Muller formulates the chief principles of spontaneous gene mutation as point effects of ultramicroscopic physico-chemical accidents; he induces such changes using X-rays
Date: 2015-10-07; view: 474.
In 1918, he proposed an explanation for the dramatic discontinuous alterations in Oenothera larmarckiana that were the basis of Hugo de Vries's theory of mutationism: "balanced lethals" allowed the accumulation of recessive mutations, and rare crossing over events resulted in the sudden expression of these hidden traits. In other words, de Vries's experiments were explainable by the Mendelian-chromosome theory. Muller's work was increasingly focused on mutation rate and lethal mutations. In 1918, Morgan—short-handed because many of his students and assistants were drafted for the U.S. entry into World War I—convinced Muller to return to Columbia to teach and to expand his experimental program.
At Columbia, Muller and his collaborator and longtime friend Edgar Altenburg continued the investigation of lethal mutations. The primary method for detecting such mutations was to measure the sex ratios of the offspring of female flies. They predicted the ratio would vary from 1:1 due to recessive mutations on the X chromosome, which would be expressed only in males (who lacked the functional allele on a second X chromosome). Muller found a strong temperature dependence in mutation rate, leading him to believe that spontaneous mutation was the dominant mode (and to initially discount the role of external factors such as ionizing radiation or chemical agents). In 1920, Muller and Altenburg coauthored a seminal paper in Genetics on "modifier genes" that determine the size of mutant Drosophila wings. In 1919, Muller made the important discovery of a mutant (later found to be a chromosomal inversion) that appeared to suppress crossing-over, which opened up new avenues in mutation rate studies. However, his appointment at Columbia was not continued; he accepted an offer from the University of Texas and left Columbia after the summer of 1920.[9]
Muller taught at The University of Texas from 1920 until 1932. Soon after returning to Texas, he married mathematics professor Jesse Marie Jacobs, whom he had courted previously. In his early years at Texas, Muller's Drosophila work was slow going; the data from his mutation rate studies were difficult to interpret. In 1923, he began using radium and X-rays, but the relationship between radiation and mutation was difficult to measure because such radiation also sterilized the flies. In this period, he became more involved with eugenics and human genetics. He carried out a study of twins separated at birth that seemed to indicate a strong hereditary component to I.Q. Muller was critical of the new directions of the eugenics movement (such as anti-immigration), but was hopeful about the prospects for positive eugenics.
Discovery of X-ray mutagenesis
1926 marked the beginning of a series of major breakthroughs. Beginning in November, Muller carried out two experiments with varied doses of X-rays, the second of which used the crossing over suppressor stock ("ClB") he had found in 1919. A clear, quantitative connection between radiation and lethal mutations quickly emerged. Muller's discovery created a media sensation after he delivered a paper entitled "The Problem of Genetic Modification" at the Fifth International Congress of Genetics in Berlin; it would make him one of the better known public intellectuals of the early 20th century. By 1928, others had replicated his dramatic results, expanding them to other model organisms such as wasps and maize. In the following years, he began publicizing the likely dangers of radiation exposure in humans (such as physicians who frequently operate X-ray equipment).
His lab grew quickly, but it shrank again following the onset of the Great Depression. Especially after the stock market crash, Muller was increasingly pessimistic about the prospects of capitalism. Some of his visiting lab members were from the USSR, and he helped edit and distribute an illegal leftist student newspaper, The Spark. It was a difficult period for Muller both scientifically and personally: his marriage was falling apart, and he was increasingly dissatisfied with his life in Texas. Meanwhile, the waning of the eugenics movement, ironically hastened by his own work pointing to the previously ignored connections between environment and genetics, meant that his ideas on the future of human evolution had reduced impact in the public sphere.
(1920s)