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Modern Meadow -- >>> Can Artificial Meat Save The World?
Traditional chicken, beef, and pork production devours resources and creates waste. Meat-free meat might be the solution.
By Tom Foster
11.18.2013
Popular Science
http://www.popsci.com/article/science/can-artificial-meat-save-world?nopaging=1
The Meat Lab Brian Klutch
On an ordinary spring morning in Columbia, Missouri, Ethan Brown stands in the middle of an ordinary kitchen tearing apart a chicken fajita strip. “Look at this,” he says. “It’s amazing!” Around him, a handful of stout Midwestern food-factory workers lean in and nod approvingly. “I’m just so proud of it.”
The meat Brown is pulling apart looks normal enough: beige flesh that separates into long strands. It would not be out of place in a chicken salad or Caesar wrap. Bob Prusha, a colleague of Brown’s, stands over a stove sautéing a batch for us to eat. But the meat Brown is fiddling with and Prusha is frying is far from ordinary. It’s actually not meat at all.
Brown is the CEO of Beyond Meat, a four-year-old company that manufactures a meat substitute made mainly from soy and pea proteins and amaranth. Mock meat is not a new idea. Grocery stores are full of plant-based substitutes—the Boca and Gardenburgers of the world, not to mention Asian staples like tofu and seitan. What sets Beyond Meat apart is how startlingly meat-like its product is. The “chicken” strips have the distinct fibrous structure of poultry, and they deliver a similar nutritional profile. Each serving has about the same amount of protein as an equivalent portion of chicken, but with zero cholesterol or saturated and trans fats.
To Brown, there is little difference between his product and the real thing. Factory-farmed chickens aren’t really treated as animals, he says; they’re machines that transform vegetable inputs into chicken breasts. Beyond Meat simply uses a more efficient production system. Where one pound of cooked boneless chicken requires 7.5 pounds of dry feed and 30 liters of water, the same amount of Beyond Meat requires only 1.1 pound of ingredients and two liters of water.
The ability to efficiently create meat, or something sufficiently meat-like, will become progressively more important in coming years because humanity may be reaching a point when there’s not enough animal protein to go around. The United Nations expects the global population to grow from the current 7.2 billion to 9.6 billion by 2050. Also, as countries such as China and India continue to develop, their populations are adopting more Western diets. Worldwide the amount of meat eaten per person nearly doubled from 1961 to 2007, and the UN projects it will double again by 2050.
In other words, the planet needs to rethink how it gets its meat. Brown is addressing the issue by supplying a near-perfect meat analogue, but he is not alone in reinventing animal products. Just across town, Modern Meadow uses 3-D printers and tissue engineering to grow meat in a lab. The company already has a refrigerator full of lab-grown beef and pork; in fact, the company’s co-founder, Gabor Forgacs, fried and ate a piece of engineered pork onstage at a 2011 TED talk. Another scientist, Mark Post at Maastricht University in the Netherlands, is also using tissue engineering to produce meat in a lab. In August, he served an entire lab-grown burger to two diners on a London stage as a curious but skeptical crowd looked on.
Chicken-Free Strips It took more than two decades to create a vegetable-based meat analogue with a consistency and texture similar to chicken; Whole Foods began selling the packaged Beyond Meat product in spring. Courtesy Beyond Meat Revolutions tend to appear revolutionary only from a distance, and as Brown walks me to the production floor, I’m struck by how similar the Beyond Meat factory looks to any other. Nondescript metal machinery churns away. Ingredients sit in plastic bulk-foods bins. We put on hairnets and white coats and walk over to a small blue conveyor belt, where Brown’s chicken strips emerge from the machinery cooked and in oddly rectilinear form. They are not yet seasoned, he says, but they are ready to eat. At the end of the conveyor belt, the still-steaming strips fall unceremoniously into a steel bucket, where they land with a dull thud.
Staring at the bucketful of precooked strips, it’s hard to imagine a future in which meat is, by necessity, not meat. Or in which meat is grown in a manufacturing facility instead of a field or feedlot. But that future is fast approaching, and here in the heart of Big Ag country, both Beyond Meat and Modern Meadow are confronting it head on.
Each year, Americans eat more than 200 pounds of meat per person, and mid-Missouri is as good a place as any to see what it takes to satisfy that appetite. Columbia sits dead center in the state, so approaching on I-70 from either direction means driving about two hours past huge tracts of farmland—soy, corn, and wheat fields and herds of grazing cattle. Giant truck stops glow on the horizon, and mile-long trains tug boxcars loaded with grain to places as far away as Mexico and California.
Beyond Meat Factory in Columbia, Missouri, food scientists transform a mix of soy and pea proteins and amaranth into “chicken” strips. Courtesy Beyond Meat
It’s rich country that for nearly 150 years has fed the nation and the world. Yet most of the crops grown around Columbia will never land on dining-room tables but rather in giant feedlot troughs. That’s not unusual. About 80 percent of the world’s farmland is used to support the meat and poultry industries, and much of that goes to growing animal feed. An efficient use of resources this is not. For example, a single pound of cooked beef, a family meal’s worth of hamburgers, requires 298 square feet of land, 27 pounds of feed, and 211 gallons of water.
Supplying meat not only devours resources but also creates waste. That same pound of hamburger requires more than 4,000 Btus of fossil-fuel energy to get to the dinner table; something has to power the tractors, feedlots, slaughterhouses, and trucks. That process, along with the methane the cows belch throughout their lives, contributes as much as 51 percent of all greenhouse gas produced in the world.
To understand how humans developed such a reliance on meat, it’s useful to start at the beginning. Several million years ago, hominids had large guts and smaller brains. That began to reverse around two million years ago: Brains got bigger as guts got smaller. The primary reason for the change, according to a seminal 1995 study by evolutionary anthropologist Leslie Aiello, then of the University College London, is that our ancestors started eating meat, a compact, high-energy source of calories. With meat, hominids did not need to maintain a large, energy-intense digestive system. Instead, they could divert energy elsewhere, namely to power big energy-hungry brains. And with those brains, they changed the world.
