Has science cracked the peanut allergy?
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Once a regular fixture, movie night had become a rarity in the Cipriano household of late. Giovanni had started high school a few weeks earlier and been given extra homework, while his mum, Georgina, was working two jobs after separating from his dad. But one evening in October 2013 they found the time to retire to the TV room at their home in Long Island, New York, where she put out a bowl of cookies and pretzels to snack on while they watched the film.
After taking a few bites, the 14-year-old started to feel unwell. “Mum, I think this has got peanuts in it,” she recalls him saying. She thought he must be mistaken. She had already checked the allergy warning on the label, which cautioned that the mixture contained tree nuts but made no mention of the peanuts to which her son was severely allergic.
The sequence of events that subsequently unfolded is so tragic, so full of ill fate, that I wonder how Georgina can bear to recount it. “It’s difficult to talk about what happened,” she says. “But it’s important to tell his story. I’m going to be his voice.”
Although peanuts had been omitted from the allergy warning box, they were in fact listed under main ingredients, as Georgina discovered when she frantically reread the discarded packet. She gave Giovanni an antihistamine and told him to get dressed for a visit to the doctor. The pair argued briefly — he thought she was making a fuss and wanted to stay home — but she insisted. “I just wanted to be safe.”
Georgina threw an EpiPen, an injection used to stave off anaphylactic shock, into her handbag, and drove Giovanni to the local urgent care centre. They arrived a few minutes after 9pm to find it had just closed its doors. Panic set in. Giovanni started having breathing difficulties; he was puffing on an asthma inhaler and asked for the EpiPen but, to Georgina’s horror, she could not find it. “It must have fallen out of my pocketbook. All I could think about now was getting to the emergency room.”
The journey from the care centre to the ER would take seven minutes, but after five Giovanni turned to his mother and spoke his last words. “I don’t think I can make this. I can’t do it. I don’t want to die.” As she turned into the hospital car park, she took her son’s hand to comfort him. “It was cold and when I looked at his face, it was grey. I started beeping the horn and screaming, ‘Please help me.’”
Giovanni was rushed into the emergency room, where doctors managed to resuscitate him but were unable to wake him from a coma. “They tried everything but his brain had been starved of oxygen for too long and his body couldn’t cope. He never woke up. Eighteen days later, he passed away.”
Shortly before he died, Giovanni had found an article online about two experimental drugs that might protect peanut allergy sufferers in cases of accidental exposure. “He was scared about going into a study,” recalls Georgina. “But he also said, ‘I hope that one day I might be able to try it.’”
Four years later, these drugs are in the final stages of clinical testing. One is a capsule that is broken and sprinkled over food, the other a stick-on skin patch placed on a patient’s back. Both are underpinned by the same scientific theory: that exposing seriously allergic children to tiny amounts of peanut flour will retrain their immune systems to cope better with the real thing. After years of research and hundreds of millions of dollars of investment, the two companies behind these drugs hope they can keep children such as Giovanni safe in the future.
The number of people afflicted with food allergies has exploded since the start of the 20th century, when two French scientists, Charles Richet and Paul Portier, described the first case of fatal anaphylactic shock. When the pair collected a Nobel Prize for their work in 1913, the illness was still a curiosity rather than a public health issue. But today roughly 15 million Americans and 17 million Europeans suffer from food allergies, with many of the most serious cases afflicting children.
Among the biggest factors behind this dramatic rise has been the soaring prevalence of peanut allergy, which accounts for more than a quarter of all childhood cases. Three million people in the US have allergies to peanuts, tree nuts or both. About 2 per cent of American children are now allergic to peanuts, a figure that has more than quadrupled since 1997. The number of fatal reactions is small, with fewer than 100 cases usually recorded each year, but the fear among parents remains high. Almost all the deaths have been people who knew they had the illness but ended up ingesting nuts by mistake.
More and more schools are going “nut free”, while some food producers are cutting peanuts out of all their products, but scientists warn that widespread abstinence will only exacerbate matters. A better solution would be to develop a treatment that would protect sufferers in the case of accidental exposure.
