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.
Scientists aim to preserve donkeys, one frozen embryo at a time
Every day for a week in 2022, Andres Gambini, a veterinarian and senior lecturer in animal science at the University of Queensland in Australia, walked into his lab—and headed straight to the video camera. Trained on an array of about 50 donkey embryos, all created by Gambini’s manual in vitro fertilization, or IVF, the camera kept an eye on their developmental progress. To eventually create a viable embryo that could be implanted into a female donkey, the embryos’ cells had to keep dividing, first in two, then in four and so on.
But the embryos weren’t cooperating. Some would start splitting up only to stop a day or two later, and others wouldn’t start at all. Every day he came in, Gambini saw fewer and fewer dividing embryos, so he was losing faith in the effort. “You see many failed attempts and get disappointed,” he says.
Gambini and his team, a group of Argentinian and Spanish researchers, were working to create these embryos because many donkey populations around the world are declining. It may sound counterintuitive that domesticated animals may need preservation, but out of 28 European donkey breeds, 20 are endangered and seven are in critical status. It is partly because of the inbreeding that happened over the course of many years and partly because in today’s Western world donkeys aren’t really used anymore.
“That's the reason why some breeds begin to disappear because humans were not really interested in having that specific breed anymore,” Gambini says. Nonetheless, in Africa, India and Latin America millions of rural families still rely on these hardy creatures for agriculture and transportation. And the only two wild donkey species—Equus africanus in Africa and Equus hemionus in Asia—are also dwindling, due to losing their habitats to human activities, diseases and slow reproduction rates. Gambini’s team wanted to create a way to preserve the animals for the future. “Donkeys are more endangered than people realize,” he says.
There’s much more to donkeys' trouble though. For the past 20 or so years, they have been facing a huge existential threat due to their hide gelatin, a compound derived from their skins by soaking and stewing. In Chinese traditional medicine, the compound, called ejiao, is believed to have a medicinal value, so it’s used in skin creams, added to food and taken in capsules. Centuries ago, ejiao was a very expensive luxury product available only for the emperor and his household. That changed in the 1990s when the Chinese economy boomed, and many people were suddenly able to afford it. “It went from a very elite product to a very popular product,” says Janneke Merkx, a campaign manager at The Donkey Sanctuary, a United Kingdom-based nonprofit organization that keeps tabs on the animals’ welfare worldwide. “It is a status symbol for gift giving.”
Having evolved in the harsh and arid mountainous terrains where food and water were scarce, donkeys are extremely adaptable and hardy. But the Donkey Sanctuary documented cases in which an entire village had their animals disappear overnight, finding them killed and skinned outside their settlement.
The Chinese donkey population was quickly decimated. Unlike many other farm animals, donkeys are finicky breeders. When stressed and unhappy, they don’t procreate, so growing them in large industrial settings isn’t possible. “Donkeys are notoriously slow breeders and really very difficult to farm,” says Merkx. “They are not the same as other livestock like sheep and pigs and cattle.” Within years the, the donkey numbers in China dropped precipitously. “China used to have the largest donkey population in the world in the 1990s. They had 11 million donkeys, and it's now down to less than 3 million, and they just can't keep up with the demand.”
To keep the ejiao conveyor going, some producers turned to the illegal wildlife trade. Poachers began to steal and slaughter donkeys from rural villages in Africa. The Donkey Sanctuary documented cases in which an entire village had their animals disappear overnight, finding them killed and skinned outside their settlement. Exactly how many creatures were lost to the skin trade to-date isn’t possible to calculate, says Faith Burden, the Donkey Sanctuary’s director of equine operations. Traditionally a poor people’s beast of burden, donkey counts are hard to keep track of. “When an animal doesn't produce meat, milk or eggs or whatever edible product, they're often less likely to be acknowledged in a government population census,” Burden says. “So reliable statistics are hard to come by.” The nonprofit estimates that about 4.8 million are slaughtered annually.
During their six to seven thousand years of domestication, donkeys rarely got the full appreciation for their services. They are often compared to horses, which doesn’t do them justice. They’re entirely different animals, Burden says. Built for speed, horses respond to predators and other dangers by running as fast as they can. Donkeys, which originate from the rocky, mountainous regions of Africa where running is dangerous, react to threats by freezing and assessing the situation for the best response. “Those so-called stubborn donkeys that won’t move as you want, they are actually thinking ‘what’s the best approach,’” Burden says. They may even choose to fight the predators rather than flee, she adds. “In some parts of the world, people use them as guard animals against things like coyotes and wolves.”
