Richard Goldschmidt: hopeful monsters and other 'heresies'

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's life and work, with an emphasis on his controversial views.     

The politics of human heredity in the USSR, 1920-1940

After the Bolshevik revolution of 1917, Iurii Filipchenko (in Petrograd) and Nikolai Koltsov (in Moscow) created centers of genetic research where eugenics prospered as a socially relevant part of the new "experimental" biology. The Russian Eugenics Society, established in 1920, was dominated by research-oriented professionals. However, Bolshevik activists in the movement tried to translate eugenics into social policies (among them, sterilization) and in 1929, Marxist geneticist Alexander Serebrovsky was stimulated by the forthcoming Five-Year Plan to urge a massive eugenic program of human artificial insemination. With the advent of Stalinism, such attempts to "biologize" social phenomena became ideologically untenable and the society was abolished in 1930. Three years later, however, a number of eugenicists reassembled in the world's first institute of medical genetics, created by Bolshevik physician Solomon Levit after this return from a postdoctoral year in Texas with H.J. Muller. Muller himself moved to the Soviet Union in 1933, where he agitated for eugenics and wrote Stalin in 1936 to urge an artificial insemination program. Shortly thereafter, Muller left Russia, several of his colleagues were shot, and the Institute of Medical Genetics was disbanded. During the next three decades, Lysenkoists regularly invoked the Soviet eugenic legacy to claim that genetics itself was fascist.     

Advances in medical genetics.

Although advances in medical genetics are designed ultimately to help human beings receive better health care, they pose many problems for society. Some of these concerns are real, but others result from misunderstanding and/or misrepresentation of the true implication of certain developments in genetics. It is obvious that the geneticist must play a dual role in society as scientist and as advocate. Although such a duality or role is not easy, it is not impossible. However, it does mean that the training of the medical geneticist must include more than exposure to the scientific approach.     

The Passion of Franz Boas

The reputation of Franz Boas as a scientist declined in the decades after his death in 1942, but his reputation as a champion of human rights and an opponent of racism remained intact. More recently, however, some writers have questioned the sincerity, the results, and the political implications of his anthropology and his work against racism and ethnocentrism. Others have been critical of his relations with colleagues and students such as Ella Deloria and Zora Neale Hurston. In this essay I discuss some of these claims and present a more positive view. Franz Boas was passionately and consistently concerned about human rights and individual liberty, freedom of inquiry and speech, equality of opportunity, and the defeat of prejudice and chauvinism. He struggled for a lifetime to advance a science that would serve humanity, and he was as much of a humanitarian in private as he was in public. [Boas, political struggles, human relations]     

James F. Crow and the art of teaching and mentoring

To honor James F. Crow on the occasion of his 95th birthday, GENETICS has commissioned a series of Perspectives and Reviews. For GENETICS to publish the honorifics is fitting, as from their birth Crow and GENETICS have been paired. Crow was scheduled to be born in January 1916, the same month that the first issue of GENETICS was scheduled to appear, and in the many years that Crow has made major contributions to the conceptual foundations of modern genetics, GENETICS has chronicled his and other major advances in the field. The commissioned Perspectives and Reviews summarize and celebrate Professor Crow's contributions as a research scientist, administrator, colleague, community supporter, international leader, teacher, and mentor. In science, Professor Crow was the international leader of his generation in the application of genetics to populations of organisms and in uncovering the role of genetics in health and disease. In education, he was a superb undergraduate teacher whose inspiration changed the career paths of many students. His teaching skills are legendary, his lectures urbane and witty, rigorous and clear. He was also an extraordinary mentor to numerous graduate students and postdoctoral fellows, many of whom went on to establish successful careers of their own. In public service, Professor Crow served in key administrative positions at the University of Wisconsin, participated as a member of numerous national and international committees, and served as president of both the Genetics Society of America and the American Society for Human Genetics. This Perspective examines Professor Crow as teacher and mentor through the eyes and experiences of one student who was enrolled in his genetics course as an undergraduate and who later studied with him as a graduate student.     

