A Mysterious Allergy, the UNC Researcher Who Helped Figure It Out, and the Cloned Pigs That Could Be the Answer

Steve Troxler first noticed something was wrong on a Sunday morning. 

In February 2017, North Carolina’s longtime agriculture commissioner had just returned from a trade mission to Brazil, where he’d feasted on steak with local officials and businessmen. He awoke with a high fever and a rash, severe enough that he went to see his doctor Monday morning, who, in turn, sent him to an infectious disease specialist. 

Before going to Brazil, Troxler had received four vaccines, including a live vaccine, which his doctors at first thought could be the source of the trouble. After that, they ran a series of tests over several weeks, looking for signs of every mosquito-borne disease known to science. A few false positives came up, but nothing helpful. 

Through it all, doctors told Troxler he needed to keep his strength up, so he should eat lots of protein. He happily obliged, filling his diet with hamburgers, barbecue, and country ham. But he still felt terrible. 

Then, one morning, he skipped his morning protein and ate a sweet roll for breakfast; his symptoms subsided. He went to work and ate meatloaf for lunch. Within a few hours, the fever and rash came back. A lightbulb went off. 

In 2009 and again in 2014, Troxler had contracted Lyme disease, which put tick-borne illnesses on his radar. And he recalled another tick-borne illness that had been linked to an allergy to red meat. In Brazil and since he’d come back, he’d eaten a lot of red meat—and the whole time, he’d been sick. 

“So I said, now, wait a minute, I think I got this thing figured out,” Troxler says. “I went back to the infectious disease doctor. I said, ‘How about testing me for the tick bite and red-meat allergy?’”

His hunch proved correct. 

Troxler, whose department regulates the state’s $84 billion agriculture industry, has what’s known as an alpha-gal allergy, a reaction triggered by mammalian meat products such as beef and pork that, in severe instances, can cause fatal anaphylaxis. 

As of this spring, there were more than five thousand confirmed alpha-gal allergy cases in the U.S., but that’s likely just the tip of the iceberg. The allergy isn’t well-known, even in the medical community. It’s only been discovered in the last twenty years, linked to ticks in the last dozen years, and the average time between when most patients first experience symptoms and when they are diagnosed is more than seven years. As an article in the journal Oxford Medical Case Reports noted last year, “The prevalence of this allergy is dramatically increasing.” 

It’s not just that researchers are becoming more aware of the allergy, either. There’s evidence it’s spreading, too. Tick-carrying deer populations are exploding around developed areas due to a decrease in hunting and the disappearance of natural predators. And, thanks to climate change, the Lone Star and other alpha-gal-spreading ticks—which have traditionally preferred warmer climates like the southeastern U.S.—are migrating further north than ever before. 

Troxler says that his allergy has been “nothing more than an inconvenience.” 

For others, however, it’s much more serious—and the answer isn’t always as simple as swearing off meat. The alpha-gal sugar that causes the allergy can show up unannounced in everything from deodorant to condoms, as well as life-saving medications and medical devices.  

A cure remains elusive, but a biotech firm in Virginia is taking a different tack: Instead of seeking to change a person’s response to the animal, it’s changing the animal. 

At a forum organized in Raleigh in August, the Food and Drug Administration announced that Revivicor’s initiative to genetically modify pigs that are free of the alpha-gal allergen had been accepted into its Veterinary Innovation Program, meaning the altered-and-cloned pigs would be ushered through the regulatory process on their way to the slaughterhouse and grocery store shelves.

And this could all happen sooner than you think. If everything goes to plan, both meat and medical products with alpha-gal-free pigs could be on the market within a year. 

If it weren’t for the alpha-gal allergy, domestic diva Martha Stewart might never have been convicted for insider trading in 2004. 

In the late 1990s and early 2000s, researchers conducting human trials on a cancer drug derived from mouse cells found that some participants were developing serious allergic reactions. One patient collapsed and died. 

The manufacturer, ImClone, had to report these reactions to the FDA. Stewart’s broker got an early heads-up, informed her, and she dumped her stock in the company before the news broke. Stewart ended up serving five months in the federal pen. 

