Friday Five: "Cyclic breathing" can increase well-being, Stanford scientists find
In this week's Friday Five, breathing this way may cut down on anxiety, a fasting regimen that could make you sick, this type of job makes men more virile, 3D printed hearts could save your life, and the role of metformin in preventing dementia.
The Friday Five covers five stories in research that you may have missed this week. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend.
Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
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Here are the promising studies covered in this week's Friday Five, featuring interviews with Dr. David Spiegel, associate chair of psychiatry and behavioral sciences at Stanford, and Dr. Filip Swirski, professor of medicine and cardiology at the Icahn School of Medicine at Mount Sinai.
- Breathing this way cuts down on anxiety*
- Could your fasting regimen make you sick?
- This type of job makes men more virile
- 3D printed hearts could save your life
- Yet another potential benefit of metformin
* This video with Dr. Andrew Huberman of Stanford shows exactly how to do the breathing practice.
This podcast originally aired on March 3, 2023.
A Million Patients Have Innovated Their Own Medical Solutions, And Doctors Are Terrified
Diabetes patient advocate Renza Scibilia with her continuous glucose monitor, used in innovative DIY health technology.
In the fall of 2017, patient advocate Renza Scibilia told a conference of endocrinologists in Australia about new, patient-developed artificial pancreas technology that helped her manage her Type 1 diabetes.
"Because it's not a regulated product, some [doctors] were worried and said 'What if it goes wrong?'"
"They were in equal measure really interested and really scared," recalled Scibilia. "Because it's not a regulated product, some were worried and said 'What if it goes wrong? What is my liability going to be?'"
That was two years ago. Asked if physicians have been more receptive to the same "looping" technology now that its benefits have been supported by considerable data (as Leapsmag pointed out in May), Scibilia said, "No. Clinicians are still really insecure. They're always going to be reluctant to accept consumer-driven technology."
This exemplifies a major challenge to the growing Do-It-Yourself (DIY) biohealth movement: physicians are unnerved and worried about innovations developed by patients and other consumers that haven't been tested in elaborate clinical trials or sanctioned by regulatory authorities.
"It's difficult for patients who develop new health technology to demonstrate the advantage in a way that physicians would accept." said Howard DeMonaco, visiting scientist at MIT's Sloan School of Management. "New approaches to the treatment of diseases are by definition suspect to clinicians. Most are risk averse unless there is a substantial advantage to the new approach and the risks in doing so appear to be minimized."
Nevertheless, the DIY biohealth movement is booming. About a million people reported that they created medical innovations to address their own medical needs in surveys conducted from 2010-2015 in the U.S., U.K., Finland, Canada and South Korea.
Add in other DIY health innovations created in homes, community biolabs and "Maker" health fairs, and it's clear that health care providers are increasingly confronted with medical devices, information technology, and even medications that were developed in unconventional settings and lack the blessing of regulatory authorities.
Researchers in Portugal have tried to spread the word about many of these solutions on the Patent Innovations website, which has more than 500 examples, ranging from a 3-D printed arm and hand to a sensor device that warns someone when an osteomy bag is full.
When Reddit asked medical professionals, "What is the craziest DIY health treatment you've seen a patient attempt?" thousands shared horror stories.
But even in this era of patient empowerment, more widespread use of DIY health solutions still depends upon the approval and cooperation of physicians, nurses and other caregivers. And health care providers still lack awareness of promising patient-developed innovations, according to Dr. Joyce Lee, a pediatric endocrinologist at the University of Michigan who advocates involving patients in the design of healthcare technology. "Most physicians are scared of what they don't know," she said.
They're also understandably worried about patients who don't know what they're doing and make irresponsible decisions. When Reddit asked medical professionals, "What is the craziest DIY health treatment you've seen a patient attempt?" thousands shared horror stories, including a man who poked a hole in his belly button with a knitting needle to relieve gas.
Yet DeMonaco and Lee think it's possible to start bridging the gaps between responsible patient innovators and skeptical doctors as well as unprepared regulatory systems.
One obstacle to consumer-driven health innovations is that clinical trials to prove their safety and effectiveness are expensive and time-consuming, as De Monaco points out in a recent article. He and his colleagues suggested that low-cost clinical trials by and for patients could help address this challenge. They urged patients to publish their own research and detail the impact of innovations on their own health, and create databases that incorporate the findings of other patients.
For example, Adam Brown, who has Type 1 diabetes, compared the effects of low and high carbohydrate diets on his blood sugar management, and conveyed the results in an online journal. "Sharing the information allowed others to copy the experiment," the article noted, suggesting that this could be a model to create multi-patient trials that could be "analyzed by expert patients and/or by professionals."
Asked how to convince health care providers to consider such research, DeMonaco cited the example of doctors prescribing "off label" drugs for purposes that aren't approved by the FDA. "The secret to off label use, like any other user innovation, is dissemination," he said. Sharing case reports and other low-cost research serves to disseminate the information "in a way that is comfortable for physicians," he said, and urged patient innovators to take the same approach.
The FDA regulates commercial products and has no authority if consumers want to use medical devices, medications, or information systems that they find on their own.
Physicians should also be encouraged to engage in patient-driven research, said Dr. Lee. She suggests forming "maker spaces in which patients and physicians are involved in designing personalized technology for chronic diseases. In my vision, patient peers would build, iterate, and learn from each other and the doctor would be part of the team, constantly assessing and evaluating the technology and facilitating the process."
Some kind of regulatory oversight of DIY health technology is also necessary, said Todd Kuiken, senior research scholar at NC State and former principal investigator at the Woodrow Wilson Center's Synthetic Biology Project.
The FDA regulates commercial products and has no authority if consumers want to use medical devices, medications, or information systems that they find on their own. But that doesn't stop regulators from worrying about patients who use them. For example, the FDA issued a warning about diabetes looping technology earlier this year after one diabetic was hospitalized with hypoglycemia.
Kuiken, for one, believes that citizen-driven innovation requires oversight "to move forward." He suggested that Internal Review Boards, with experts on medical technology, safety and ethics, could play a helpful role in validating the work of patient innovators and others engaged in DIY health research. "As people are developing health products, there would be experts available to take a look and check in," he said.
Kuiken pointed out that in native American territories, tribally based IRBs working with the national Indian Health Services help to oversee new health science research. The model could be applied more broadly.
He also offered hope to those who want to integrate the current health regulatory structure into the ecosystem of DIY health innovations. "I didn't expect people from the FDA or NIH to show up" he said about a workshop on citizen-driven biomedical research that he helped organize at the Wilson Center last year. But senior officials from both agencies attended.
He indicated they "were open to new ideas." While he wouldn't disclose contributions made by individual participants in the workshop, he said the government staffers were "very interested in figuring out how to engage with citizen health innovators, to build bridges with the DIY community."
"Why should we wait for regulatory bodies? Why wait for trials that take too long?"
Time will tell whether those bridges will be built quickly enough to increase the comfort of physicians with health innovations developed by patients and other consumers. In the meantime, DIY health innovators like patient advocate Scibilia are undeterred.
"Why should we wait for regulatory bodies?" she asked. "Why wait for trials that take too long? There are plenty of data out there indicating the [diabetes looping] technology works. So we're just going to do it. We're not waiting."
With Lab-Grown Chicken Nuggets, Dumplings, and Burgers, Futuristic Foods Aim to Seem Familiar
Shiok Meat's lab-grown "shrimp" dumplings, alongside a photo of the company's CTO, Ka Yi Ling, in a lab.
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.