Which Allergens Are in Your Food? You Can’t Always Tell From the Labels

When you’re shopping for someone who has a food allergy, a trip to the grocery store is like a police investigation. Each product must be scrutinized. Labels are examined, each ingredient studied.

My 5-year-old son, Alexander, is allergic to almonds and hazelnuts, so my wife and I spend a lot of time trying to decipher food labels. If you miss something, even one word, you risk an allergic reaction.

Although federal law requires manufacturers to include allergen warnings on prepackaged foods, it’s not always clear which products contain allergens and which do not. The regulation doesn’t cover all types of foods, nor instances in which trace amounts of allergens may be present.

This has created a confusing and risky marketplace for my family and millions of others — roughly 8 percent of children have a food allergy. I set out to better understand allergen labeling and the problems consumers face. Here’s what I learned.

Congress passed the Food Allergen Labeling and Consumer Protection Act in 2004, a rule book for manufacturers. Companies must place special warnings on prepackaged foods if they were made using certain allergens: milk, eggs, fish, shellfish, peanuts, wheat, soybeans and tree nuts.

If I grab a box of cookies from the store shelf, I might find a special warning printed near the ingredients list — “contains almonds” — because almonds are part of the tree nut family. If I don’t see one, I can be assured that the product wasn’t made using almonds.

Sesame is the ninth most prevalent food allergy among adults in the United States. But the food was left off the list of major food allergens in the labeling law passed by Congress.

Manufacturers do not have to print a “contains sesame” message. It may even be hidden under “natural flavors” or “spices” on the ingredients label.

“I can’t even trust what’s written on the label anymore,” said Madeline L. Whitney, 18, a freshman at the University of Notre Dame who is allergic to sesame.

When Ms. Whitney sat down to take the exam, she started experiencing signs of an anaphylactic reaction. She readied her EpiPen.

“All of the sudden my tongue is just totally swollen and my throat is closing,” said Ms. Whitney. The reaction was so severe that she had to be injected with two doses of epinephrine before recovering at the university’s health clinic.

Stories like Ms. Whitney’s are driving a push by advocacy groups to mandate sesame labeling. The Food and Drug Administration is considering whether to add sesame to the list of major allergens.

“Sesame should be included as one of the top allergens that needs to be disclosed on labels,” said Lisa G. Gable, chief executive of Food Allergy Research & Education, a nonprofit organization based in McLean, Va.

Sesame labeling is already mandated in Canada, the European Union and Australia.

Here’s where it gets even more complicated. Even if my box of cookies doesn’t include one of the mandated warning labels, the cookies may still contain an allergen.

Let’s say, back at the manufacturer, my cookies were put on the same conveyor belt used for almond cookies. Small bits of almond might have made it into my seemingly almond-free cookies.

This is called cross contact. And there’s no surefire way I can know it happened — the federal government does not require manufacturers to include labeling for possible cross contact of allergens.

As a result, food manufacturers developed their own unregulated labeling practices to alert consumers to potential cross contact. Here’s a sampling from a recent trip to the grocery store:

  • Cookies: “May contain peanuts and tree nuts.”

  • Chocolate bar: “Manufactured on the same equipment that processes almonds.”

  • Bread: “Made in a bakery that may also use tree nuts.”

These short descriptions, often called “precautionary allergen labeling,” may alert consumers to some risks, but because the labels are unregulated, their meanings differ from company to company.

A 2017 study, published in The Journal of Allergy and Clinical Immunology: In Practice showed that consumers make “risk assessments” based on the words used in this kind of labeling.

“We’re making consumers decide, based on the wording of that precautionary allergen label, what seems safe for themselves or their child, and I think that’s a huge issue,” said Dr. Ruchi S. Gupta, a professor of pediatrics at Northwestern Medicine in Chicago and an author of the study.

My child hasn’t had a reaction from cross contact in prepackaged food, fortunately. But other children certainly have.

“The whole world of food labeling is almost like a foreign language,” said Allison A. Ososkie of Vienna, Va.

Her 2-year-old son, Lincoln, is allergic to egg, milk, peanuts, tree nuts, soy and shellfish. This past spring, he had an anaphylactic reaction to crackers that may have been processed on equipment with milk products.

Anna M. Francis, an acupuncturist in Wheat Ridge, Colo., has a 6-year-old daughter, Penelope, who is allergic to egg, dairy, cashew, pistachio, cherry and blackberry. In 2015, Ms. Francis thought the snack bar she was giving her daughter was safe. She even called the company to ask about its equipment-cleaning process.

“My daughter had a bite and had an anaphylactic reaction,” said Ms. Francis. She wants the government’s regulation to include labeling for possible cross contact of allergens.

There’s something else consumers with food allergies have to worry about: incorrect packaging. Sometimes, during the manufacturing process, food made using one of the eight major allergens isn’t properly labeled.

In 2018, about one-third of F.D.A. recalls involved prepackaged foods that were erroneously labeled, according to data compiled by the agency.

Remember my box of cookies? Let’s say I put it back on the shelf and head over to the store’s bakery for freshly prepared treats instead. Sadly, foods produced in a bakery or deli and “placed in a wrapper or container in response to a consumer’s order” are not covered under federal labeling requirements. The label on my box of cookies, packaged by a bakery worker, will not have any federally regulated allergen labels on it.

The labeling on the side of my box of cookies — whether it says “contains almonds,” “may contain almonds” or nothing at all — is determined by the food manufacturer.

So what goes into making the food that ends up on a shelf? And what kind of consideration is given to people with food allergies?

At Nestlé’s American operation, the key is applying “allergen management” across the expansive and complex operation, said David C. Clifford, director of food safety at Nestlé USA. He described the company’s approach as “objective, science-based, risk-based.”

“It’s a very serious responsibility that we have to feed the public, and the responsibilities around these systems extend horizontally across the organization,” said Mr. Clifford, who added that his team conducts allergen safety training throughout the company.

The Hershey Company also runs a training program for employees, it said in a statement. The training “includes video interviews with allergic children and their families who face the challenges of allergen management on a personal level every day of their lives.”

Given everything we know about food allergen labeling, here is some advice.

When you’re scanning the shelves, if you spot precautionary labels beginning with “may contain” or “processed in the same facility as,” don’t buy them if they refer to your allergy, said Dr. Scott H. Sicherer, chief of pediatric allergy and immunology at the Icahn School of Medicine at Mount Sinai in New York.

“You shouldn’t make risk decisions based on what precautionary words are used on the label,” said Dr. Sicherer. “But rather, to be 100 perfect safe, just avoid products that have the precautionary label, if that’s a food that you’re avoiding.”

Instead of guessing what a label might mean, a few parents I spoke to take a proactive approach: calling companies to get answers, even if it is time-consuming.

“Maybe once a month I’m calling and trying to track something down,” said Julie V. Lunn, a bookkeeper and entrepreneur in Havre de Grace, Md., whose 3-year-old daughter, Alafair, is allergic to a variety of foods.

One way to simplify things is to seek out products made in allergen-free plants.

Enjoy Life Foods has one such facility, said Joel D. Warady, general manager of the company. He said employees are forbidden from bringing peanuts to work, and they must wear company-issued shoes that don’t leave the factory, in Jefferson, Ind.

