With Lab-Grown Chicken Nuggets, Dumplings, and Burgers, Futuristic Foods Aim to Seem Familiar
Sandhya Sriram is at the forefront of the expanding lab-grown meat industry in more ways than one.
"[Lab-grown meat] is kind of a brave new world for a lot of people, and food isn't something people like being brave about."
She's the CEO and co-founder of one of fewer than 30 companies that is even in this game in the first place. Her Singapore-based company, Shiok Meats, is the only one to pop up in Southeast Asia. And it's the only company in the world that's attempting to grow crustaceans in a lab, starting with shrimp. This spring, the company debuted a prototype of its shrimp, and completed a seed funding round of $4.6 million.
Yet despite all of these wins, Sriram's own mother won't try the company's shrimp. She's a staunch, lifelong vegetarian, adhering to a strict definition of what that means.
"[Lab-grown meat] is kind of a brave new world for a lot of people, and food isn't something people like being brave about. It's really a rather hard-wired thing," says Kate Krueger, the research director at New Harvest, a non-profit accelerator for cellular agriculture (the umbrella field that studies how to grow animal products in the lab, including meat, dairy, and eggs).
It's so hard-wired, in fact, that trends in food inform our species' origin story. In 2017, a group of paleoanthropologists caused an upset when they unearthed fossils in present day Morocco showing that our earliest human ancestors lived much further north and 100,000 years earlier than expected -- the remains date back 300,000 years. But the excavation not only included bones and tools, it also painted a clear picture of the prevailing menu at the time: The oldest humans were apparently chomping on tons of gazelle, as well as wildebeest and zebra when they could find them, plus the occasional seasonal ostrich egg.
These were people with a diet shaped by available resources, but also by the ability to cook in the first place. In his book Catching Fire: How Cooking Made Us Human, Harvard primatologist Richard Wrangam writes that the very thing that allowed for the evolution of Homo sapiens was the ability to transform raw ingredients into edible nutrients through cooking.
Today, our behavior and feelings around food are the product of local climate, crops, animal populations, and tools, but also religion, tradition, and superstition. So what happens when you add science to the mix? Turns out, we still trend toward the familiar. The innovations in lab-grown meat that are picking up the most steam are foods like burgers, not meat chips, and salmon, not salmon-cod-tilapia hybrids. It's not for lack of imagination, it's because the industry's practitioners know that a lifetime of food memories is a hard thing to contend with. So far, the nascent lab-grown meat industry is not so much disrupting as being shaped by the oldest culture we have.
Not a single piece of lab-grown meat is commercially available to consumers yet, and already so much ink has been spilled debating if it's really meat, if it's kosher, if it's vegetarian, if it's ethical, if it's sustainable. But whether or not the industry succeeds and sticks around is almost moot -- watching these conversations and innovations unfold serves as a mirror reflecting back who we are, what concerns us, and what we aspire to.
The More Things Change, the More They Stay the Same
The building blocks for making lab-grown meat right now are remarkably similar, no matter what type of animal protein a company is aiming to produce.
First, a small biopsy, about the size of a sesame seed, is taken from a single animal. Then, the muscle cells are isolated and added to a nutrient-dense culture in a bioreactor -- the same tool used to make beer -- where the cells can multiply, grow, and form muscle tissue. This tissue can then be mixed with additives like nutrients, seasonings, binders, and sometimes colors to form a food product. Whether a company is attempting to make chicken, fish, beef, shrimp, or any other animal protein in a lab, the basic steps remain similar. Cells from various animals do behave differently, though, and each company has its own proprietary techniques and tools. Some, for example, use fetal calf serum as their cell culture, while others, aiming for a more vegan approach, eschew it.
"New gadgets feel safest when they remind us of other objects that we already know."
According to Mark Post, who made the first lab-grown hamburger at Maastricht University in the Netherlands in 2013, the cells of just one cow can give way to 175 million four-ounce burgers. By today's available burger-making methods, you'd need to slaughter 440,000 cows for the same result. The projected difference in the purely material efficiency between the two systems is staggering. The environmental impact is hard to predict, though. Some companies claim that their lab-grown meat requires 99 percent less land and 96 percent less water than traditional farming methods -- and that rearing fewer cows, specifically, would reduce methane emissions -- but the energy cost of running a lab-grown-meat production facility at an industrial scale, especially as compared to small-scale, pasture-raised farming, could be problematic. It's difficult to truly measure any of this in a burgeoning industry.