As time progressed, meat became culturally important too. Hunting fostered cooperation; cooking and eating the kill brought communities together over shared rituals—as it still does in backyard barbecues. Neal Barnard, a nutrition author and physician at George Washington University, argues that today the cultural appeal of meat trumps any physiological benefits. “We have known for a long time that people who don’t eat meat are thinner and healthier and live longer than people who do,” he says. Nutritionally, meat is a good source of protein, iron, and vitamin B12, but Barnard says those nutrients are easily available from other sources that aren’t also heavy in saturated fats. “For the millennia of our sojourn on Earth, we have been getting more than enough protein from entirely plant-based sources. The cow gets its protein that way and simply rearranges it into muscle. People say, ‘Gee if I don’t eat muscle, where will I get protein?’ You get it from the same place the cow got it.”
To Barnard, the simple conclusion is that everyone should stick to eating plants—and he’s right that it would be a far more efficient use of all that cropland. And yet to most people, meat tastes good. Studies suggest that eating meat activates the brain’s pleasure center in much the same way chocolate does. Even many vegetarians say bacon smells great when it’s cooking. For whatever reason, most people simply love to eat meat—myself included. And that makes
re-creating it, whether from vegetables or cells in a lab, exceedingly difficult.
* * *
In the mid-1980s, a food scientist named Fu-hung Hsieh moved to Columbia, Missouri, to start a food-engineering program at the University of Missouri. Hsieh was coming to academia from a successful career in the processed-foods industry, at Quaker Oats, and he convinced the university to buy him a commercial-grade extrusion machine, nearly unheard of in an academic setting.
Modern Meadow Modern Meadow grows beef and pork cells in heated incubator Courtesy Modern Meadow
An extruder is one of the processed-food industry’s most important and versatile pieces of equipment, the invention responsible for Froot Loops and Cheetos and premade cookie dough. Dry and wet ingredients are poured into a hopper on one end of the machine and a rotating auger pushes them through a long barrel, where they are subjected to varying levels of heat and pressure. At the barrel’s end, the ingredients pass through a die that forms them into whatever shape and texture the machine has been programmed to produce. The mixture emerges at the far end as a continuous ribbon of food, which is sliced into the desired portions.
On one level, an extruder is a simple piece of technology—something like a giant sausage maker—but producing the desired result can be devilishly complicated. “Some people say extrusion cooking is an art form,” says Harold Huff, a meat-loving Missouri native who works with Hsieh as a senior research specialist. Around 1989, Hsieh and Huff took an interest in using the extruder to make the first realistic meat analogue. “We didn’t worry about flavor or anything else,” Hsieh tells me. “We wanted it to tear apart like chicken—it was all just about initial appearance.” They knew there wasn’t a single physical or chemical adjustment that would bring about a solution. They just had to experiment. “You have to have the right ingredients, the right temperature, the right hardware,” Huff says. “You try things, make observations, and make adjustments” for years, even decades. And so it went, until Ethan Brown came calling in 2009.
Brown, a vegan environmentalist, had been working for a fuel-cell company and had become frustrated by his colleagues’ ignorance of meat’s role in climate change. “We would go to conferences and sit there wringing our hands over all these [energy] issues, and then we’d go to dinner and people would order huge steaks,” he says. “I was like, ‘This is stupid, I want to go work on that problem.’?” To the ridicule of old friends, who joked that he was moving to the country to start a tofu factory, he started poring over journal articles and casting around for meat analogues to market—which is how he heard about Hsieh’s work.
Brown licensed the veggie chicken and began fine-tuning it with the scientists for mass consumption. “If we used too much soy, it was too firm, and if we reduced it too much, it became soft, like tofu,” Brown remembers. “It took us two years to figure that out, and it’s still not perfect.”
Lab grown meat Karoly Jakab of Modern Meadow pulls a tray of lab-grown meat from a refrigerator Courtesy Modern Meadow
As Brown and Hsieh refined the product, it began to gain notice. Bill Gates, who has adopted the meat-production crisis as one of his signature issues, published a report about the issue on his blog, The Gates Notes, in which he endorsed Beyond Meat as an important innovation. “I couldn’t tell the difference between Beyond Meat and real chicken,” he wrote. Perhaps more impressive, New York Times food correspondent and best-selling cookbook author Mark Bittman tried Beyond Meat in a blind taste test last year (at the behest of Brown, who served Bittman a burrito) and said that it “fooled me badly.” Twitter co-founder Biz Stone invested in the company last year, not long after the powerful Silicon Valley venture-capital firm Kleiner Perkins Caufield & Byers bought a stake.
“We are going to be meat. We’ll just be slaughtering plants instead of animals.”“One of the partners at Kleiner asked me to meet with Ethan and give them feedback, because they knew I was a vegan. I said yes, really as a favor,” Stone says. “I went into it thinking it’s going to be a boutiquey thing, for well-to-do vegans. Instead, I was introduced to this big-science approach. Ethan was talking about competing in the multibillion-dollar meat business. We are going to be meat, he said, we are just going to be slaughtering plants instead of animals. And here are all the ways it matters, in terms of global health, resource scarcity, number of people in the world. I was like, ‘Oh, my god. They are thinking completely differently.’”
The day I visit, the factory in Columbia is humming because the company is preparing its first shipment of packaged product to Whole Foods, which agreed to sell it nationwide after a successful trial in some California stores. On the production floor, the extruder is roaring away, pumping out strips ready for seasoning, flash-freezing, or quick grilling. A digital readout shows the configuration of the die that gives Beyond Meat its chicken-like structure. It is the company’s secret sauce, the result of all those years of research, and Brown darts over to block my view of the readout as we approach. It’s the one thing that’s not entirely transparent about the operation.
Brown has set up a taste test: three plates of Beyond Meat in three preseasoned flavors. I pop one of the Southwest-flavored strips into my mouth, and it tastes, well, a bit like soy in the form of chicken, sprinkled with chipotle dust. That’s also how it chews—very chicken-like but somehow just shy of chicken. After all the buildup, I’m a little disappointed. But I also have the distinct impression that I’m eating something more like meat than veggies. And I’m eating it unadorned, as opposed to in Bittman’s burrito.