MadeGood Foods, based in Ontario, swabs hands and tables to test for allergens, said Janice A. Harada, the company’s marketing manager.

Manufacturers like these cater to the allergy community, using branding to make it clear their foods are clear of allergens.

And that box of cookies I’ve been looking for? If its label says “made in a dedicated allergen-free facility,” it should be safe to give to my son.


This article was originally published in The New York Times. Read the original article.

Happy Thanksgiving! You’re about to enjoy one of the most wonderful meals of the year with family and friends. And you’re probably looking forward to a plate full of food that you, or someone you care about, spent a lot of time preparing.

Or maybe they ordered it from a caterer. That’s fine, we don’t judge.

As you give thanks for the bounty of this meal and the company you share it with, spend some time thinking about some of the scientific facts that made your meal possible. Biology. Chemistry. Physics. It’s all there on your plate.

Here are some things we’ve learned about your Thanksgiving meal. If all else fails, these facts might make for nice conversation starters with that step-cousin you only see once a year.

Turkeys were first domesticated in Mexico 1,500 or so years ago, earlier than previously thought.CreditCaitlin Ochs for The New York Times

Turkeys were first domesticated in Mexico 1,500 or so years ago, earlier than previously thought.CreditCaitlin Ochs for The New York Times

While turkeys share a name with the country at the crossroads of Europe and the Middle East, they originated in the Americas. And people have been raising them for food and other reasons longer than we previously knew.

In 2016, scientists published new research showing that the Zapotec people living in what is now Mexico kept whole turkey eggs in their households as long ago as 400 to 500 A.D., using them for ritualistic purposes. The discovery pushed back the earliest known domestication of turkeys by 100 to 200 years.

“It’s the earliest solid evidence of domesticated turkey in southern Mexico that we have to date,” said Gary Feinman, an archaeologist from the Field Museum in Chicago, in an interview last year. Learn more about the origins of turkeys.

There are many different ways to make good stuffing.CreditKarsten Moran for The New York Times


There are many different ways to make good stuffing.CreditKarsten Moran for The New York Times

Is it safe to cook stuffing inside your turkey? It’s possible, according to the Agricultural Department, but it’s not without risk. Some years back, a chemist named Robert L. Wolke explained why this was a physics problem:

A turkey is shaped physically like a big round ball, and when you’re roasting it the heat has to come in from the outside. That makes the inner parts of the turkey the last to become hot enough to kill dangerous bacteria; the U.S.D.A. recommends at least 165 degrees.

But by the time the inner thighs get to that temperature, the breast is overcooked. And if the bird is stuffed, the stuffing may never get that hot, and at lower temperatures stuffing is a wonderful growth medium for bacteria.

There are a lot of other good ways to make stuffing, or dressing; perhaps you should try one. Read more of Dr. Wolke’s interview.

Beets get their red color from a different compound than cranberries or other red fruits and vegetables.CreditKarsten Moran for The New York Times


Beets get their red color from a different compound than cranberries or other red fruits and vegetables.CreditKarsten Moran for The New York Times

You’re probably enjoying some cranberry sauce with your turkey. Perhaps you’re eating roasted beets, too. They’re both red, but the chemical processes that give them their hues are completely unrelated.

Cranberries are made red by pigments called anthocyanins. These compounds are a common source of red coloration in the plant kingdom, from fall foliage to raspberries, apples and cherries.

But beets have something different going on.

Their brilliant reds result from substances called betalains. Scientists recently reported that in their evolutionary history, beets figured out how to harness a surplus of an amino acid called tyrosine. This is the same substance that helps opium poppies produce their narcotic effect. But while most plants switch off the process that yields tyrosine, the beet keeps it going until it becomes such a beautiful shade of red.

Get the full story on the chemistry that makes beets so red.

Brussels sprouts, the most cunning of Thanksgiving vegetables.CreditKarsten Moran for The New York Times


Brussels sprouts, the most cunning of Thanksgiving vegetables.CreditKarsten Moran for The New York Times

Hopefully you’re eating something green, too. Perhaps it’s a side of brussels sprouts. They may be the craftiest thing on your plate.

Scientists found that when a brussels sprout plant detects eggs laid on its surface by a type of butterfly, it responds by manufacturing a chemical. That chemical sends a signal to parasitic wasps, sort of like a last-minute invitation to a Thanksgiving meal. The wasps lay their own eggs, which eat the growing butterflies, and the brussels sprouts are saved.

Not that we’re saying that digging into those delicious green orbs will attract wasps. Enjoy!

Here’s an overview about that and other surprising things that plants can do.

The pumpkins that fill your pie, and their cousins like squash and cucumbers, share a melon-like fruit as a common ancestor.CreditAndrew Scrivani for The New York Times


The pumpkins that fill your pie, and their cousins like squash and cucumbers, share a melon-like fruit as a common ancestor.CreditAndrew Scrivani for The New York Times

You shouldn’t? You must. Here’s a nice slice of pumpkin pie. We baked it ourselves.

Instead of the whipped topping, we’ll offer you this fact: your dessert is the product of an evolutionary quirk that transpired some 100 million years ago.

Pumpkins, along with their cucurbitaceae family members like squash, watermelons and cucumbers, were born when the genome of a melon-like fruit duplicated itself. As we explained a couple of months ago in this article, this act of duplication set off a course of adaptations to environmental changes. Millions of years later, the descendants of that fruit ended up in a can that was pried open, poured in a pie crust and baked with love so you’d have something delicious to finish your meal.

There’s still some left. We’ll wrap up a slice for you to take home.

Roaming turkeys in San Rafael, Calif., earlier this month.CreditBill Disbrow/SF Gate, via Associated Press


Roaming turkeys in San Rafael, Calif., earlier this month.CreditBill Disbrow/SF Gate, via Associated Press

Now that you’ve finished the meal, it’s time to take up one of our most important Thanksgiving traditions: blaming the tryptophan for your drowsiness.

Blame something else.

Tryptophan is one amino acid among many in turkey, and in combination with the others, its soporific effects are constrained.

The real source of your fluttering eyelids? Too many yams. Too many mashed potatoes. Too many brussels sprouts. Too many biscuits. That second slice of pie. Find the full details explaining why tryptophan is not to blame in this quick article.

Better ask for a cup of coffee before you get in the car and go through the woods and over the river to get home.


This article was originally published in The New York Times.  Read the original article.

The Problem With Probiotics

Even before the microbiome craze — the hope that the bacteria in your gut holds the key to good health — people were ingesting cultures of living micro-organisms to treat a host of conditions. These probiotics have become so popular that they’re being marketed in foods, capsules and even beauty products.

Probiotics have the potential to improve health, including by displacing potentially harmful bugs. The trouble is that the proven benefits involve a very small number of conditions, and probiotics are regulated less tightly than drugs. They don’t need to be proved effective to be marketed, and the quality control can be lax.

In a recent article in JAMA Internal Medicine, Pieter Cohen, an associate professor of medicine at Harvard Medical School, urges us to consider the harms as well as the benefits. Among immune-compromised individuals, for instance, probiotics can lead to infections.

