhaps most importantly, and, in 2004; the prospect that Services in 2006; (COTS) Transportation Earth sector was private shift to the activities in low orbit would no longer an uncertainty—it inevitable. was funds for emerged without sole dependence on government These startups with parties are working both private support. engineeringand public, to problems both orbital new solutions seen billions of dollars of investment They have and terrestrial. on perspective already started to change humanity’s and have its place in the stars. and a philosophy. once a movement NewSpace is at to space, as It is a product of policy shifts decades in the making as well The US government of essential technology. the rapid evolution while and maintained vital subsidies, its oversight has relaxed bolstered by manufacturers, and software hardware private lighter, smaller, continue to create global competition, robust of which can be used off-the-shelf many devices, more powerful by NewSpace startups. The following and capital. policy, technology, tem of startups, a succinct overview of the current of aims to provide state the NewSpace by analyzing market trends and investigating technologies make it all possible. that 1 From Space Race to NewSpace From Space Race

In the early 1980s and into the 1990s, the economies of col- In the early 1980s and into the 1990s, The US government, for example, recruited contrac- private for example, The US government, Then, in the early 2000s, with US government programs with US government in the early 2000s, Then, laboration were changing. NASA began to experiment shift- with changing. were laboration sector within certaining more responsibility to the private facets effortsThe failed to gain serious traction. of the space program. and the X-33 / X-34 space- like SPACEHAB But initiatives Kistler along with companies like Pioneer Rocketplane, planes, the private that proved and Orbital Sciences Corp. Aerospace, and capability to reach orbit. passion, sector had the interest, tors to assist in the production of mission-specific componen- try while retaining strict engineering and strategic oversight. contractors the private vital to the US space In some ways, they that and so supervised, so integrated, program were essentially served as arms Such collaboration of NASA itself. responsibilities to different congressiohelped NASA delegate - ensuring political sustainability while accelerating nal districts, technological progress far the confines of the space beyond program. On October 4, 1957, the Soviet satellite Sputnik chirped satellite to the Soviet 1957, On October 4, Age had The Space Earth of low life from the vacuum orbit. and with it an unprecedented period and of scientific begun, those following decades five nearly For engineering innovation. competed largest governments world’s the first transmissions, more complex craft into to put progressively and collaborated been the domain of government, have While orbit may space. verygetting there was much a joint effort and public between sectors. private

entirely new. new. entirely of daring, invention, and the pursuit of something of the pursuit and something invention, of daring, ethos it embodies is as old as humanity itself. It is one It itself. as humanity is as old it embodies ethos new modes of thinking, new so urces of funding, but the the but of urces so funding, new of modes thinking, new The NewSpace industry may be built with new technology, technology, be industry new with built may NewSpace The like Alternate Access to Station (AAS) in 2000; Constellation Constellation (AAS) in 2000; Access to Station Alternate like

TOUGH TECH 02 | 44 | THE NEW WORLD OF NEW SPACE | 47 | photo by SpaceX flight on 6 February 2018. flight on Peter Beck, Rocket Lab’s Founder, Founder, Rocket Lab’s Beck, Peter CTO, and CEO, notes that with Rocket notes that and CEO, CTO, - the small satel Electron rocket, Lab’s to compromise. will not have lite owner hitch a they don’t “On a small rocket, the big That’s ride—they the ride. own a small rocket When you’re difference. just you riding on a large launch vehicle, on You’re goes. to go where the bus have going to time schedule, someone else’s where the prime to go. customer wants a you have fine when Ride share works to want you technology demonstration up or an early stage spacecraft, throw a actually need to build when you but need to deploy in space and you business spacecraft to a particular orbit in a time- then makes commercial sense, frame that hitching a ride on a big rocket just does not work.” Cape Canaveral Landing Zones 1 and 2 following test and 2 following Zones 1 Landing Canaveral Cape Falcon Heavy reusable side boosters land in unison at in unison land side boosters reusable Heavy Falcon As the small satellite market grows, market grows, As the small satellite DIVERSITY OF OF DIVERSITY OPTIONS LAUNCH Small satellites often hitch ridesSmall satellites into to larger space on launches dedicated A client with a large satellite customers. with the will book a rocket and work to determinelaunch provider when that rocket launches and where it ultimately owners can purchase Small satellite goes. a ride on the same rocket in the remain- often referreding space (a strategy to as or ride sharing). “piggybacking” so does the market to design rockets to its launch needs. specifically catered American Rocket Lab launch provider which the Electron rocket, is developing is designed to send up to approximately Compare 225 kg into low-earth orbit. which can 9, Falcon this to SpaceX’s carry 22,800 kg to the approximately same orbit. While large reusable rockets are top- In 2017, SpaceX President and COO In 2017, the com- that stated Gwynne Shotwell 30-40 achieve to eventually hopes pany launches annually (SpaceX flew 18 times in 2017 and has completed 16 successful commercial flights plus one test flight of in the first Heavy ten months of Falcon put those numbers in To 2018 alone). - there are approximate today perspective, an- ly 80-90 orbital launches worldwide been only around nually and there have 5,400 launches since the beginning of SpaceX is consistently the space age. accounting for more and more of the global market share. other companies ping launch headlines, that new vehicles to develop are working specifically to the small cater growing market. satellite LAUNCH RATE