Over the course of the next month, I replace boneless chicken breasts with the lightly seasoned strips in various meals: an omelet with spinach and feta, a plate of fajitas, a wok-ful of fried rice. I’m never once fooled that it’s chicken. For me, chicken is the whole sensory package—crisp skin, the roasting pan, the juices—and when I want one, I make one. But when I want lean, chewy protein as a flavor medium in some other dish, I find I don’t care whether it comes from an animal or vegetable. But what if it comes from neither?
* * *
On the other side of Columbia, at a biotech start-up incubator on the edge of the University of Missouri campus, the scientists at Modern Meadow are working on a very different solution to the meat-production crisis. When I visit, a 3-D printer about the size of an HP desktop unit streams a line of yellowish goo onto a petri dish. Back and forth, the machine creates a series of narrow rows a hair’s breadth apart. After covering a few inches of the dish, the printer switches direction and lays new rows atop the first ones in a crosshatch pattern. There’s no noise but an electric whir, no smell, nothing to suggest that the goo is an embryonic form of meat that will turn into a little sausage. Once the printer finishes its run, the result looks something like a large Band-Aid.
To reach this stage, about 700 million beef cells spent two weeks growing in a cell-growth medium in a wardrobe-size incubator. The cells were then spun free in a centrifuge, and the resulting slurry, which is the consistency of honey, was transferred to a large syringe that acts as the business end of the printer.
The printed cells will now go back into an incubator for a few more days, during which time they will start to develop an extracellular matrix, a naturally occurring scaffold of collagens that gives cells structural support. The result is actual muscle tissue.
The technology in front of me is the work of Gabor Forgacs, a Hungarian-born theoretical physicist who turned to developmental biology mid-career. In 2005, he led a team that developed a process to print multicellular aggregates rather than individual cells. His printer produces physiologically viable tubes of cells that can adhere to create large complex structures.
Modern Meadows Co-Founders Gabor and Andras Forgacs, the father and son co-founders of Modern Meadow Courtesy Modern Meadows
In 2007, Gabor and his son, Andras, helped found a company called Organovo that uses Gabor’s technology to print human tissue for medical applications (pharmaceutical testing, for instance) and aims one day to print functioning human organs for transplants. Gabor was the science mind behind the company, and Andras worked in various roles on the business side.
“Fairly early on, people asked us, ‘Hey, could you make meat?’?” Andras remembers. “And we were pretty dismissive of the idea”—it was simply too far from Organovo’s mission. But by 2011, Organovo had brought on a new management team and laid plans to go public (which it did in early 2012). Gabor began brainstorming new projects with his two closest scientific collaborators—Françoise Marga and Karoly Jakab. Andras, meanwhile, had moved to Shanghai to work in venture capital. He saw how diets in China were changing and how much of the meat came from places as far away as Latin America and Australia.
“If we can make living tissues, then we can certainly make food-grade ones.”That confluence of factors made bio-fabricated meat appear more attractive. Even better, Gabor suspected meat would be simpler to produce than functioning human parts. “If we can make living tissues, then certainly we can make food-grade tissues, which don’t have to be as exacting,” he says. “We do not have to worry about immune compatibility, for instance.”
In late 2011, Andras returned to the U.S., and the team landed a USDA Small Business Innovation Research grant shortly thereafter. It then received a grant from Breakout Labs, an arm of Peter Thiel’s foundation. (Thiel is a co-founder of PayPal and a tech investor and futurist.) With help from the grant, Andras set up a business office at Singularity University on the campus of NASA’s Silicon Valley research park, and Gabor set up his scientific headquarters in Columbia. Modern Meadow was born.
As ghoulish as growing lab meat sounds, the concept has a long history, and not just in science fiction. In 1931, Winston Churchill wrote, “Fifty years hence, we shall escape the absurdity of growing a whole chicken in order to eat the breast or wing, by growing these parts separately under a suitable medium.” He was wrong about the date, but the same sentiment drives the meat-alternatives community today. If you consider the conditions under which meat is produced—how the animals are treated and how much waste is involved—factory farming, not tissue culture, seems the ghoulish option. By comparison, lab meat looks both humane and sensible; a study for the EU predicted that, if produced on a large scale, lab-grown meat would use 99.7 percent less land and 94 percent less water than factory farming, and it would contribute 98.8 percent fewer greenhouse gases.
Over the past few decades, a handful of scientists have pursued lab-grown meat, most notably Mark Post in the Netherlands. Post created the burger for his London taste test using a different tissue-engineering process that involves growing cells around a cylindrical scaffold. According to Isha Datar, the director of New Harvest, a nonprofit research and advocacy group that focuses on meat alternatives, Post’s process may actually be “more amenable to mass production, theoretically” than Modern Meadow’s 3-D printing. On the other hand, Datar points to the head start Modern Meadow has: “It’s an actual business. The other groups are all academic, and you never know if they have the power to get out of the lab.”
By August, Modern Meadow was experimenting with other bio-assembly techniques that could quickly lay down large cell arrays. And Mark Post revealed his own high-profile Silicon Valley backer: Google co-founder Sergey Brin, whose track record bringing improbable products to market isn’t bad.
But being first to market doesn’t matter if the meat coming out of the labs isn’t appetizing. Post’s burger got tepid reviews from his two tasters. And Modern Meadow’s current product is hardly even recognizable as meat; it lacks blood and fat, which are responsible for most of actual meat’s color, flavor, and juicy texture. Karoly Jakab shows me a couple of the samples he’s storing in the lab refrigerator: They look like tiny beige-gray sausages—fully grown, rolled-up versions of the Band-Aid I saw coming out the printer—about the size of an infant’s pinkie finger.
Lab-Grown Burger In August, Mark Post of Maastricht University in the Netherlands served a lab-grown hamburger to two diners. One said it “wasn’t unpleasant.” REUTERS/David Parry/poo
To make the meat more appealing, Modern Meadow has enlisted the Chicago chef Homaro Cantu, whose restaurant, Moto, has become an icon of molecular gastronomy. For Modern Meadow, he’ll be working on what Andras calls “last-mile issues” like texture, flavor, appearance, and mouthfeel by, for instance, suggesting how much fat to add and what kind. And sometime in the next couple of years, Andras says, with Cantu’s help, Modern Meadow plans to start conducting invitation-only tasting sessions, where friends of the company will sign waivers and sample dishes.
