That year, von Mutius took her research with her to Tuscon, Arizona, where she worked on a fellowship at the University of Arizona under her mentor, Dr. Fernando Martinez, the well-known asthma researcher who today is the director of the Arizona Respiratory Center. One day he read a medical paper out of Britain about something called “the hygiene hypothesis”.
The author of that paper, an epidemiologist named David Strachan, had conducted a study of over 17,000 British children and found that youngsters who had older siblings and were exposed to more infections and bacteria early in life were less likely to develop hay fever or eczema. Writing in that same pivotal year of 1989, Strachan had theorized that smaller family sizes and higher levels of hygiene in modern Western homes may have been contributing directly to the increased prevalence of allergy.
Martinez was intrigued. What, he asked, would happen if von Mutius took into account the sizes of her East German and West German families? The data were incomplete, but it was the less allergic East Germans who clearly had more children per family. She and Martinez followed up with a study comparing family sizes and allergy in Munich and Leipzig (and a neighboring city).
A pattern emerged: the most allergic were the Munich kids with one or no siblings; the least allergic were the East Germans with two or more brothers and sisters. Children in the larger families were being exposed to more germs. It fit with this rudimentary hygiene hypothesis. “It took off from there,” says von Mutius.
Back to the Land
Where the hygiene theory took off to was a place caught in a time warp: the traditional European farm, where father, mother and children still do all the manual labor, from milking to sweeping out the stables. The idea to look at the family-run farm actually came from a school doctor in a Swiss village. He noticed that farm children under his care, unlike other kids, never seemed to get hay fever.
Struck by this observation, he began writing to allergy experts in Basel, research colleagues of von Mutius. At first they were skeptical of the rural doctor’s notion, but then a few Swiss professors ran a small study. The findings were compelling: there was markedly less allergy and asthma on the farms in question. This merited further examination.
And so in 1998, von Mutius began her long-running involvement in a series of European farm studies that have become the underpinning of current allergy research. The first was ALEX (the Allergy and Endotoxin Study), involving scientists from Germany, Austria and Switzerland. The team began gathering and publishing data, and the central findings were consistent: children who lived on these farms were significantly less inclined to have allergies and asthma than children in the neighboring village.
Then came other major studies of the family farms: the multi-center PARSIFAL study of children enrolled in Steiner schools (akin to Waldorf education), which involved 6,600 pupils in five countries; and the PASTURE study, which examined children’s exposure to microbes on farms across Europe. With each study, with each new set of samples of stable and mattress dust, with each new set of blood-test results for environmental and food allergies, a little more was known. “We are getting somewhere,” says von Mutius, taking stock for a moment. “There are now 17 papers [since 1999] that all show the same things.”
They reveal what’s termed “the farming effect,” a phenomenon that protects against allergic disease. Von Mutius and her colleagues have narrowed the effect down to three key factors: livestock (specifically cows, pigs or poultry); type of fodder (for instance, whether it’s fresh grass or hay); and drinking of raw farm milk.
The findings have been generally consistent – about 1 to 2 per cent of the farm children in the studies had asthma compared to 12 per cent of local, non-farm children in control groups. “I’m completely convinced that this is real,” says von Mutius. “The question is – are we going to be able to solve the puzzle.” She chuckles: “For that we need a lot of luck.”
To that end, today von Mutius is co-leader of a massive European Commission project called GABRIEL, which involves 14 countries and 40,000 test subjects. Among its goals is to identify what in those three key elements of livestock, fodder and unpasteurized milk confers protection against allergy, whether it acts alone or in combination with other farm factors as well as the genetic background, and how this all takes place.
For a while, some thought a key was endotoxin in the barns – that’s the membrane of certain bacteria that stimulates the immune system and can cause illness. But fungal spores are also proving important. At this stage, von Mutius finds endotoxin a minor player. “It’s not just endotoxin, of that I’m pretty sure. We think it is microbial factors on the farms – it’s probably anything that’s bacterial, or molds, maybe yeasts. We’re trying to develop new tools to measure those exposures.”