Consumers can’t always count on what they’re getting. From 2016 to 2017, the Food and Drug Administration inspected more than 650 facilities that produce dietary supplements, and determined that more than 50 percent of them had violations. These included issues with the purity, strength and even the identity of the promised product.

Probiotic supplements have also been found to be contaminated with organisms that are not supposed to be there. In 2014, such a supplement’s contamination arguably caused the death of an infant.

Given all of this, what are the benefits? The most obvious use of probiotics would be in the treatment of gastrointestinal disorders, given that they are focused on gut health. There have been many studies in this domain, so many that early this year the journal Nutrition published a systematic review of systematic reviews on the subject.

The takeaway: Certain strains were found useful in preventing diarrhea among children being prescribed antibiotics. A 2013 reviewshowed that after antibiotic use, probiotics help prevent Clostridium difficile-associated diarrhea. A review focused on acute infectious diarrhea found a benefit, again for certain strains of bacteria at controlled doses. There’s also evidence that they may help prevent necrotizing enterocolitis (a serious gastrointestinal condition) and death in preterm infants.

Those somewhat promising results — for very specific uses of very specific strains of bacteria in very specific instances — are just about all the “positive” results you can find.

Many wondered whether probiotics could be therapeutic in other gastrointestinal disorders. Unfortunately, that doesn’t appear to be the case. Probiotics didn’t show a significant benefit for chronic diarrheaThree reviews looked at how probiotics might improve Crohn’s disease, and none could find sufficient evidence to recommend their use. Four more reviews looked at ulcerative colitis, and similarly declared that we don’t have the data to show that they work. The same was true for the treatment of liver disease.

Undaunted, researchers looked into whether probiotics might be beneficial in a host of disorders, even when the connection to gut health and the microbiome was tenuous. Reviews show that there is insufficient evidence to recommend their use to treat or prevent eczemapreterm laborgestational diabetesbacterial vaginosisallergic diseases or urinary tract infections.

Reviews looking at the treatment or prevention of vulvovaginal candidiasis in womenpneumonia in patients hooked up to respirators, and colds in otherwise healthy people show some positive results. But the authors note that the studies are almost all of low quality, small in size, and often funded by companies with significant conflicts of interest.

Individual studies are similarly disappointing for probiotics. One examining obesity found limited effects. Another showed they don’t prevent cavities in teeth. They don’t help prevent infant colic, either.

None of this has prevented probiotics from becoming more popular. In 2012, almost four million Americans used them. In 2014, the global market for probiotics was more than $32 billion.

It’s not clear why. Even in specific diarrhea-focused areas, the case for them isn’t as strong as many think. As with nutrition research, much of this has to do with study design and how proof of efficacy doesn’t translate into real-world applications.

“Sometimes small studies suggest strains work, but when a larger more well-done study is performed, they no longer seem to,” Dr. Cohen said.

When research is done on probiotics, it usually involves a specific organism, defined by genus, species and even strain. When used in studies, they are pure and carefully dosed. But when we buy probiotics off the shelf, especially when they are in food products, we often have no idea what we’re getting.

Further, there’s still a lot we don’t know. A recent study published in Cell compared how the microbiome of the gut reconstituted itself after antibiotic treatment with and without probiotic administration. The researchers found that probiotics (which might have improved diarrhea symptoms) led to a significant delay in microbiome reconstitution, if it occurred at all. And — again — this study was with purified strains of bacteria, which is not what you’re getting in probiotic-containing food.

Of course, people with no immune deficiencies should feel free to eat yogurt and sauerkraut, which can absolutely be part of a healthy diet. Eat them because they’re delicious, and most likely better for you than many other foods, not because of any health claims.

“It’s important that consumers understand that all those nicely labeled containers on store shelves are not vetted by the F.D.A.,” Dr. Cohen said. “They’re not carefully watching over the probiotic space, leaving consumers to be the guinea pigs for these science experiments.”

For too long we’ve assumed that probiotics are doing some good and little harm. That might be true for some, but it’s not assured in the current environment.


This article was originally published in The New York Times.  Read the original article.

Switching to plant-based protein could increase America’s food supply by a third

VEGANS are good for the environment. Growing their food requires less land than raising meat does. Animals do not turn all the energy in the crops they eat into calories in their muscles. They need some of that energy to stay alive—and while that overhead is good for the animals, from a food-production standpoint it looks like a waste. This waste means you need more land per calorie of food if you are producing beef than if you are producing broccoli. Admittedly, a lot of grazing is on land that would not necessarily be suitable for arable farming. But the finding from the UN’s Food and Agriculture Organisation that raising livestock takes about 80% of all agricultural land and produces just 18% of the world’s calories is still telling.

Alon Shepon of the Weizmann Institute and colleagues have looked at this in terms of opportunity costs. Choosing to make a gram of protein by feeding an egg-laying hen, rather than getting the equivalent of a gram of egg protein from plants, has an opportunity cost of 40%. Getting the gram of protein from beef represents an opportunity cost of 96%. They argue that if America stopped paying these opportunity costs and got the protein from plants in the first place, it would be equivalent to increasing the food supply by a third—or eliminating all of the losses due to food waste.


This article was originally published in The Economist. Read the original article.

Seriously, Juice Is Not Healthy

Obesity affects 40 percent of adults and 19 percent of children in the United States and accounts for more than $168 billion in health care spendingeach year. Sugary beverages are thought to be one of the major drivers of the obesity epidemic. These drinks (think soda and sports drinks) are the largest single source of added sugars for Americans and contribute, on average, 145 added calories a day to our diets. For these reasons, reducing sugary beverage consumption has been a significant focus of public health intervention. Most efforts have focused on sodas.

But not juice. Juice, for some reason, gets a pass. It’s not clear why.

Americans drink a lot of juice. The average adult drinks 6.6 gallons per year. More than half of preschool-age children (ages 2 to 5) drink juice regularly, a proportion that, unlike for sodas, has not budged in recent decades. These children consume on average 10 ounces per day, more than twice the amount recommended by the American Academy of Pediatrics.

Parents tend to associate juice with healthfulness, are unaware of its relationship to weight gain and are reluctant to restrict it in their child’s diet. After all, 100 percent fruit juice — sold in handy individual servings — has been marketed as a natural source of vitamins and calcium. Department of Agriculture guidelines state that up to half of fruit servings can be provided in the form of 100 percent juice and recommend drinking fortified orange juice for the vitamin D. Some brands of juice are evenmarketed to infants.

Government programs designed to provide healthy food for children, such as the Special Supplemental Nutrition Program for Women, Infants, and Children, offer juice for kids. Researchers have found that children in the program are more likely to exceed the recommended daily fruit juice limit than those who are similarly poor but not enrolled.

[Here’s a guide to reducing your sugar consumption.]

Despite all the marketing and government support, fruit juices contain limited nutrients and tons of sugar. In fact, one 12-ounce glass of orange juice contains 10 teaspoons of sugar, which is roughly what’s in a can of Coke.