There will be plenty of technical hurdles just to get to that point, but putting lab-grown meat in the hands of the masses could be even trickier because there is no regulatory precedent. Meat falls under the USDA’s jurisdiction, but Andras expects the FDA to be involved too. “They have the sophistication and understanding of how tissue engineering works in medicine,” he says. Approval could take at least 10 years.
In the meantime, Modern Meadow needs to make money, so the team is focusing heavily on growing leather, which turns out to be easier than meat and won’t face as many regulatory hurdles. Gabor hands me a pepperoni-size disc of dark-brown leather, indistinguishable from the stuff used in one of my favorite pairs of shoes. It even smells like leather. It is leather. Much as the company is partnering with chef Cantu on perfecting the meat, it’s in talks with fashion brands and automakers to create products with the lab-grown leather.
* * *
Ethan Brown folds his lanky frame into one of the metal chairs at the Main Squeeze, an organic juice café in downtown Columbia, and begins talking about how he’ll define success for Beyond Meat in the near term. “I want to be in the meat aisle,” he says. “You go to the grocery store, and they sell meat in one section and vegetable-based proteins in another section. Why are they penalizing the non-meat?” He points to the rise of soy milk and its eventual inclusion in the dairy aisle—which helped to drive a 500 percent increase in sales since 1997—as his model.
Ethan Brown Ethan Brown of Beyond Meat Jennifer Smith/Beyond Meat
“Our earliest adopters are the vegans and locavore types who prefer tofu and beans and quinoa,” he says. “But the sweet spot for us is folks who are simply cutting down on their meat consumption. They still eat at Taco Bell, but they know they shouldn’t do it that much.”
There’s an uncanny valley of food. Until engineered meat is perfect, it will be creepy.
Appealing to those people with a near-perfect imitation of meat makes sense on one level. But there’s also a risk, Andras Forgacs says. In the world of animation and robotics, there’s a concept called the “uncanny valley,” which states that if a simulated human too closely resembles the real thing, it will repel people. “There’s also an uncanny valley of food,” Andras says. “Until it becomes perfect, it’s going to be creepy.”
I’ve seen the uncanny valley response up close, when I’ve tried to serve my wife Beyond Meat. She has no problem eating processed meats that bear no resemblance to the animal they come from: hot dogs, say, or on the high end, goose liver pâté. And she’ll eat other soy proteins, such as tofu, that don’t pretend to be meat. But she won’t touch Beyond Meat. To her, it imitates the real thing just a little too closely.
Modern Meadow may simply back away from the uncanny valley, rather than try to cross it. “I have an analogy that goes back to Organovo,” Gabor says. “We will never be able to print a heart exactly as it appears in nature—but we don’t have to. What we need is to create an organ that functions as well as your heart, or better, from your own cells so that it works in your body. That we can do. And the same goes for meat. What we are going to put into your mouth is not what you’d get when you slaughter a cow. But from all other points of view—nutritional value, taste—it will be just like the real thing. You recognize it as meat, but it’s a different kind of meat.” Like a hot dog or goose liver pâté.
And if fake meat doesn’t have to perfectly mimic real meat, it can be made even better than the real thing. The teams at Beyond Meat and Modern Meadow envision super meats enhanced with things like omega-3 fatty acids and extra vitamins. “You could eat a Beyond Meat Philly cheesesteak that lowers your cholesterol and gives you sexual prowess,” Brown says. He is only half joking.
However they move forward, neither company envisions its product entirely replacing meat, nor do they see themselves as being in competition with each other. Isha Datar of New Harvest predicts a portfolio of approaches that would address the meat-production crisis: lab-grown meat and plant-based meats, yes, but also sustainably raised livestock and less meat-intensive diets. A 2012 study at the University of Exeter in the U.K. calculated the degree to which diets must change in order to feed the world in 2050 and stave off catastrophic climate change. The researchers found that average global meat consumption would have to decrease from 16.6 percent of average daily calorie intake to 15 percent. That may not sound like much, but it translates to roughly halving the amount of meat in Western diets—a major change, but conceivable with high-quality meat alternatives.
One theme cuts through all those visions of the future: Educated consumers who have the benefit of total transparency into the meat-production process. Brown has considered installing cameras on the Beyond Meat production floor and streaming the video online so people can see for themselves how harmless the process is. The contrast to the secretive policies of industrial slaughterhouses would be stark.
Andras Forgacs Courtesy Modern Meadow
Andras Forgacs imagines something even more dramatic. He pictures Modern Meadow’s production facilities as regional petting zoos. “You’d need to replenish the cell source periodically so all we’d really need is a few animals from which we could take occasional biopsies. They’d be like mascots. Other than getting poked every month or so, they would lead these perfectly charmed lives.” People could come meet the animals as they grazed and then make their way into a facility to watch a giant 3-D printer stream the cells onto trays, where they would grow into pork chops and steaks.
“Would you rather visit a slaughterhouse and see a cow get killed, skinned, and disemboweled right before you go eat a steak dinner, or would you rather visit a petting zoo and a facility that looks a little Willy Wonka–ish and then go eat the meat right afterward?”
It’s a dream, but Andras insists it’s not outlandish. “Bio-fabrication already exists, and it’s inevitable that in the coming decades there will be applications beyond medicine—consumer applications, like food.” The question is whether the world will be ready for them.
Tom Foster’s last piece for Popular Science, about the Leap Motion interface, appeared in the August issue. This article originally appeared in the November 2013 issue of Popular Science.
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Organovo -- >>> Backround info on Organovo founders Andras Forgacs and Gabor Forgacs, from the Modern Meadow website -
>>> Modern Meadow was founded in 2011 by some of the leading tissue engineers and co-inventors of bioprinting. Since its inception, the company has attracted a world class team, advisors and investors who share the aim of leveraging advances in tissue engineering to solve global resource challenges.
http://modernmeadow.com/team/management/
Andras Forgacs, Co-founder and Chief Executive
Andras is an entrepreneur and venture investor in technology and life science. He co-founded Modern Meadow in 2011. Previously, he had also co-founded Organovo, a leader in tissue engineering which pioneered the use of 3D bio-printing to create human tissue for a range of medical applications. Organovo’s bio-printer was named one of the top inventions of 2010 by Time Magazine and the company was recognized by MIT Technology Review on its TR50 list of most innovative companies for 2012.
