Elucidating the cause of disease is often not easy and may require answers to many questions. Perhaps the most important questions have been rather simply stated in verse by Rudyard Kipling.1 I keep six honest serving men; (They taught me all I knew) Their names are What and Why and When and How and Where and Who. In terms of neural tube defects, many of these servants of Mr Kipling have provided valuable epidemiologic clues as to the cause of neural tube defects (NTDs),2 but the specific mechanism responsible for this disabling birth defect has so far escaped definition.