5 photo by SpaceX Titanium grid fins. Carbon fiber landing legs are de- can withstand higher reentry speeds and requires less refurbishment (it doesn’t material require repainting with ablative after each landing). helping before landing, seconds ployed further stabilize the rocket on the pad. All of the SpaceX landing systems are and adjusted duringautomated each launch using real-time flight data. (2) Wall, Mike. “Wow! SpaceX Lands Orbital Rocket Successfully in His- toric First.” Space.com, Space.com, 22 Dec. 2015, www.space.com/31420- spacex-rocket-landing-success.html. (3) Grush, Loren. “A Successful SpaceX Falcon Heavy Launch Gives NASA New Options.” The Verge, The Verge, 2 Feb. 2018, www.theverge. com/2018/2/2/16954582/spacex-falcon- heavy-rocket-launch-impact-nasa-deep- space-travel. (4) Burns, Matt, and Brian Heater. “Blue Origin Successfully Lands Both Booster and Crew Capsule after Test Launch.” TechCrunch, TechCrunch, 18 July 2018, techcrunch.com/2018/07/18/ blue-origin-successfully-lands-both- booster-and-crew-capsule-after-test- launch/. (5) “GRID FINS.” SpaceX, SpaceX, 1 Sept. 2015, www.spacex.com/ news/2015/08/31/grid-fins. While it did not have the seismic worldwide effects of Sput- the seismic worldwide While it did not have nik or Vostok or Mercury or Apollo, the success of the mission Apollo, or Mercury or Vostok nik or could successfully, company a private doubt that erased any realized We glimpsed the future. We reach orbit. and repeatedly, the satellites, the stuff of NewSpace—the could deliver we that that a cost the as-yet-imagined at craft—to orbit ISS payloads, experimentation, only serve exploration, to accelerate would and the NewSpace economy. 2 To solve it, SpaceX developed a SpaceX developed it, solve To flagship SpaceX’s 9, The Falcon SpaceX In addition to the extra fuel, those on Unlike traditional grid fins, HOW TO LAND A ROCKET Landing a rocket is not unlike balanc- ing a large broomstick vertically on the there hand—to succeed, palm of one’s that are hundreds of small movements must be choreographedfault. without at traveling imagine rocket was Now that 6,000 km/h and had to come speeds over minutes. to a complete stop within five a profoundly difficult challenge. It’s unique system of complementary con- and processes. components, trols, an ad- is designed with launch vehicle, ditional fuel margin the engines so that can be reignited multiple times to slow the rocket before it reaches the landing These engines are also able to be pad. last-second corrective enabling gimbaled, maneuvers. 9 with has also equipped the Falcon nitrogen gas thrusters and foldable heat These as gridresistant wings known fins. fins help further steer the rocket to the landing target. While 9 are bare titanium. the Falcon than their predecessor more expensive titanium used painted aluminum, that Better, Cheaper Rides to Space Rides Cheaper Better, 4 These numbers can fluctuate, These numbers can fluctuate, 3 A SpaceX Falcon 9 launch, for ex- 9 launch, A SpaceX Falcon Blue Origin, while it has yet to launch while it has yet Blue Origin, According to early estimates, a Falcon a Falcon According to early estimates, ample, costs approximately $62 million, $62 million, costs approximately ample, not reusable, but while the comparable, V rocket United Launch Alliance Atlas $109 million to costs approximately launch. Traditional rockets are expendable—fly rockets are expendable—fly Traditional cargo into orbit and dump the booster like Companies it there. brought that SpaceX and Blue Origin this see don’t They are as a viable long-term strategy. reusable rockets with hopes developing the to reduce launch costs and accelerate pace of progress. industry’s THE ECONOMICS OF OF THE ECONOMICS VEHICLE LAUNCH REUSABILITY It was a moment that captured the public’s imagination like no the public’s captured a moment that It was had before. other NewSpace mission On December 21, 2015, SpaceX stuck the vertical landing of 2015, On December 21, deliv- Falcon 9 rocket after successfully the first of its stage As SpaceX founder Elon Musk ering into orbit. 11 satellites brought an orbital class one has ever “No the time, remarked at recoveryof the rocket in a achieved We booster back intact. This is a fundamental 11 satellites. also deployed mission that flown.” ever rocket that’s other to any step change compared - has prov its first reusable orbital rocket, en the capability of its suborbital New crew Shepard rocket and accompanying and be reused land, capsule to launch, on multiple flights. Heavy, currently SpaceX’s largest launch currently SpaceX’s Heavy, and a half will cost about two vehicle, times less to reach orbit than its closest the non-reusable United competitor, Alliance Delta IV Heavy. Launch but overall, SpaceX, with its reusable SpaceX, overall, but offers significantly more af- 9, Falcon fordable rides to space.

TOUGH TECH 02 | 46 | THE NEW WORLD OF NEW SPACE | 49 | photo by Doug Levy. Analytical Space. Nathaniel Brewster photo by Nathaniel Dan Nevius, COO & Co-Founder, Justin Oliveira, CEO & Co-Founder; including a flight battery pack and a magnetic torque rod panel. including a flight battery pack and Engineers at Analytical Space assembling a partial chassis for a 3U CubeSat, Engineers at Analytical Space assembling (7) Argent, Anne-Wainscott. “Small- er Is Better How Small Satellites Have Become a Compelling Option - Via Satellite-.” Via Satellite, Via Satellite, 21 Aug. 2013, www. satellitetoday.com/government-military/2011/07/01/smaller-is-better- how-small-satellites-have-become-a- compelling-option/. (8) “Planet Labs Targets a Search En- gine of the World.” NASASpaceFlight. com, www.nasaspaceflight.com/2018/01/ planet-labs-targets-search-engine- world/. (9) “OneWeb Asks FCC to Authorize 1,200 More Satellites.” SpaceNews. com, 20 Mar. 2018, spacenews.com/oneweb-asks-fcc-to-authorize-1200-more- satellites/. (10) Brodkin, Jon. “FCC Tells SpaceX It Can Deploy up to 11,943 Broad- band Satellites.” Ars Technica, Ars Technica, 15 Nov. 2018, arstechnica. com/information-technology/2018/11/ spacex-gets-fcc-approval-for-7500- more-broadband-satellites/. In 10