At this point, growing something like an intact shrimp tail or a marbled steak in a lab is still a Holy Grail. It would require reproducing the complex musculo-skeletal and vascular structure of meat, not just the cellular basis, and no one's successfully done it yet. Until then, many companies working on lab-grown meat are perfecting mince. Each new company's demo of a prototype food feels distinctly regional, though: At the Disruption in Food and Sustainability Summit in March, Shiok (which is pronounced "shook," and is Singaporean slang for "very tasty and delicious") first shared a prototype of its shrimp as an ingredient in siu-mai, a dumpling of Chinese origin and a fixture at dim sum. JUST, a company based in the U.S., produced a demo chicken nugget.
As Jean Anthelme Brillat-Savarin, the 17th century founder of the gastronomic essay, famously said, "Show me what you eat, and I'll tell you who you are."
For many of these companies, the baseline animal protein they are trying to innovate also feels tied to place and culture: When meat comes from a bioreactor, not a farm, the world's largest exporter of seafood could be a landlocked region, and beef could be "reared" in a bayou, yet the handful of lab-grown fish companies, like Finless Foods and BlueNalu, hug the American coasts; VOW, based in Australia, started making lab-grown kangaroo meat in August; and of course the world's first lab-grown shrimp is in Singapore.
"In the U.S., shrimps are either seen in shrimp cocktail, shrimp sushi, and so on, but [in Singapore] we have everything from shrimp paste to shrimp oil," Sriram says. "It's used in noodles and rice, as flavoring in cup noodles, and in biscuits and crackers as well. It's seen in every form, shape, and size. It just made sense for us to go after a protein that was widely used."
It's tempting to assume that innovating on pillars of cultural significance might be easier if the focus were on a whole new kind of food to begin with, not your popular dim sum items or fast food offerings. But it's proving to be quite the opposite.
"That could have been one direction where [researchers] just said, 'Look, it's really hard to reproduce raw ground beef. Why don't we just make something completely new, like meat chips?'" says Mike Lee, co-founder and co-CEO of Alpha Food Labs, which works on food innovation more broadly. "While that strategy's interesting, I think we've got so many new things to explain to people that I don't know if you want to also explain this new format of food that you've never, ever seen before."
We've seen this same cautious approach to change before in other ways that relate to cooking. Perhaps the most obvious example is the kitchen range. As Bee Wilson writes in her book Consider the Fork: A History of How We Cook and Eat, in the 1880s, convincing ardent coal-range users to switch to newfangled gas was a hard sell. To win them over, inventor William Sugg designed a range that used gas, but aesthetically looked like the coal ones already in fashion at the time -- and which in some visual ways harkened even further back to the days of open-hearth cooking. Over time, gas range designs moved further away from those of the past, but the initial jump was only made possible through familiarity. There's a cleverness to meeting people where they are.
"New gadgets feel safest when they remind us of other objects that we already know," writes Wilson. "It is far harder to accept a technology that is entirely new."
Maybe someday we won't want anything other than meat chips, but not today.
Measuring Success
A 2018 Gallup poll shows that in the U.S., rates of true vegetarianism and veganism have been stagnant for as long as they've been measured. When the poll began in 1999, six percent of Americans were vegetarian, a number that remained steady until 2012, when the number dropped one point. As of 2018, it remained at five percent.
In 2012, when Gallup first measured the percentage of vegans, the rate was two percent. By 2018 it had gone up just one point, to three percent. Increasing awareness of animal welfare, health, and environmental concerns don't seem to be incentive enough to convince Americans, en masse, to completely slam the door on a food culture characterized in many ways by its emphasis on traditional meat consumption.
"A lot of consumers get over the ick factor when you tell them that most of the food that you're eating right now has entered the lab at some point."
Wilson writes that "experimenting with new foods has always been a dangerous business. In the wild, trying out some tempting new berries might lead to death. A lingering sense of this danger may make us risk-averse in the kitchen."
That might be one psychologically deep-seated reason that Americans are so resistant to ditch meat altogether. But a middle ground is emerging with a rise in flexitarianism, which aims to reduce reliance on traditional animal products. "Americans are eager to include alternatives to animal products in their diets, but are not willing to give up animal products completely," the same 2018 Gallup poll reported. This may represent the best opportunity for lab-grown meat to wedge itself into the culture.
Quantitatively predicting a population's willingness to try a lab-grown version of its favorite protein is proving a hard thing to measure, however, because it's still science fiction to a regular consumer. Measuring popular opinion of something that doesn't really exist yet is a dubious pastime.
