Waddington's metaphor kicked off the principle of self-organization in biology

A decade later, the central dogma of molecular biology , established the molecular basis of genetic inheritance. From gene to RNA to protein. Straight genotype-to-phenotype mapping indeed solid the foundation of Neo-Darwinian at that time. But what if a genotype does not translate in an obvious manner into a corresponding phenotype – or worse, if genes are not even the sole basis of inheritance? It was first articulated by C. Waddington when he coined the term ‘epigenetics’, at roughly the same time as the consolidation of the Modern Synthesis. The Waddington landscape is an abstract metaphor frequently used to represent the relationship between gene activity and cell fates during development, which conceptualise the emergence of developmental choices as the result of intrinsic constraints (regulatory interactions) shaped during evolution.  Over the last few years it has become a useful framework for interpreting results from single-cell transcriptomics experiments.

Waddington drew a number of representations of his famed landscape but two have come to be identified with his views on development and evolution. In the most prevailed one, a cell, which looks like a ball, begins at the top of a hill and follows existing paths in the landscape driven by a gravitational force which leads it into one of several possible fates represented as valleys.

A formal underpinning of the landscape was first suggested by S. Kaufmann in 1969 who formalized the landscape by identifying the valleys with attractors in Boolean networks. Later, S. Huang developed this notion further into a multidimensional dynamical systems framework. In this formalism, Waddington’s intuition of genetic control of the landscape is brought to light using gene expression profiles projected onto an n-dimensional phase-space with vector fields where stable states act as attractors. It is these frameworks that have perhaps become most popular when invoking the Waddington landscape as a reference to interpret gene expression data in development and disease.

To be general, from a historical view, Waddington's epigenetic view posed challenges to the Neo-Darwinism at that time. But now we know there exist the origin order and prefabricated module of biology from field of physics, chemistry and others that can hardly be directly included into the framework of Darwinism. This non-linear mono-causal genotype-to-phenotype mapping actually ask us to rethink the quantitative description of natural selection.