9 8 But success for OneWeb or Starlink But success for OneWeb SpaceX has a similar proposal called - estimat Gwynne Shotwell April of 2018, cost around $10 billion it would ed that this fleet of satellites. to deploy upon a sound is not just predicated Dozens of enabling strategy. investment technologies must be refined enough to launch and profitable, ensure consistent, Dependence on those tech- operations. nologies poses a fundamental risk for the as well internetsatellite model, business as other space-based ventures. to the world. The company has startedThe company to the world. construction on its proposed fleet of and has currently1,980 satellites raised $2 billion. approximately Starlink, though the estimated size of its though the estimated Starlink, 11,900. is over constellation satellite The data gathered by satellite imaging by satellite companies like Planet gathered The data At its factory in San Francisco, Planet Labs can produce up At its factory in San Francisco, notes, CEO of Planet Labs, Co-founder and Will Marshall, due Planet Labs lost 34 total satellites In 2014 and 2015, Labs is of little use without interpretation and analysis. A select Labs is of little use without interpretation and analysis. Orbital Insight, group startups of software is out to do just that. AI use and SpaceKnow UrsaDescartes Space Systems, Labs, to drive insights into everythingfrom retail foot traffic to urban and crop health. development multi-spectral imagery good as (resolution as from satellites analysis of larger farmsoverall well as for as feet per pixel) five the high-resolution imagery from terrestrial feet per pixel) (two certaindrones to hone in on areas. manufacturing satellite per week—a achievement to 40 Doves to rap- the capability Having industry. unheard of in the space the startup allows their idly produce satellites to quickly update fleet with new technologies and capabilities. one $500 spent 10 years building can imagine if you that “You By using the failure is simply not an option. million satellite, are able to build we same technology found in smartphones, As very are highly capable yet affordable. that smaller satellites that knowing more and take more risks, many build we a result, not a big deal.” it’s fail, if one or two within one year lose 34 satellites To failure. to launch vehicle because but killed most NewSpace businesses, have would Planet Labs easy to replace, relatively were those satellites the largest operates the company Today, survived this setback. in history. constellation satellite (Such a concept was attempted attempted (Such a concept was plans to launch hundreds OneWeb were located in high orbits and were only in high orbits and were located were inter- high-latency (slow) able to provide low-latency supply To net to select areas. constel- a satellite broadband internet, in low-Earth must be built lation orbit. in such an orbit can pro- While satellites they vide internet without much delay, at of the world only see one small swath this problem, solve To moment. given any or potentially of hundreds, a constellation is needed. of satellites thousands, Microsoft-backed In 1994, before. nearly 800 proposed launching Teledesic global broadband in- to deliver satellites Costs and terrestrialternet. competition Teledesic’s to be too much and proved constructionsatellite halted in 2002.) into low-earthof satellites orbit and bring faster-than-broadband internet 7 Trends in Satellite Manufacturing in Satellite Trends Previous satellite internetPrevious satellite pursuits Today, satellite internet satellite start-ups have Today, Farm owners, for example, often use a combination of a combination often use example, for Farm owners, Imaging our planet is not new, but the frequency but of those Imaging our planet is not new, San Francisco-based Planet Labs uses a constellation of over of over constellation San Francisco-based Planet Labs uses a As a result of this profound miniaturization, for the first time As a result of this profound miniaturization, It is hard to overstate how different these new satellites new satellites different these how It is hard to overstate billions of dollars’ worth of investments. worth of investments. billions of dollars’ It is one of the largest funded sectors in Because Why? the NewSpace industry. and launches are cheaper than satellites before. ever The idea of internet from space is not internet Satellite has been pursued new. as with other commercial but for decades, approaches the traditional space ventures, technology. by their era’s stifled were INTERNET ORBIT FROM Today’s satellites have smartphones de- to thank for their ever have satellites Today’s greater- afford and ever capability, ever-increasing creasing size, As the smartphone market has become more competi- ability. accelerometers, cameras, technologies its core (batteries, tive, Now, more capable. become smaller and etc…) have radios, can purchase much of the technology NewSpace companies because the core tech is already And, they need off-the-shelf. and lighter, are smaller, they build the satellites miniaturized, into space. cheaper to launch ultimately images is. Planet Labs is providing the ability to watch the the ability to watch Planet Labs is providing images is. a year: over than year rather day, over change day world has garneredcapability that from the agriculture interest and and media. governments, maritime industries, 100 CubeSats to image the entire Earth every day. CubeSats CubeSats to image the entire Earth100 CubeSats every day. are the industry are satellites—they for miniature standard 10x10x10 cm cubes (one cube is referred to as 1 unit or 1U). “Doves,” refers to as the company which Planet Labs satellites, are 3U CubeSats. ever, NewSpace companies have the option to design a business the option to design a business NewSpace companies have ever, around a fleet of satellites. are in both form factor- and cost from their traditional coun to cost hundreds of satellites not unusual for It was terparts. a school and be as large take years make, to millions of dollars, just as heavy). (and bus

TOUGH TECH 02 | 48 | THE NEW WORLD OF NEW SPACE | 51 | Accion Systems. A postage stamp photo by Accion Systems photo by Accion Systems sized thruster chip. Natalya Bailey, Co-Founder & CEO, (13)“Dime-Size Thrusters Could Propel Satellites, Spacecraft.” Space.com, Space.com, 23 Mar. 2017, www.space. com/36180-dime-size-accion-thrusters- propel-spacecraft.html. (14)Campbell, Ashley. “Optical Commu- nications.” NASA, NASA, 16 Oct. 2017, www.nasa.gov/directorates/heo/scan/ opticalcommunications/. 14,15 These thrusters 91 provided 13 Accion uses a different source of The company is building miniature miniature is building The company aster- Vesta mission to the The Dawn satellite can performsatellite multiple tasks.” ions—a salty liquid propellant—in its thrusters, instead of compressed gasses This of traditional ion engines. like that the use of large them to avoid allows pressurized tanks, chambers and valves, and external cathodes. ion thrusters, each about the size of originally using technology a quarter, These thrusters are MIT. at developed inherently different than traditional ion spacecraft. engines used on today’s by three powered was for example, oid, traditional ion engine thrusters- measur ing 30.5 cm in diameter and 33 cm in length. mN of thrust. Accion’s thrusters, on the Accion’s mN of thrust. are only 3x7x12 cm in there other hand, and can provide smallest configuration enough to propel a .05 mN of thrust, spacecraft up to 200 kg. Natalya Bailey, the founder and CEO Bailey, Natalya PROPULSION had no Until recently small satellites method of propulsion while in orbit. short—many only lasted were Their lives months or a few short years in orbit before succumbing to atmospheric drag If the small satellite and burning up. - small sat is to trulyrevolution take root, a reliable and capable ellites must have propulsion system. a startup working Accion Systems, of to bring propulsion to small satellites - reflects on the advan for the first time, “When a small tages of such a system, has positioning capabilities from satellite its mission lifetime a propulsion system, fewer is greatly extended meaning that need to be launched and one satellites 11 12 Nine of Rocket Lab’s 3D printed Nine of Rocket Lab’s also de- a company Space, Relativity Stargate, which the company claims which the company Stargate, Space has raised more than Relativity (11)Nasa. (2015) Dawn at Ceres. (12)“TILE.” Accion Systems - A New Ion Engine, www.accion-systems.com/tile/. the small satellite market, is 3D printing market, the small satellite The most of its primary rocket engine. as elec- uses a process known company NASA’s like which, tron beam melting, harnesses an electron beam. technology, this beam to melt But they instead use metal powder. Rutherford Engines bring 150 kN of liftoff thrust to the Electron first stage while a single Rutherford Engine- pro vides 22 kN of thrust to its second stage. the company According to Rocket Lab, can print the enginejust 24 hours—a in staggering achievement. to wants small launch vehicles, veloping furthergo even by 3D printing an entire Tim Ellis and Jordan Founders rocket. Noone—former SpaceX and Boeing engineers—are to reduce the on a mission partsnumber of moving in its company’s increasing its mechanical efficien- rocket, cy and reducing the number of potential Space Shuttle NASA’s failure points. The 2.5 million parts. had an estimated a 3D-print goal is to create - stated duo’s parts. ed rocket with just 1,000 moving had to build the company But to do that, 3D specialized metal powder-fed its own printer as Stargate. known is the world’s largest metal 3D printer, largest metal 3D printer, is the world’s by three robotic arms and is powered is capable of printing 95% of Relativity 1 rocket in a proprietary Terran Space’s high-strength aluminum alloy. funding and an $45 million in venture $1 billion worthestimated of nonbinding launch term sheets and letters of intent. 1 Terran plans to test its The company rocket in 2020. In 2015, NASA printed its first full- In 2015, be an excellent thermalCopper may a launch company Rocket Lab, subtractive manufacturingsubtractive counterparts, further costs. cutting production While scale copper rocket engine part. conducting good at copper is extremely making it particularly useful within heat, it is chamber, the lining of a combustion this same property it difficult makes that to melt during the 3D printing process. a NASA invented this problem, solve To as GRCo-84—a known new copper-alloy can be melted continuously that powder for 3D printing, maintain the con- and duction properties necessary for a rocket chamber. combustion engine’s com- weak it is relatively but conductor, this reason, For pared to other metals. a 3D printing process NASA developed Fabrication called E-Beam Free Form which deposits a nickel-alloy Technology, using an liner on top of the copper-alloy electron beam and solid wire feedstock. rockets for small relatively developing and Materials of NewSpace Materials and The Manufacturing Techniques Techniques Manufacturing The The advantages of additive manufac- of additive The advantages 3D-printed copper combustion chamber. NASA/MSFC/Emmett Given photo by: turing are many. Aside from reducing Aside from reducing turing are many. which points, the number of welding and po- production time, reduces costs, 3D printing wastes tential failure points, significantly less stock compared to its MANUFACTURING entered the age in which have We that the flight hardware aerospace parts, can be helps propel rockets into orbit, of metal-based The maturation printed. 3D printing techniques and material have alloys in metal science advancement enabled NewSpace companies to use this solely to the once relegated technology, for production of realm of prototypes, aerospace-grade components. ADDITIVE ADDITIVE

