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.
Later this year, Verve Therapeutics of Cambridge, Ma., will initiate Phase 1 clinical trials to test VERVE-101, a new medication that, if successful, will employ gene editing to significantly reduce low-density lipoprotein cholesterol, or LDL.
LDL is sometimes referred to as the “bad” cholesterol because it collects in the walls of blood vessels, and high levels can increase chances of a heart attack, cardiovascular disease or stroke. There are approximately 600,000 heart attacks per year due to blood cholesterol damage in the United States, and heart disease is the number one cause of death in the world. According to the CDC, a 10 percent decrease in total blood cholesterol levels can reduce the incidence of heart disease by as much as 30 percent.
Verve’s Founder and CEO, Sekar Kathiresan, spent two decades studying the genetic basis for heart attacks while serving as a professor of medicine at Harvard Medical School. His research led to two critical insights.
“One is that there are some people that are naturally resistant to heart attack and have lifelong, low levels of LDL,” the cardiologist says. “Second, there are some genes that can be switched off that lead to very low LDL cholesterol, and individuals with those genes switched off are resistant to heart attacks.”
Kathiresan and his team formed a hypothesis in 2016 that if they could develop a medicine that mimics the natural protection that some people enjoy, then they might identify a powerful new way to treat and ultimately prevent heart attacks. They launched Verve in 2018 with the goal of creating a one-time therapy that would permanently lower LDL and eliminate heart attacks caused by high LDL.
"Imagine a future where somebody gets a one-time treatment at the time of their heart attack or before as a preventive measure," says Kathiresan.
The medication is targeted specifically for patients who have a genetic form of high cholesterol known as heterozygous familial hypercholesterolemia, or FH, caused by expression of a gene called PCSK9. Verve also plans to develop a program to silence a gene called ANGPTL3 for patients with FH and possibly those with or at risk of atherosclerotic cardiovascular disease.
FH causes cholesterol to be high from birth, reaching levels of 200 to 300 milligrams per deciliter. Suggested normal levels are around 100 to 129 mg/dl, and anything above 130 mg/dl is considered high. Patients with cardiovascular disease usually are asked to aim for under 70 mg/dl, but many still have unacceptably high LDL despite taking oral medications such as statins. They are more likely to have heart attacks in their 30s, 40s and 50s, and require lifelong LDL control.
The goal for drug treatments for high LDL, Kathiresan says, is to reduce LDL as low as possible for as long as possible. Physicians and researchers also know that a sizeable portion of these patients eventually start to lose their commitment to taking their statins and other LDL-controlling medications regularly.
“If you ask 100 patients one year after their heart attack what fraction are still taking their cholesterol-lowering medications, it’s less than half,” says Kathiresan. “So imagine a future where somebody gets a one-time treatment at the time of their heart attack or before as a preventive measure. It’s right in front of us, and it’s something that Verve is looking to do.”
In late 2020, Verve completed primate testing with monkeys that had genetically high cholesterol, using a one-time intravenous injection of VERVE-101. It reduced the monkeys’ LDL by 60 percent and, 18 months later, remains at that level. Kathiresan expects the LDL to stay low for the rest of their lives.
Verve’s gene editing medication is packaged in a lipid nanoparticle to serve as the delivery mechanism into the liver when infused intravenously. The drug is absorbed and makes its way into the nucleus of the liver cells.
Verve’s program targeting PCSK9 uses precise, single base, pair base editing, Kathiresan says, meaning it doesn't cut DNA like CRISPR gene editing systems do. Instead, it changes one base, or letter, in the genome to a different one without affecting the letters around it. Comparing it to a pencil and eraser, he explains that the medication erases out a letter A and makes it a letter G in the A, C, G and T code in DNA.
“We need to continue to advance our approach and tools to make sure that we have the absolute maximum ability to detect off-target effects,” says Euan Ashley, professor of medicine and genetics at Stanford University.
By making that simple change from A to G, the medication switches off the PCSK9 gene, automatically lowering LDL cholesterol.
“Once the DNA change is made, all the cells in the liver will have that single A to G change made,” Kathiresan says. “Then the liver cells divide and give rise to future liver cells, but every time the cell divides that change, the new G is carried forward.”
Additionally, Verve is pursuing its second gene editing program to eliminate ANGPTL3, a gene that raises both LDL and blood triglycerides. In 2010, Kathiresan's research team learned that people who had that gene completely switched off had LDL and triglyceride levels of about 20 and were very healthy with no heart attacks. The goal of Verve’s medication will be to switch off that gene, too, as an option for additional LDL or triglyceride lowering.
“Success with our first drug, VERVE-101, will give us more confidence to move forward with our second drug,” Kathiresan says. “And it opens up this general idea of making [genomic] spelling changes in the liver to treat other diseases.”
The approach is less ethically concerning than other gene editing technologies because it applies somatic editing that affects only the individual patient, whereas germline editing in the patient’s sperm or egg, or in an embryo, gets passed on to children. Additionally, gene editing therapies receive the same comprehensive amount of testing for side effects as any other medicine.