Drinking fruit juice is not the same as eating whole fruit. While eating certain fruits like apples and grapes is associated with a reduced risk of diabetes, drinking fruit juice is associated with the opposite. Juices contain more concentrated sugar and calories. They also have less fiber, which makes you feel full. Because juice can be consumed quickly, it is more likely than whole fruit to contribute to excess carbohydrate intake. For example, research has found that adults who drank apple juice before a meal felt hungrier and ate more calories than those who started with an apple instead. Children who drink juice instead of eating fruit may similarly feel less full and may be more likely to snack throughout the day.

Juice may also be a “gateway beverage” — 1-year-olds who drank more juice also drank more sugary beverages, including more soda, in their school-age years. Children’s excessive consumption of juice has been linked to an increased risk of weight gainshorter stature and cavities. Even in the absence of weight gain, sugar consumption worsens blood pressure and increases cholesterol.

It’s tempting to minimize the negative contributions of juice to our diets because it’s “natural” or because it contains “vitamins.” Studies that support this view exist, but many are biased and have been questioned.

And we doubt you’d take a multivitamin if it contained 10 teaspoons of sugar.

[Children and adults are downing sugary drinks far less often than they used to, a new study finds.]

There is no evidence that juice improves health. It should be treated like other sugary beverages, which are fine to have periodically if you want them, but not because you need them. Parents should instead serve water and focus on trying to increase children’s intake of whole fruit. Juice should no longer be served regularly in day care centers and schools. Public health efforts should challenge government guidelines that equate fruit juice with whole fruit, because these guidelines most likely fuel the false perception that drinking fruit juice is good for health.

It’s much easier to prevent obesity than it is to reverse it. We need to teach kids how to eat healthier when they’re young so that they develop good habits to carry on for the rest of their lives. In the past decade or so, we have succeeded in recognizing the harms of sugary beverages like soda. We can’t keep pretending that juice is different.

The Dilemma of the Gluten-Free Diet

It’s not unusual after eating that the symptoms set in for Lee Graham : severe stomach pain and worse.

“It’s always sort of a game of Russian roulette when you go out to eat,” says Ms. Graham, executive director of the National Celiac Association, a Needham, Mass.-based nonprofit that advocates for people with celiac disease.

What’s frustrating for Ms. Graham is that this can happen even when she’s eating what is supposed to be a gluten-free meal.

A new study in the American Journal of Clinical Nutrition shows that eating gluten-free is nearly impossible, underscoring the need for better treatments for patients with celiac disease.

The good news: About half a dozen potential treatments are in the works, ranging from a vaccine to a capsule designed to regulate the gut. But most are at least a couple of years from entering the market. And celiac patients would still have to maintain a gluten-free diet, which is currently the only answer for the disease.

Experts say up to 1% of the global population has celiac disease, an autoimmune condition in which people develop an immune reaction to gluten. Gluten is a protein that appears in any food containing wheat, barley and rye. The immune system reaction results in inflammation and damage in the lining of the small intestine, which can lead to medical complications, such as acute stomach pain and failure to absorb nutrients.

The odds of getting celiac disease in the U.S. have increased four- to fivefold over four decades, says Peter Green, director of the Celiac Disease Center at Columbia University Medical Center, but have leveled off in recent years.

“There has been this increased rate of diagnosis as well, but there’s still a lot of people with celiac disease who don’t know they have it,” Dr. Green says. He was an author on another study looking at the global prevalence of celiac disease published in 2017 in the journal Clinical Gastroenterology and Hepatology.

Dr. Green says it’s unclear what the lowest level of gluten is that causes intestinal damage in patients. “About 30% of people don’t get better on a gluten-free diet,” he says.

Manufacturers of gluten-free food go through the painstaking task of trying to ensure that there’s no gluten in products. The U.S. Food and Drug Administration requires that foods that are labeled gluten-free contain fewer than 20 parts per million of gluten.
Manufacturers of gluten-free food go through the painstaking task of trying to ensure that there’s no gluten in products. The U.S. Food and Drug Administration requires that foods that are labeled gluten-free contain fewer than 20 parts per million of gluten.PHOTO: NATALIE BEHRING/BLOOMBERG NEWS

The American Journal of Clinical Nutrition study used data from three prior clinical trials to estimate how much gluten 246 celiac patients were ingesting. The gluten measurements were based on either a stool or urine sample.

The study found that on average patients were ingesting 200 to 250 milligrams of gluten a day, says Jack Syage, CEO of ImmunogenX, a Newport Beach, Calif.-based biotechnology company, and first author on the study. Someone without celiac disease eats about 7,500 to 10,000 milligrams of gluten a day.

The study didn’t look at where the gluten comes from. Dr. Syage says researchers guess much of it is inadvertently consumed when food is contaminated during processing or preparation.

Those with celiac disease typically need to limit exposure to under 100 milligrams, but the threshold can vary depending on a person’s sensitivity, says Joseph Murray, a professor of gastroenterology at the Mayo Clinic in Rochester, Minn.

The U.S. Food and Drug Administration requires that packaged foods labeled gluten-free contain fewer than 20 parts per million of gluten—the equivalent of 20 milligrams of gluten in one kilogram of food. Gluten Free Watchdog, a group that tests packaged gluten-free foods, has found that foods test at or above 20 parts per million of gluten about 4% of the time.

Dr. Murray is working with ImmunogenX on developing an enzyme called latiglutenase, designed to be taken with meals to help patients digest gluten. ImmunogenX acquired the enzyme mixture from Alvine Pharmaceuticals in 2016 after a Phase 2 trial failed to demonstrate healing of the small intestine. The study showed improvement of symptoms for a subgroup of celiac patients. The current ImmunogenX trial will focus on the 20% of celiac patients who have persistent symptoms while following a gluten-free diet.

The company is launching a final Phase 2 clinical trial in a few months. If successful, it would have to do a Phase 3 trial before applying to the FDA for approval as a drug. The earliest a commercially available drug could hit the market is late 2020.

Innovate Biopharmaceuticals in Raleigh, N.C., expects to launch a Phase 3 trial later this year for larazotide acetate, a drug taken as a capsule that would be taken before every meal.

Jay Madan, founder and president of the company, says the drug helps regulate the leakiness of the gut. Results from Phase 2 clinical trials showed improvement in abdominal symptoms. The drug isn’t absorbed by the body and was well tolerated in more than 500 patients.

ImmusanT, a Cambridge, Mass.-based biotechnology company, will enter into a Phase 2 clinical trial of its vaccine, Nexvax2, this year, says Leslie Williams, president and CEO of the company.

The vaccine doesn’t prevent celiac disease but is a therapeutic treatment akin to an allergy shot, she says. It would require self-injecting weekly to maintain non-responsiveness to gluten.

“Our initial approach is to protect patients against inadvertent exposure to gluten,” Dr. Williams says. “Ultimately we will see if we can get them to reintroduce gluten, too.”

Researchers will present the results of Phase 2 clinical trials of the drug AMG 714 in June, says Francisco Leon, the co-founder and former CEO of Celimmune, which was recently acquired by Amgen .

Dr. Leon, who now works as a consultant to Amgen, says the drug is an antibody that blocks interleukin-15, a protein that stimulates the immune system in the gut, causing damage and gastrointestinal symptoms.