TOUGH TECH 02 | 50 | THE NEW WORLD OF NEW SPACE | 53 | /

22 The DOD also has a vested interest in the United States States interest in the United The DOD also has a vested the goal of that Wilson has said Secretary Air Force Heather to fly commercial payloads, yet While these companies have can be launched a payload key benefits: has two This strategy (18)Bryce Space and Technology. (2017) 2017 State of the Satellite Industry. (19)Messier, “NASA’s Commercial Crew Program By the Doug. Numbers.” Parabolic Arc, www.parabolicarc.com/2016/10/24/na- sas-84-billion-commercial-crew-program/. (20)Grush, “NASA Coughs up $490 Million for Six More Loren. Seats on Russia’s Soyuz Rocket.” The Verge, The Verge, 6 Aug. 2015, www.theverge.com/2015/8/6/9108703/nasa-buys- seats-russia-soyuz-rocket-490-million. (21)“Pentagon Funds ‘Small Launch Services’ to Gain Budget Greater Access to Space.” SpaceNews.com, 15 Feb. 2018, spacenews.com/pentagon-budget-funds-small-launch-services-to- gain-greater-access-to-space/. tive to develop American-made rides quickly. to develop tive excelling in launch technology, specifically on-demand launch specifically excelling in launch technology, services can quickly replace military Recent- that in orbit. assets services proposed a small launch Air Force program that the ly, years the course to of five distribute $192.5 million over would Virgin Orbit and Stratolaunch. new launch providers like a variety of launch capabilities in order “have this program is to assured access to space.” to have Virgin to the DOD be- are interesting Orbit and Stratolaunch enable faster may access launch strategy cause the companies’ Instead of today. the rocket companies available to space over companies fly these two launching a rocket from a launchpad, rockets up to 35,000 feet with specially modified airplanes and launch them mid-air. as long as it has a large enough virtually in the world anywhere and perhaps more importantly one of they can avoid runway, weather. for rocket launches: the most common delays 20 The Policies That Help The Policies That Make NewSpace Possible In recent years, NASA has paid as In recent years, 21 Both NASA and the Department of Defense have shown a shown Both NASA and the Departmenthave of Defense NASA has facilitated the development a decade, over For As John Logsdon, Former Space Policy Director at George Director at Policy Former Space Logsdon, As John orbital of human-rated NASA subsidized the development much as $81.6 million per seat, so one can imagine- the incen much as $81.6 million per seat, Recent policy initiatives are undeniably influencing the direc- are undeniably Recent policy initiatives These policies tion in which the NewSpace industry is moving. programsinclude government subsidize the development that clarifyto passed laws new as well as certainof companies, space rules space-based initiatives. around keen interest in helping certain succeed. NewSpace companies ATK Orbital SpaceX, of orbital rockets and space capsules at (recently acquired by Northrop and the Sierra Grumman), pri- through two Corporationcontracts awarded via Nevada Services Transportation mary Commercial Orbital programs: NASA benefits from these and Commercial Resupply Services. American-made ridesprograms to the International by having the while these companies benefit from having Space Station, customer for a certain as a guaranteed government number of customers 70% of in 2016 government provided In fact, flights. for orbital launches of satellites. the revenues Washington University, observes, “The government interest in “The government observes, University, Washington the stimulates new business Creating NewSpace is multifold. of these many Also, more tax revenue. and creates economy new technologies carry help the government - busi out its own like cheaper access to space for example.” ness, SpaceX and Boeing through contracts rockets and capsules at A particularly important via the Commercial Crew Program. considering once the Space Shuttle retired in 2011, initiative American astronauts the Russians to send NASA began paying NASA paid the Russians over From 2011-2018, into space. $3 billion for these rides. 17 16 But laser transmission is not without is not without But laser transmission and laser systems, With a mix of radio the University of a team at This is why has been testing its RemoveDEBRIS (15)Campbell, Ashley. “Optical Commu- nications.” NASA, NASA, 16 Oct. 2017, www.nasa.gov/directorates/heo/scan/opticalcommunications/. (16)Mosher, Dave. “The US Government Logged 308,984 Potential Space-Junk Collisions in 2017 - and the Problem Could Get Much Worse.” Business Insid- er, Business Insider, 15 Apr. 2018, www.businessinsider.com/space-junk-collision-statistics-government-tracking-2017-2018-4. (17)NASA, www.nasa.gov/mission_pages/ station/research/experiments/explorer/ Investigation.html. its tradeoffs. Unlike radio waves, which waves, Unlike radio its tradeoffs. covering out in a broad beam can be sent narrow width beam a laser’s a large area, espe- positioning, requires more precise cially when trying with to communicate a ground hundreds of kilometers station can be waves And while radio away. all types of through used to transfer data issues with have laser waves atmosphere, requiring- the vac either clouds and mist, skies to operate. uum of space or clear to accommodate Analytical Space hopes as clients’ scenarios as well all weather and ground capabilities. satellite station Currentaround the Earth. methods of altering a space- final orbits or allowing orbital decay craft to succumb to natural - when a sat do not scale well—especially ellite goes defunct before it can initiate its end-of-life plan Surrey a project in London is developing to launch a net called RemoveDEBRIS capable of capturing defunct spacecraft. After capturing with a net, the satellite a drag sail the team could either deploy increases aerody- (a large membrane that or launch a tethered harpoon namic drag), with the net and reel in the satellite. net technology for six years on parabolic flights (airplane simulate flights that the team This year, a weightlessness). completed its first successful in-flight net Over capture. and satellite deployment will begin to the company the next year, technology test its cameras and LIDAR its harpoon to identify orbital debris, as its drag sail. as well technology, frequencies. Optical communication sys- communication Optical frequencies. secure. lighter and more tems are also 18 Analytical Space aims to solve this Space aims to solve Analytical to transfer data Analytical Space plans speeds at These pieces are travelling the Space Surveillance In 2017, The challenge of orbital debris will transfer paradigm looks like this: data is data this: looks like paradigm transfer - is physi orbit until a satellite in “stuck” a particular ground over cally positioned send can the satellite only then station, line of sight. all about its data—it’s re- of shoebox-size problem with dozens to bring wants If a company satellites. lay the satellite but quickly, down its data of view of its in the field yet ground isn’t to data that “pass” they could station, by the owned satellite a well-positioned startup faster. down to get its data and laser waves. through a mix of radio for telecom- Laser-based technology is particularly munications attractive is capable because the optical wavelength than radio rates of 40 times higher data esti- however, models, Statistical debris. more than 500,000 pieces of that mate human-made debrisa marble larger than and millions of pieces as small as a fleck of paint are also in orbit. fast enough to damage of 28,163 km/h, this, Because of spacecraft and satellites. the US military-operated Space Surveil- tracks debris all times at lance Network are ownersand notifies spacecraft if any potential threats. 300,000 instances had over Network of notable concern of debris impacting were 655 of those events a spacecraft. in emergency 579 of which were reports, low-earth orbit. only become more complex as a greater number of spacecraft are stationed One Boston-based company, Analyti- One Boston-based company, Analytical Space. photo by Analytical Space. The Radix CubeSat being launched from the ISS. DEALING WITH WITH DEALING DEBRIS SPACE - approx identified systems have Tracking 20,000 pieces of space debrisimately larger than a softball orbiting the Earth These include defunct satellites; today. discarded equipment and rocket stages; - from an anti-satel remnants left over lite test conducted by China in 2007 more than 3,000 pieces created that and an accidental of trackable debris; American and Russian collision between in 2009 that satellites communication 2,000 pieces of trackable over generated cal Space, gives companies in industries cal Space, from agriculture goods to consumer the ability to harness in gathered data The current data near real time. orbit at Like propulsion, there are technolo- Like propulsion, gies of the to take advantage poised fundamental most NewSpace industry’s them with while providing platforms, more useful capabilities. greater, SYSTEMS LASER