In 2002, Dr. Thomas Platt-Mills, the director of the Division of Allergy and Clinical Immunology at the University of Virginia School of Medicine, linked those reactions to the alpha-gal carbohydrate in mouse cells. 

A quick biology lesson: Within every cell are proteins responsible for most cellular functions. Attached to these proteins are sugars. Alpha-gal is one of these sugars, but it only appears among most non-primate mammals—i.e., not humans. It does, however, appear in mice, as well as the mammals that humans consume. 

Not long after Platt-Mills published his findings, Dr. Scott Commins, now a professor at the UNC School of Medicine, began his residency and then a fellowship at UVA. With Platt-Mills, he began seeing patients at the UVA allergy clinic who had suddenly developed a reaction to red meat after safely eating it their whole lives. Oddly, their reactions were delayed, usually by several hours, and were most severe after they ingested fatty meat. (It takes the body about three hours to begin digesting animal fat.) This was unlike other food allergies, which occur instantaneously. 

They quickly understood that their patients had developed an allergy to meat, but they didn’t know how it was being spread. 

Geography held the answer.

Platt-Mills and Commins went back to the cancer study. Patients from California didn’t react to the drug at all, but about a quarter of those from the Southeast did. 

From there, they figured out that a map of participants who’d had reactions to the drug correlated to places that had seen outbreaks of Rocky Mountain spotted fever, a potentially deadly bacterial infection spread by ticks and most commonly reported in the rural Southeast. 

Then, a lab tech working on the alpha-gal puzzle developed a beef allergy after going hiking and receiving several tick bites. The tech found an attached female Lone Star tick that left a “persistent itchy spot for several weeks.” 

That, Commins says, “provided a clue that perhaps ticks were part of the story.”

The tech wasn’t alone. Multiple alpha-gal patients in the UVA clinic recounted irksome tick bites—especially from the Lone Star tick, the most common transmitter of the alpha-gal allergy in the U.S.—before they became symptomatic. 

Intuitively, this made sense. 

As with other tick-borne illnesses, a tick could carry an alpha-gal molecule from an animal it had bitten and then transmit it into a person’s body. The molecule could then trigger an immune system reaction to red meat: anything from hives and swelling of the face or tongue to abdominal pain, headaches, and lightheadedness. 

In the most extreme cases, this reaction could cause anaphylaxis—a potentially fatal reaction that restricts breathing.

Like Steve Troxler, Beth Carrison diagnosed herself with the alpha-gal allergy. Many patients do. 

According to a 2017 study in the Journal of Primary Care Community Health, which conducted interviews with twenty-eight patients at Commins’s allergy clinic at UNC, alpha-gal sufferers were correctly diagnosed by doctors less than 10 percent of the time, and more self-diagnosed than were accurately diagnosed by a physician. 

Researchers believe that 20–25 percent of southeastern U.S. residents carry the alpha-gal allergen, though only 1 percent of carriers are symptomatic. Scientists also think that many previously unexplained anaphylactic reactions may stem from alpha-gal allergies. 

Carrison, who co-founded the Pittsboro-based organization Tick-Borne Conditions United in 2018, says the information gap on the alpha-gal allergy within the medical community is more like a chasm. 

“I self-diagnosed for both [the alpha-gal allergy] and Lyme because I connected the dots and then brought the information to my physician,” Carrison says. “In both cases, he refused to test me.”

So she found a new doctor who was willing to listen to her story and her recollection of being bitten by a Lone Star tick. He’d just come back from a conference where Platt-Mills had spoken, and he agreed to test her. The test confirmed her self-diagnosis; her symptoms appear about two hours after she ingests pork—or within minutes after she’s exposed to red meat particles in the air. 

Indeed, ingesting red meat isn’t the only way to trigger an alpha-gal reaction. 