Andras also served as Managing Director with Richmond Global, an international technology-focused venture fund. Previously, Andras was a consultant in the New York office of McKinsey & Company focused on biopharma and private equity. Earlier, he was a founding member of Citigroup’s corporate and investment banking e-commerce group where he led a team that developed award winning financial technology products and advised large cap corporate clients on a range of corporate finance challenges.
He is also co-founder and Chairman Emeritus of the international non-profit Resolution Project. Andras is a Kauffman Fellow with the Center for Venture Education and a Term Member with the Council on Foreign Relations. Andras holds an MBA from the Wharton School of Business and a Bachelor of Arts with honors from Harvard University.
Gabor Forgacs, Co-founder and Chief Scientific Officer
Dr. Gabor Forgacs is a theoretical physicist turned bioengineer turned innovator and entrepreneur. He is the George H. Vineyard Professor of Biological Physics at the University of Missouri-Columbia, the Executive and Scientific Director of the Shipley Center for Innovation at Clarkson University and scientific founder of Organovo, Inc. and Modern Meadow, Inc.
He was trained as a theoretical physicist at the Roland Eotvos University, Budapest, Hungary and the Landau Institute of Theoretical Physics, Moscow, USSR. He also has a degree in biology. His research interests span from topics in theoretical physics to physical mechanisms in early embryonic development.
He is the co-author of the celebrated text in the field, “Biological Physics of the Developing Embryo” (Cambridge University Press, 2005) that discusses the fundamental morphogenetic mechanisms evident in early development. These mechanisms are being applied to building living structures of prescribed shape and functionality using bioprinting, a novel tissue engineering technology he pioneered. He is the author of over 160 peer-reviewed scientific articles and 5 books.
He has been recognized by numerous awards and citations. In particular, he was named as one of the “100 most innovative people in business in 2010” by FastCompany.
Francoise Marga, Co-founder and Senior Scientist
Dr. Francoise Marga is a co-founder and a Senior Scientist at Modern Meadow. She joined Dr. Forgacs’ laboratory in 2003 and played a crucial role in the development of the bioprinting technology and its two medical applications: the vascular graft and the nerve graft.
She is co-inventor on several related patents, either licensed to Organovo or key to the foundation of Modern Meadow. She was the lead investigator for both companies in their first awarded SBIR grants.
Francoise is a food biochemist by training. Before joining Dr. Forgacs’s laboratory, she worked on the biochemical and biophysical characterization of biopolymers. She holds a PhD from the University of Technology Compiegne (UTC) in France. She came to Canada as postdoctoral fellow and worked at Armand-Frappier Institute in Laval, Quebec on polysaccharide-degrading enzymes. She then moved to Lafayette, LA and worked on cuticle composition in relation with its elastic properties. She came to Columbia as a research associate in the Department of Biological Sciences prior to joining the Forgacs Lab. She is the co-author on several seminal publications on the bioprinting technology.
Karoly Jakab, Co-founder and Senior Scientist
Dr. Karoly Jakab is a co-founder of Modern Meadow. He worked with Dr. Forgacs for over a decade on several biophysics research projects and developed extensive expertise in the biomechanics of cells and tissues.
Karoly’s contribution was instrumental in developing the first generation bioprinters used to create living 3D tissues for regenerative medicine. He co-authored key publications related to bioprinting in the field of biological physics, tissue engineering and biotechnology. Beside his contribution to the basic science in tissue and cell biomechanics, he is also co-inventor on core bioprinting patents currently licensed in the industry of bioprinting.
A physicist by training with strong engineering skills, he designed and built several prototype research instruments and devices, many of them crucial elements in the company’s current manufacturing process.
Karoly holds a Ph.D. in biological physics, his training includes two postdoctoral fellowships in developmental biology (University of Virginia) and vascular tissue engineering (University of Missouri), respectively.
Sarah Sclarsic, Director of Business
Sarah Sclarsic is an entrepreneur with a background in biotechnology. She co-founded Getaround, an innovative peer-to-peer carsharing company. At Getaround Sarah guided operations and business development, crafting novel business relationships within the transportation and insurance industries. She previously worked in venture capital as an investment analyst with Canaan Partners, focusing on early-stage technology companies.
Sarah holds a BA in Bioethics and Public Policy from Harvard University, where she also performed research in a molecular and cellular biology lab. After college she worked in sub-Saharan Africa helping the Clinton Foundation scale up treatment of HIV/AIDS. Sarah is a graduate of Singularity University, a technology studies program based at NASA Ames, and has advised early-stage startups on business strategy, product, and business development.
Hemanth Varadaraju, Process Engineering
Hemanthram Varadaraju manages process engineering for Modern Meadow. Prior to Modern Meadow, he worked for Lonza (Walkersville, MD) as a process engineer to scale-up cell therapy manufacturing processes. He has a broad experience in de-risking operations involved in stem cell manufacturing processes from upstream to downstream. Apart from process development, he has expertise in process modeling to evaluate cost of goods, debottlenecking and optimizing workflow. Earlier, Hemanth was an intern at Monsanto and contributed for process development engineering.
Hemanth holds a Masters in chemical engineering from South Dakota School of Mines and Technology and his graduate research includes applications of nanofiber membranes as an adsorptive medium for bioseparations.
Ryan Kaesser, Research Associate
Ryan Kaesser is a graduate from the University of Missouri – Columbia with a Bachelor of Science in Biological Sciences. During his studies he interned and performed laboratory research on autoimmune disorders. In 2009, he joined the Forgacs Lab. While there he worked with the current Modern Meadow team helping to develop the technology that would lead to the launching of the company. Ryan joined Modern Meadow in June 2012.
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>>> Printing a bit of me
Bioprinting: Building living tissue with a 3D printer is becoming a new business, but making whole organs for transplant remains elusive
The Economist
Mar 8th 2014
http://www.economist.com/news/technology-quarterly/21598322-bioprinting-building-living-tissue-3d-printer-becoming-new-business
IN A state-of-the-art clean room, a scientist clad in a full-body containment suit, a hair net and blue gloves is preparing some printing cartridges—filled not with ink but a viscous milky liquid. Next to her sits a computer connected to a machine that resembles a large ice-cream dispenser, except that each of its two nozzles is made of a syringe with a long needle. Once the scientist clicks on the “run program” button, the needles extrude not a vanilla or chocolate-flavoured treat, but a paste of living cells. These bioinks are deposited in precise layers on top of each other and interspersed with a gel that forms a temporary mould around the cells.
