 A fifth discovery was the realization that one of the major environmental agents effecting development were symbiotic microbes (McFall-Ngai 2002; Gilbert et al. 2012, 2015). The notion of the holobiont (i.e. an integrated composite organism composed of microbial and host eukaryotic species) organized much of the data to look at the roles of microbes in causing both the normal development of the organism and variations of normal development (in disease and evolution) (Rosenberg &amp; Zilber-Rosenberg 2016; see entry  biological individuals).  For instance, in the mouse, the normal development of the immune system and the gut capillary network depends upon specific bacteria obtained during birth. These bacteria induce the expression of particular genes in the eukaryotic cells, and the proteins made by these genes influence cell fate (Hooper et al. 2001; McFall-Ngai et al. 2013). In other words, the bacteria can act as an embryonic cell would, regulating gene expression in neighboring cells. Here, the eukaryotic organism needs and expects these bacteria to be present for normal development.