What comes first: the chicken or the egg? ARTURO ELIZONDO’S biotech is reinventing protein, reshaping global diet and future-proofing the food industry. read on about the world’s first liquid egg made without hens.



Protein water, protein ice cream, protein pasta, protein cookies and protein cereal.



These are just a few of the interesting products on-shelf for anyone looking to increase their daily protein intake. With analysts forecasting that the global protein ingredients’ market will reach $47.4 billion by 2032, there’s no doubt that this macronutrient is having a moment. We have become protein-obsessed but it’s not all about meat. 



Plant-based options are coming into their own as biotech companies create innovative ingredients that mimic animal meat characteristics while meeting consumer protein needs. A great example is heme, the molecule that gives meat its characteristic color and flavor. Heme is also found in plants and microorganisms so through fermentation or genetic engineering, it can be produced from plant or microbial sources. When heme is added to plant-based meat, it becomes eerily similar to the real thing. It’s an incredibly complex process that’s hard to scale, which is why Arturo Elizondo, the co-founder and CEO of The EVERY Company, started with an egg.



One of the biggest obstacles with bio-based products is the ‘valley of death’. Many innovative products die before they hit the market. “It’s one of the challenges with alternative proteins,” explains Elizondo. “So, our big focus, from the beginning, was choosing a technology that could scale; that had already scaled globally.” This is one of the reasons Elizondo chose fermentation for The EVERY Company – he could plug into existing, large-scale fermentation facilities without spending millions of dollars.



“Brewers use yeast to convert sugar into alcohol; we can use yeast to convert sugar into protein,” he says.



Protein is a megatrend that isn’t going away anytime soon. Elizondo says that even though it’s a big part of diet culture – both the keto and the caveman eating plans focus heavily on protein – there are benefits beyond satiety. “It’s the only macromolecule that hasn’t been demonized,” he says. “There are four macromolecules – protein, fats, carbohydrates and alcohol. Fats, carbs and alcohol are all controversial, but protein has maintained its halo.” There’s also the fact that globally, diets are dominated largely by animal proteins which, when farmed industrially, have a significant impact on the environment. “We have to start evolving the way we product protein because the demand isn’t going away,” he adds. As an alternative to the factory farming model, Elizondo believes we can use technology to produce protein in a healthier and more sustainable way. It’s not only about making products that look and taste similar to something else, he says that technology, in the long run, can create better food (and food systems) designed for humans.



One of the proteins Elizondo’s company is relooking is the egg. Although egg consumption in Africa is beyond the global average, it’s estimated that around 1.6 trillion eggs enter the market every year. “And it’s not suddenly going to stop. We’re not all going to start eating lentils and tofu,” he laughs. What makes The EVERY Company a little different is that it is an ingredients company. They’re not simply producing a consumer facing substitute for eggs (although they do have a few), they’re working with major industry players to integrate EVERY Company’s alternative protein ingredient into existing products and supply chains. 



“The unsexy thing about food is the supply chain. When the Covid pandemic happened and countries shut down their borders, it was a big wake-up call for the companies who import their animal protein,” says Elizondo. Another challenge is avian influenza, also known as bird flu. The poultry industry suffers, the price of eggs goes up and the manufacturers that use eggs are forced to adjust production schedules or reformulate recipes to cope with shortages. 



“How do we build a more resilient food system that can withstand the pressures of pandemics, climate change and zoonotic diseases? It’s a very fragile system,” he says. 



At the same time, many big food companies have ESG targets to cut carbon emissions and keep their supply chains steady. This usually means more consistent sourcing, avoiding rushed shipping and relying less on resource-heavy practices (like industrial egg farming which produces high levels of waste and emissions). “This is why we exist and how we can make impact at scale. We can support the entire industry and not be seen as adversarial. We’re building a better food system,” he says. For Elizondo, this is the future of food. In addition to working with major food producers on the ingredients side, The EVERY Company will be entering the mass market in 2025 with the EVERY Egg, the world’s first liquid egg made without hens. It’s not an elitist product that only expensive grocery stores will carry but rather an item everyone can find, afford and most importantly, eat.



Functionality first



As an industry, plant-based protein companies face a lot of challenges. In France, the words ‘steak’, ‘bacon’, and ‘sausage’ have been outlawed for meat alternatives. In South Africa, the High Court overturned an attempt by the Department of Agriculture, Land Reform and Rural Development (DALRRD) to impose similar restrictions. The issue took two years to resolve, and certain products were removed in the interim from retail shelves.



“This is why it’s so important to partner with the incumbents and work with them, not against them. There’s this huge gap in ingredients that no one talks about and that’s where our focus lies. It’s not about taste, it’s about functionality,” says Elizondo. “If you look at ingredient labels, it’s almost impossible to avoid eggs, they’re everywhere because they’re functional. They foam, bind and gel in ways that nothing else can.”