In 2015, University of Wisconsin School of Public Health researchers Linnea Laestadius and Mark Caldwell conducted a study using online comments on articles about lab-grown meat to suss out public response to the food. The results showed a mostly negative attitude, but that was only two years into a field that is six years old today. Already public opinion may have shifted.
Shiok Meat's Sriram and her co-founder Ka Yi Ling have used online surveys to get a sense of the landscape, but they also take a more direct approach sometimes. Every time they give a public talk about their company and their shrimp, they poll their audience before and after the talk, using the question, "How many of you are willing to try, and pay, to eat lab-grown meat?"
They consistently find that the percentage of people willing to try goes up from 50 to 90 percent after hearing their talk, which includes information about the downsides of traditional shrimp farming (for one thing, many shrimp are raised in sewage, and peeled and deveined by slaves) and a bit of information about how lab-grown animal protein is being made now. I saw this pan out myself when Ling spoke at a New Harvest conference in Cambridge, Massachusetts in July.
"A lot of consumers get over the ick factor when you tell them that most of the food that you're eating right now has entered the lab at some point," Sriram says. "We're not going to grow our meat in the lab always. It's in the lab right now, because we're in R&D. Once we go into manufacturing ... it's going to be a food manufacturing facility, where a lot of food comes from."
The downside of the University of Wisconsin's and Shiok Meat's approach to capturing public opinion is that they each look at self-selecting groups: Online commenters are often fueled by a need to complain, and it's likely that anyone attending a talk by the co-founders of a lab-grown meat company already has some level of open-mindedness.
So Sriram says that she and Ling are also using another method to assess the landscape, and it's somewhere in the middle. They've been watching public responses to the closest available product to lab-grown meat that's on the market: Impossible Burger. As a 100 percent plant-based burger, it's not quite the same, but this bleedable, searable patty is still very much the product of science and laboratory work. Its remarkable similarity to beef is courtesy of yeast that have been genetically engineered to contain DNA from soy plant roots, which produce a protein called heme as they multiply. This heme is a plant-derived protein that can look and act like the heme found in animal muscle.
So far, the sciencey underpinnings of the burger don't seem to be turning people off. In just four years, it's already found its place within other American food icons. It's readily available everywhere from nationwide Burger Kings to Boston's Warren Tavern, which has been in operation since 1780, is one of the oldest pubs in America, and is even named after the man who sent Paul Revere on his midnight ride. Some people have already grown so attached to the Impossible Burger that they will actually walk out of a restaurant that's out of stock. Demand for the burger is outpacing production.
"Even though [Impossible] doesn't consider their product cellular agriculture, it's part of a spectrum of innovation," Krueger says. "There are novel proteins that you're not going to find in your average food, and there's some cool tech there. So to me, that does show a lot of willingness on people's part to think about trying something new."
The message for those working on animal-based lab-grown meat is clear: People will accept innovation on their favorite food if it tastes good enough and evokes the same emotional connection as the real deal.
"How people talk about lab-grown meat now, it's still a conversation about science, not about culture and emotion," Lee says. But he's confident that the conversation will start to shift in that direction if the companies doing this work can nail the flavor memory, above all.
And then proving how much power flavor lords over us, we quickly derail into a conversation about Doritos, which he calls "maniacally delicious." The chips carry no health value whatsoever and are a native product of food engineering and manufacturing — just watch how hard it is for Bon Appetit associate food editor Claire Saffitz to try and recreate them in the magazine's test kitchen — yet devotees remain unfazed and crunch on.
"It's funny because it shows you that people don't ask questions about how [some foods] are made, so why are they asking so many questions about how lab-grown meat is made?" Lee asks.
For all the hype around Impossible Burger, there are still controversies and hand-wringing around lab-grown meat. Some people are grossed out by the idea, some people are confused, and if you're the U.S. Cattlemen's Association (USCA), you're territorial. Last year, the group sent a petition to the USDA to "exclude products not derived directly from animals raised and slaughtered from the definition of 'beef' and meat.'"
"I think we are probably three or four big food safety scares away from everyone, especially younger generations, embracing lab-grown meat as like, 'Science is good; nature is dirty, and can kill you.'"
