I am on my way to meet Tami McGraw, who lives with her husband and the youngest of their kids in a sprawling development of old trees and wide lawns just south of Chapel Hill. Before I reach her, McGraw emails. She wants to feed me when I get there:
Why so many people are becoming allergic to meat
"Would you like to try emu?" she asks. "Or perhaps some duck?"
These are not normal breakfast offerings. But for years, nothing about McGraw's life has been normal. She cannot eat beef or pork, or drink milk or eat cheese or snack on a gelatine-containing dessert without feeling her throat close and her blood pressure drop.
Wearing a wool sweater raises hives on her skin; inhaling the fumes of bacon sizzling on a stove will knock her to the ground. Everywhere she goes, she carries an array of tablets that can beat back an allergy attack, and an auto-injecting EpiPen that can jolt her system out of anaphylactic shock.
McGraw is allergic to the meat of mammals and everything else that comes from them: dairy products, wool and fiber, gelatin from their hooves, char from their bones.
This syndrome affects some thousands of people in the USA and an uncertain but likely larger number worldwide, and after a decade of research, scientists have begun to understand what causes it. It is created by the bite of a tick, picked up on a hike or brushed against in a garden, or hitchhiking on the fur of a pet that was roaming outside.
The illness, which generally goes by the name "alpha-gal allergy" after the component of meat that triggers it, is a trial that McGraw and her family are still learning to cope with. In much the same way, medicine is grappling with it too.
Allergies occur when our immune systems perceive something that ought to be familiar as foreign. For scientists, alpha-gal is forcing a remapping of basic tenets of immunology: how allergies occur, how they are triggered, whom they put in danger and when.
For those affected, alpha-gal is transforming the landscapes they live in, turning the reliable comforts of home -- the plants in their gardens, the food on their plates -- into an uncertain terrain of risk.
In 1987, Dr Sheryl van Nunen was confronted with a puzzle. She was the head of the allergy department at a regional hospital in the suburbs of Sydney, Australia, and had a reputation among her colleagues for sorting out mysterious episodes of anaphylaxis. This time, a man had been sent to see her who kept waking up, in the middle of the night, in the grip of some profound reaction.
Van Nunen checked the man for the obvious irritants and, when those tests came up negative, took a thorough look at his medical history and did a skin test for everything he had eaten and touched in the hours before bedtime. The only potential allergen that returned a positive result was meat.
Then a few more such patients came her way. There were six additional ones across the 1990s; by 2003, she had seen at least 70, all with the same problem, all apparently affected by meat they had eaten a few hours before. Groping for an explanation, she lengthened the list of questions she asked, quizzing the patients about whether they or their families had ever reacted to anything else: detergents, fabrics, plants in their gardens, insects on the plants.
"And invariably, these people would say to me: 'I haven't been bitten by a bee or a wasp, but I've had lots of tick bites," Van Nunen recalls.
When a new disease is discovered, there is usually a long, painful period of time, before it becomes the focus of scientific research. In this case, an odd set of coincidences brought alpha-gal allergy to the attention of researchers almost as soon as it occurred in patients.
The story begins with a cancer drug called cetuximab, which came onto the market in 2004. In clinics in North Carolina and Tennessee, 25 of 88 recipients were hypersensitive to the drug, with some so sick they needed emergency shots of epinephrine and hospitalization. At about the same time, a patient who was receiving a first dose of cetuximab in a cancer clinic in Bentonville, Arkansas, collapsed and died.
News of this death soon reached Dr Thomas Platts-Mills, an allergy researcher at the University of Virginia, who saw these reactions as an intriguing research opportunity.
Platts-Mills pulled together a team, and fairly quickly, they discovered the source of the problem. People were reacting to the drug because they had a pre-existing sensitivity, indicated by a high level of antibodies (called immunoglobulin E, or IgE for short) to a sugar that is present in the muscles of most mammals, though not in humans or other primates. The name of the sugar was galactose-alpha-1,3-galactose, known for short as alpha-gal.
Team members scrutinized the patients and their famlilies for anything that could explain the problem. The reactions appeared regional -- patients in Arkansas and North Carolina and Tennessee experienced the hypersensitivity, but ones in Boston and northern California did not. They investigated parasites, moulds and diseases that occur only in pockets of the USA.
Then Dr Christine Chung, a Nashville researcher recruited to the team, stumbled on an intriguing clue. Almost one in five of the patients enrolled at a cancer clinic at her hospital had high levels of IgE to alpha-gal. But when she checked those patients' near neighbors, treating them as a control group -- that is, people who lived their lives in the same way, but did not have cancer and had no reason to have received the drug -- almost one in five had antibodies to alpha-gal as well.
Almost a decade later, that correlation still makes Platts-Mills chuckle. The alpha-gal reaction "had nothing to do with cancer," he says. "It had everything to do with rural Tennessee."
The question then became: what in rural Tennessee could trigger a reaction like this?
The answer arose from a second coincidence. Dr Jacob Hosen, a researcher in Platts-Mills's lab, stumbled across a map drawn by the Centers for Disease Control and Prevention (CDC) showing the prevalence of an infection called Rocky Mountain spotted fever. It exactly overlapped the hot spots where the cetuximab reactions had occurred.
Rocky Mountain spotted fever is transmitted by the bite of a tick: Amblyomma americanum, one of the most common ticks in south-eastern USA. It's known as the lone star tick for a blotch of white on the back of the female's body.
The researchers wondered -- if the mystery reactions shared a footprint with a disease, and ticks caused the disease, could ticks be linked to the reactions too?
Dr Scott Commins, another postgraduate fellow in Platts-Mills's group, took it upon himself to phone every new patient to ask whether they'd ever suffered a tick bite. "I think 94.6 per cent of them answered affirmatively," he says. "And the other few per cent would say, 'You know, I'm outdoors all the time. I can't remember an actual tick that was attached, but I know I'd get bites.'"
Meat from mammals inevitably contains alpha-gal -- so in already sensitized individuals, eating meat might constitute a second exposure, in the same way infusing cetuximab had been.
If tick bites had sensitized them, then the alpha-gal reaction might be a food allergy as well as a drug reaction. But the connection was speculative, and cementing cause and effect would take one final, extraordinary coincidence.