Researchers tested the drugs in a pair of Phase 2 studies. One featured patients with refractory celiac disease type 2, the most severe form of celiac disease. It affects about 1 in 200 celiac patients and is considered lymphoma of the gut. Doctors also tested the drug with a larger population of celiac disease patients.

Several other treatments are in earlier stages of development. Cour Pharmaceutical in Chicago and Takeda Pharmaceutical in Japan are using nanotechnology to try to reprogram the body’s immune system to enable patients to develop a tolerance to gluten and potentially reverse symptoms of the disease.

The companies launched a Phase 1 trial in February which they expect to complete in March 2019.


This article was originally published in The Wall Street Journal. Read the original article.

The Dangers of Belly Fat

If you do nothing else today to protect your health, consider taking an honest measurement of your waist. Stand up straight, exhale (no sucking in that gut!) and with a soft tape measure record your girth an inch or two above your hip bones.

The result has far greater implications than any concerns you might have about how you look or how your clothes fit. In general, if your waist measures 35 or more inches for women or 40 or more inches for men, chances are you’re harboring a potentially dangerous amount of abdominal fat.

Subcutaneous fat that lurks beneath the skin as “love handles” or padding on the thighs, buttocks or upper arms may be cosmetically challenging, but it is otherwise harmless. However, the deeper belly fat — the visceral fat that accumulates around abdominal organs — is metabolically active and has been strongly linked to a host of serious disease risks, including heart disease, cancer and dementia.

You don’t even have to be overweight or obese to face these hazards if you harbor excess fat inside your abdomen. Even people of normal weight can accumulate harmful amounts of hidden fat beneath the abdominal wall. Furthermore, this is not fat you can shed simply by toning up abdominal muscles with exercises like situps. Weight loss through a wholesome diet and exercise — activities like walking and strength-training — is the only surefire way to get rid of it.

Until midlife, men usually harbor a greater percentage of visceral fat than women do, but the pattern usually reverses as women pass through menopause. Few females seem to escape a midlife waistline expansion as body fat redistributes and visceral fat pushes out our bellies. Even though in my eighth decade I weigh less than I did at age 13, my waist is many inches bigger.

Here’s why visceral fat cells are so important to your well-being. Unlike the cells in subcutaneous fat, visceral fat is essentially an endocrine organ that secretes hormones and a host of other chemicals linked to diseases that commonly afflict older adults. One such substance is called retinol-binding protein 4 (RBP4) that was found in a 16-year study of nurses to increase the risk of developing coronary heart disease. This hazard most likely results from the harmful effects of this protein on insulin resistance, the precursor to Type 2 diabetes, and development of the metabolic syndrome, a complex of cardiac risk factors.

The Million Women Study conducted in Britain demonstrated a direct link between the development of coronary heart disease and an increase in waist circumference over a 20-year period. Even when other coronary risk factors were taken into account, the chances of developing heart disease were doubled among the women with the largest waists. Every additional two inches in the women’s waist size raised their risk by 10 percent.

Cancer risk is also raised by belly fat. The chances of getting colorectal cancer were nearly doubled among postmenopausal women who accumulate visceral fat, a Korean study found. Breast cancer risk increases as well. In a study of more than 3,000 premenopausal and postmenopausal women in Mumbai, India, those whose waists were nearly as big as their hips faced a three- to four-times greater risk of getting a breast cancer diagnosis than normal-weight women.

Dutch study published last year linked both total body fat andabdominal fat to a raised risk of breast cancer. When the women in the study lost weight — about 12 pounds on average — changes in biomarkers for breast cancer, like estrogen, leptin and inflammatory proteins, indicated a reduction in breast cancer risk.

Given that two-thirds of American women are overweight or obese, weight loss may well be the single best weapon for lowering the high incidence of breast cancer in this country.

Perhaps most important with regard to the toll on individuals, families and the health care system is the link between abdominal obesity and risk of developing dementia decades later. A study of 6,583 members of Kaiser Permanente of Northern California who were followed for an average of 36 years found that those with the greatest amount of abdominal obesity in midlife were nearly three times more likely to develop dementia three decades later than those with the least abdominal fat.

Having a large abdomen raised dementia risk in the women even if they were of normal weight overall and lacked other health risks related to dementia like heart disease, stroke and diabetes.

Among other medical problems linked to abdominal fat are insulin resistance and the risk of Type 2 diabetes, compromised lung function and migraine headaches. Even asthma risk is raised by being overweight and especially by abdominal obesity, a study of 88,000 California teachersfound.

Over all, according to findings among more than 350,000 European men and women published in The New England Journal of Medicine, having a large waist can nearly double one’s risk of dying prematurely even if overall body weight is normal.

All of which raises the question: How best to shed abdominal fat and, even more important, how to avoid accumulating it in the first place?

Chances are you’ve periodically seen ads on the internet for seemingly magical ways to reduce belly fat. Before you throw good money after bad, let it be said that no pill or potion has been scientifically shown to dissolve abdominal fat. You have to work at it. And that means avoiding or drastically limiting certain substances in your diet, controlling overall caloric intake and engaging in exercise that burns calories.

Perhaps the worst offender is sugar — all forms and especially fructose, which makes up half of sucrose and 55 percent of high-fructose corn syrup. One of the best ways to reduce your sugar intake is to stop drinking sodasand other sweet drinks, including fruit juices. Limiting alcohol, which may suppress fat-burning and add nutritionally empty calories, and avoiding refined carbohydrates like white bread and white rice are also helpful.

Make sure your diet contains adequate amounts of protein and dietary fiber, including vegetables, beans and peas and whole grains.

Get enough sleep — at least seven hours a night. In a study of 68,000 women followed for 16 years, those who slept five hours or less were a third more likely to gain 32 pounds.

Finally, move more. In a major national study, inactivity was more closely linked to weight gain and abdominal obesity than caloric intake.

This article was originally published in The New York Times.  Read the original article.

Food Tailored to Our Genes May Be on the Menu Soon

What if you could take a blood test to determine the best diet for you?

Right now most dietary guidelines are developed by looking at an average population. But not everyone responds to a given diet the same way. Some ethnic groups, for instance, are more prone than others to high blood pressure, abnormal cholesterol levels and excess body fat on certain diets.


New research raises the tantalizing possibility of creating personalized diets. The study, published by the journal Genetics, suggests genes play a strong role in influencing how our bodies respond to diets. Based on the results, the authors hope that someday people will be able to take a blood test to determine if a given diet is likely to work for them.

“The idea that as long as you stick to a certain diet you’ll do well is probably not the complete story,” says David Threadgill, the study’s co-author and a professor in the departments of veterinary pathobiology and molecular and cellular medicine at Texas A&M University.

In the study, mice with different genes were fed popular human diets: a typical North American diet, high in refined carbohydrates and fat; a Mediterranean diet, high in fiber; a Japanese diet, which for mice consisted of rice and green tea extract; and a ketogenic diet, based on the diet eaten by the Maasai in Kenya, which is high in fat and lacks carbohydrates entirely.

Researchers collected data on measures of metabolic health, such as body-mass index, glucose regulation, cholesterol levels and liver function.