At 105, Dr Bill Frankland has more than earned his status as the “grandfather of allergy”. The evening we speak, the British immunologist is about to rush out but he still has time to regale me with stories from his long career, including the time in 1979 when he treated Saddam Hussein, the late Iraqi dictator. “People have been eating eggs and peanuts and dairy for years, so why is this happening now?” he asks. “There are so many reasons, it is multifactorial: general pollution, diesel fumes and so on, but also because allergy is now more recognised as a chronic disease, so doctors are very interested in it.
“One thing you mustn’t put the increase down to is genes,” he adds. Although some people are more genetically predisposed to developing food allergies, the proportion has not changed over time, he says, meaning environmental factors must be to blame. “Now we’re very interested in the beginning of a baby’s life — what they’re eating and what they’re breathing in, and we need to do more research on that.”
Frankland is puzzled as to why it has taken so long to develop treatments that might protect peanut allergy sufferers. He recalls that, 60 years ago, he successfully treated people with severe fish, egg and milk allergies by admitting them to hospital and giving them controlled injections containing the very substances that could kill them. “They were in for 12 or 13 days and they went out cured,” he says.
Progress in tackling peanuts has been much slower, in part because even tiny amounts can prove fatal. Researchers experimented with peanut injections in the early 1990s but the results were not encouraging. Although some patients were successfully desensitised, a significant number had severe reactions. One study was shut down after a participant died of anaphylactic shock.
In 2009, a team of scientists led by Dr Wesley Burks, then a paediatrician at Duke University in North Carolina, published a small trial that is now widely hailed as a breakthrough. “The concept was to give someone something in a very small amount and increase it over time,” Burks recalls. “The desensitisation started with a thousandth of a peanut and we increased that. Then, all of a sudden, we were giving the children a peanut every day and they were not having serious reactions.” After 10 months, some could ingest as many as 15 peanuts a day, giving them a meaningful buffer in the event of accidental exposure.
This pioneering treatment gave birth to a cottage industry in the US: some allergists now offer their own home-brew versions of Burks’ “oral immunotherapy” in their practices. But the majority do not want to offer a makeshift solution, for fear they would be held liable if something went wrong.
Burks’ research also caught the attention of advocacy group Food Allergy Research and Education (FARE), which tried to persuade several large drugmakers to turn it into an approved drug. Big Pharma was unmoved, believing it would be impossible to patent a medicine that was essentially a ground-up peanut. So FARE’s leaders decided to back efforts to start a new company. They secured $12m of seed funding from wealthy investors, including David Bunning, the Citadel financier whose children suffer from severe food allergies. The company, now known as Aimmune, went on to raise a further $414m.
Aimmune has used the cash to develop a low-dose version of Burks’ therapy that can be professionally manufactured at scale: a capsule containing pharmaceutical-grade peanut protein, which is snapped open and sprinkled over an appropriate food, such as chocolate pudding. After more than four years of clinical trials, this drug, codenamed AR101, is in the final stages of testing, with results due either at the end of this year or in early 2018. In small studies, patients were able to tolerate the equivalent of between two and three peanuts after nine months of treatment, and research suggests this will increase over time.
Three peanuts might not sound a lot but it would be sufficient to protect a person against accidental ingestion. It would also probably convince US regulators to approve the medicine for children aged between four and 17. Shares in Aimmune have appreciated by around a third over the past 12 months, giving the company a market value of almost $1bn, as investors bet that the Food and Drug Administration and European regulators will give a green light to the medicine in 2019. Analysts at Credit Suisse predict the drug will generate sales that will crest at $1.4bn a year in 2024.
Success is not guaranteed. The history of drug development is littered with examples of medicines that looked like a sure thing but went on to fail. Nor is treatment with AR101 a panacea. It takes a long time, involves regular trips to an allergist and is quite unpleasant. “It’s not for everyone, because there are side effects associated with the treatment and you have to invest time and effort in repeated visits to the doctor,” says Stephen Dilly, chief executive of Aimmune and a former vice-president of pharmaceutical company SmithKline Beecham. “The utility of our treatment tends towards the super-sensitive patient that is more likely to have a life-threatening reaction if they get exposed.”
