This timeline tries to capture the origin of key insights that led to the birth of the study of inborn errors of metabolism. Inborn errors of metabolism (IEM) represent an evergrowing group of diseases, that are individually rare but together affect up to 1 in 1000 humans. These diseases are caused by discrete defects in the function of particular enzymes, and thus cause a deranged metabolism of simple nutrients, or more complex molecules that are vital for normal function of a cell. Their basis is mostly DNA mutation that renders important proteins inactive. By extension, they belong to an even larger group of extremely rare genetic diseases, together referred to as 'orphan diseases', as patients suffering from those afflictations are too often let without structural help, because of insufficient insight in the rare disease process, because current technology does not yet offer hope for cure, but also because there are insufficient private or public resources to design adequate treatment. The study of IEM was particularly important for the development of modern medicine and its fundamental disciplines, such as genetics and biochemistry. IEM represent natural 'experiments of nature' that enabled researchers to show that revolutionary observations in plants and lower animal species also occurred in humans. We will try to sketch the development of key ideas that led to the birth of this discipline. We will try to sketch mutual influences between protagonist scientists, but also illlustrate the nowadays inconceivable lack of knowledge transfer between those protagonists in the pre-internet area.