The Reputational Consequences of Failed Replications and Wrongness Admission among Scientists

Scientists are dedicating more attention to replication efforts. While the scientific utility of replications is unquestionable, the impact of failed replication efforts and the discussions surrounding them deserve more attention. Specifically, the debates about failed replications on social media have led to worry, in some scientists, regarding reputation. In order to gain data-informed insights into these issues, we collected data from 281 published scientists. We assessed whether scientists overestimate the negative reputational effects of a failed replication in a scenario-based study. Second, we assessed the reputational consequences of admitting wrongness (versus not) as an original scientist of an effect that has failed to replicate. Our data suggests that scientists overestimate the negative reputational impact of a hypothetical failed replication effort. We also show that admitting wrongness about a non-replicated finding is less harmful to one’s reputation than not admitting. Finally, we discovered a hint of evidence that feelings about the replication movement can be affected by whether replication efforts are aimed one’s own work versus the work of another. Given these findings, we then present potential ways forward in these discussions.     

Methodology in Aristotle’s Theory of Spontaneous Generation

Aristotle’s theory of spontaneous generation offers many puzzles to those who wish to understand his theory both within the context of his biology and within the context of his more general philosophy of nature. In this paper, I approach the difficult and vague elements of Aristotle’s account of spontaneous generation not as weaknesses, but as opportunities for an interesting glimpse into the thought of an early scientist struggling to reconcile evidence and theory. The paper has two goals: (1) to give as charitable and full an account as possible of what Aristotle’s theory of spontaneous generation was, and to examine some of its consequences; and (2) to reflect on Aristotle as a scientist, and what his comments reveal about how he approached a difficult problem. In particular, I propose that the well-recognized problem of the incompatibility between Aristotle’s concept of spontaneity and his theory of spontaneous generation presents an opportunity for insight into his scientific methodology when approaching ill-understood phenomena.     

Darwin and the origin of interspecific genetic incompatibilities

Darwin's Origin of Species is often criticized for having little to say about speciation. The complaint focuses in particular on Darwin's supposed failure to explain the evolution of the sterility and inviability of interspecific hybrids. But in his chapter on hybridism, Darwin, working without genetics, got as close to the modern understanding of the evolution of hybrid sterility and inviability as might reasonably be expected. In particular, after surveying what was then known about interspecific crosses and the resulting hybrids, he established two facts that, while now taken for granted, were at the time radical. First, the sterility barriers between species are neither specially endowed by a creator nor directly favored by natural selection but rather evolve as incidental by-products of interspecific divergence. Second, the sterility of species hybrids results when their development is "disturbed by two organizations having been compounded into one." Bateson, Dobzhansky, and Muller later put Mendelian detail to Darwin's inference that the species-specific factors controlling development (i.e., genes) are sometimes incompatible. In this article, I highlight the major developments in our understanding of these interspecific genetic incompatibilities--from Darwin to Muller to modern theory--and review comparative, genetic, and molecular rules that characterize the evolution of hybrid sterility and inviability.     

Scientific Discrimination and the Activist Scientist: L.C. Dunn and the Professionalization of Genetics and Human Genetics in the United States

During the 1920s and 1930s geneticist L.C. Dunn of Columbia University cautioned Americans against endorsing eugenic policies and called attention to eugenicists’ less than rigorous practices. Then, from the mid-1940s to early 1950s he attacked scientific racism and Nazi Rassenhygiene by co-authoring Heredity, Race and Society with Theodosius Dobzhansky and collaborating with members of UNESCO (United Nations Educational, Scientific, and Cultural Organization) on their international campaign against racism. Even though shaking the foundations of scientific discrimination was Dunn’s primary concern during the interwar and post-World War II years, his campaigns had ancillary consequences for the discipline. He contributed to the professionalization of genetics during the 1920s and 1930s and sought respectability for human genetics in the 1940s and 1950s. My article aims to elucidate the activist scientist’s role in undermining scientific discrimination by exploring aspects of Dunn’s scientific work and political activism from the 1920s to 1950s. Definitions are provided for scientific discrimination and activist scientist.     