Eggs may seem like an impossible ingredient to replace but that’s where the biggest opportunity for The EVERY Company lies. In some ways, Elizondo compares the path he’s following to insulin. In 1922, insulin came from the pancreatic tissue of cows (and later pigs). It was produced at scale by Eli Lily to treat diabetes but still came from animals. But then, in 1978, the first genetically engineered, synthetic ‘human’ insulin was produced using E. coli bacteria. “This company found a way to make insulin through protein fermentation technology and within 15 years, it dominated the market. And now, 99% of insulin in the world is made using the same technology,” says Elizondo. Protein fermentation technology moved to the cheese industry and replaced animal rennet with bio-identical chymosin, an enzyme essential for curdling milk. It’s a technique also used to create vitamins and to extend the freshness of baked goods by synthesizing enzymes that improve texture and shelf life. Protein is more than a megatrend, “it’s the best-kept secret in the food industry,” exclaims Elizondo. “And if we can make these ingredients a little bit better, a little bit safer, a little bit more sustainable, that’s worth fighting for.”

Arturo Elizondo in The EVERY kitchen; Image supplied

The Future Of Food: Hatching A Protein Revolution

hen&nbsp;<a href="https://www.forbes.com/pictures/mkg45mjhl/rachel-haurwitz-28/#5a3a19963b10" target="_blank" rel="noreferrer noopener">Rachel Haurwitz</a>&nbsp;started her biology Ph.D. at the University of California, Berkeley, the award-winning biochemist Jennifer Doudna suggested Haurwitz investigate part of a bacterial immune system. She studied how microbes store genetic mementos of attacking viruses and recognize them to fight off future assaults. “It was an esoteric project,” Haurwitz says.&nbsp;



It’s esoteric no more. This system, called Crispr, has become one of the hottest technologies in biology, with the potential to give scientists control of the building blocks of life and give investors rich rewards. Crispr had no obvious relevance to human health when it was first described in 1987, but Doudna, who won the Breakthrough Prize in Life Sciences for her Crispr work, and other pioneers have discovered ways to turn it into a gene-editing tool. Haurwitz and Doudna helped found Caribou Bio­sciences in 2011 to get in on the action. Haurwitz, still in her 20s, became CEO the next year.&nbsp;



Haurwitz is not the only young entrepreneur who sees opportunity in gene editing. Doudna cofounded Mammoth Bio­sciences with some of her other doctoral students and two Stanford Ph.D.s.&nbsp;<a href="https://www.forbes.com/sites/michelatindera/2018/11/13/meet-the-2019-30-under-30-in-healthcare/#15467cf173a9" target="_blank" rel="noreferrer noopener">Trevor Martin, the company’s 30-year-old CEO</a>, has raised $23 million from such investors as Apple CEO Tim Cook. In 2015, in Cambridge, Massachusetts, 29-year-old Luhan Yang founded eGenesis with her mentor,&nbsp;<a href="https://www.forbes.com/forbes/2009/0427/020-biofuels-biotech-genetics-ideas-opinions.html#32dea2e05083" target="_blank" rel="noreferrer noopener">Harvard geneticist George Church</a>, to use Crispr to help transplant pig organs into people. Omar Abudayyeh and Jonathan Gootenberg, also in their 20s,&nbsp;<a href="https://www.forbes.com/sites/elliekincaid/2019/03/21/with-launch-of-new-crispr-company-competition-extends-to-diagnostics/#6e643e4f501e" target="_blank" rel="noreferrer noopener">cofounded Sherlock Biosciences</a>&nbsp;with another Crispr pioneer, 37-year-old Feng Zhang of the Broad Institute of MIT and Harvard.



“They may be young, but in both cases these are people at the top of their game scientifically,” Doudna says of her cofounders. “They’re fearless in all the right ways and very aware of the ethical challenges.” &nbsp;&nbsp;



Given that no one had built a Crispr company until a few years ago, “there’s maybe more of an opportunity for people with nontraditional backgrounds,” Haurwitz says.



Crispr is an acronym for “clustered regularly interspaced short palindromic repeats.” It refers to the way bacteria store, in their genomes, snippets of viral DNA, like mug shots. Those markers&nbsp;are used to identify invaders that return, much as a human immune system uses telltale elements of a polio virus remembered from a vaccine.



If an invading virus matches a stored mug shot, enzymes associated with Crispr break the virus’ lethal DNA into harmless pieces. Doudna and others figured out how to use those enzymes to snip DNA at precise points in order to insert or modify genes. Thus does Crispr promise to make the expensive and buggy process of rewriting DNA easier, opening up new ways to treat dis­eases caused by genetic mutations, create cheaper diagnostic tests and engineer cells that kill cancer.



Eight years after its start in Berkeley, Caribou has raised $41 million and cut licensing deals—potentially worth hundreds of millions of dollars—with DuPont Pioneer, Novartis and others. It’s starting to develop medical therapies.