"I have this working hypothesis that if you look at the nation in 50-year spurts, we revolve back and forth between artisanal, all-natural food that's unadulterated and pure, and food that's empowered by science," Lee says. "Maybe we've only had one lap around the track on that, but I think we are probably three or four big food safety scares away from everyone, especially younger generations, embracing lab-grown meat as like, 'Science is good; nature is dirty, and can kill you.'"
Food culture goes beyond just the ingredients we know and love — it's also about how we interact with them, produce them, and expect them to taste and feel when we bite down. We accept a margin of difference among a fast food burger, a backyard burger from the grill, and a gourmet burger. Maybe someday we'll accept the difference between a burger created by killing a cow and a burger created by biopsying one.
Looking to the Future
Every time we engage with food, "we are enacting a ritual that binds us to the place we live and to those in our family, both living and dead," Wilson writes in Consider the Fork. "Such things are not easily shrugged off. Every time a new cooking technology has been introduced, however useful … it has been greeted in some quarters with hostility and protestations that the old ways were better and safer."
This is why it might be hard for a vegetarian mother to try her daughter's lab-grown shrimp, no matter how ethically it was produced or how awe-inspiring the invention is. Yet food cultures can and do change. "They're not these static things," says Benjamin Wurgaft, a historian whose book Meat Planet: Artificial Flesh and the Future of Food comes out this month. "The real tension seems to be between slow change and fast change."
In fact, the very definition of the word "meat" has never exclusively meant what the USCA wants it to mean. Before the 12th century, when it first appeared in Old English as "mete," it wasn't very specific at all and could be used to describe anything from "nourishment," to "food item," to "fodder," to "sustenance." By the 13th century it had been narrowed down to mean "flesh of warm-blooded animals killed and used as food." And yet the British mincemeat pie lives on as a sweet Christmas treat full of -- to the surprise of many non-Brits -- spiced, dried fruit. Since 1901, we've also used this word with ease as a general term for anything that's substantive -- as in, "the meat of the matter." There is room for yet more definitions to pile on.
"The conversation [about lab-ground meat] has changed remarkably in the last six years," Wurgaft says. "It has become a conversation about whether or not specific companies will bring a product to market, and that's a really different conversation than asking, 'Should we produce meat in the lab?'"
As part of the field research for his book, Wurgaft visited the Rijksmuseum Boerhaave, a Dutch museum that specializes in the history of science and medicine. It was 2015, and he was there to see an exhibit on the future of food. Just two years earlier, Mark Post had made that first lab-grown hamburger about a two-and-a-half hour drive south of the museum. When Wurgaft arrived, he found the novel invention, which Post had donated to the museum, already preserved and served up on a dinner plate, the whole outfit protected by plexiglass.
"They put this in the exhibit as if it were already part of the historical records, which to a historian looked really weird," Wurgaft says. "It looked like somebody taking the most recent supercomputer and putting it in a museum exhibit saying, 'This is the supercomputer that changed everything,' as if you were already 100 years in the future, looking back."
It seemed to symbolize an effort to codify a lab-grown hamburger as a matter of Dutch pride, perhaps someday occupying a place in people's hearts right next to the stroopwafel.
"Who's to say that we couldn't get a whole school of how to cook with lab-grown meat?"
Lee likes to imagine that part of the legacy of lab-grown meat, if it succeeds, will be to inspire entirely new fads in cooking -- a step beyond ones like the crab-filled avocado of the 1960s or the pesto of the 1980s in the U.S.
"[Lab-grown meat] is inherently going to be a different quality than anything we've done with an animal," he says. "Look at every cut [of meat] on the sphere today -- each requires a slightly different cooking method to optimize the flavor of that cut. Who's to say that we couldn't get a whole school of how to cook with lab-grown meat?"
At this point, most of us have no way of trying lab-grown meat. It remains exclusively available through sometimes gimmicky demos reserved for investors and the media. But Wurgaft says the stories we tell about this innovation, the articles we write, the films we make, and yes, even the museum exhibits we curate, all hold as much cultural significance as the product itself might someday.
Many leaders at top companies are trying to get workers to return to the office. They say remote and hybrid work are bad for their employees’ mental well-being and lead to a sense of social isolation, meaninglessness, and lack of work-life boundaries, so we should just all go back to office-centric work.
One example is Google, where the company’s leadership is defending its requirement of mostly in-office work for all staff as necessary to protect social capital, meaning people’s connections to and trust in one another. That’s despite a survey of over 1,000 Google employees showing that two-thirds feel unhappy about being forced to work in the office three days per week. In internal meetings and public letters, many have threatened to leave, and some are already quitting to go to other companies with more flexible options.
