A few years ago, Dr. Thomas Platts-Mills, the director of the University of Virginia School of Medicine’s allergy division, conducted an informal experiment. He spent five hours hiking and bushwhacking in the Blue Ridge Mountains, near his home in Charlottesville, Virginia. Afterward, his feet itched. When he pulled off his shoes and socks, the skin around his ankles was rough and pimpled. He suspected that he had stumbled into a nest of lone-star ticks, the most abundant species of tick in the southeastern United States, named for a distinctive, Texas-shaped white splotch that forms on the backs of adult females. “There were ticks all over the house,” he told me. “Luckily, my wife was not home.”
Adult lone-star ticks can carry the pathogens that cause several diseases: Rocky Mountain spotted fever; Southern tick-assocated rash illness, which manifests in Lyme-like symptoms; and ehrlichiosis, a cluster of related bacterial illnesses. (Michael Specter wrote about tick-borne disease in the magazine last year.) But Platts-Mills, who is the only allergist in the Royal Society, embarked on the hike because he believed that the ticks could cause another ailment: an allergy to red meat.
Platts-Mills first heard about allergic reactions to meat over twenty years ago, when a handful of patients at his practice claimed that a few hours after eating meat at dinner they woke up slicked in sweat, their throats closing, with blotchy rashes splashed across their torsos. Platts-Mills told them to avoid beef, pork, lamb, or venison, but suspected that the allergy was psychosomatic, and gave it little further thought.
Then, in the spring of 2000, one of Platts-Mills’s colleagues, Roger B. Cohen, now at the University of Pennsylvania, came to him with a problem. Cohen had been working on clinical trials for cetuximab, a drug therapy that slows the growth of certain cancer cells. Despite its promise in treating cancer, cetuximab occasionally caused allergic reactions in patients, comparable to bad bee stings. Platts-Mills worked to unravel the root cause of the allergy, but it eluded him.
In 2004, cetuximab received F.D.A. approval for treating colorectal cancer. Soon afterward, Bert O’Neil, then an oncologist in Chapel Hill, North Carolina, reported that nearly a quarter of his patients suffered from itching, swelling, and a dangerous drop in blood pressure when they took the drug. Curiously, however, the reactions were regional: they were about ten times as likely to occur in the southeast as elsewhere in the country; a patient in Tennessee died. (O’Neil says his team’s allegation seemed so unlikely that an oncologist in New York “thought we were lying or crazy.”)
Working with Bristol-Myers Squibb, cetuximab’s distributor, and numerous colleagues, Platts-Mills returned to his study of the drug, and began comparing blood drawn from patients with allergic reactions to control samples from California, Boston, and Tennessee. In a study published in the New England Journal of Medicine, he identified the cause of the symptoms: the allergic patients had preëxisting antibodies to alpha-gal, a sugar found in non-primate mammals, that cetuximab, derived from genetically modified mice, contains.
Mystery solved, mostly. What doctors lacked, however, was a satisfying explanation for what caused the antibodies, known as Immunoglobulin E, or IgE, that made patients so sensitive to alpha-gal; suspects included mice and tapeworms, an insidious mold creeping across the South, or a contagion that seemed to coincide with summer heat and humidity. (The packaging for cetuximab warns about the possibility of severe allergic reactions, and a spokeswoman for Bristol Myers-Squibb says that the reason for hypersensitivity to the drug is still unknown.) As Platts-Mills pondered a list of possible parasites, a technician in his lab, Jacob Hosen, noticed that states with a large number of reactions to cetuximab neatly overlapped with the range of Rocky Mountain spotted fever. As Platts-Mills began to suspect that ticks were connected to the alpha-gal sensitivity, a forty-three-year-old hunter came into his clinic claiming that he had suffered from three separate severe allergic reactions to eating beef, which contains alpha-gal. When Platts-Mills asked about ticks, the hunter revealed that his feet were covered with bites. Platts-Mills began to screen patients who reported tick bites or red-meat allergies for IgE.
Shortly afterward, Platts-Mills went on his own tick-infested journey through the woods, half-attempting to prove his theory. When he ran samples of his own blood, he found that his IgE antibody count had spiked. Later that year, he ate three lamb chops for dinner. Several hours later, around 1 A.M., he woke up covered in hives.
Over the next two years, Platts-Mills and his colleague Scott Commins screened twenty-four patients with red-meat allergies, and found that more than eighty per cent reported being bitten by a tick. In another study, in 2011, the two linked tick bites with a twenty-fold increase in alpha-gal antibodies, giving rise to their theory that the saliva of lone-star ticks sensitizes humans’ immune systems to alpha-gal, triggering the release of histamines when red meat is ingested.
Richard Ostfeld, a disease ecologist at the Cary Institute of Ecosystem Studies, in Millbrook, New York, said that it’s a plausible hypothesis. “Tick saliva has so many different bioactive compounds. If you think about it from the tick’s point of view, they have to get a ton of blood without being detected and destroyed by a host.” Given the diverse pharmacopeia found in tick saliva, Ostfeld said it was not surprising that one compound might mimic the blood sugar found in its warm-blooded hosts—non-primates like deer, mice, and rabbits, which have alpha-gal in their blood. When tick saliva perforates human skin, some people’s immune systems treat the sugar as a foreign antigen, producing an extraordinary reaction to red meat.
Similar correlations between tick bites and meat allergies have recently been reported in Australia and Sweden, but establishing that the ticks are a definitive cause has remained difficult. “It’s as good as we can get,” Platts-Mills said. “I can’t get permission to put ticks on people.”
Peter Andrey Smith is a writer based in Brooklyn.
Photograph: Kallista Images/Getty