Haurwitz grew up in Austin, Texas, and earned a bachelor’s degree in biology at Harvard. She didn’t have a clear plan when she went on to UC Berkeley, but she thought she might later become a patent attorney.&nbsp;



That thinking changed as her Ph.D. work got more exciting. Haurwitz and Doudna spent a lot of time talking about how they could repurpose Crispr for modifying genomes to cure disease. Program the naturally occurring Crispr system to cut the gene you want to modify, and it’s theoretically possible to use it to change the genetic code to either fix “misspellings” that cause illness or disrupt the production of an unwanted protein.



Caribou started out with the notion of making Crispr technology available for DNA editing in applications such as drug development, agriculture and basic biological research. Haurwitz’s cofounders didn’t want to leave academia and were “crazy enough to let a 26-year-old who had never worked for a company in her life take on the role of president and CEO,” she says.&nbsp;



Haurwitz took a few business classes before getting her Ph.D., then pitched venture capitalists on funding a technology they didn’t really understand. Caribou was securing an exclusive license to some Crispr patents held by the University of California system and the University of Vienna. Still, “pretty much every VC we ­talked to kind of said, ‘Meh,’ ” Haurwitz remembers. This was 2012, and they thought she was overestimating Crispr’s potential.&nbsp;



The papers that propelled Crispr into the limelight came the next year, and investor dollars and a wave of new companies quickly followed. Editas Medicine, cofounded by Sherlock’s Feng Zhang, raised $43 million to apply the technology to medical therapies. Next was Intellia Therapeutics, cofounded by Caribou, which raised $15 million in its 2014 launch. And Crispr Therapeutics, founded by Crispr pioneer Emmanuelle Charpentier, raised $89 million. The three went public in 2016 and now have a combined market capitalization of $3.8 billion.



Meanwhile, Haurwitz was being cold-called by plant-breeding and drug companies. DuPont led an $11 million investment in 2015. Caribou raised another $30 million the next year and has been able to sustain itself on that funding and payments from licensing and partnership deals.



Caribou licensed to Integrated DNA Technologies the right to sell biology researchers what they’d need for gene-editing experiments. Genus, an animal genetics firm, paid Caribou an undisclosed amount for the exclusive right to use its proprietary Crispr technology to engineer the genes of pigs and other livestock. Similarly, the Jackson Laboratory is paying Caribou to use Crispr to engineer new populations of research mice that model human diseases.&nbsp;



Haurwitz will soon have to seek venture capital again, as Caribou has pivoted to drug development, which is expensive but potentially more lucrative. Her first focus: improve on existing cancer therapies that take patients’ immune cells and train them to attack cancer. Crispr, she says, could be used to edit the DNA of immune cells from healthy donors so that these cells could be given to any cancer patient. The company plans to start trials in humans next year. There’s competition, from Allogene Therapeutics and its partner Cellectis, which have a combined market cap of $3.9 billion.



Caribou is also developing a program in another buzzy area: the microbiome, or the many bacteria that inhabit all parts of the human body, particularly the gut. This time, investors know what Crispr is, and Haurwitz has already won some over. “She’s one of the few people that I’ve met in my life that is able to toggle between business talk and scientific talk in a heartbeat,” says Ambar Bhattacharyya, a Caribou investor at Maverick Ventures.



Beyond the competition, there is an intellectual property conflict. Overlapping patent claims from the University of California and the Broad Institute emerged for the foundational technology, which involves an enzyme called Cas9, used to cut DNA. A lawsuit between the institutions was decided in favor of the Broad, but the U.S. Patent Office has granted patents to both. UC’s patents claim broader rights than were demonstrated in its application, says Lisa Ouellette, a Stanford Law School professor, and could make them vulnerable to a legal challenge. (UC disagrees.)



Whoever owns the technology will command fat fees. Caribou might run trials related to a particular gene, but if other companies want to run trials related to other genes, they may have to approach Caribou, says Jacob Sherkow, a professor at New York Law School. “They’re going to have to pay handsomely.”



Legal battles aside, the new field risks public backlash. In November, Chinese scientist He Jiankui announced he’d used Crispr to tinker with the genomes of human embryos born as twin girls, thereby heightening pressure on ­Crispr scientists to consider the ethics of how they’re using the life-altering tech. Caribou’s license agreements include language to prevent its use on human embryos, Haurwitz says. 



Doudna says researchers need to vet the science of editing the genes of embryos, and then people need to discuss how to use it responsibly. “Are there real unmet medical needs that would require this kind of editing or not? I think that’s one question.”



Debate over the answer will shape Crispr’s path to commercialization, one that holds immense potential for its youthful founders—and the likelihood of yet more controversy and conflict.



-Michela Tindera;Forbes Staff



-Ellie Kincaid;Forbes Staff

Tag: Biotech

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