For Annie Mae King, who owns Harper’s Grill in Bear Creek, a small community in Chatham County, even exposure to airborne meat particles can lead to nausea, vertigo, and fatigue. She’s no longer able to taste her restaurant’s food, cook, or even be in the kitchen. Her business is up for sale.

Byproducts harvested from animals that carry the alpha-gal sugar can also cause reactions, and they’re found in all sorts of things. Glycerin made from beef fat can be used in tapioca pudding, shaving cream, and condoms. The musk in some perfumes comes from deer, and sheep-derived lanolin is used in some lipsticks and deodorants.     

Medical products aren’t immune, either. Gelatin capsules and gummy vitamins have components made from animal hooves. Vitamin D3 is derived from sheep. Heparin, pancreatic enzymes, and thyroid medications are made from pigs. Premarin, a hormone used by menopausal women, is produced from horses. These are but a few of the mammalian-based medications commonly found in medicine cabinets.

And animal-derived materials are also found in medical implants. They’re used in polymers and the coatings of synthetic devices, bone substitutes, and collagen injections. Cows and, more commonly, pigs are sources for heart valves. 

For a heart-valve recipient who also has an undiagnosed alpha-gal allergy, this can lead to a life-threatening rejection until the valve is removed and replaced with a mechanical valve (which carries a greater clotting risk). 

At UVA, surgeons are familiar with alpha-gal because of Platt-Mills’s work; elsewhere, however, many patients aren’t tested for the allergy before heart-valve surgery. 

Rejections are often attributed to unknown causes, researchers say. 

In August, Steve Solomon, the director of the FDA’s Center for Veterinary Medicine, came to Raleigh for a press conference with Dr. David Ayares, the CEO of a Blacksburg, Virginia-based biotech company called Revivicor. 

A spinoff of the British company that created Dolly the sheep, the world’s first cloned animal, in 2003, Revivicor has been developing what it calls GalSafe pigs—hogs that have been genetically modified to remove the alpha-gal sugar. 

Solomon was there to announce that the FDA was conferring these pigs fast-track status through the regulatory process.

“For consumers like Commissioner Troxler that have this allergic condition, this is a significant change,” Solomon said. 

Revivicor’s nondescript headquarters in a cookie-cutter office park in Blacksburg belies the whiz-bang nature of the work done inside. Even the lab where pigs are cloned looks more high school biology classroom than Star Trek. 

The company was founded to address the shortage of organs and tissues available for human implantation through xenotransplantation, or animal to human transplantation. The biggest challenge with this work is rejection—and alpha-gal is the largest provocateur of rejection response, says Ayares. 

The Revivicor team modified pig genes to essentially remove instructions that told the pigs to produce the alpha-gal sugar. They then used these manipulations to clone genetically engineered pigs. 

They’ve produced multiple generations since the original manipulations, with enough pigs to now have breeding herds that solely consist of GalSafe livestock.

Final FDA approval hinges on showing that the engineered pigs are otherwise identical in every way to their unaltered relatives, from appearance to anatomy to the taste and aroma of the meat. 

After that, Revivicor will partner with a slaughterhouse as well as a harvester for medical products and a meatpacker and retailers. 

So far, the company appears to have encountered little resistance from anti-GMO groups. Perhaps that’s because of the nature of the modification—removing a trait rather than adding genes or creating or hybrid—or maybe it’s because its work, and the alpha-gal phenomenon generally, isn’t well-known. 

Either way, it’s a different reception than the first genetically modified food received. 

In 1989, AquaBounty first combined the Atlantic and Chinook salmon with the eel-like ocean pout to create Aquadvantage, a fish that grows faster and can be brought to market quicker than typical salmon. The product went on sale in Canada in 2016, but its sale in the U.S. was held up in Congress as lawmakers battled over labeling. Recently cleared, AquaBounty could be in stores next year, though it remains controversial.

Troxler doesn’t think Revivicor’s pigs will take nearly as long to reach the market—for food, drugs, or medical devices. 

And the commissioner, who’s had to go without meat much longer than he’d like, is impatient for progress. 

“The first piece of pork off the grill is mine,” he says.  

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