Among the mice tested, each genetic subgroup had a unique response, with certain diets working for some groups, but not others. The mice generally did worst on the American diet and best on the Japanese diet, just like an average group of people.

But what was really striking, Dr. Threadgill says, “is that every strain had a unique pattern where it was optimally healthy.”

For example, one strain, when put on the ketogenic diet, overate and then became obese and developed metabolic syndrome, while another strain also overate on the ketogenic diet, but didn’t gain weight. The mice in that second group, in effect, could eat whatever they wanted without getting heavy. Rather than conserving energy, their bodies burned it off by raising their body temperature.

The researchers next are trying to identify genetic factors that allow one strain to overconsume without health effects, and to identify the specific genes causing each mouse strain to respond the way it did. “That will then allow us to actually go into human populations and start looking at how individuals respond based on their genotype,” says Dr. Threadgill.

The scientists are also looking for biomarkers that could enable doctors to use a blood test to predict a diet’s effectiveness. Dr. Threadgill cautions, however, that scientists don’t know enough yet to use genetic testing to recommend a diet. He believes that is several years away.

“It may happen sooner,” he says, “but it’s going to require a more in-depth understanding.”


This article was originally published in The Wall Street Journal. Read the original article.

What We Know (and Don’t Know) About How to Lose Weight

The endless array of diets that claim to help you shed pounds tend to fall into two camps: low fat or low carbohydrate. Some companies even claim that genetics can tell us which diet is better for which people.

A rigorous recent study sought to settle the debate, and it had results to disappoint both camps. On the hopeful side, as The New York Times noted, people managed to lose weight no matter which of the two diets they followed.

The study is worth a closer look to see what it did and did not prove.

Researchers at Stanford University took more than 600 people (which is huge for a nutrition study) aged 18 to 50 who had a body mass index of 28 to 40 (25-30 is overweight, and 30 and over is obese). The study subjects had to be otherwise healthy. They couldn’t even be on statins, or drugs for Type 2 diabetes or hypertension, which might affect weight or energy expenditure. They were all randomly assigned to a healthful low-fat or a healthful low-carbohydrate diet, and they were clearly not blinded to which group they were in.

All participants attended 22 instructional sessions over one year in groups of about 17 people. The sessions were held weekly at first and were then spaced out so that they were monthly in the last six months. Everyone was encouraged to reduce intake of the avoided nutrient to 20 grams per day over the first eight weeks, then participants slowly added fats or carbohydrates back to their diets until they reached the lowest level of intake they believed could be sustained for the long haul.

Everyone was followed for a year (which is an eternity for a nutrition study). Everyone was encouraged to maximize vegetable intake; to minimize added sugar, refined flour and trans fat intake; and to focus on whole foods that were minimally processed. The subjects were also encouraged to cook at home as much as possible.

All the participants took a glucose tolerance test as a measurement of insulin sensitivity. Some believe that insulin resistance or sensitivity may affect not only how people respond to diets, but also how well they adhere to them. The participants were also genotyped, because some believe that certain genes will make people more sensitive to carbohydrates or fat with respect to weight gain. About 40 percent of participants had a low-fat genotype, and 30 percent had a low-carbohydrate genotype.

Data were gathered at the beginning of the study, at six months and at one year. At three unannounced times, researchers checked on patients to see how closely they were sticking to the instructions.

This was a phenomenally well-designed trial.

People did change their diets according to their group assignment. Those in the low-fat group consumed, on average, 29 percent of their calories from fats, versus 45 percent in the low-carbohydrate group. Those in the low-carbohydrate group consumed 30 percent of their calories from carbohydrates, versus 48 percent in the low-fat group.

They did not, however, lose meaningfully different amounts of weight. At 12 months, the low-carbohydrate group had lost, on average, just over 13 pounds, compared with more than 11.5 pounds in the low-fat group. The difference was not statistically significant.

Insulin sensitivity didn’t make a difference. People who secreted more or less insulin lost no more or less weight in general on either a low-fat or low-carbohydrate diet. Genetics didn’t make a difference either. People who had genes that might indicate that they would do better on one diet or the other didn’t.

In fact, when you look at how every single participant in this study fared on the diet to which he or she was assigned, it’s remarkable how both diets yielded an almost identical, curving range of responses — from lots of weight lost to a little gained. It wasn’t just the averages.

Some have taken this study to prove that avoiding processed foods, eating more whole foods, and cooking at home leads to weight loss. While I’d like that to be true — I have advocated this healthful approach in my Upshot article on food recommendations and in a recent book — that’s not what this study showed. Although that advice was given to all participants, there was no control group in which that advice was omitted, and so no conclusions can be made as to the efficacy of these instructions.

Others have taken this study as evidence debunking the idea that counting calories is the key to weight loss. While that wasn’t the main thrust of this study, nor the instructions given, participants did reduce their intake by an average of 500-600 calories a day (even if they didn’t count them). This study didn’t prove the unimportance of calories.

The researchers also asked everyone, not just those in the low-carb group, to avoid “added sugars.” Therefore, we can’t really say anything new about added sugars and weight loss.

What this study does show is that people who have staked a claim on one diet’s superiority over another don’t have as strong a case as they think. It’s hard to overstate how similarly these two diets performed, even at an individual level.

It shows us that the many people, and the many studies, suggesting that we can tell which diets are best for you based on genetics or based on insulin levels might not be right either. Almost all of the studies that backed up such ideas were smaller, of shorter duration or less robust in design than this one. Granted, it’s still possible that there might be some gene discovered in the future that makes a difference, but those who think they’ve found it already might want to check their enthusiasm.


This study was focused mostly on people who were obese, so people looking to lose just a few pounds might benefit more from one diet or the other; we don’t know. It’s also worth noting that the people in this study received significant support on both diets, so the results seen here might not apply to those attempting to lose weight on their own.

You should be wary of those who tell you that they know what diet is best for you, or that there’s a test out there to tell you the same. Successful diets over the long haul are most likely ones that involve slow and steady changes. The simplest approach — and many have espoused it, including Jane Brody recently here at The Times — is to cut out processed foods, think about the calories you’re drinking, and try not to eat more than you intend to.

The bottom line is that the best diet for you is still the one you will stick to. No one knows better than you what that diet might be. You’ll most likely have to figure it out for yourself.



This article was originally published in The New York Times.  Read the original article.

These Are Not Your Father’s GMOs

hen I visited Jason McHenry’s farm in South Dakota, the young farmer, dressed in worn jeans and sunglasses, led me up a slippery steel ladder on the side of a grain bin. We tumbled through the manhole into a shifting mountain of soybeans. You could sift them through your fingers and taste their sweet, cloudy flavor.

The U.S. soybean crop is four billion bushels a year, about 240 billion pounds. It generates the most cash receipts for American farms after cattle and corn. Of those beans, more than 90 percent are genetically modified organisms, or GMOs—that is, they’ve been genetically enhanced, most often through the addition of a gene from a soil bacterium that renders them immune to the weed killer glyphosate, commonly known as Roundup. 