“We need to continue to advance our approach and tools to make sure that we have the absolute maximum ability to detect off-target effects,” says Euan Ashley, professor of medicine and genetics at Stanford University and founding director of its Center for Inherited Cardiovascular Disease. Ashley and his colleagues at Stanford’s Clinical Genomics Program and beyond are increasingly excited about the promise of gene editing.
“We can offer precision diagnostics, so increasingly we’re able to define the disease at a much deeper level using molecular tools and sequencing,” he continues. “We also have this immense power of reading the genome, but we’re really on the verge of taking advantage of the power that we now have to potentially correct some of the variants that we find on a genome that contribute to disease.”
He adds that while the gene editing medicines in development to correct genomes are ahead of the delivery mechanisms needed to get them into the body, particularly the heart and brain, he’s optimistic that those aren’t too far behind.
“It will probably take a few more years before those next generation tools start to get into clinical trials,” says Ashley, whose book, The Genome Odyssey, was published last year. “The medications might be the sexier part of the research, but if you can’t get it into the right place at the right time in the right dose and not get it to the places you don’t want it to go, then that tool is not of much use.”
Medical experts consider knocking out the PCSK9 gene in patients with the fairly common genetic disorder of familial hypercholesterolemia – roughly one in 250 people – a potentially safe approach to gene editing and an effective means of significantly lowering their LDL cholesterol.
Nurse Erin McGlennon has an Implantable Cardioverter Defibrillator and takes medications, but she is also hopeful that a gene editing medication will be developed in the near future.
Erin McGlennon
Mary McGowan, MD, chief medical officer for The Family Heart Foundation in Pasadena, CA, sees the tremendous potential for VERVE-101 and believes patients should be encouraged by the fact that this kind of research is occurring and how much Verve has accomplished in a relatively short time. However, she offers one caveat, since even a 60 percent reduction in LDL won’t completely eliminate the need to reduce the remaining amount of LDL.
“This technology is very exciting,” she said, “but we want to stress to our patients with familial hypercholesterolemia that we know from our published research that most people require several therapies to get their LDL down., whether that be in primary prevention less than 100 mg/dl or secondary prevention less than 70 mg/dl, So Verve’s medication would be an add-on therapy for most patients.”
Dr. Kathiresan concurs: “We expect our medicine to lower LDL cholesterol by about 60 percent and that our patients will be on background oral medications, including statins that lower LDL cholesterol.”
Several leading research centers are investigating gene editing treatments for other types of cardiovascular diseases. Elizabeth McNally, Elizabeth Ward Professor and Director at the Center for Genetic Medicine at Northwestern University’s Feinberg School of Medicine, pursues advanced genetic correction in neuromuscular diseases such as Duchenne muscular dystrophy and spinal muscular atrophy. A cardiologist, she and her colleagues know these diseases frequently have cardiac complications.
“Even though the field is driven by neuromuscular specialists, it’s the first therapies in patients with neuromuscular diseases that are also expected to make genetic corrections in the heart,” she says. “It’s almost like an afterthought that we’re potentially fixing the heart, too.”
Another limitation McGowan sees is that too many healthcare providers are not yet familiar with how to test patients to determine whether or not they carry genetic mutations that need to be corrected. “We need to get more genetic testing done,” she says. “For example, that’s the case with hypertrophic cardiomyopathy, where a lot of the people who probably carry that diagnosis and have never been genetically identified at a time when genetic testing has never been easier.”
One patient who has been diagnosed with hypertrophic cardiomyopathy also happens to be a nurse working in research at Genentech Pharmaceutical, now a member of the Roche Group, in South San Francisco. To treat the disease, Erin McGlennon, RN, has an Implantable Cardioverter Defibrillator and takes medications, but she is also hopeful that a gene editing medication will be developed in the near future.
“With my condition, the septum muscles are just growing thicker, so I’m on medicine to keep my heart from having dangerous rhythms,” says McGlennon of the disease that carries a low risk of sudden cardiac death. “So, the possibility of having a treatment option that can significantly improve my day-to-day functioning would be a major breakthrough.”
McGlennon has some control over cardiovascular destiny through at least one currently available technology: in vitro fertilization. She’s going through it to ensure that her children won't express the gene for hypertrophic cardiomyopathy.
More than 20 percent of American adults suffer from chronic pain. And as many as one in four of those prescribed opioids to manage that pain go on to misuse – or abuse – them, often with devastating consequences. Patients afflicted by both chronic pain and opioid addiction are especially difficult to treat, according to Eric Garland, PhD, Director of the University of Utah’s Center on Mindfulness and Integrative Health Intervention Development, because opioid overuse increases pain sensitivity, and pain promotes relapse among those being treated for addiction.
A new study, however, shows that a mindfulness-based therapy can successfully tackle both problems at once, pointing to a tool that could potentially help in fighting the opioid crisis. “This is the first large-scale clinical trial to show that any psychological intervention can reduce opioid misuse and chronic pain for the long term,” says Garland, lead author of the study, published February 28th in JAMA Internal Medicine.
