Well, we did because we published a paper in 1990 where we reported that not only was PI3K activated by growth factors like EGF and PDGF, but it was also activated by insulin [2]. In fact, insulin turned out to be the very best way to activate it. As we continued to pursue that finding through the very early 1990s, we and others found that virtually everything that insulin did required the activity of PI3K. In other words, inhibitors of PI3K or knockouts of PI3K in mice abrogated insulin signaling. Insulin-dependent glucose uptake, for example, required PI3K.

And as we were doing our work in mammalian systems - on cell lines and mouse knock-outs - other labs were studying worms and flies, and the gene encoding PI3K popped up in genetic mutants of flies, in a pathway that was downstream of the insulin/insulin-like growth factor (IGF) receptor. While mammals have separate but related receptors for insulin and IGF1, flies and worms have a single receptor that is the ancestor of these two receptors. So PI3K showed up genetically in the insulin/IGF-1 signaling pathway that controls cell growth in flies. In worms, it popped up in a nutrient-dependent age-related phenotype. In fact, it was called 'age-1' before it was identified as PI3K because loss-of-function mutations in the gene dramatically extend the lifespan of worms. The genetic network for ageing turned out to be the insulin receptor, IRS-1, PI3K, AKT, FoxO network - the same network that we were uncovering in mammalian systems.