Richard Doll and Alice Stewart: reputation and the shaping of scientific "truth"

As the world watched the Fukushima reactors release radionuclides into the ocean and atmosphere, the warnings of Dr. Alice Stewart about radiation risk and the reassurances of Sir Richard Doll assumed renewed relevance. Doll and Stewart, pioneer cancer epidemiologists who made major contributions in the 1950s-he by demonstrating the link between lung cancer and smoking, she by discovering that fetal X-rays double the chance of a childhood cancer-were locked into opposition about low-dose radiation risk. When she went public with the discovery that radiation at a fraction of the dose "known" to be dangerous could kill a child, her reputation plummeted, whereas Doll, foremost among her detractors, was knighted and lauded as "the world's most distinguished medical epidemiologist" for his work. Their lives and careers, so closely intertwined, took contrary courses, he becoming "more of the establishment" (as he said), while she became more oppositional. When it was discovered, after his death, that he'd been taking large sums of money from industries whose chemicals he was clearing of cancer risk, his reputation remained unscathed; it is now enshrined in the "Authorized Biography" (2009) commissioned by the Wellcome Institute, along with Doll's denigration of Stewart as an "embittered" woman and biased scientist. Stewart lived long enough to see radiation science move her way, to see international committees affirm, in the 1990s, that there is no threshold beneath which radiation ceases to be dangerous; recent evidence from Chernobyl is bearing out her warnings. But a look at the making and breaking of these reputations reveals the power of status, position, and image to shape scientific "knowledge" and social policy.     

Fluctuations of Fitness Distributions and the Rate of Muller's Ratchet

The accumulation of deleterious mutations is driven by rare fluctuations that lead to the loss of all mutation free individuals, a process known as Muller's ratchet. Even though Muller's ratchet is a paradigmatic process in population genetics, a quantitative understanding of its rate is still lacking. The difficulty lies in the nontrivial nature of fluctuations in the fitness distribution, which control the rate of extinction of the fittest genotype. We address this problem using the simple but classic model of mutation selection balance with deleterious mutations all having the same effect on fitness. We show analytically how fluctuations among the fittest individuals propagate to individuals of lower fitness and have dramatically amplified effects on the bulk of the population at a later time. If a reduction in the size of the fittest class reduces the mean fitness only after a delay, selection opposing this reduction is also delayed. This delayed restoring force speeds up Muller's ratchet. We show how the delayed response can be accounted for using a path-integral formulation of the stochastic dynamics and provide an expression for the rate of the ratchet that is accurate across a broad range of parameters.     

The Ideological Bases of Lévi-Strauss's Structuralism

It is clear that Lévi-Strauss combines in his writings, and often inextricably, the roles of anthropologist (read scientist) and philosopher (read ideologist). This rather unusual combination of anthropological and philosophical dimensions of Lévi-Strauss's thought is the result of two tendencies that often seem to be pulling in different directions: his scientific conception of socio-cultural phenomena (or the delineation of a scientific method for harnessing human behavior under the rubric of sociological laws), on the one hand, and his conception of what society should be (or the ideological statement of what constitutes a "good sociological life"), on the other. In order to understand the nature of structuralism and Lévi-Strauss's contributions to anthropological theory and practice, these two aspects of his thought must be clearly distinguished. This is what I hope to accomplish in this article.     

Profiles in genetics: George Wells Beadle and the origins of the gene-enzyme concept.

Beadle's success in establishing biochemical genetics on a firm foundation was due to a combination of several circumstances. These include the following: 1. Apt timing of his work, which Garrod's work clearly lacked, was important. Geneticists were receptive to his ideas and conclusions. As Beadle (1967, 1974) himself acknowledged, much ground was prepared earlier by Garrod and Haldane, who discussed gene action in terms of biochemical reactions, although it was largely ignored. The physiology of gene action was discussed and speculated on to a great extent in the preceding years by Bridges, Goldschmidt, Muller, and Wright. 2. Beadle's selection of Neurospora was most appropriate. It was a haploid organism (with no complications of dominance and recessivity) that could be grown and manipulated easily for isolating mutants to study their segregation and recombination within a short time. Its cytogenetics and the method of growing on chemically defined media were already worked out. It was devoid of the long generation time and more complex sex cycle (among other problems) that complicated the biochemical study of higher plants (e.g., Primula), which Haldane and Scott-Moncrieff had attempted earlier. 3. Beadle's striking ability to shift from one organism to another--from corn to Drosophila to Neurospora--must be acknowledged. He saw the limitations of existing methods and had the courage and skill to move on to more successful methods: from conventional breeding to tissue transplants to microbiological techniques. 4. Beadle's own curiosity about the biochemical nature of gene action and his good fortune in having had such outstanding teachers as Emerson, as well as his ability to collaborate with Ephrussi and Tatum, contributed largely to his success.     

