The essay here frames and presents materials on the emergence and development of hygiene hypotheses in asthma research, as researchers sought to explain seemingly counterintuitive correlations: why children who grew up in "unhygienic" environments -- polluted cities in (then-)East Germany, for example, or farms full of animals and allergens -- were in some case significantly less likely to be diagnosed with asthma later in life. The essay foregrounds the work of one researcher who came to be most often associated with "the hygiene hypothesis" as it pertained to asthma, Erika von Mutius.
In the mid-1980s Von Mutius had been studying the effects of air pollution on croup in children at University Children’s Hospital in Munich, and “felt it had just all been a mess.” Wanting to avoid running another project, she cast her next proposal in such large and ambitious terms that she expected it to go unfunded. It did not. That surprising event was accompanied by another, the fall of the Berlin Wall and the reunification of Germany. That provided an opportunity to collect health and environmental data in a way that had not been possible for decades, and Von Mutius designed a study that would compare asthma rates and prevalence in Munich and Leipzig, populations that could be considered bio-ethnically identical but had experienced strikingly different environments. “I’d long been thinking that air pollution levels were very low in Munich and had to be very high in industrial East Germany,” she recalled to the Lancet, but I knew that for propaganda reasons the [Communist] regime would never allow a comparative study.” She struck up a collaboration with two other doctors in Leipzig and Halle, “where the river Saale had run violet with toxic waste,” and prepared to document strikingly high asthma rates in the former East Germany. But that would be the third surprise: “when her team analysed their results they were left speechless: the prevalence of hay fever and allergic sensitisation was about 50% lower in these areas than in and around Munich.” (more...)
"These observations do not support suggestions that viral infections, particularly of the respiratory tract, are important precipitants of the expression of atopy. They could, however, be explained if allergic diseases were prevented by infection in early childhood, transmitted by unhygienic contact with older siblings, or acquired prenatally from a mother infected by contact with her older children. Later infection or reinfection by younger siblings might confer additional protection against hay fever. Over the past century declining family size, improvements in household amenities, and higher standards of personal cleanliness have reduced the opportunity for cross infection in young families. This may have resulted in more widespread clinical expression of atopic disease, emerging earlier in wealthier people, as seems to have occurred for hay fever."
Initially expecting to find a linear effect in which a polluted environment causes increased asthma and allergy rates, von Mutius ended up affirming, or at the very least adopting as an explanation to explore, a version of David Strachan’s “hygiene hypothesis,” in which early childhood (later research would extend it to prenatal) exposure to microbes, or microbial products, or something in an environment confers some small but not insignificant protective effect on at least some individuals in a population.
Von Mutius’s research focus shifted from urban settings to more rural ones, and from daycare centers to farms. With growing cohort sizes and growing number of collaborators going hand in hand—solicitude needs a social engine—a series of publications in the late 1990s substantiated the hygiene hypothesis. By 2001 Von Mutius and (by then) 9 co-authors, plus another 7 members of “the ALEX [Allergy and Endotoxin] Study Team,” scattered across Munich, Basel, and Salzburg, could confidently state that “growing up on a farm protects against allergic sensitisation and development of childhood allergic diseases,” including asthma, and that “regular contact with farm animals confers an important protective effect in such an environment.” The large number of participants gave their studies the statistical power to validate such claims, but even though the statistical correlations were robust, they were still in the dark when it came to actual mechanisms and molecules, including genes:
"The mechanism by which time spent in a stable and consumption of farm milk protect against development of asthma and atopic sensitisation is not known… Farm children are exposed to higher inhaled concentrations of endotoxin in stables and in dust from kitchens and mattresses than non-farming children. However, swallowing could be another route of exposure to bacterial products. This theory is lent support by the independent protective effect on atopic sensitisation of… farm milk consumption and exposure to stables in the first year of life. Farm milk, which is usually raw, contains more gram-negative bacteria and thus lipopolysaccharide, than pasteurised milk. Therefore, the protective factor associated with consumption of farm milk could be associated with ingestion of non-infectious microbial components, with resultant changes to the commensal gut flora, or both."