PERSPECTIVES Morgan and his students were building TIMELINE on the foundation laid by Sturtevant’s con- struction of the first chromosome map. It was an exciting time. Everyone worked in Hermann Joseph Muller, Evolutionist the same room and the talk was continuous; ideas were bandied about and progress was James F. Crow astonishingly rapid. Muller’s first faculty position was at the Abstract | This essay is dedicated to the A brief biography Rice Institute in Houston, Texas, where he proposition that Hermann Joseph Muller, Hermann Joseph Muller — Joe to his enjoyed fellowship with Julian Huxley. After widely regarded as the greatest geneticist friends — was born on 21 December 1890, 3 years he returned to Columbia, in the hope of the first half-century of the subject, was in New York City. His father, also Hermann of securing a permanent position; however, also one of the greatest evolutionists of this J. Muller, led his class at City College, New his stay lasted only 2 years, and in 1920 he period. His Nobel Prize-winning work, which York, and started on a career in international accepted an offer from the University of showed that radiation increases the mutation law. Although he was forced to interrupt his Texas. It was there that Muller made the dis- rate, is in every genetics textbook, and his studies to take over the family business after covery that made him famous: the production prescient ideas have influenced almost every the death of his own father, Muller retained of mutations by X-radiation2,3,7. However, aspect of the discipline. Here I emphasize his intellectual interests and, in particular, his socio-political ideas made his stay in the his less well-known contribution to the imparted the idea of Darwinian evolution to United States uncomfortable; he became neo-Darwinian theory of evolution. his young son. He died when his son was 10 increasingly distressed by racism and capital- years old. ist exploitation in the United States, and in Although Hermann Joseph Muller is 1932 he decided to leave. By then he had best remembered for his discovery that Education and early academic career. also made himself unpopular by sponsoring X-irradiation induces genetic mutations1, Muller’s widowed mother was left poor, a left-wing student newspaper. for which he won the Nobel Prize, he made which meant that young Muller had to many influential contributions to evolution- work his way through high school. Despite Germany and Russia. Discouraged, and ary biology. Muller was the first to emphasize this, he had an outstanding record and having burned his bridges in Texas, Muller a gene-centred view of evolution, and he made showed a remarkable inventiveness: for accepted a fellowship to work in Berlin both experimental and theoretical contribu- example, he devised a system of shorthand with Nikolai W. Timofeeff-Ressovsky, tions to our understanding of speciation. He to speed up note taking. (Late in his life he who shared his interest in mutation and also reached insightful conclusions about attached wheels to his suitcase; now we see in applying the principles of physics to how genes interact, how they are acted on by hardly any other kind.) Being valedictorian genetics. Muller was particularly attracted natural selection, and how their evolution is of his high-school class led to a scholarship; to Max Delbrück, a physicist in Timofeeff’s influenced by sexual reproduction and popu- this partially alleviated his financial diffi- group, who later became a leader in phage lation structure. His influence on genetics and culties but still required him to work many genetics in the United States. But this was evolution was therefore substantial and wide- hours. His undergraduate course in biology 1932; within a year Hitler came to power ranging (for a book-length biography, see REF. 2; at Columbia College was crucial in deter- and Muller’s hopes for Germany becoming for excerpts from his collected papers, see mining the direction of his career; here, a leader in genetics research were dashed. REF. 3). In fact, Muller’s interest in evolution he took a course with Edmund B. Wilson, He was ready to move on and his deep pervaded his entire career. As a student, he America’s leading cytologist and author of sympathy for communism induced him to organized a biology club in which ideas about the definitive textbook on cytogenetics5, accept an invitation from Nikolai I. Vavilov evolution permeated the discussions. Later on, which whetted Muller’s appetite for more to move to Leningrad and later to Moscow. it was the interest in evolutionary mechanisms genetics. He started graduate school and, This led to a highly productive programme that inspired his emphasis on mutation. along with Alfred H. Sturtevant and Calvin in Drosophila genetics, with emphasis on In this essay, after a short digression into B. Bridges, became one of the three brilliant