Last month, GM rolled out a policy similar to Google’s, but had to backtrack because of intense employee opposition. The same is happening in some places outside of the U.S. For instance, three-fifths of all Chinese employers are refusing to offer permanent remote work options, according to a survey this year from The Paper.
For their claims that remote work hurts well-being, some of these office-centric traditionalists cite a number of prominent articles. For example, Arthur Brooks claimed in an essay that “aggravation from commuting is no match for the misery of loneliness, which can lead to depression, substance abuse, sedentary behavior, and relationship damage, among other ills.” An article in Forbes reported that over two-thirds of employees who work from home at least part of the time had trouble getting away from work at the end of the day. And Fast Company has a piece about how remote work can “exacerbate existing mental health issues” like depression and anxiety.
For his part, author Malcolm Gladwell has also championed a swift return to the office, saying there is a “core psychological truth, which is we want you to have a feeling of belonging and to feel necessary…I know it’s a hassle to come into the office, but if you’re just sitting in your pajamas in your bedroom, is that the work life you want to live?”
These arguments may sound logical to some, but they fly in the face of research and my own experience as a behavioral scientist and as a consultant to Fortune 500 companies. In these roles, I have seen the pitfalls of in-person work, which can be just as problematic, if not more so. Remote work is not without its own challenges, but I have helped 21 companies implement a series of simple steps to address them.
Research finds that remote work is actually better for you
The trouble with the articles described above - and claims by traditionalist business leaders and gurus - stems from a sneaky misdirection. They decry the negative impact of remote and hybrid work for wellbeing. Yet they gloss over the damage to wellbeing caused by the alternative, namely office-centric work.
It’s like comparing remote and hybrid work to a state of leisure. Sure, people would feel less isolated if they could hang out and have a beer with their friends instead of working. They could take care of their existing mental health issues if they could visit a therapist. But that’s not in the cards. What’s in the cards is office-centric work. That means the frustration of a long commute to the office, sitting at your desk in an often-uncomfortable and oppressive open office for at least 8 hours, having a sad desk lunch and unhealthy snacks, sometimes at an insanely expensive cost and, for making it through this series of insults, you’re rewarded with more frustration while commuting back home.
In a 2022 survey, the vast majority of respondents felt that working remotely improved their work-life balance. Much of that improvement stemmed from saving time due to not needing to commute and having a more flexible schedule.
So what happens when we compare apples to apples? That’s when we need to hear from the horse’s mouth: namely, surveys of employees themselves, who experienced both in-office work before the pandemic, and hybrid and remote work after COVID struck.
Consider a 2022 survey by Cisco of 28,000 full-time employees around the globe. Nearly 80 percent of respondents say that remote and hybrid work improved their overall well-being: that applies to 83 percent of Millennials, 82 percent of Gen Z, 76 percent of Gen Z, and 66 percent of Baby Boomers. The vast majority of respondents felt that working remotely improved their work-life balance.
Much of that improvement stemmed from saving time due to not needing to commute and having a more flexible schedule: 90 percent saved 4 to 8 hours or more per week. What did they do with that extra time? The top choice for almost half was spending more time with family, friends and pets, which certainly helped address the problem of isolation from the workplace. Indeed, three-quarters of them report that working from home improved their family relationships, and 51 percent strengthened their friendships. Twenty percent used the freed up hours for self-care.
Of the small number who report their work-life balance has not improved or even worsened, the number one reason is the difficulty of disconnecting from work, but 82 percent report that working from anywhere has made them happier. Over half say that remote work decreased their stress levels.
Other surveys back up Cisco’s findings. For example, a 2022 Future Forum survey compared knowledge workers who worked full-time in the office, in a hybrid modality, and fully remote. It found that full-time in-office workers felt the least satisfied with work-life balance, hybrid workers were in the middle, and fully remote workers felt most satisfied. The same distribution applied to questions about stress and anxiety. A mental health website called Tracking Happiness found in a 2022 survey of over 12,000 workers that fully remote employees report a happiness level about 20 percent greater than office-centric ones. Another survey by CNBC in June found that fully remote workers are more often very satisfied with their jobs than workers who are fully in-person.