The first visit takes three hours, during which the doctors slowly increase the dose of AR101 until they work out the maximum tolerable amount. The child must then return every fortnight to see whether he or she is ready to progress to a larger pill. The vast majority will experience nasty reactions, such as hives or stomach aches, and the process typically takes between 24 and 26 weeks before the patient can go on a regular maintenance capsule. Although the company says it is not a treatment for life, it is still unclear how long a patient might have to take the drug.
Aimmune has ties to the food industry, which has a vested interest in finding treatments for allergies. Its largest investor is Nestlé, which acquired a 15 per cent stake for $145m in November 2016. The success of AR101 and other treatments could help protect the food giant’s core business, which sells many products containing peanuts and other allergens.
The peanut trade also has a lot riding on the success of these treatments, with one of the largest companies, Golden Peanut, agreeing to provide the protein for the capsules under an exclusive 10-year deal. Dilly says it is more than just a commercial arrangement. “They’re very interested in being seen to be helping us,” he says. “Because they’ve gone from being good old peanut farmers in Georgia to being the people that produce stuff that kills people.”
For Bob Parker, president of the National Peanut Board, the reputational hit hurts. He has spent a lifetime in the industry and grew up in the heart of peanut country in Georgia, where, at the age of six, he was selling bags of boiled nuts at the side of the road. Today, everyone he meets asks him the same two questions. Has he met Jimmy Carter, the former US president and world’s most famous peanut farmer? “Many times. He’s a fine man.” And how is the industry coping with a spike in peanut allergy? “It’s the single largest barrier to consumption.”
It is early spring, and New York’s Central Park basks in glorious sunshine. The smell of recently cut grass hangs in the air. But for Hayley Maultasch, a seven-year-old attending a clinic a few blocks away, today means one thing: allergies. She has already taken an antihistamine for her hay fever and her mum, Erica, has put in drops to stop her eyes streaming.
Hayley was diagnosed with suspected peanut allergy six months ago. Today she has come to get a conclusive answer at the Jaffe Food Allergy Institute at Mount Sinai Hospital, where she will eat crackers spread with ever-greater amounts of peanut butter to see if they elicit a reaction. Dr Malika Gupta, an assistant professor of paediatrics, is conducting the test, armed with an EpiPen in case anything should go awry.
At first, Hayley is a bundle of excitement, recounting a string of stories, including the time her mum appeared in a TV advert for a local party store. She requests a tissue, takes a theatrical blow of the nose, and giggles loudly. “She’s really shy,” quips Erica. “We’re working on it.”
But just before the challenge begins, Hayley falls silent. She hunches her shoulders up into her pink love-heart T-shirt, and her face — all smiles until now — becomes pensive. “I’m nervous,” she says. “This kinda test is way more nerve-racking than a school test; that is just a grade, but this is my whole life.” It might sound dramatic but to hear her recount the past few months is to understand how a peanut allergy diagnosis can turn the world of a child upside down.
Hayley tested positive for the allergy in December, following a skin test after a peanut-butter sandwich caused hives around her mouth. The allergist advised her mother to cut peanuts out of Hayley’s diet completely, prompting her to seek a second opinion at Mount Sinai.
The biggest upheaval has been at school, which has joined many public institutions in taking a tough approach to the spike in childhood food allergies. Pupils with a diagnosis must sit at a separate table in the canteen, and are excluded from the tradition of celebrating everyone’s birthday, unless the birthday boy or girl brings something in from home that is entirely free of allergens. “There’s a special table for kids that have allergies and no one sits there — it’s like the emptiest table in the canteen,” says Hayley. (In an act of kindness, one of her best friends has cut nuts out of her diet so they can sit together.)
Nor has it been much easier for Hayley outside of school: the family recently went to dinner at her favourite restaurant, an Asian “hibachi” place where the food is cooked at the centre of the table. Her dish had to be prepared in the back, and tasted less good than before. “She actually cried that night,” recalls Erica.
Gupta asks the photographer and me to leave the clinic before Hayley completes the food challenge, on the grounds that it would be unethical for us to be there if she were to have a bad reaction. A few days later, I text Erica to find out how it went. “She passed :-)”
It turns out that Hayley’s earlier reaction was probably caused by a seasonal allergy to birch tree pollen, which contains a protein similar to one found in some foods, including peanuts. Sometimes the body can mistake the peanut protein for the pollen, causing hives and hay fever-like symptoms, although not anaphylactic shock. “She’s so happy,” says Erica. “But I’m not going to lie to you — she still hasn’t eaten anything with peanuts in it.”