Forty minutes later, the task is finished. Depending on the choice of bioink and printing pattern, the result could have been any number of three-dimensional biological structures. In this case, it is a strand of living lung tissue about 4cm in length and containing about 50m cells.
Since its inception in 2007, researchers at San Diego-based Organovo have experimented with printing a wide variety of tissues, including bits of lung, kidney and heart muscle. Now the world’s first publicly traded 3D bioprinting company is gearing up for production. In January samples of its first product—slivers of human liver tissue—were delivered to an outside laboratory for testing. These are printed in sets of 24 and take about 30 minutes to produce, says Keith Murphy, the firm’s chief executive. Later this year Organovo aims to begin commercial sales.
Each set consists of a plate with 24 wells containing a piece of liver tissue 3mm square and 0.5mm deep. Although prices have not been fixed, a set of tissues like this can sell for $2,000 or more for laboratory use. It might seem expensive, but it could save pharmaceutical companies a lot of money. This is because Organovo’s research indicates that the slivers of liver respond to drugs in many ways like a fully grown human liver would. If this is confirmed by outside testing, researchers could use the printed tissues to test the toxicity of new drugs before deciding whether to embark on expensive clinical trials with patients.
The invention of 3D printing in the 1980s provided a technology now used to manufacture everything from aircraft parts to prosthetic limbs. But the promise of 3D bioprinting is even larger: to create human tissues—layer by layer—for research, drug development and testing, and ultimately as replacement organs, such as a kidney or pancreas, for patients desperately in need of a transplant. Bioprinted organs could be made from patients’ own cells and thus would not be rejected by their immune systems. They could also be manufactured on demand.
At present only a handful of companies are trying to commercialise the production of bioprinted tissues. But Thomas Boland, an early pioneer in the field, says that plenty of others are interested and estimates that about 80 teams at research institutions around the world are now trying to print small pieces of tissues as varied as skin, cartilage, blood vessels, liver, lung and heart. “It’s a wonderful technology to build three-dimensional biological structures,” says Gabor Forgacs, who co-founded Organovo in 2007 and was the company’s scientific mastermind.
Don’t hold your breath
Organ and tissue structures vary in complexity, and some are much harder to make than others
Despite all this interest, the age of organ printing is not just around the corner. Not surprisingly, printing with living cells to create tissues is much more complex than printing objects in plastic or metal. Printing whole organs made from human cells was Dr Forgacs’s original idea when he started Organovo, but it has proved elusive. Yet he and other tissue engineers are hopeful that it will, one day, be possible.
Dr Boland started experimenting in the summer of 2000 using an old Lexmark inkjet printer that was sitting in his former lab at Clemson University in South Carolina. (He is now director of biomedical engineering at the University of Texas at El Paso.) At the time he wasn’t looking to print 3D biological structures, just proteins or cells in two-dimensional patterns. As it turned out, typical inkjet nozzles then were just large enough to accommodate most human cells, which tend to be around 25 microns in diameter (a micron is a millionth of a metre). “The printers at the time were really fulfilling all of the requirements that we would use for cell printing,” says Dr Boland.
Building additively
The potential of the technology quickly became apparent to other scientists. By the early 2000s, several research teams from different laboratories had begun to develop or modify printers to print cells in three dimensions. In Dr Boland’s case, he simply added to an HP printer a platform that could move up and down. In 2003 he filed for his first cell-printing patent and collaborated with Dr Forgacs and three other colleagues on a paper for Trends in Biotechnology in which they predicted that in this century “cell and organ printers will be as broadly used as biomedical research tools as was the electron microscope in the 20th century.” And in September 2004 the University of Manchester in Britain hosted the First International Workshop on Bioprinting and Biopatterning, with 22 speakers from ten countries.
Around the same time, Dr Forgacs began developing the technology that became the basis for Organovo. He devised a technique that could print a large number of cells at one time. Instead of an inkjet’s tiny nozzle that allows only droplets with individual cells to squeeze through, Dr Forgacs invented an extrusion-based printing process that uses a syringe with a needle or micropipette with an orifice that may be as large as several hundred microns. That made it possible to deposit large cell aggregates, in spheroid or cylindrical form. Pressure was applied to push them out, typically using an automated plunger.
Bioprinting is very different to standard tissue-engineering, in which cells are cultured and then seeded onto individual biodegradable moulds or scaffolds whose shapes resemble that of the organ or tissue they are replacing. Depending on the architectural needs of the organ and its function, a scaffold’s properties and structure need to vary as well, says Anthony Atala, a leader in this field and director of the Wake Forest Institute for Regenerative Medicine in North Carolina.
In the case of a blood vessel, the scaffold would have to be thin and elastic. “The scaffold really is acting like a prosthesis, like a device, until the cells are able to take over and lay down their own matrix,” Dr Atala explains. The timing of the scaffold’s demise is critical, he adds. If it degrades too quickly, the transplant is going to fail. But if it degrades too late, after the cells have made their own structure, the patient may end up with scarring.
Dr Atala and his team used to create scaffolds by hand and seeded the cells with a hand-held pipette. 3D printing helped to scale up the process, automate it and make it more precise because the printers run under computer control. His institute now has half-a-dozen 3D printers at its disposal, and in most cases researchers print the scaffold and the cells together. That way, says Dr Atala, “we could not just create one organ at a time, but create many organs at the same time.”
Organ and tissue structures vary in complexity, and some are much harder to make than others. From an architectural standpoint, flat structures, like skin or cartilage, are less complex than tubular ones, such as blood vessels or windpipes, says Dr Atala. Hollow, non-tubular organs, like the bladder, stomach or uterus, are trickier. But the most complex are relatively solid organs, such as the heart, liver or kidneys, which consist of many more cells and an extensive vascular structure.
Transplanted parts
So far, surgeons have been able to implant a variety of engineered flat, tubular and hollow tissues into patients, including skin, cartilage and muscle. Dr Atala has also successfully implanted lab-grown bladders and urethras into young patients. But solid organs are another matter. “That”, he says, “is really the next frontier.”