The 4,000 bushels McHenry and I were sitting in, however, represent a new type of plant that’s been modified using gene editing. A startup had employed the technology to introduce changes in two genes involved in fatty-acid synthesis, so that oil pressed from the beans is more like olive oil than typical soy oil.

McHenry first heard the pitch for the beans last December, at a hotel near the cooperative of South Dakota soybean processors. “We have something new and exciting,” a salesman told the farmers. “You’ve heard about the ban on trans fats?” Soybean oil has been losing market share since the U.S. government banned unhealthy fats created when soy oil is partially hydrogenated and turns to a solid  (think Crisco). Those fats have been killing people. They’re bad food.

Oil from the gene-edited beans could solve that problem, because it doesn’t need to be processed in the same way. Any farmer who agreed to plant the beans, McHenry heard, would be part of the wave of innovation filling store shelves with Greek yogurts, green packaging, and healthy ingredients. What’s more, it would mean a few quarters more per bushel. “You make a little more money, you have a great experience, and you are part of a revolution,” said the pitchman, Thomas Stoddard, a lanky biologist turned seed seller who visited McHenry’s farm with me.

To McHenry, a farmer just starting out with his own acres, his own debts, and his own decisions, the pitch made sense. The Roundup-resisting beans his father still plants are expensive. What’s more, the tumbleweeds have evolved to survive spraying and grow as high as your waist. “Looking at the market as a whole, Europe and China are questioning GMOs,” McHenry says. “You have to keep your finger on what the consumer wants, and as a farmer, you have to differentiate yourself. If you are looking at a market that could be gone, you have to think about alternatives.”

Jason McHenry on the South Dakota land where he grows soybeans created with gene editing.

The new beans are the creation of a startup called Calyxt, located 300 miles away,  near Minneapolis, where Stoddard works, and nearly a straight shot east on Highway 90 from McHenry’s farm. At the company’s greenhouses, thousands of plants are being altered with gene editing every week. The virtue of the technology is that it lets scientists create designer plants that don’t have foreign DNA in them. The technique, which adds or deletes snippets of genetic information, is similar to what could be achieved through conventional breeding, only much faster. In essence, if there’s some quality about a soybean that you like, and if you know the genetic instructions responsible, gene editing can move them to another bean in a single molecular step.

To many scientists, the potential of gene editing seems nearly limitless, offering a new way to rapidly create plants that are drought-resistant, immune to disease, or improved in flavor. A supermarket tomato that tastes good? That could happen if scientists restore the flavor-making genes that make heirloom varieties delicious. What about a corn plant with twice as many kernels? If nature allows it, scientists believe, gene editing could let them build it.

There is another reason gene editing is causing excitement in industry. The U.S. Department of Agriculture has concluded that the new plants are not “regulated articles.” The reason is a legal loophole: its regulations apply only to GMOs constructed using plant pathogens like bacteria, or their DNA. That means Calyxt can commercialize its beans without going through the process of permits, inspections, and safety tests required for other genetically modified crops. It’s counting on that to cut at least half the 13 years and $130 million that companies have, on average, invested in order to create a new GMO and get it into farmers’ hands.

To GMO opponents, the new, unregulated plants are a source of alarm. For years, they have argued that GMOs should be opposed because they might be unsafe. What if they cause allergies or poison butterflies? Now the battle lines are shifting because companies like Calyxt can create plants without DNA from a different species in them. They can argue that gene editing is merely “accelerated breeding technology.” 

To the critics, any attempt to reclassify engineered plants as natural is a dangerous fiction. “If they don’t have to go through the regulatory requirements, then it is game on again for genetic modification in agriculture,” says Jim Thomas, head of a nonprofit called the ETC Group that lobbies on environmental issues. “That is the prize. They are constructing a definition of a GMO so that gene editing falls outside it.”

University of Minnesota geneticist Dan Voytas develops new plants using genetic engineering. “The genie is out of the bottle,” he says.

Already, the effort to persuade governments and food groups is reaching a planetary scale. New Zealand decided that the new plants are GMOs after all, and so did the USDA’s own organic council. The Netherlands and Sweden don’t think they are. China hasn’t said. The European Union still has to make up its mind. Billions in global grain exports could ultimately hang in the balance.

Opponents say they’re ready to fight for rules, regulations, and labels. “Our position has never changed. This is just a form of genetic engineering, so the same things should happen—there should be required safety assessments,” says Michael Hansen, a staff scientist at the Consumers Union, a lobby group attached to Consumer Reportsmagazine. “I can’t see this being resolved anytime soon.”

Designer plants grow under artificial light at the greenhouse of Calyxt, a gene-editing startup in Minneapolis.

But McHenry has already accepted the argument. Pointing to his rows of grain bins, he ticked off whether the beans inside were GMOs or not. The one full of Calyxt beans he called “non-GMO.” “To me a GMO is [adding] an outside organism into a plant. The way I understand it there’s no foreign DNA put into the seed,” said McHenry. “It’s like we found a switch to make people’s lives easier. If it’s that easy, it makes sense to me.”

Drug companies see gene-editing technology as a versatile molecular scissors that could offer a radical new means to cure genetic diseases such as muscular dystrophy (see “Can CRISPR Save Ben Dupree?”). What’s not so widely appreciated is how close the technology is to large-scale implementation in agriculture and in our food. By the end of 2018, Calyxt says, it will be crushing beans and selling oil, potentially becoming the first company to enter the market with a gene-edited crop. At least one other crop is nearing commercialization from DuPont, which used gene editing to create a starchier corn plant.

To be sure, neither product is expected to take over farmland the way herbicide-resisting GMOs did. Instead, these initial examples are niche products with prosaic objectives. DuPont’s “waxy” corn is going to end up in glue sticks and as an emulsifier in salad dressing. Calyxt’s oil will fry doughnuts and chips. Even so, the mountain of beans at McHenry’s farm shows how quickly these crops could arrive. McHenry, making some fast calculations, estimated that we were sitting on 600 million of them. By then Stoddard, the salesman, had climbed into the story-tall grain bin too. “Gene editing is the future, and the first place it’s growing at scale is here in South Dakota,” he said reverently, letting beans drift through his hands.

Flipping a switch

The beans at McHenry’s farm are all descendants of a single soybean cell modified in 2012 by Dan Voytas, the cofounder of Calyxt and a professor of genetics at the University of Minnesota. Voytas told me he inherited a scientific interest in plants from his father, a government forest manager. “It was ‘Okay, son, what tree is that? Latin name, please,” he recalls.

I met Voytas at the startup’s greenhouse outside of Minneapolis, where he showed me fluid-mixing robots and a tall gene gun that fires the DNA into a plant cell. Green blobs growing on clear jelly in petri dishes were canola plants “regenerating” from a single cell after receiving new genetic instructions. The company has a staff of 35, two-thirds of whom are scientists. “We have a long list of ideas,” says Voytas. “But you can get a great oil and a sick plant. A lot of it is experimental.”

The startup uses a gene-editing technology called TALEN that Voytas helped develop—and patented. By the late 1990s, he had been part of a small group of biologists trying to move past the first round of GM plants not by adding entire genes, but instead by using cutting enzymes, called nucleases, to precisely sever the DNA chain—the life instructions found inside every living cell. To make Calyxt’s beans, Voytas used his technology to disable two genes.