Theories behind the reason for the recent spike in food allergies differ, although they would all fit quite neatly under the heading, “The Way We Live Now”: high levels of pollution, intensive farming, processed food and a childhood where dirty, scraped knees have been replaced by a coddled existence.
Dr Burks, now executive dean at UNC School of Medicine, says the increasing incidence of allergy closely tracks other diseases linked to modern life. “If you go to a scientific talk about rates of diabetes, auto-immune diseases like arthritis, and allergies, then all the introductory PowerPoint slides are exactly the same,” he says. “The rises in the past 20 to 30 years parallel each other. We are breathing more diesel exhaust particles, which causes inflammation as we inhale them, and feeding practices have changed.”
Some scientists also believe changing diets are affecting the microbiome, a vast and poorly understood population of microbes in the human gut, which is increasingly thought to play a leading role in disease. “There is a symbiosis between the immune system and the bacteria that resides within us. If it’s disturbed, it will promote inflammation,” says Burks, noting that allergy rates are much lower in Amish communities that shun modernity in favour of an old-fashioned rural life. Other allergists subscribe to the hygiene hypothesis, which holds that the immune system has evolved to deal with the much stronger stuff it contends with today. In the absence of any real invaders to go to war with, it instead overreacts to something relatively benign, such as peanuts. “We evolved as an organism that was used to seeing lots of bacteria from outside our world, including fecal matter from animals,” says Dr Stephen Tilles, an allergist in Seattle. “As we have become more developed economically, that has gone away.”
In the case of peanut allergy, there has been an aggravating factor that some scientists blame for a recent acceleration in the number of cases: for almost a decade between 2000 and 2008, American parents were told by public health officials to avoid feeding peanuts to children under the age of three. It turns out the advice, which echoed around the world, was entirely wrong and could have contributed to some children developing peanut allergies.
The recommendation was based on the assumption that avoiding exposure to the allergen could protect people. But the theory was turned on its head following a groundbreaking study led by Dr Gideon Lack, a professor at King’s College London. He started to question conventional thinking after noticing that rates of peanut allergy were extremely low in Israel, where almost every child is given Bamba, a teething snack that contains peanuts.
Lack’s initial study, published in 2008, found that rates of the condition among Jewish children in Britain were around 10 times higher than in Israel. A subsequent placebo-controlled trial was published in 2015, which found that infants who had been given foods such as peanut butter were far less likely to become allergic.
The American Academy of Pediatrics had already dropped its avoidance recommendation in 2008 and, at the start of this year, it said most babies should start eating foods containing peanuts well before their first birthday. It was a complete reversal of its previous stance. “By having patients avoid peanuts, we were systematically exposing them to peanut allergy,” says Tilles.
Spencer Baty is peering over the top of a Reese’s Peanut Butter Cup that has been cut into 12 pieces. Every night, the 13-year-old eats one small square. “It’s pretty cool to have candy as your medicine,” he says, placing air quotes around the word “medicine”.
A few years ago, the idea of consuming anything containing peanuts would have been unthinkable because Spencer is severely allergic. “It felt like somebody was choking me from the inside,” he says of the anaphylactic shocks that hospitalised him on several occasions.
His parents first knew something was amiss when, at the age of three, Spencer opened the freezer, removed a block of ice, and placed it on his tongue. He had just eaten some peanuts and the inside of his mouth and cheeks had swollen up. As the emergency room visits racked up, he started to become anxious whenever peanuts were in the house. His parents likened him to a “little drug dog”: he was able to tell if they had ordered takeaway containing nuts — even if he was sitting several rooms away. His father David thought the peanut allergy was exacerbating his already picky eating habits and started to worry that Spencer would be consigned to a lifelong diet of hamburgers and chicken nuggets.