All tissue engineers have the same goal—to create human organs for transplant—but their approaches differ. In particular, they are divided on how much of a support structure or scaffold they need to provide for the cells, and what building materials are the most suitable.
Dr Forgacs believes that any type of scaffold interferes with a cell’s natural biology. His approach relies on the cells’ intrinsic ability to develop an innate shape and structure, which is akin to the differentiation and developmental processes that occur inside an embryo. Instead of a scaffold he uses what he calls “biopaper”, a water-based gel that is printed along with the bioink and surrounds the cell aggregates. Dr Forgacs calls this process “scaffold-free” bioprinting. The gel is not going to be part of the biological tissue, but a structure that holds the printed material together until the cell clusters themselves begin to fuse.
Because gels could interact with the cells, it is best to remove them quickly, usually in less than 24 hours, concurs Mr Murphy. “Our goal is to make something that’s 100% tissue as quickly as possible,” he says. In the case of Organovo, scientists do it by formulating the gel so they can dissolve it chemically or physically peel it off.
Brian Derby of the University of Manchester and author of a review in Science on printing tissues and scaffolds, emphasises that in some cases it is beneficial to use a scaffold. “People use scaffolds for a reason,” he says, “and that’s because gels have little or no structural integrity.” Rigid tissues, such as bone, require a structure that provides mechanical strength while the cells lay down their own matrix.
One of the biggest challenges facing tissue engineers is creating the necessary blood flow and vascular structure to supply organs with nutrients and oxygen, so they can thrive and survive in the long term. The heart and other solid organs in particular require an entire vascular tree, which is comprised of large blood vessels that branch into smaller and smaller vessels. So far, researchers have been able to make simple blood-vessel structures but not more complex vasculatures that could nourish solid organs.
Bioprinters could potentially construct a series of channels into each layer of cells, and these channels might be used to supply blood to tissue, says Dr Boland, who is working on the problem. His approach is to create hollow tubes from fibrin, a protein involved in blood clotting, surrounded by fat cells. On their inside, the tubes entrap endothelial cells, a type of cell that naturally forms blood vessels. The tubes serve as scaffolds for the cells, which—after being printed—go through a growing phase in an incubator. The structure is then implanted in mice and, if all goes well, connects up and integrates with surrounding tissues. If this approach works out, it could also prove useful for Dr Boland’s company, TeVido BioDevices, which aims to develop custom bioprinted implants and grafts for breast-cancer patients made from their own fat cells.
Organovo is licensing Dr Boland’s original cell-printing patent and has incorporated inkjet technology into its current systems (though the company will not disclose whether it plans to use it to help manufacture liver tissues). While Dr Forgacs’s extrusion process creates larger cell structures very quickly, one important feature of the inkjet-printing approach is its high resolution. It can be used to add detail and to apply thin layers of cells and patterns within layers, says Mr Murphy.
Several laboratories are currently working on developing bioprinters that could print skin cells directly onto wounds and burn injuries. At Wake Forest, researchers use a printer in conjunction with a laser to scan the size and depth of an injury. It produces a topological 3D map of the wound, which is used to determine how much material to deposit at any one spot, explains John Jackson, a member of Wake Forest’s skin-printing team.
Although the majority of bioprinters at Wake Forest are inkjet based, the researchers opted for a pressurised version. This is because of the difficulty of getting cells through the inkjet nozzle. “You get a lot of clogs,” says Dr Jackson. With the system they have chosen the researchers can change nozzle sizes, and the machine can print up to eight different types of cell. Recent studies on animals have shown that it is successful in printing precise layers of cells and cell types onto wounds. The process takes about 20-30 minutes for a wound that is around 10cm in length and width and up to 1cm deep.
The current treatment for burn patients is to take skin grafts from other areas of their body and transplant them onto the wounds. But the supply of skin from the body is limited, and the graft has to be prepared for transplantation. So, asks Dr Atala, why not save a step and print skin cells directly onto the patient? “The patient itself is the best incubator,” he believes. This process might also work for people with diabetes and for the elderly, whose wounds often do not heal well. Dr Jackson hopes, if things go according to plan, that the skin printer could be used in clinical trials within three or four years.
Dr Forgacs’s latest project does not involve bioprinting for medical purposes, but a simplified printing process to create meat for people to eat. When Organovo went public in 2012, he decided to leave the board (though he is still a consultant for the company) and devote more time to being chief scientific officer of Modern Meadow, a startup which he co-founded in 2011. As producing biomaterials for human consumption will probably involve lots of regulatory testing before any products can be brought to market, the company will initially concentrate on making leather (although not with a bioprinting process, but with some other form of biofabrication, says Dr Forgacs). Leather-goods manufacturers will be intrigued to see what he comes up with.
Dr Forgacs is hopeful that scientists will be able to build major organs eventually, although he does not believe they will ever be able to recreate a heart or kidney in the same minute detail as those organs exist inside the body. Instead he suggests researchers should look at building biological structures that function the same way. These will not look like the organs people have, he says, but they will be able to perform some of the same functions.
Mini organs
Organovo is conducting animal tests with structures that are not organs but smaller, patch-sized tissues that it can build. These structures could work like miniature organs and assist damaged tissue to function as normally as possible. For example, a heart-muscle patch could help repair the heart after a myocardial infarction. Or a patch could be used to bypass a blocked blood vessel. These are early-stage studies and no results have yet been disclosed. The company will evaluate a number of tissues which might be bioprinted as patches or mini organs, and then choose one or two with which it may proceed to clinical trials, possibly within the next five years, says Organovo’s Mr Murphy.
Ibrahim Ozbolat from the University of Iowa co-wrote a review of bioprinting and organ fabrication last year. He believes miniature organs are an important step towards creating fully functional organs, as they may be able to perform the most vital functions, such as the secretion of insulin to help the pancreas regulate glucose levels. The mini organs or patches may not cure patients, but could improve their quality of life. “The good news is the field is growing tremendously,” says Dr Boland. The arrival of the first products on the market will encourage more people to start working on bioprinting, and thus further breakthroughs.