Scientists believe that domestic donkeys take their origin from Equus africanus or African wild ass, originally roaming where Kenya, Ethiopia and Eritrea are today. Having evolved in the harsh and arid mountainous terrains where food and water were scarce, they are extremely adaptable and hardy. Research finds that they can go without water for 72 hours and then drink their fill without any negative consequences. Their big jaws let them chew tough desert shrubs, which horses can’t exist on. Their large ears help dissipate heat. Their little upright hooves are a perfect fit for the uneven rocky or other dangerous grounds. Accustomed to the mountain desert climate with hot days and cold nights, they don’t mind temperature flux.
“The donkey is the most supremely adapted animal to deal with hostile conditions,” Burden says. “They can survive on much lower nutritional quality food than a cow, sheep or horse. That’s why communities living in some of the most inhospitable places will often have donkeys with them.” And that’s why losing a donkey to an illegal skin trade can devastate a family in places like Eritrea. Suddenly everything from water to firewood to produce must be carried by family members—and often women.
Workers unloading donkeys at the Shinyanga slaughterhouse in Tanzania. Fearing a future in which donkeys go extinct, scientists have found ways to cryopreserve a donkey embryo in liquid nitrogen.
TAHUCHA
One can imagine a time when worldwide donkey populations may dwindle to the point that they would need to be restored. That includes their genetic variability too. That’s where the frozen embryos may come in handy. We may be able to use them to increase the genetic variability of donkeys, which will be especially important if they get closer to extinction, Gambini says. His team had already created frozen embryos for horses and zebras, an idea similar to a seed bank. “We call this concept the Frozen Zoo.”
Creating donkey embryos proved much harder than those of zebras and horses. To improve chances of fertilization, Gambini used the intracytoplasmic sperm injection or ICSI, in which he employed a tiny needle called a micropipette to inject a donkey sperm into an egg. That was a step above the traditional IVF method, in which the egg and a sperm are left floating in a test tube together. The injection took, but during the incubating week, one after the other, the embryos stopped dividing. Finally, on day seven, Gambini finally spotted the exact sight he was hoping to see. One of the embryos developed into a burgeoning ball of cells.
“That stage is called a blastocyst,” Gambini says. The clump of cells had a lot of fluids mixed within them, which indicated that they were finally developing into a viable embryo. “When we see a blastocyst, we know we can transfer that into a female.” He was so excited he immediately called all his collaborators to tell them the good news, which they later published in the journal of Theriogenology.
The one and only embryo to reach that stage, the blastocyst was cryopreserved in liquid nitrogen. The team is waiting for the next breeding season to see if a female donkey may carry it to term and give birth to a healthy foal. Gambini’s team is hoping to polish the process and create more embryos. “It’s our weapon in the conservation ass-enal,” he says.
Lina Zeldovich has written about science, medicine and technology for Popular Science, Smithsonian, National Geographic, Scientific American, Reader’s Digest, the New York Times and other major national and international publications. A Columbia J-School alumna, she has won several awards for her stories, including the ASJA Crisis Coverage Award for Covid reporting, and has been a contributing editor at Nautilus Magazine. In 2021, Zeldovich released her first book, The Other Dark Matter, published by the University of Chicago Press, about the science and business of turning waste into wealth and health. You can find her on http://linazeldovich.com/ and @linazeldovich.
Too much of this ingredient leads to autoimmune diseases, new research shows. Here's how to cut back.
For more than a century, doctors have warned that too much salt in your diet can lead to high blood pressure, heart disease and stroke - and many of the reasons for these effects are well known. But recently scientists have been looking deeper, into the cellular level, and they are finding additional reasons to minimize sodium intake; it is bad for immune cells, creating patterns of gene expression and activity seen in a variety of autoimmune diseases such as multiple sclerosis, lupus, rheumatoid arthritis, and type-1 diabetes.
Salt is a major part of the ocean from which life evolved on this planet. We carry that legacy in our blood, which tastes salty. It is an important element for conducting electrical signals along nerves and balancing water and metabolites transported throughout our bodies. We need to consume about 500 milligrams of salt each day to maintain these functions, more with exercise and heavy sweating as that is a major way the body loses salt. The problem is that most Americans eating a modern western diet consume about 3400 milligrams, 1.5 teaspoons per day.
Evidence has been accumulating over the last few years that elevated levels of sodium can be harmful to at least some types of immune cells. The first signal came in monocytes, which are immune cells that travel to various tissues in the body, where some of them turn into macrophages, a subset of white blood cells that can directly kill microorganisms and make chemical signals that bring other types of immune cells into play.