“We were getting kind of frustrated because we felt like it was having a big influence on his food choices, which were really narrowing,” recalls David. “And then one day I heard about the trials on the radio and I called his allergist. ‘Are you doing any studies?’ I asked. I just kept bugging them.” Eventually, when Spencer was nine, he got a place on a clinical trial. Rather than the oral immunotherapy being developed by Aimmune, he was given a skin patch containing a tiny amount of peanut protein that is placed on a patient’s back. When the trials ended last year, his allergist switched him to the Reese’s Peanut Butter Cup to maintain his levels of desensitisation. “Sometimes, I still just get a tiny little reaction, a little tingling in my mouth,” says Spencer. “But most of the time, there’s nothing at all — it just tastes like candy, which is good. My goal is to eat a whole Snickers bar.”
The Viaskin patch is being developed by DBV, a French company. Like AR101, the patch is in the final stage of clinical trials, with results due in the second half of this year. A small study published in March found that 76 per cent of patients responded to the treatment after three years; they were either able to consume a gram of peanut protein — the equivalent of four nuts — or tolerate an amount 10 times larger than when they entered the trial. If the results are replicated in larger studies, the group could win approval in the US and Europe and launch the product at some point next year.
If both products are given a green light, then parents of children with peanut allergies will soon have two options — a capsule and a patch. The advantage of Viaskin is that it is easier: there are fewer visits to the allergist and almost no chance of severe side effects, although almost all patients develop a rash. The big drawback, say allergists, is that it takes longer to desensitise a patient using the patch than it does with Aimmune’s product.
Spencer’s allergist is Dr Tilles, who is based a few miles away from the Baty household in Seattle. On his office wall is a poster he was given for his 50th birthday, entitled “Conquering 50 Years of Life!” Yet many of the parents in his practice fear their children will not live to see 15, let alone 50. It is this crippling fear that demands a treatment is found rather than the absolute number of peanut allergy deaths, he says.
“Death is a very rare outcome, so in my opinion the main drive for pursuing treatments is not that. Otherwise we should all be working hard to make cars safer, because cars are much more dangerous for peanut allergy sufferers.”
Tilles says many parents of children with peanut allergy struggle to let go when their offspring become teenagers. Having managed to stave off a deadly anaphylactic shock for so many years, they worry that their kids will make one fatal mistake: eating the wrong snack after their first taste of alcohol or forgetting their EpiPen on a night out.
“It is well documented that the adolescent-to-young-adult age group is at much higher risk of a fatal or at least near-fatal outcome because of accidental exposure,” he says.
Every allergist will tell you tales of overbearing parenting, like the mother who secretly destroyed birthday invitations so her child would not find them, or the father who turned up to the start of every high-school sleepover to scour the house for peanuts and disinfect the surfaces. The children can develop anxiety themselves, says Tilles. “Some kids pick up on all of it and refuse to eat, so they lose weight. There is a lot of counselling going on.”
However, it is not hard to find allergists who think the treatments being developed by Aimmune and DBV are the wrong answer. Dr Robert Wood, a professor of paediatrics at Johns Hopkins, says most parents will think again when they learn of the huge commitment required for the capsule.
“Once they dive in, they realise that the reality is that it has significant risks,” he says, pointing to the high incidence of side effects. “The most informative statistic is that if you’re treated with oral immunotherapy, you’re definitely going to have more reactions than if you were practising strict avoidance.”
Wood is even more critical of the patch, which he thinks could lull patients into a false sense of security. He points out that in clinical trials there has been a sizeable minority of patients who do not respond to the treatment. “They may be put at a higher level of risk by thinking they do have some protection when they don’t,” he argues. “The reality is that abstinence works very well in these days of good labelling.”
But as Georgina Cipriano will attest, abstinence cannot stave off every anaphylactic shock or save every life. Shortly after her son died, she set up a foundation, Love for Giovanni, to improve awareness of food allergies. “I hear stories like mine all the time,” she says. “We were very strict, we never had anything with peanuts in the house, and we thought we practised good label reading. But we were not as safe as we should have been. We didn’t know enough.”
David Crow is the FT’s senior US business correspondent
Portraits by Adam Golfer and Andrew Miksys
Still-life photographs by John Gribben
The FT is interested to hear from readers who have had experience with peanut allergies and/or the treatments described. Share your story in the comments below. The author, David Crow, will be responding intermittently to your questions and thoughts.
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