Conrad Hal Waddington's Organisers and Genes, published in 1940, is a summary of available research and theoretical framework for many concepts related to tissue differentiation in the developing embryo. The book is composed of two main conceptual sections. The first section explores the action and nature of the organizer, while the second section delves into genes and their influence on development.
Conrad Hal Waddington was an embryologist and theoretical biologist. His early experimental work investigated aspects of embryonic induction and the properties of the organizer first identified by Hans Spemann and Hilde Mangold, while his later studies focused on genetic assimilation. Waddington is probably best known for developing the concept of the epigenetic landscape, and he also held significant interest in many different areas ranging from the visual arts and poetry to philosophy. Throughout his career, Waddington maintained that the arts were integral to science, and he continued to draw inspiration from the arts for his own work.
Research in chemical induction seeks to identify the compound or compounds responsible for differentiation in a developing embryo. Soren Lovtrup compared the search for these compounds to the search for the philosopher's stone. It was based on the assumption that the differentiating agents have to be chemical substances either within cells or in the extracellular matrix. However, despite numerous efforts to understand them, the nature of these substances remained largely a mystery from the 1930s until the 1980s, when the new era of molecular induction based on molecular genetics provided a new perspective. During the period of emphasis on chemical induction, a variety of different experiments were conducted aimed at discovering the chemical nature of the inducer. In some experiments, the organizer region was killed by heat to assess the inducing ability of a dead organizer. Other experiments used natural and synthetic compounds to attempt. Although none of these experiments identified a chemical inducer with any certainty, they did discover many related properties of the developing embryo.
Conrad Hal Waddington's "Experiments on the Development of Chick and Duck Embryos, Cultivated in vitro," published in 1932 in Philosophical Transactions of the Royal Society of London, Series B, compares the differences in the development of birds and amphibians. Previous experiments focused on the self differentiation of individual tissues in birds, but Waddington wanted to study induction in greater detail. The limit to these studies had been the amount of time an embryo could be successfully cultivated ex vivo. Waddington applied in vitro cell culturing techniques to this experiment, as opposed to the chorio-allantoic technique used in many earlier studies. Culturing in vitro consisted of placing the embryo on a clot of adult chicken blood plasma and chick embryo extract in a watch glass. Experiments reported in this paper were divided into three main sections: the development of the embryos in vitro, induction by the endoderm, and induction by the primitive streak.
The epigenetic landscape is a concept representing embryonic development. It was proposed by Conrad Hal Waddington to illustrate the various developmental pathways a cell might take toward differentiation. The epigenetic landscape integrates the connected concepts of competence, induction, and regulative abilities of the genes into a single model designed to explain cellular differentiation, a long standing problem in embryology.
Molecular Epigenetics and Development: Histone Conformations, DNA Methylation and Genomic Imprinting
Introduced by Conrad Hal Waddington in 1942, the concept of epigenetics gave scientists a new paradigm of thought concerning embryonic development, and since then has been widely applied, for instance to inheritable diseases, molecular technologies, and indeed the human genome as a whole. A genome contains an embedded intricate coding template that provides a means of genetic expression from the initial steps of embryonic development until the death of the organism. Within the genome there are two prominent components: coding (exons) and non-coding (introns) sequences. Exons provide coding by transcribing a gene into a protein, while introns do not have this capacity. On top of these coding sequences lie mechanisms that dictate the overall capability of a gene without changing the underlying nucleotide sequence of DNA; these mechanisms are primarily known as epigenetic factors.
Conrad Hal Waddington's "Experiments on Embryonic Induction III," published in 1934 in the Journal of Experimental Biology, describes the discovery that the primitive streak induces the mammalian embryo. Waddington's hypothesis was that a transplanted primitive streak could induce neural tissue in the ectoderm of the rabbit embryo. The primitive streak defines the axis of an embryo and is capable of inducing the differentiation of various tissues in a developing embryo during gastrulation. In this experiment Waddington was, in fact, able to induce neural differentiation. Waddington noted that the tissue is "competent"; for a chick organizer, and by deduction a mammalian organizer must exist. Competence refers to a cell's ability to respond to an inducing signal, which is temporally limited to certain developmental stages. Waddington's initial work laid the foundation for many decades of research to follow, including further experiments by Waddington with the mammalian organizer.