Academic peer-reviewed research provides further support. Consider a 2022 study published in the International Journal of Environmental Research and Public Health of bank workers who worked on the same tasks of advising customers either remotely or in-person. It found that fully remote workers experienced higher meaningfulness, self-actualization, happiness, and commitment than in-person workers. Another study, published by the National Bureau of Economic Research, reported that hybrid workers, compared to office-centric ones, experienced higher satisfaction with work and had 35 percent more job retention.
What about the supposed burnout crisis associated with remote work? Indeed, burnout is a concern. A survey by Deloitte finds that 77 percent of workers experienced burnout at their current job. Gallup came up with a slightly lower number of 67 percent in its survey. But guess what? Both of those surveys are from 2018, long before the era of widespread remote work.
By contrast, in a Gallup survey in late 2021, 58 percent of respondents reported less burnout. An April 2021 McKinsey survey found burnout in 54 percent of Americans and 49 percent globally. A September 2021 survey by The Hartford reported 61 percent burnout. Arguably, the increase in full or part-time remote opportunities during the pandemic helped to address feelings of burnout, rather than increasing them. Indeed, that finding aligns with the earlier surveys and peer-reviewed research suggesting remote and hybrid work improves wellbeing.
Remote work isn’t perfect – here’s how to fix its shortcomings
Still, burnout is a real problem for hybrid and remote workers, as it is for in-office workers. Employers need to offer mental health benefits with online options to help employees address these challenges, regardless of where they’re working.
Moreover, while they’re better overall for wellbeing, remote and hybrid work arrangements do have specific disadvantages around work-life separation. To address work-life issues, I advise my clients who I helped make the transition to hybrid and remote work to establish norms and policies that focus on clear expectations and setting boundaries.
For working at home and collaborating with others, there’s sometimes an unhealthy expectation that once you start your workday in your home office chair, and that you’ll work continuously while sitting there.
Some people expect their Slack or Microsoft Teams messages to be answered within an hour, while others check Slack once a day. Some believe email requires a response within three hours, and others feel three days is fine. As a result of such uncertainty and lack of clarity about what’s appropriate, too many people feel uncomfortable disconnecting and not replying to messages or doing work tasks after hours. That might stem from a fear of not meeting their boss’s expectations or not wanting to let their colleagues down.
To solve this problem, companies need to establish and incentivize clear expectations and boundaries. They should develop policies and norms around response times for different channels of communication. They also need to clarify work-life boundaries – for example, the frequency and types of unusual circumstances that will require employees to work outside of regular hours.
Moreover, for working at home and collaborating with others, there’s sometimes an unhealthy expectation that once you start your workday in your home office chair, and that you’ll work continuously while sitting there (except for your lunch break). That’s not how things work in the office, which has physical and mental breaks built in throughout the day. You took 5-10 minutes to walk from one meeting to another, or you went to get your copies from the printer and chatted with a coworker on the way.
Those and similar physical and mental breaks, research shows, decrease burnout, improve productivity, and reduce mistakes. That’s why companies should strongly encourage employees to take at least a 10-minute break every hour during remote work. At least half of those breaks should involve physical activity, such as stretching or walking around, to counteract the dangerous effects of prolonged sitting. Other breaks should be restorative mental activities, such as meditation, brief naps, walking outdoors, or whatever else feels restorative to you.
To facilitate such breaks, my client organizations such as the University of Southern California’s Information Sciences Institute shortened hour-long meetings to 50 minutes and half-hour meetings to 25 minutes, to give everyone – both in-person and remote workers – a mental and physical break and transition time.
Very few people will be reluctant to have shorter meetings. After that works out, move to other aspects of setting boundaries and expectations. Doing so will require helping team members get on the same page and reduce conflicts and tensions. By setting clear expectations, you’ll address the biggest challenge for wellbeing for remote and hybrid work: establishing clear work-life boundaries.
In May 2022, Californian biotech Ultima Genomics announced that its UG 100 platform was capable of sequencing an entire human genome for just $100, a landmark moment in the history of the field. The announcement was particularly remarkable because few had previously heard of the company, a relative unknown in an industry long dominated by global giant Illumina which controls about 80 percent of the world’s sequencing market.
Ultima’s secret was to completely revamp many technical aspects of the way Illumina have traditionally deciphered DNA. The process usually involves first splitting the double helix DNA structure into single strands, then breaking these strands into short fragments which are laid out on a glass surface called a flow cell. When this flow cell is loaded into the sequencing machine, color-coded tags are attached to each individual base letter. A laser scans the bases individually while a camera simultaneously records the color associated with them, a process which is repeated until every single fragment has been sequenced.