Two years ago, Dominik N. Müller from the Max-Delbrueck-Center in Berlin, Germany and Markus Kleinewietfeld, an immunologist at Hasselt University in Belgium, ran a study where they fed people pizza and then measured their immune cell function. “We saw that in any monocytes, metabolic function was down, even after a single salty meal,” Kleinewietfeld says. It seemed to be the cellular equivalent of the sluggish feeling we get after eating too much. The cells were able to recover but more research is needed to answer questions about what dose of sodium causes impairment, how long the damage lasts, and whether there is a cumulative effect of salt toxicity.
Kleinewietfeld and his colleagues have hypothesized that too much salt could be a significant factor in the increased number of autoimmune diseases and allergies over the last few generations.
The latest series of experiments focused on a type of T cell called T regulatory cells, or Tregs. Most T cells release inflammatory mediators to fight pathogens and, once that job is done, Tregs come along to calm down their hyperactive brethren. Failure to do so can result in continued inflammation and possibly autoimmune diseases.
In the lab, Kleinewietfeld and his large team of international collaborators saw that high levels of sodium had a huge effect on Tregs, upregulating 1250 genes and downregulating an additional 1380 genes so that they looked similar to patterns of gene expression seen in autoimmune diseases.
Digging deeper, they found that sodium affected mitochondria, the tiny organelles inside of cells that produce much of its energy. The sodium was interfering with how the mitochondria use oxygen, which resulted in increased levels of an unstable form of oxygen that can damage cell function. The researchers injected those damaged Tregs into mice and found that they impaired the animals' immune function, allowing the inflammation to continue rather than shutting it down.
That finding dovetailed nicely with a 2019 paper in Nature from Navdeep Chandel's lab at Northwestern University, which showed in mice that inhibiting the mitochondrial use of oxygen reduced the ability of Tregs to regulate other T cells. “Mitochondria were controlling directly the immunosuppressive program, they were this master regulator tuning the right amount of genes to give you proper immunosuppression,” Chandel said. “And if you lose that function, then you get autoimmunity.”
Kleinewietfeld's team studied the Treg cells of humans and found that sodium can similarly decrease mitochondrial use of oxygen and immunosuppressive activity. “I would have never predicted that myself,” Chandel says, but now researchers can look at the mitochondria of patients with autoimmune disease and see if their gene expression also changes under high salt conditions. He sees the link between the patterns of gene expression in Tregs generated by high salt exposure and those patterns seen in autoimmune diseases, but he is cautious about claiming a causal effect.
Kleinewietfeld and his colleagues have hypothesized that too much salt could be a significant factor in the increased number of autoimmune diseases and allergies over the last few generations. He says a high salt diet could also have an indirect effect on immune function through the way it affects the gut microbiome and the molecules made by microbes when they break down food. But the research results are too preliminary to say that for sure, much less parse out the role of salt compared with other possible factors. “It is still an exciting journey to try to understand this field,” he says.
Additionally, it is difficult to say precisely how this research in animals and human cell cultures will translate into a whole human body. Individual differences in genetics can affect how the body absorbs, transports, and gets rid of sodium, such that some people are more sensitive to salt than are others.
So how should people apply these research findings to daily life?
Salt is obvious when we sprinkle it on at the table or eat tasty things like potato chips, but we may be unaware of sodium hidden in packaged foods. That's because salt is an easy and cheap way to boost the flavor of foods. And if we do read the labeled salt content on a package, we focus on the number for a single serving, but then eat more than that.
Last September, the U.S. Food and Drug Administration (FDA) began a process to update labels on the content of food, including what is meant by the word “healthy” and how food manufacturers can use the term. Many in the food industry are resisting those proposed changes.
Chandel cautions against trying to counter the effects of salt by reaching for foods or supplements full of antioxidants, which, in theory, could reduce the harmful effects on mitochondria caused by a heavy hand with the salt shaker.
Until labels are updated, it would be prudent to try to reduce sodium intake by cutting down on packaged foods while making your own food at home, where you know just how much salt has been added. The Mayo Clinic offers guidance on how to become more aware of the sodium in your diet and eat less of it.
Chandel thinks many people will struggle with minimizing salt in their diets. It’s similar to the challenge of eating less sugar, in that the body craves both, and it is difficult to fight that. He cautions against trying to counter the effects of salt by reaching for foods or supplements full of antioxidants, which, in theory, could reduce the harmful effects on mitochondria caused by a heavy hand with the salt shaker. “Dietary antioxidants have failed in just about every clinical trial, yet the public continues to take them,” Chandel says. But he is optimistic that research will lead us to a better understanding of how Tregs function, and uncover new targets for treating autoimmune diseases.