TOUGH TECH 02 | 52 | THE NEW WORLD OF NEW SPACE | 55 | 2024 Blue Origin plans moon landing 2022 2022 SpaceX aims to send first missioncargo to Mars SpaceX plans to launch their first humans into space with 9 the Falcon rocket 2019 is a data and analytics company company and analytics Global is a data Spire of small satellites. by a constellation powered portions that of the globe cover These satellites untracked due to accessibility often remain weather, maritime, helps empower data its issues; industries- with unique and action and aviation able insights. Joel CTO: | Founder, Platzer Peter CEO: Founder, Cappaert Jeroen CTO: | Founder, Spark system to SpinLaunch is designing a catapult Using the mo- into space. launch small satellites mentum from a fast-spinning centrifuge to fling remove would the company into orbit, payloads reducing the need for chemical propellants, launch costs dramatically. Yaney Jonathan CEO: Founder, largest the world’s is building Stratolaunch an altitude at plane in order to launch vehicles The carrier aircraft is capable of of 35,000 ft. carrying a variety a space plane of rockets and which will bring of up to 6,000 kg and payloads to orbit. crew the rest of the way eventually Floyd Jean Allen | CEO: G. Paul Chairman: Founder, solely for the launch vehicles is creating Vector The company’s market. small satellite burgeoning rocket design enables frequent and reliable access - satel prices at should empower that to space, more often. lite-startups to send more to space, President Jim Cantrell | Founder, CEO: Founder, CTO: Garvey John of Launch Services: | Founder, Chief Sales and Marketing Eric Besnard | Founder, Coleman Shaun B. Officer & SVP/GM GalacticSky: a mobile air-launch Orbit is developing Virgin system using a modified 747 airplane (named Cosmic Girl) to carry its LauncherOne rocket to The rocket will ignite mid-air and carry 35,000 ft. Cosmic Girl of up to 500 kg to orbit. a payload can runway that can theoretically take off on any customers enabling to reach a 747, accommodate Thanks to hybrid addi- orbital inclinations. many Virgin Orbit can manufacturing, tive-subtractive manufacture around 24 of its rockets per year. Dan Hart CEO: President, Rocket Lab Rocket performs first commercial launch of its Electron rocket, deploying 6 small into satellites orbit is engineering- an air-breath Blue Origin successfully launches and lands its New rocket Shepard time the ninth for is a pioneer in the reusable launch transmit the satellite signals to a user’s device via device signals to a user’s satellite transmit the radios. and 2G WiFi/LTE/3G Adrian Steckel | CEO: Wyler Greg Founder: a and manages launched, Labs created, Planet Triple-CubeSats of Earth-imagingconstellation The image the entire Earth(3U) that every day. monitoring analytics platforms and company’s help customers interpret and act upon these images as they happen. Chief Will Marshall | Founder, CEO: Founder, Robbie Schingler Strategy Officer: Relativity Space is pioneering an autonomous rocket factory and launch service. It is spearhead- metal 3D printing the to create ing massive-scale, first 3D-printed rocket. world’s Jordan CTO: Ellis | Founder, Tim CEO: Founder, Noone Engines Reaction ing rocket engine that for reusable launch vehicles can be used both in the air and in the vacuum which combines the Its technology, of space. fuel efficiency and of a jet engine with the power of will enable a new generation speed of a rocket, capabilities for air and space vehicles. Wood Mark Engineering Director: COO, Varvill RIchard Chief Engineer: CTO, expendable launch vehicles Lab creates Rocket is made the Electron, Its rocket, for small satellites. from carbon composites and uses a 3D-printed mass produce rock- aims to The company engine. ets and bring to the small launch customization customer. satellite Beck Peter Founder: CTO, CEO, SpaceX has successfully The company market. vehicle In 2019, reused more than 12 first stage boosters. The SpaceX plans to fly its first humans into orbit. is also pursuing internetcompany satellite and the a settlement on Mars. prospects of creating Gwynne Shotwell Elon Musk | COO: CEO: Mueller Tom of Propulsion: CTO Leading NewSpace Companies NewSpace Leading SpaceX successfully launches Falcon Heavy, recovering two of the three stage first boosters 2018 2018 2017 2017 FCC grants grants FCC OneWeb approval to launch an initial constellation 720 low- of Earth orbit satellites 2015 2015 is developing high-quality, high-quality, is developing Systems Accion technologiesaffordable propulsion enable that size Its postage-stamp to space. increased access the most chal- ion engineseven will help meet lenging for CubeSats, propulsion requirements interplanetary or even missions. GEO satellites, Chief Bailey | Founder, Natalya CEO: Founder, Louis Perna Scientist: Analytical an orbital network Space is building - to help data-gathering sat relays of shoebox-size faster, ellites get more information to the ground, changes to existing hardware. without any COO: | Founder, Justin Oliveira CEO: Founder, Al Husseini | Abdul Mohsen Dan Nevius | CTO: Kathawalla Tanveer CFO: Blue Origin is a manufacturer of orbital and The company suborbital reusable rocket systems. aims to pioneer space tourism with its New Shep- and carryard rocket system, people and payloads into space aboard the New Glenn heavy-lift It also manufactures en- rocket launch vehicle. gines used by other NewSpace launch providers. Bob Smith | CEO: Bezos Jeff Founder: constellationDigitalGlobe a satellite operates The high-resolution Earth provides that imagery. platformscloud-based uses thisanalyze to company imagery corporations and governments and provide with the insights to make sound critical decisions. Dr. VP: Exec. | CTO, Dan Jablonsky President: Scott Walter the firstICEYE operates under 100kg to satellite carry Its tech- synthetic-aperture radar (SAR). the Earth images of nology helps create are that - It is devel and time of day. unaffected by weather in satellites of SAR-enabled oping a constellation Agency. conjunction with the European Space Founder: | CSO, Modrzewski Rafal Founder: CEO, Laurila Pekka of 1,980 is producing a constellation OneWeb the planet with high will provide that satellites It is also broadband internet access. speed, producing ground-based user terminals will that SpaceX lands 9 its Falcon orbital booster time the first for BILLIONS 4.6 Launch Industry Made In Space the first 3D prints object in space on the ISS board 2014 2014 555 47 Are located in California Investors BILLIONS Satellite Manufacturing 15.5 SpaceX successfully launches first satellite commercial orbit into 2013 2013 BILLIONS Observation, Venture Capital Firms Angel Investors Corporations Private Equity Banks Telecom, Earth 126.7 Science, National Security Worldwide INVESTORS IN START-UP 2000 SINCE COMPANIES SPACE