Instead, Ultima has found a series of shortcuts to slash the cost and boost efficiency. “Ultima Genomics has developed a fundamentally new sequencing architecture designed to scale beyond conventional approaches,” says Josh Lauer, Ultima’s chief commercial officer.
This ‘new architecture’ is a series of subtle but highly impactful tweaks to the sequencing process ranging from replacing the costly flow cell with a silicon wafer which is both cheaper and allows more DNA to be read at once, to utilizing machine learning to convert optical data into usable information.
To put $100 genome in perspective, back in 2012 the cost of sequencing a single genome was around $10,000, a price tag which dropped to $1,000 a few years later. Before Ultima’s announcement, the cost of sequencing an individual genome was around $600.
Several studies have found that nearly 12 percent of healthy people who have their genome sequenced, then discover they have a variant pointing to a heightened risk of developing a disease that can be monitored, treated or prevented.
While Ultima’s new machine is not widely available yet, Illumina’s response has been rapid. Last month the company unveiled the NovaSeq X series, which it describes as its fastest most cost-efficient sequencing platform yet, capable of sequencing genomes at $200, with further price cuts likely to follow.
But what will the rapidly tumbling cost of sequencing actually mean for medicine? “Well to start with, obviously it’s going to mean more people getting their genome sequenced,” says Michael Snyder, professor of genetics at Stanford University. “It'll be a lot more accessible to people.”
At the moment sequencing is mainly limited to certain cancer patients where it is used to inform treatment options, and individuals with undiagnosed illnesses. In the past, initiatives such as SeqFirst have attempted further widen access to genome sequencing based on growing amounts of research illustrating the potential benefits of the technology in healthcare. Several studies have found that nearly 12 percent of healthy people who have their genome sequenced, then discover they have a variant pointing to a heightened risk of developing a disease that can be monitored, treated or prevented.
“While whole genome sequencing is not yet widely used in the U.S., it has started to come into pediatric critical care settings such as newborn intensive care units,” says Professor Michael Bamshad, who heads the genetic medicine division in the University of Washington’s pediatrics department. “It is also being used more often in outpatient clinical genetics services, particularly when conventional testing fails to identify explanatory variants.”
But the cost of sequencing itself is only one part of the price tag. The subsequent clinical interpretation and genetic counselling services often come to several thousand dollars, a cost which insurers are not always willing to pay.
As a result, while Bamshad and others hope that the arrival of the $100 genome will create new opportunities to use genetic testing in innovative ways, the most immediate benefits are likely to come in the realm of research.
Bigger Data
There are numerous ways in which cheaper sequencing is likely to advance scientific research, for example the ability to collect data on much larger patient groups. This will be a major boon to scientists working on complex heterogeneous diseases such as schizophrenia or depression where there are many genes involved which all exert subtle effects, as well as substantial variance across the patient population. Bigger studies could help scientists identify subgroups of patients where the disease appears to be driven by similar gene variants, who can then be more precisely targeted with specific drugs.
If insurers can figure out the economics, Snyder even foresees a future where at a certain age, all of us can qualify for annual sequencing of our blood cells to search for early signs of cancer or the potential onset of other diseases like type 2 diabetes.
David Curtis, a genetics professor at University College London, says that scientists studying these illnesses have previously been forced to rely on genome-wide association studies which are limited because they only identify common gene variants. “We might see a significant increase in the number of large association studies using sequence data,” he says. “It would be far preferable to use this because it provides information about rare, potentially functional variants.”
Cheaper sequencing will also aid researchers working on diseases which have traditionally been underfunded. Bamshad cites cystic fibrosis, a condition which affects around 40,000 children and adults in the U.S., as one particularly pertinent example.
“Funds for gene discovery for rare diseases are very limited,” he says. “We’re one of three sites that did whole genome sequencing on 5,500 people with cystic fibrosis, but our statistical power is limited. A $100 genome would make it much more feasible to sequence everyone in the U.S. with cystic fibrosis and make it more likely that we discover novel risk factors and pathways influencing clinical outcomes.”
For progressive diseases that are more common like cancer and type 2 diabetes, as well as neurodegenerative conditions like multiple sclerosis and ALS, geneticists will be able to go even further and afford to sequence individual tumor cells or neurons at different time points. This will enable them to analyze how individual DNA modifications like methylation, change as the disease develops.
In the case of cancer, this could help scientists understand how tumors evolve to evade treatments. Within in a clinical setting, the ability to sequence not just one, but many different cells across a patient’s tumor could point to the combination of treatments which offer the best chance of eradicating the entire cancer.
