Richard Goldschmidt: hopeful monsters and other \u27heresies\u27

Richard Goldschmidt is remembered today as one of the most controversial biologists of the twentieth century. Although his work on sex determination and physiological genetics earned him accolades from his peers, his rejection of the classical gene and his unpopular theories about evolution significantly damaged his scientific reputation. This article reviews Goldschmidt\u27s life and work, with an emphasis on his controversial views

Some thoughts on the association of polled trait and intersexuality in goats

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Early 20th-century research at the interfaces of genetics, development, and evolution: Reflections on progress and dead ends

AbstractThree early 20th-century attempts at unifying separate areas of biology, in particular development, genetics, physiology, and evolution, are compared in regard to their success and fruitfulness for further research: Jacques Loeb's reductionist project of unifying approaches by physico-chemical explanations; Richard Goldschmidt's anti-reductionist attempts to unify by integration; and Sewall Wright's combination of reductionist research and vision of hierarchical genetic systems. Loeb's program, demanding that all aspects of biology, including evolution, be studied by the methods of the experimental sciences, proved highly successful and indispensible for higher level investigations, even though evolutionary change and properties of biological systems up to now cannot be fully explained on the molecular level alone. Goldschmidt has been appraised as pioneer of physiological and developmental genetics and of a new evolutionary synthesis which transcended neo-Darwinism. However, this study concludes that his anti-reductionist attempts to integrate genetics, development and evolution have to be regarded as failures or dead ends. His grand speculations were based on the one hand on concepts and experimental systems that were too vague in order to stimulate further research, and on the other on experiments which in their core parts turned out not to be reproducible. In contrast, Sewall Wright, apart from being one of the architects of the neo-Darwinian synthesis of the 1930s, opened up new paths of testable quantitative developmental genetic investigations. He placed his research within a framework of logical reasoning, which resulted in the farsighted speculation that examinations of biological systems should be related to the regulation of hierarchical genetic subsystems, possibly providing a mechanism for development and evolution. I argue that his suggestion of basing the study of systems on clearly defined properties of the components has proved superior to Goldschmidt's approach of studying systems as a whole, and that attempts to integrate different fields at a too early stage may prove futile or worse

Genetic and developmental analysis of the sex-determining gene ‘double sex' (dsx) of Drosophila melanogaster

Sex determination in Drosophila depends on the ratio of X chromosomes to sets of autosomes (X:A). This chromosomal signal is used to regulate a few control genes whose state of activity selects either the male or the female sexual pathway. We have studied the structure and function of dsx (double sex) which appears to be the last regulatory gene on whose function the sexual pathway eventually depends. We have mutagenized the locus, varied the doses of dominant dsx-mutations and wildtype alleles, and combined different dsx-alleles with recessive mutations in other sex-determining genes, such as ix, tra-2 and tra. The locus dsx harbours two genetic functions, dsxm to implement the male program, dsxf to implement the female program. We found that dsxm and dsxf can mutate independently although most mutations abolish both functions. We conclude that dsxm and dsxf each have their specific domain, but also share a large region of DNA that is essential for both functions. We present evidence that the dominant mutations correspond to a constitutive expression of the male-determining function dsxm, with the simultaneous abolishment of the female-determining function dsxf. This effect can be counteracted by two doses of expressed dsxf so that a female phenotype results. The products of one dose of expressed dsxm and one dose of expressed dsxf in the same cell appear to neutralize each other which leads to a null phenotype. The mutant combinations suggest that the product of dsxf requires the products of ix+, tra-2+ and tra+ to become functiona

The mode of action of intersex in terminal sexual differentiation in Drosophila.

The intersex gene (2-60.5) lies at the terminus of the regulatory pathway that determines sex-type in Drosophila. Its product functions with the female-specific product of doublesex, another gene in the self-determination regulatory pathway, to regulate female-specific differentiation. However, the mechanism of this regulation has not been clearly demonstrated. Using a temperature-sensitive allele at intersex to eliminate its function at time points both during development and in the adult stage, the mode by which intersex regulates female determination was addressed. When chromosomal females bearing a temperature-sensitive intersex allele are raised at a permissive temperature, they develop as phenotypic females. Animals raised at a restrictive temperature also develop as normal females. In contrast, animals kept at a restrictive temperature past the mid-pupal stage, or animals raised at a permissive temperature and then shifted to a restrictive temperature before the mid-pupal stage develop as sterile females. Therefore, the fertility to be retained, intersex function must be present at least until the mid-pupal stage. To determine if the function of intersex is also required in the adult to maintain the female differentiated state, as well as to address its mode of action, intersex function was eliminated in the adult female. To this end, diplo-X females bearing a temperature-sensitive intersex allele were place at a restrictive temperature as adults and used to analyze whether intersex exerts transcriptional control over the female-specific expression of the yolk protein gene, yp1. Even after placing animals bearing the temperature-sensitive allele at a restrictive temperature for up to twenty days, yp1 transcription persisted at levels equivalent to sibling controls having normal intersex function. These data suggest that intersex does not function to positively regulate female-specific gene expression, but does not rule out that intersex functions to repress male-type gene expression in females