SpaceX Dragon SpaceX Dragon berths with ISS, becoming the first space commercial to do so vehicle 2012 2012 *Billions BILLIONS 130 Are located in the US 119.8 $18.4* Consumer Equipment Network Equipment & 2010 2010 SpaceX publishes its launch prices NanoRacks launches platform to the ISS and becomes the commercial first in space laboratory BILLIONS 268.6 Satellite Industry THE SATELLITE INDUSTRY SATELLITE THE $6.3* 2008 SpaceX Falcon SpaceX Falcon 1 becomes the privately- first developed liquid-fuel launch vehicle orbit to reach $4.5* $2.5* $2.3* 195 Worldwide BILLIONS Spaceflight 2006 79.3 2000 2017 NASA establishes establishes NASA Orbital Commercial Transportation Services (COTS) program Government Budgets & Commercial Human

Invested In Debt Financing Invested Since Seed Financing Venture Capital

BILLIONS 35O Early And Late Stage Space Industry 2005 Data from: Bryce Space and Technology, 2018 State of Satellite Industry. NASA NASA Administrator Griffin Mike challenges U.S. industry private space to develop transportation capabilities that the could meet the ISS needs of Landmarks in NewSpace Landmarks in NewSpace START-UP COMPANIES WORLDWIDE START-UP SPACE INVESTMENTS SPACE START-UP SINCE 2000 THE SPACE INDUSTRY THE SPACE The NewSpace Market NewSpace The

TOUGH TECH 02 | 54 | THE ENGINE PORTFOLIO COMPANIES | 57 |

Kytopen Manufacturing Advanced Sciences & Life Biotech, RadixBio Sciences Biotech & Life Things, Internet of Deep Software, Robotics, Suono Bio Sciences Biotech & Life Via Separations Manufacturing Advanced MaterialsAdvanced & Energy, Zapata Computing Quantum Computing Software Analytical Space Analytical Things InternetSpace & of C2Sense Things MaterialsAdvanced Internet & of Electronics Cambridge Semiconductors Biotech Cellino Sciences Biotech & Life Fusion Systems Commonwealth Energy E25Bio Science Biotech & Life Form Energy Energy HyperLight MaterialsAdvanced ISEE AI & Deep Software

THE FOUNDERS THE redefine the future. that hold the potential to that hold the potential converging technologies converging technologies breakthroughs and are working on scientific are working on scientific founders they represent— founders they represent— These 14 companies—and the These 14 companies—and audacious,and the new. transformative, the We invest in the We invest

Companies

Portfolio Portfolio The The

TOUGH TECH 02 | 56 | THE ENGINE PORTFOLIO COMPANIES | 59 | |1| Irene Bosch; Lee Gehrke Bosch; Lee |1| Irene Sanofi Genzyme, Harvard, MIT, Sciences & Life Biotech