“What happens at the moment with a solid tumor is you treat with one drug, and maybe 80 percent of that tumor is susceptible to that drug,” says Neil Ward, vice president and general manager in the EMEA region for genomics company PacBio. “But the other 20 percent of the tumor has already got mutations that make it resistant, which is probably why a lot of modern therapies extend life for sadly only a matter of months rather than curing, because they treat a big percentage of the tumor, but not the whole thing. So going forwards, I think that we will see genomics play a huge role in cancer treatments, through using multiple modalities to treat someone's cancer.”
If insurers can figure out the economics, Snyder even foresees a future where at a certain age, all of us can qualify for annual sequencing of our blood cells to search for early signs of cancer or the potential onset of other diseases like type 2 diabetes.
“There are companies already working on looking for cancer signatures in methylated DNA,” he says. “If it was determined that you had early stage cancer, pre-symptomatically, that could then be validated with targeted MRI, followed by surgery or chemotherapy. It makes a big difference catching cancer early. If there were signs of type 2 diabetes, you could start taking steps to mitigate your glucose rise, and possibly prevent it or at least delay the onset.”
This would already revolutionize the way we seek to prevent a whole range of illnesses, but others feel that the $100 genome could also usher in even more powerful and controversial preventative medicine schemes.
Newborn screening
In the eyes of Kári Stefánsson, the Icelandic neurologist who been a visionary for so many advances in the field of human genetics over the last 25 years, the falling cost of sequencing means it will be feasible to sequence the genomes of every baby born.
“We have recently done an analysis of genomes in Iceland and the UK Biobank, and in 4 percent of people you find mutations that lead to serious disease, that can be prevented or dealt with,” says Stefansson, CEO of deCODE genetics, a subsidiary of the pharmaceutical company Amgen. “This could transform our healthcare systems.”
As well as identifying newborns with rare diseases, this kind of genomic information could be used to compute a person’s risk score for developing chronic illnesses later in life. If for example, they have a higher than average risk of colon or breast cancer, they could be pre-emptively scheduled for annual colonoscopies or mammograms as soon as they hit adulthood.
To a limited extent, this is already happening. In the UK, Genomics England has launched the Newborn Genomes Programme, which plans to undertake whole-genome sequencing of up to 200,000 newborn babies, with the aim of enabling the early identification of rare genetic diseases.
"I have not had my own genome sequenced and I would not have wanted my parents to have agreed to this," Curtis says. "I don’t see that sequencing children for the sake of some vague, ill-defined benefits could ever be justifiable.”
However, some scientists feel that it is tricky to justify sequencing the genomes of apparently healthy babies, given the data privacy issues involved. They point out that we still know too little about the links which can be drawn between genetic information at birth, and risk of chronic illness later in life.
“I think there are very difficult ethical issues involved in sequencing children if there are no clear and immediate clinical benefits,” says Curtis. “They cannot consent to this process. I have not had my own genome sequenced and I would not have wanted my parents to have agreed to this. I don’t see that sequencing children for the sake of some vague, ill-defined benefits could ever be justifiable.”
Curtis points out that there are many inherent risks about this data being available. It may fall into the hands of insurance companies, and it could even be used by governments for surveillance purposes.
“Genetic sequence data is very useful indeed for forensic purposes. Its full potential has yet to be realized but identifying rare variants could provide a quick and easy way to find relatives of a perpetrator,” he says. “If large numbers of people had been sequenced in a healthcare system then it could be difficult for a future government to resist the temptation to use this as a resource to investigate serious crimes.”
While sequencing becoming more widely available will present difficult ethical and moral challenges, it will offer many benefits for society as a whole. Cheaper sequencing will help boost the diversity of genomic datasets which have traditionally been skewed towards individuals of white, European descent, meaning that much of the actionable medical information which has come out of these studies is not relevant to people of other ethnicities.
Ward predicts that in the coming years, the growing amount of genetic information will ultimately change the outcomes for many with rare, previously incurable illnesses.
“If you're the parent of a child that has a susceptible or a suspected rare genetic disease, their genome will get sequenced, and while sadly that doesn’t always lead to treatments, it’s building up a knowledge base so companies can spring up and target that niche of a disease,” he says. “As a result there’s a whole tidal wave of new therapies that are going to come to market over the next five years, as the genetic tools we have, mature and evolve.”