Today, a different gene-editing technology, CRISPR, dominates the headlines, because it is easy to employ and inexpensive. However, because TALEN was developed two years earlier than CRISPR, the technique has advanced further toward commercial crops. Moreover, other plant biotech companies have been slowed by an ongoing patent fight over CRISPR, which left it unclear which of them would be able to use that technique.

Grain bins in Clark, South Dakota.

In the meantime, Calyxt says, it has already used TALEN to design 19 plants and is banking on gene editing to make it one of the first small companies to introduce a successful genetically engineered crop. It says the USDA has already confirmed that six of its plants won’t be regulated, including, in September, an alfalfa plant modified to have less lignin, making it easier for cows and horses to digest. The company, which went public in July, has spent only $47 million so far.

Until now, every successful GMO on the market has had as its objective increasing the yield from each acre of farmland. Marketing “healthier” food made from GMOs has been a taller order. But if gene-edited plants can avoid the stigma of GMOs, that could change. In Calyxt’s view, that would open up valuable new uses of genetic engineering. In addition to its soybean oil, Calyxt claims it has changed wheat plants so they can be ground into white flour with three times as much fiber as usual. A bread company might even be able to claim that hamburger rolls help prevent cancer.

Some of the more radical changes gene editing may bring were apparent the day I visited Voytas at his university laboratory. He was meeting with his students, who diagrammed their plans on a whiteboard. (By now, all the students are using CRISPR.) A woman from Ethiopia wanted to change a local grain plant, teff, so that it stands up straight instead of drooping and losing seeds. Another student was investigating how to inject DNA into the stem cells found in the roots and shoots of growing plants. “We’re almost getting to the point where if you ask ‘What’s the best oil crop?’ we could create the genome to make that plant,” Voytas says.

Some significant obstacles remain. Drug companies working on gene therapy have learned it is easier to design and make DNA strands than to get them inside a person’s cells. That is also true of many plants, where delivery of the gene-editing ingredients is still difficult. Understanding which genes should be edited is yet another roadblock. Scientists know a lot about how oils are synthesized and why fruit turns brown. But the list of valuable plant traits whose genetic causes are both well understood and easy to alter drops off quickly after that. “Right now it’s a grab bag of traits,” says Rebecca Bart, a plant scientist at the Danforth Center, in St. Louis. “We still need to have pretty significant investment in discovery before you can manipulate them with gene editing. It has to go in that order.”

What’s more, for traits that are well understood, gene editing isn’t the only way to create such plants—just the newest. For instance, Calyxt’s soybeans will face competition from beans with similar oil content that are already on the market, including one, called Vistive Gold and sold by Monsanto, that was created via old-fashioned GMO technology. Voytas acknowledges that his beans aren’t entirely novel but says they will be a useful test of Calyxt’s fast-to-market business model and a way to prove to investors that the company can make money. “Calyxt is the first plant gene-editing company out there and needs to show it can commercialize products,” he says. “The advantage is getting to revenue in the short term.”

Some entrepreneurs think gene editing will have a big impact only when it can change the amount of food an acre can produce. “In real estate, the saying is ‘Location, location, location.’ Well, in agriculture, it’s ‘Yield, yield, yield,’” says Oliver Peoples, CEO of Yield10, a plant-engineering company in Cambridge, Massachusetts.

Canola plants “regenerate” from individual cells following a round of gene editing.

So Calyxt is also working on plants that could increase the amount of food farmers can reap, like a wheat plant resistant to powdery mildew. To date, no GMO wheat has ever been commercialized, partly because, as happens with many plants, wheat’s genome accumulates extra DNA like a closet that never gets cleared out. In fact, wheat is hexaploid—its cells harbor six mostly identical copies of every chromosome. That has made it massively complicated to genetically engineer, but Voytas says that with gene editing it is fairly easy. In a single reaction, the TALEN tools can search out and cut all six copies of any wheat gene they want to remove.

GMO or not?

Outside of Penn Station, in Manhattan, a 10-story-tall advertisement for Ketel One, a brand of vodka, declares that it is “made with 100% NON GMO grain.” At any supermarket, it is easy to find a profusion of similar claims, even for products like salt, which don’t contain plant material. About 40 percent of U.S. adults think foods made from GMOs are less healthy to eat.

Such beliefs are the result of warring messages from scientists, agriculture lobbies, and nonprofits like Greenpeace that stir doubts about the safety of GM organisms. The result for the first generation of GMOs has been a global split decision. While GMOs cover millions of acres of cropland in the U.S., Brazil, Argentina, and India, governments have banned the cultivation of such plants through much of the rest of the world, including France, Germany, China, and Russia.

Now the question is whether gene-edited crops can dodge the GMO label. Broadly speaking, companies argue that these plants should be unregulated because they could have been created by conventional breeding. The proof? In many cases, there would be no way to tell a gene-edited plant from a natural one.

Editing one gene makes wheat resist mildew.

GMO critics now fear a tidal wave of “frankenfood” if such plants slip through regulations, something that is already occurring in the U.S. The reason gene-edited plants can be exempt from USDA rules is that the agency employs an outdated 30-year-old definition of a GMO that is triggered only if a plant was modified using plant bacteria, as early products were. The agency, in January 2017, acknowledged that plants with even profound genetic alterations “may entirely escape regulation” depending on how they are made. Since then, four more gene-edited plants have been waved forward, including a salt- and drought-tolerant soybean developed by the USDA itself, Calyxt’s alfalfa plant, a type of camelina grass created by Yield10, and a species of millet with a delayed flowering time. “They’re trying to fit a square peg in a round hole of old laws not meant to address these new technologies,” says Gregory Jaffe, who follows biotechnology at the Center for Science in the Public Interest, in Washington, D.C.

What’s missing, then, is enough scrutiny of whether the plants could harm insects, spread their genetic enhancements to wild cousins, or create superweeds like the ones resistant to Roundup. Companies do typically consult with the U.S. Food and Drug Administration to confirm that their plants are safe to eat. But that process is voluntary. Jaydee Hanson, senior policy analyst at the Center for Food Safety, which promotes organic farming, thinks companies have been astute in starting with simple, even obscure, products. “The public has not had a chance to say ‘Wait a second,’” he says. “As we move into more complicated gene editing, there are going to be more questions. And we could see the same kind of kickback we saw before.”

The “GMO or not” question is going to be a global one. Food regulators will have to decide if store packaging needs to disclose the presence of gene-edited plants. Some organic associations have already said such plants cannot carry that label, reasoning that they really are GMOs. The European Court of Justice, meanwhile, is set to weigh in on the issue in Europe, where scientists have argued that gene editing is simply an advanced form of breeding. Opponents are counting on Europe to classify the plants as GMOs, a decision that would frustrate the technology’s spread.

“It would be sad if opponents won,” Voytas told me. We were in his office and students were passing outside his window, waiting to for a chance to review their gene-editing plans with him. Even undergraduates, he noted, are now able to edit plants. “In some sense,” he said, “I think the genie is out of the bottle.”



This article was originally published in MIT News. Read the original article.