Why of allergies

The master immunologist with a controversial answer to why allergies exist

Sensitivities to particular substances, from peanuts to pollen, make millions of us miserable, and can be fatal. The mechanism or ‘how’ of allergies is understood, but the ‘why’ is still open to debate. Master immunologist, Ruslan Medzhitov of the Yale School of Medicine, believes his research into the ‘why’ of allergies could eventually lead to dramatic changes in how they are treated.

ANYONE with an allergy has their origin story, a tale of how they discovered that their immune system goes haywire when some arbitrarily particular molecule gets into their body. There are hundreds of millions of these stories, and the list of allergens includes – but is not limited to – latex, gold, pollen, penicillin, insect venom, peanuts, papayas, jellyfish stings, perfume, eggs, the faeces of house mites, pecans, salmon, beef and nickel.

Once these substances trigger an allergy, the symptoms can run the gamut from annoying to deadly. Hay fever brings sniffles and stinging eyes; allergies to food can cause vomiting and diarrhoea. For an unlucky minority, allergies can trigger a potentially fatal whole-body reaction known as anaphylactic shock.

The collective burden of these woes is tremendous, yet the treatment options are limited. EpiPens save lives, but the available long-term treatments offer mixed results. Antihistamines can often reduce symptoms, but these drugs also cause drowsiness, as do some other treatments.

We might have more effective treatments if scientists understood allergies, but a maddening web of causes underlies allergic reactions. And there’s an even bigger mystery underlying this biochemical web: why do we even get allergies at all?

Ruslan Medzhitov“That is exactly the problem I love,” Ruslan Medzhitov of the Yale School of Medicine says. “It’s very big, it’s very fundamental, and completely unknown.”

Over the past 20 years, he has made fundamental discoveries about the immune system, for which he has been awarded a string of major prizes. Now he is turning his attention to a question that could change immunology yet again: why do we get allergies? No one has a firm answer, but what is arguably the leading theory suggests they are a misfiring of a defence against parasitic worms – which makes us miserable in the process.

Medzhitov thinks that’s wrong. Allergies are not simply a biological blunder but an essential defence against noxious chemicals – and one that has served our ancestors for tens of millions of years. It’s controversial, he acknowledges. But he’s also confident that history will prove him right.

The physicians of the ancient world knew about allergies. 3,000 years ago, Chinese doctors described a “plant fever” that caused runny noses in autumn. There is evidence that the Egyptian pharaoh Menes died from the sting of a wasp in 2641 BCE. Two and a half millennia later, the Roman philosopher Lucretius wrote, “What is food to one is to others bitter poison.”

But it was a little more than a century ago that scientists realised these diverse symptoms are different heads on the same hydra. By then researchers had discovered that many diseases are caused by bacteria and other pathogens, and that we fight these invaders with an immune system – an army of cells that can unleash deadly chemicals and precisely targeted antibodies. They soon realised that the immune system can also cause harm.
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In the early 1900s, the French scientists Charles Richet and Paul Portier injected small doses of poison from sea anemones into dogs, then waited a week or so before delivering an even smaller dose. Within minutes, the dogs went into shock and died. Instead of protecting the animals from harm, the immune system appeared to make them more susceptible.

Other researchers observed that some medical drugs caused hives and other symptoms. And this sensitivity increased with exposure – the opposite of the protection antibodies provided against diseases. And in the decades that followed, scientists discovered that the molecular stages of these reactions were remarkably similar. The process begins when an allergen lands on one of the body’s surfaces – skin, eye, nasal passage, mouth, airway or gut. These surfaces are loaded with immune cells that act as border sentries. When a sentry encounters an allergen, it first engulfs and demolishes the invader, then decorates its outer surface with fragments of the substance. Next the cell locates some lymph tissue. There it passes on the fragments to other immune cells, which produce a distinctive fork-shaped antibody, known as immunoglobulin E, or IgE.

These antibodies will trigger a response if they encounter the allergen again. The reaction begins when an antibody activates something called a mast cell, which then blasts out a barrage of chemicals. Some of these latch onto nerves, triggering itchiness and coughing. Sometimes mucus is produced. Airway muscles can contract, making it hard to breathe.

This picture, built up in labs over the past century, answered the “How?” Left unanswered, however, was “Why?” It was hard to see how natural selection could have produced allergies. Reacting to harmless things with a huge immune response probably wouldn’t have aided the survival of our ancestors. Also, only some people have allergies and only some substances are allergens. Sometimes people develop allergies relatively late in life; sometimes childhood allergies disappear. And for decades, nobody could even figure out what IgE was for. It was as if we evolved one special kind of antibody just to make us miserable.

One early clue came in 1964. A parasitologist named Bridget Ogilvie was investigating how the immune system repelled parasitic worms, and she noticed that rats infected with worms produced large amounts of what would later be called IgE. Subsequent studies revealed that the antibodies signalled the immune system to unleash a damaging assault on the worms…..[do read on, this is a small portion of a very interesting article. Ed!]

The Independent: Read the full article