Modern biology has not yet come to terms with the presence of many organic codes in Nature, despite the fact that we can prove their existence. As a result, it has not yet accepted the idea that the great events of macroevolution were associated with the origin of new organic codes, despite the fact that this is the most parsimonious and logical explanation of those events. This is probably due to the fact that the existence of organic codes in all fundamental processes of life, and in all major transitions in the history of life, has enormous theoretical implications. It requires nothing less than a new theoretical framework, and that kind of change is inevitably slow. There are too many facts to reconsider, too many bits of history to weave together in a new mosaic. But this is what science is about, and the purpose of the present paper is to show that it can be done. More precisely, it is shown that the whole natural history of the brain can be revisited in the light of the organic codes. What is described here is only a bird's-eye view of brain macroevolution, but it is hoped that the extraordinary potential of the organic codes can nevertheless come through. The paper contains also another message. The organic codes prove that life is based on semiosis, and are in fact the components of organic semiosis, the first and the most diffused form of semiosis on Earth, but not the only one. It will be shown that the evolution of the brain was accompanied by the development of two new types of sign processes. More precisely, it gave origin first to interpretive semiosis, mostly in vertebrates, and then to cultural semiosis, in our species.