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Organovo -- >>> The next frontier in 3-D printing: Human organs
Brandon Griggs, CNN
April 3, 2014
http://www.cnn.com/2014/04/03/tech/innovation/3-d-printing-human-organs/index.html
Their precise process can reproduce vascular systems required to make organs viable
(CNN) -- The emerging process of 3-D printing, which uses computer-created digital models to create real-world objects, has produced everything from toys to jewelry to food.
Soon, however, 3-D printers may be spitting out something far more complex, and controversial: human organs.
For years now, medical researchers have been reproducing human cells in laboratories by hand to create blood vessels, urine tubes, skin tissue and other living body parts. But engineering full organs, with their complicated cell structures, is much more difficult.
Enter 3-D printers, which because of their precise process can reproduce the vascular systems required to make organs viable. Scientists are already using the machines to print tiny strips of organ tissue. And while printing whole human organs for surgical transplants is still years away, the technology is rapidly developing.
"The mechanical process isn't all that complicated. The tricky part is the materials, which are biological in nature," said Mike Titsch, editor-in-chief of 3D Printer World, which covers the industry. "It isn't like 3-D printing plastic or metal. Plastic doesn't die if you leave it sitting on an open-air shelf at room temperature for too long."
Lawrence Bonassar, a professor of biomedical engineering at Cornell University, with an artificial ear made via 3-D printing and injectable molds.
The idea of printing a human kidney or liver in a lab may seem incomprehensible, even creepy. But to many scientists in the field, bioprinting holds great promise. Authentic printed organs could be used for drug or vaccine testing, freeing researchers from less accurate methods such as tests on animals or on synthetic models.
Then there's the hope that 3-D printers could someday produce much-needed organs for transplants. Americans are living longer, and as we get deeper into old age our organs are failing more. Some 18 people die in the United States each day waiting in vain for transplants because of a shortage of donated organs -- a problem that Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine and a pioneer in bioprinting, calls "a major health crisis."
An 'exciting new area of medicine'
Bioprinting works like this: Scientists harvest human cells from biopsies or stem cells, then allow them to multiply in a petri dish. The resulting mixture, a sort of biological ink, is fed into a 3-D printer, which is programmed to arrange different cell types, along with other materials, into a precise three-dimensional shape. Doctors hope that when placed in the body, these 3-D-printed cells will integrate with existing tissues.
The process already is seeing some success. Last year a 2-year-old girl in Illinois, born without a trachea, received a windpipe built with her own stem cells. The U.S. government has funded a university-led "body on a chip" project that prints tissue samples that mimic the functions of the heart, liver, lungs and other organs. The samples are placed on a microchip and connected with a blood substitute to keep the cells alive, allowing doctors to test specific treatments and monitor their effectiveness.
"This is an exciting new area of medicine. It has the potential for being a very important breakthrough," said Dr. Jorge Rakela, a gastroenterologist at the Mayo Clinic in Phoenix and a member of the American Liver Foundation's medical advisory committee.
One of Organovo's engineers oversees the construction of a vascular tissue construct on a NovoGen MMX bioprinter.
"Three-D printing allows you to be closer to what is happening in real life, where you have multiple layers of cells," he said. With current 2-D models, "if you grow more than one or two layers, the cells at the bottom suffocate from lack of oxygen."
To accelerate the development of bioprinted organs, a Virginia foundation that supports regenerative medicine research announced in December it will award a $1 million prize for the first organization to print a fully functioning liver.
One early contender for the prize is Organovo, a California start-up that has been a leader in bioprinting human body parts for commercial purposes. Using cells from donated tissue or stem cells, Organovo is developing what it hopes will be authentic models of human organs, primarily livers, for drug testing.
The company has printed strips of human liver tissue in its labs, although they are still very small: four by four by one millimeter, or about one-fourth the size of a dime. Each strip takes about 45 minutes to print, and it takes another two days for the cells to grow and mature, said Organovo CEO Keith Murphy. The models can then survive for about 40 days.
Organovo has also built models of human kidneys, bone, cartilage, muscle, blood vessels and lung tissue, he said.
"Basically what it allows you to do is build tissue the way you assemble something with Legos," Murphy said. "So you can put the right cells in the right places. You can't just pour them into a mold."
Ethical concerns
Not everyone is comfortable with this bold new future of lab-built body parts, however.
A research director at Gartner Inc., the information-technology research and advisory firm, believes 3-D bioprinting is advancing so quickly that it will spark a major ethical debate by 2016.
A 3-D printer at Cornell University produces an artificial ear.
"Three-D bioprinting facilities with the ability to print human organs and tissue will advance far faster than general understanding and acceptance of the ramifications of this technology," Pete Basiliere said in a recent report.
"These initiatives are well-intentioned, but raise a number of questions that remain unanswered," Basiliere added. "What happens when complex 'enhanced' organs involving nonhuman cells are made? Who will control the ability to produce them? Who will ensure the quality of the resulting organs?"
Bioprinted organs are also likely to be expensive, which could put them out of reach of all but the wealthiest patients.
Murphy said Organovo only uses human cells in creating tissues, and doesn't see any ethical problems with what his company is doing.
"People used to worry about doing research on cadavers ... and that dissipated very quickly," he said. "We don't think there's any controversy if you're producing good data and helping people with health conditions."
Most experts, including Wake Forest's Atala, don't think we'll see complex 3-D-printed organs, suitable for transplants, for years if not decades. Instead, they believe the next step will be printing strips of tissue, or patches, that could be used to repair livers and other damaged organs.
Organovo's NovoGen MMX bioprinter is small enough to fit into a cabinet.
"We are very eager to put pieces of tissue to work for surgical transplants," said Organovo's Murphy, who hopes his company will be ready to begin clinical trials within five years.
Of course, any use of 3-D-printed tissue in surgical procedures would require approval by the U.S. Food and Drug Administration. That review process could take up to a decade.
By then, the notion of a surgeon putting a 3-D-printed kidney into a patient may not seem so bizarre. Then again, this swiftly evolving technology may create new moral conundrums.
"The ethical questions are bound to be the same concerns we have seen in the past. Many major medical breakthroughs have suffered moral resistance, from organ transplants to stem cells," said Titsch of 3D Printer World.
"Will only the rich be able to afford it? Are we playing God? In the end, saving lives tends to trump all objections."
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