THE FOUNDERS THE infectious disease response system will empower patients, patients, infectious disease response system will empower E25Bio’s and public health officials to stem the spread of healthcare workers, knows after all, Disease, strike. it may wherever a potential epidemic, no borders. has worked with image recognition expertsE25Bio has worked a to create mobile-based platform the results of their test along with to catalog will be used by local The data corresponding time and location. a near real-time portrait to create governments epidemic of a potential measures while the spread of disease and take necessary preventative is still controllable. Though the form factor may be simple and affordable, it is a vehicle a vehicle it is Though the form factor be simple and affordable, may E25Bio has developed antibodies. for something far more valuable: well as (as dengue the first test of this kind to distinguish between The lack and Zika. chikungunya, all four subtypes of the disease), misdiagnosis and help eliminate of cross-reactivity in the test will or insufficient treatment. inaccurate The test, a nitrocellulose diagnostic strip a nitrocellulose diagnostic (similar to those found in The test, engineered was for its accuracy pregnancy tests), over-the-counter and affordability. has developed a rapid, point-of-care infectious disease a rapid, E25Bio has developed detects mosquito-borneresponse system that infectious diseases to public health officials with the data while providing in minutes, pinpoint infected areas. deadly infectious diseases. deadly infectious of-care response system for of-care response Pioneering a rapid, point- Pioneering a rapid, E25Bio E25Bio Background Industry Founders

TOUGH TECH 02 | 58 | THE ENGINE PORTFOLIO COMPANIES | 61 | everything. Advanced Materials Advanced Marko Loncar, Cheng Wang Loncar, |1| Mian Zhang, |2| Marko Laboratory for Nanoscale Optics at Harvard University University Nanoscale Harvard at for Optics Laboratory HyperLight Background Founders Industry From the confines of a quantum computer, to data centers, to centers, to data computer, From the confines of a quantum nondescript our city cables spanning our oceans or threaded beneath and profound connectivity. optical fiber enables instant streets, our most fundamental technologies rely on The connections between high at electricity and light waves signals between a device to convert the electro-optic modulator. speeds: are the (LN) Electro-optic modulators with Lithium Niobate made ability to efficiently convert long-known most common due to LN’s LN has remained However, electrical and optical domains. between difficult to fabricate on the chip scale using microfabrication discrete, modulators which has left electro-optic in bulky, processes, integrate with CMOS electronics, forms cannot scale, expensive that certainor achieve platforms Photonics performance based metrics. come with but on-chip integration, on other materials do provide performance trade-offs due to non-ideal material properties. both to achieve way HyperLight has unlocked a foundational unprecedented performance and scalability from LN. through and Marko Loncar, Wang, Cheng The team of Mian Zhang, out of the Laboratory Harvardwork for Nanoscale Optics at chip-scale a method of fabricating integrated, discovered University, devices are key These signal loss. LN modulators with extremely low adding exponentially enablers communications, for the future of data while consuming significantly less power more capacity and speed, than their traditional counterparts. with the power to change with the power to A chip, powered by light, A chip, powered by |2| |1| THE FOUNDERS THE

TOUGH TECH 02 | 60 | THE ENGINE PORTFOLIO COMPANIES | 63 | |1| Dhash Shrivathsa |1| Dhash Shrivathsa MIT Media Lab Olin College, Things, of Internet Deep Software, Robotics, Sciences & Life Biotech

THE FOUNDERS THE

system for biology labs. system for biology Creating a universal operating Creating a universal designed its software to be as accessible and fluid as to be Radix Labs designed its software infrastructure within the existing possible—it had to work of the lab By distancing the specification its users. not intimidate, and empower, of the program—in this case the lab protocol—from the execution, giving them time in the lab, Radix Labs hopes to reduce a biologist’s more time to focus on experimental design and analysis. is driven by the central belief that a biology lab is not just Radix Labs is driven by the central belief that a series a very but of disconnected steps and parts, big and very real In And every a programming computer needs language. computer. programming language unites scientist its declarative case, Radix’s Dhash The software and lab machinery unit. in one automated a typical lab protocol into a runnable translates created Shrivathsa laboratory manages disparate program systematically machines that and human tasks. For all the wonders of its science, today’s biology lab is inefficient today’s science, of its all the wonders For the equipment machines, Its incredible and prone to human error. don’t most profound mysteries, tasked with unlocking some of life’s Humans perform tasks by hand without repetitive talk to each other. Reproducibility of results by peers is difficult precise documentation. or impossible. Radix LabsRadix Background Industry Founder

TOUGH TECH 02 | 62 | THE ENGINE PORTFOLIO COMPANIES | 65 | Cellino The cell therapy industry has great promise to currently but enable the future of medicine, Cellino is supply chain problem. has a massive mix of solving this problem by applying its novel Their and biology to stem cells. optics, nanotech, proprietary “digitally steers” delivery technology cell type any creating stem cells to differentiate, will. at Impact platform for the high-throughput Cellino’s digitization of engineering human cells will making cell-based transform industry, the biotech therapies a staple of 21st-century medicine. Background School of Department, Harvard Physics Harvard Engineering and Applied Sciences (SEAS), Lab Medical School, The Church Harvard & LifeSciences Biotech Founders Wagner, Matthias Stan Wang, Nabiha Saklayen, Marinna Madrid Industry Cambridge Cambridge Electronics Background MTL, Department Laboratories Technology Microsystems Electrical Science EECS Engineering and Computer of Semiconductors Modern-day electronics rely on silicon Cambridge but Electronics aims to processing, bring a revolutionary semiconductor material communications electronics and to power based on their proprietary gallium nitride proprietary The company’s (GaN) technology. technology is targeted to bring energy savings 5G electric cars, centers, to electronics for data consumer devices— the entire communication, energy processing landscape. Impact Cambridge Electronics is transforming a fundamental and ubiquitous technology to an exponentially more efficient and help power exciting future. Founders Palacios Tomas Bin Lu, Industry Founders Nevius Dan Oliveira, Justin Background Industry Analytical Space NASA, Planetary Resources, White House, HBS House, White Resources, NASA, Planetary of in-orbit a network Analytical Space is building use laser that satellites relay communication to offer expanded connectivity communication change to existing without any transfer, for data This results in faster downloading, data hardware. lower windows, more access to download while cost structures, and improved latency, with heritage and new being compatible satellites alike. satellites Impact terabytes and deliver Analytical Space will liberate by hundreds of gathered of untapped data giving humanity a more informed and satellites, dynamic picture of everything from industrial agriculture to weather. Space & Internet of Things of Space & Internet THE FOUNDERS THE

