In 1961, Van Reeth and colleagues described the presence of intracellular inclusion bodies in the anterior horn cells of a patient with Pick dementia and atypical amyotrophic lateral sclerosis (ALS). A year later, Tat’yana Bunina, a neuropathologist from the USSR, described inclusion bodies with almost identical morphology, in the spinal cords and brain stems of two cases of familial ALS. She initially believed that they were a virus. However, electron microscopy and subsequent work involving intracerebral inoculation with material from various forms of ALS failed to demonstrate any signs of transmissibility. It is intriguing to speculate that Bunina’s original description of Bunina bodies may have been the original first clue on a path to unravelling the pathogenetic process in ALS.