Hypothesis: amyotrophic lateral sclerosis and environmental pollutants.

Genetic, epigenetic, and environmental factors are relevant in the causation of amyotrophic lateral sclerosis (ALS) in a multistep cascade. We suggest that exposure to environmental pollutants in early life is one such factor. ALS was first described in the 19th century in the context of the Industrial Revolution that began more than 50 years earlier. The rising incidence of ALS thereafter correlates with increasing longevity, but this is an incomplete association. We suggest that increasing exposure to environmental pollutants due to industrial activity, acting over a lifetime, is also important. The combination of genetic mutations and pollutant exposure, with increased life expectancy, may account for the apparent variations in incidence of the disease in different countries and continents and even regionally within a given country. This hypothesis is testable by focused epidemiological studies, evaluating early and lifelong industrial pollutant exposure of differing types, within the Bradford Hill framework.