Garland’s study focused on 250 adults who had received opioid therapy for chronic pain for 90 days or longer, randomly assigning them to eight weeks of either a standard psychotherapy support group or Mindfulness-Oriented Recovery Enhancement (MORE) therapy, which combines mindfulness training, cognitive-behavioral therapy (CBT) and positive psychology. Nine months after getting these treatments in primary care settings, 45 percent of patients in the MORE group were no longer misusing opioids, compared to 24 percent of those in group therapy. In fact, about a third of the patients in the MORE group were able to cut their opioid dose in half or reduce it even further.
Patients treated with MORE also experienced more significant pain relief than those in support groups, according to Garland. Conventional approaches to treating opioid addiction include 12-step programs and medically-assisted treatment using drugs like methadone and Suboxone, sometimes coupled with support groups. But patients with Opioid Use Disorder (OUD) – the official diagnosis for opioid addiction – have high relapse rates following treatment, especially if they have chronic pain.
While medically-assisted treatments help to control drug cravings, they do nothing to control chronic pain, which is where psychological therapies like MORE come in.
“For patients suffering from moderate pain and OUD, the relapse rate is three times higher than in patients without chronic pain; for those with severe chronic pain, the relapse rate is five times higher,” says Amy Wachholtz, PhD, Director of Clinical Health Psychology and associate professor at University of Colorado in Denver. “So if we don’t treat the chronic pain along with the OUD addiction simultaneously, we are setting patients up for failure.”
Unfortunately, notes Garland, the standard of care for patients with chronic pain who are misusing their prescribed painkillers is “woefully inadequate.” Many patients don’t meet the criteria for OUD, he says, but instead fall into a gray zone somewhere between legitimate opioid use and full-blown addiction. And while medically-assisted treatments help to control drug cravings, they do nothing to control chronic pain, which is where psychological therapies like MORE come in. But behavioral therapies are often not available in primary care settings, and even when clinicians do refer patients to behavioral health providers, they often prescribe CBT. A large scale study last year showed that CBT – without the added components of mindfulness training and positive psychology – reduced pain but not opioid misuse.
Psychotherapist Eric Garland teaches mindfulness.
University of Utah
Reward Circuitry Rewired
Opioids are highly physiologically addictive. Repeated and high-dose drug use causes the brain to become hypersensitive to stress, pain, and drug-related cues, such as the sight of one’s pill bottle, says Garland, while at the same time becoming increasingly insensitive to natural pleasures. “As an individual becomes more and more dependent on the opioids just to feel okay, they feel less able to extract a healthy sense of joy, pleasure and meaning out of everyday life,” he explains. “This drives them to take higher and higher doses of the opioid to maintain a dwindling sense of well-being.”
The changes are not just psychological: Chronic opioid use actually causes changes in the brain’s reward circuitry. “You can see on brain imaging,” says Garland. “The brain’s reward circuitry becomes more responsive when a person is viewing opioid related images than when they are viewing images of smiling babies, lovers holding hands, or sunsets over the beach.” MORE, he says, teaches “savoring” – a tenet of positive psychology – as a means of restructuring the reward processes in the brain so the patient becomes sensitive to pleasure from natural, healthy rewards, decreasing cravings for drug-related rewards.
Mindfulness and Addiction
Mindfulness, a form of meditation that teaches people to observe their feelings and sensations without judgement, has been increasingly applied to the treatment of addiction. By observing their pain and cravings objectively, for example, patients gain increased awareness of their responses to pain and their habits of opioid use. “They learn how to be with discomfort, whether emotional or physical, in a more compassionate way,” says Sarah Bowen, PhD, associate professor of psychology at Pacific University in Oregon. “And if your mind gives you a message like ‘Oh, I can’t handle that,’ to recognize that that’s a thought that might not be true.”
Bowen’s research is focused on Mindfulness-Based Relapse Prevention, which addresses the cravings associated with addiction. She has patients practice what she calls “urge surfing”: riding out a craving or urge rather than relying on a substance for immediate relief. “Craving will happen, so rather than fighting it, we look at understanding it better,” she says.
MORE differs from other forms of mindfulness-based therapy in that it integrates reappraisal and savoring training. Reappraisal is a technique often used in CBT in which patients learn to change negative thought patterns in order to reduce their emotional impact, while savoring helps to restructure the reward processes in the brain.
Mindfulness training not only helps patients to understand and gain control over their behavior in response to cravings and triggers like pain, says Garland, but also provides a means of pain relief. “We use mindfulness to zoom into pain and break it down into its subcomponents – feelings of heat or tightness or tingling – which reduces the impact that negative emotions have on pain processing in the brain.”
Eric Garland examines brain waves.
University of Utah
Powerful interventions
As the dangers of opioid addiction have become increasingly evident, some scientists are developing less addictive, non-opioid painkillers, but more trials are needed. Meanwhile, behavioral approaches to chronic pain relief have continued to gain traction, and researchers like Garland are probing the possibilities of integrative treatments to treat the addiction itself. Given that the number of people suffering from chronic pain and OUD have reached new heights during the COVID-19 pandemic, says Wachholtz, new treatment alternatives for patients caught in the relentless cycle of chronic pain and opioid misuse are sorely needed. “We’re trying to refine the techniques,” she says, “but we’re starting to realize just how powerful some of these mind-body interventions can be.”