The basic information and methods of biochemistry, molecular biology, cell biology, and genetics were not yet available to analyze cell-cell signaling and transcriptional regulation in embryos. In light of discouraging results, some embryologists considered that the organizer concept was faulty and that inducers were an experimental artifact (see later discussion for recent successes in understanding inductions). Although Morgan and other early geneticists had proposed that inducers and cytoplasmic localizations elicit specific gene expression and that development was in large part a problem of ever-changing patterns of gene expression (Morgan 1934), the means were not at hand to pursue those insights. Roux, Spemann, and Harrison had outlined plausible lines of inquiry into determination and morphogenesis in the early part of the twentieth century; however, the means were also not available to pursue those questions at that time.

To many scientists in the 1940-1970 period, the study of development seemed messy and intractable. Researchers turned to more informative subjects such as the new molecular genetics of bacteria and phages (viruses that infect bacteria). From those inquiries came new insights in the 1950-1965 period on the nature of the gene and the code and the processes of replication, transcription, translation, enzyme induction, and enzyme repression. For example, it was only in 1961 that Monod and Jacob described gene regulation in bacteria in terms of promoters, operators, and repressor proteins (Monod and Jacob 1961). Those authors immediately saw the relevance to animal development. All of their insights made possible the invention of techniques for gene isolation and amplification, for in vitro expression of genes, for genome analysis, and, thereafter, for the new developmental biology.

With so little molecular information about developmental processes, there was scarcely any understanding of the action of developmental toxicants. For example, Wilson (1973) in his book Environment and Birth Defects could only raise the following possibilities for connections between inductions and developmental defects:

It has long been accepted that cell interactions (induction) are an important part of normal embryogenesis, despite the fact that specific “inducer substances” have not been identified. [Failures] of normal interactions which may lead to deviations in development include, for example, lack of usual contact or proximity, as of optic vesicle with presumptive lens ectoderm; or the incompetence of target tissue to be activated in spite of its usual relationship with activator tissue, as in certain mutant limb defects; or the inappropriate timing of the interrelation, even though all parts are potentially competent. That the nature of cell-to-cell contacts and the manner of their adhesion are important determinants in both normal and abnormal development has been demonstrated…. Insufficient or inappropriate cellular interactions usually result in arrested or deviant development in the tissue ordinarily induced or activated by the interaction.

This committee will later argue that Wilson’s insight was well directed and is now ready to be pursued.

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