gene structure and mutation, and that made Muller’s colourful personal life, I discuss the students that Thomas Hunt Morgan assem- use of the recently discovered giant SALIVARY many important ways in which he contributed bled in the famous ‘fly room’ at Columbia GLAND CHROMOSOMES (see Glossary). However, to evolution. More details are given in REF. 4. University6. this research lasted only a few years. NATURE REVIEWS | GENETICS VOLUME 6 | DECEMBER 2005 | 941 © 2005 Nature Publishing Group PERSPECTIVES Muller spent the rest of the war years at the basic phenomenology of mutation was Amherst teaching biology to unappreciative understood, thanks mainly to the Morgan army trainees and doing research with a group: the gene is equally stable before and minimum of equipment and assistance. He after mutation; mutation of a gene occurs knew that this was a temporary appointment, independently of other genes, even its allele; which would end when the war was over. By the process is independent of the external then we were close friends and I remember environment (of course this changed when being appalled that this man, arguably the Muller himself discovered radiation muta- world’s greatest geneticist, would soon be genesis); and, most importantly, mutations unemployed. are random with respect to phenotypic There were several reasons he was not effect, and therefore most are harmful. Figure 1 | Hermann Joseph Muller with a hired. Having been to Russia, he was branded Muller emphasized the information- student, Dale Wagoner, at Indiana University. as a communist, and having spoken out carrying capacity and self-replicating ability against Lysenko, he was branded as a fascist. of the gene, but he added a third property, Muller had gone to Russia with high With wry amusement, he once said that at the ability to replicate mistakes. He argued idealism, as he thought that in a classless least both could not be true. In addition, that it is this ability that makes evolution society, social and economic justice would Muller had the (not undeserved) reputation possible: once an entity exists that can faith- prevail and genetic research would thrive. of being a ‘difficult’ personality. fully replicate its rare errors, even if only a Alas, the idealistic social aims were far from At last, in 1945 Muller obtained a perma- small fraction are favourable, then natural fulfilled and genetics was completely cor- nent position. At the age of 54 he joined the selection can operate to produce ever-higher rupted by Trofim Lysenko’s naive lamarck- faculty of Indiana University, where he had levels of adaptation. Needless to say, Muller ian ideas, which had found favour with a well-equipped laboratory, assistants and was greatly excited by the Watson–Crick Stalin. graduate students (FIG. 1). Except for short stays model, which all but shouted the mechanis- at other universities, he spent the rest of his life tic basis for what he had thought the gene The war years. By 1937, on advice from at Indiana. He was awarded almost all the hon- must do. Vavilov, Muller decided to leave Russia. It was ours that a biologist can aspire to, including the Muller made one of his most prophetic decided that the best way to avoid harming Nobel Prize, which he received in 1946. statements in a lecture in Toronto in 1921 his remaining colleagues was for Muller to Despite the many migrations, setbacks and REF. 8. He told his audience that the recently join the Spanish Republican Army. For sev- disappointments, Muller held on to his ideal- discovered d’Herelle bodies, now called eral months he worked there in a blood bank, istic views. He also retained his indefatigable bacteriophages, offered the possibility of before moving to a research position at the work habits: he regularly worked long hours studying genes by direct chemical means. He University of Edinburgh. Notably, during this in a 7-day week. At Indiana he taught three famously said: “Must we geneticists become time, he discussed with his student, Charlotte courses; one was on evolution, which started bacteriologists, physiological chemists, and Auerbach, the possibility of studying chemi- with the origin of the solar system and ended physicists, simultaneously with being zoolo- cal mutagens. Her colleague J. M. Robson, with human cultural evolution. During his gists and botanists? Let us hope so.” Indeed, noting the similarity of burns produced by lifetime he wrote more than 300 papers, sev- shortly after the end of the Second World War, mustard gas and X-rays, suggested that mus- eral of which were path-breaking. His death bacterial and virus genetics led the way to a tard gas might be mutagenic. Auerbach sub- came on 5 April 1967 REF. 3 TIMELINE. much finer resolution in genetic analysis. At sequently found this to be the case, but her the same time, chemical manipulation of large findings were a military secret.