TOUGH TECH 02 | 64 | THE ENGINE PORTFOLIO COMPANIES | 67 | ISEE Founders Chris Baker Yu, Debbie Zhao, Yibiao Background Science Group & Cognitive MIT Computational Industry & AI Deep Software ISEE is engineering next-generation, humanisticISEE is engineering next-generation, core Their cognitive AI for autonomous vehicles. can reason through an uncertain future without sole reliance on hand-coded rules or rote pattern theory modeling, ISEE uses predictive recognition. the to create and probabilistic reasoning of mind, core. cognitive Impact technology will ISEE’s core, Built on a cognitive of safe autonomous vehicles, usher in a world without accident and without the need foroperating human intervention. Founders Wiley, Ted Jaramillo, Chiang, Mateo Yet-Ming Ferrara Marco William Woodford, Background Energy A123, Tesla Technologies, 24M DMSE MIT, Industry Energy Form Energy will solve large-scale renewable Form Energy will solve fundamental limitation—reliability— most energy’s than thinking Rather through energy storage. simply as of batteries in the traditional sense, bidirectional Form is designing storage vessels, to displace fossil fuel baseload Built plants. power core technology Form Energy’s plants, generation via the will store and supply hundreds of megawatts existing energy grid. Impact Form Energy will help usher in a future of clean energy from renewable, baseload humanity’s wind and solar power. Form Energy Form Impact on anBy making gases detectable and trackable improves C2Sense reduces waste, industrial scale, a more and builds safety and health of employees, world. efficient and productive C2Sense & Leadership Founders Linscott George Keller, Eric Tim Swager, Jan Schnorr, Background Lab MIT Tim Swager Industry Things of & Internet Materials Advanced A digital olfactory sensor platform for industry, technology transforms smell into real- C2Sense’s With high- can be accessed remotely. that time data pricefidelity electrochemical sensorsat a low point, a broad array of industriesC2Sense will empower power in food supply, including those involved and chemical production to take control generation, of their environments.

THE FOUNDERS THE Industry Energy Background Center MIT Plasma Science and Fusion Founders Martin Greenwald, Sorbom, Hartwig,Zach Brandon Brunner Dan Bob Mumgaard, Dennis Whyte, Fusion energy is the holy grail of clean energy: Fusion energy is the holy grail of clean energy: baseload, no greenhouse gases, limitless, and no proliferation. no meltdown, concentrated, energy systems will be the world’s If successful, transformed. Impact Commonwealth Fusion Systems (CFS) aims to Commonwealth by combining to fusion power a new path provide with revolutionarymagnet fusion physics proven economic working, the firsttechnology to deploy team will The fusion reactors to the world. superconducting magnets based on a develop superconductor new class of high temperature fusion reactors allow materials times to be 10 that in and operational economically feasible, smaller, the next 10 years.

Fusion Systems Fusion Commonwealth Commonwealth

TOUGH TECH 02 | 66 | THE ENGINE PORTFOLIO COMPANIES | 69 | Zapata Computing Founders Johnson, Alán Aspuru-Guzik, Peter Chris Savoie, Cao Olson, Yudong Jonathan Fontalvo, Romero Jhonathan Background Group Research Aspuru-Guzik Industry Computing Software Quantum Computing writesZapata algorithms that to help of quantum computing harness the power most some of the universe’s predict and simulate molecules behave like how complex interactions, in tandem withWhen used level. an atomic at practical industrial they have quantum hardware, like predicting the structure and applications, effect of new pharmaceutical drugs before they’re for example. synthesized in the lab, Impact algorithmsBy creating bridge in that advances and commercialquantum computing hardware has the potential of helping Zapata applications, energy efficient molecules, new life-saving discover and much more. materials, 12% of all US energy consumption is spent chemical components from one anotherseparating These using thermal like distillation. processes processes help make everything fromseparative But they are grossly inefficient. fertilizer to plastics. a new molecular has developed Via Separations filter using a oxide scaffold and a uniquegraphene manufacturing process to ensure a consistent pore And they’ve the size of the filter. no matter size, specifically designed it to be durable enough for chemical plants. Impact technology can filtration passive The company’s processes by reduce energy used in separative of all the energy 90%—or nearly the equivalent transportation in the US. used for gasoline-powered Via Separations Founders Grossman Jeff Keller, Brent Dave, Shreya Background MIT Group The Grossman Industry Manufacturing Advanced Materials, Advanced & Energy Impact challenging treat Suono Bio will more effectively enable newchronic gastrointestinal diseases and challenges liketherapies for other pressing health and viral infections. cancer, diabetes, Suono Bio Suono & Leadership Founders Schulman, Amy Langer, Robert Carl Schoellhammer, Lisa Ricciardi Gio Traverso, Background Langer Lab MIT Industry Sciences & Life Biotech Suono Bio has reimagined ultrasound as a effective and elegant delivery mechanism for the most Its technology can push therapeutics. delicate proteins directly and RNA, molecules like DNA, into cells without disrupting the surrounding tissue andThe flexibility or harming the molecule itself. efficacyof the Suono Bio therapeutic platform brings and cure diseases with it the potential to treat with targets once deemed undruggable. solution will TM

THE FOUNDERS THE Industry Manufacturing Advanced Sciences, & Life Biotech Background Mechanical Engineering MIT Kytopen Founders Cullen Buie Garcia, Paulo reduce the cost and accelerate time to market forreduce the cost and accelerate and manufacturingdiscovering cell next-generation and gene therapies. Impact non-viral Flowfect The startup’s The technology also enables continuous flow of cells in a platformgenetic manipulation can that and can be used to processbe easily automated both small and large sample volumes. Kytopen aims to improve the efficiency of the aims to improve Kytopen regardless of thegenetic engineering of cells, the With its microfluidic-based tool, application. the genetic and automate can accelerate company engineering of cells 10,000x times faster than current methods.

TOUGH TECH 02 | 68 | “Solving problems that are societally important, not just personally convenient.”| “Bringing the best of the best together to innovate for a better world.” |“Societal impact rather than new toys and amusements.”| “The frontier technology that makes the unimaginable possible.” |“Technical challenges that could generate wealth while improving the lives of 10^6s-10^9s of people.” |“Solving hard problems the right way.” |“Tech that is grounded in deep science that is tough to commercialize due to significant technical risk.” |“It’s what moves the needle.”| “It’s harder, it can take longer, but the payoffs are higher.” |“Frontier science and breakthrough engineering tackling the world’s biggest challenges.”| “Tough Tech is the backbone of any respectable industry.”|“Non trivial solutions to critical problems.” |“Problems too complex for academia and too hard for normal venture capital.” |“A Tough Tech company is a trailblazer, inventing new technologies that disrupts and transforms the status quo.” |“Tough Tech is faith in the power of curiosity.”|“Fundamental changes to human capabilities.” |“Non-trivial technology that has the power to change the way we as a species both live and interact with the world.”