Timeline: Hermann Joseph Muller, evolutionist

This essay is dedicated to the proposition that Hermann Joseph Muller, widely regarded as the greatest geneticist of the first half-century of the subject, was also one of the greatest evolutionists of this period. His Nobel Prize-winning work, which showed that radiation increases the mutation rate, is in every genetics textbook, and his prescient ideas have influenced almost every aspect of the discipline. Here I emphasize his less well-known contribution to the neo-Darwinian theory of evolution.     

Garland Allen,Thomas Hunt Morgan,and Development

Garland E. Allen’s 1978 biography of the Nobel Prize winning biologist Thomas Hunt Morgan provides an excellent study of the man and his science. Allen presents Morgan as an opportunistic scientist who follows where his observations take him, leading him to his foundational work in Drosophila genetics. The book was rightfully hailed as an important achievement and it introduced generations of readers to Morgan. Yet, in hindsight, Allen’s book largely misses an equally important part of Morgan’s work – his study of development and regeneration. It is worth returning to this part of Morgan, exploring what Morgan contributed and also why he has been seen by contemporaries and historians such as Allen as having set aside some of the most important developmental problems. A closer look shows how Morgan’s view of cells and development that was different from that of his most noted contemporaries led to interpretation of his important contributions in favor of genetics. This essay is part of a special issue, revisiting Garland Allen's views on the history of life sciences in the twentieth century.     

Memorial museum to Academician O.V. Palladin (on the 25th anniversary of the foundation

In the article the short information about A.V. Palladin Memorial Museum, displaying some documentary materials on the life, scientific, scientific-administrative and enlightenment activity of the founder of the Institute of Biochemistry and Ukrainian Biochemical school, President of UkSSR Academy of Sciences (1946-1962), outstanding scientist and public figure, Academician Alexander Vladimirovich Palladin (1885-1972). The Museum created according to the Resolution of the UkSSR Soviet of Ministers due to the efforts of the Institute personnel, is officially considered as an affiliate of the State Historical Museum of Kiev and acquired a wide-spread reputation as a center of propagation and study of the history of Ukraine biochemical science, its achievements, contribution of the native scientists into the world treasury of the life sciences.     

Gentlemanly Men of Science: Sir Francis Galton and the Professionalization of the British Life-Sciences

Because Francis Galton (1822–1911) was a well-connected gentleman scientist with substantial private means, the importance of the role he played in the professionalization of the Victorian life-sciences has been considered anomalous. In contrast to the X-clubbers, he did not seem to have any personal need for there forms his Darwinist colleagues were advocating. Nor for making common cause with individuals haling from social strata clearly inferior to his own. However, in this paper I argue that Galton quite realistically discerned in the reforming endeavors of the1860s, and beyond, the potential for considerably enhancing his own reputation and standing within both the scientific community and the broader Victorian culture. In addition, his professionalizing aspirations, and those of his reformist allies, were fully concordant with the interests, ambitions and perceived opportunities of his elite social group during the Victorian period. Professionalization appealed to gentlemen of Galton's status and financial security as much as it did to the likes of Thomas Huxley and John Tyndall, primarily because it promised to confer on the whole scientific enterprise an unprecedented level of social prestige. This revised version was published online in July 2006 with corrections to the Cover Date.     

Genetic bottlenecks and population passages cause profound fitness differences in RNA viruses.

Repeated clone-to-clone (genetic bottleneck) passages of an RNA phage and vesicular stomatitis virus have been shown previously to result in loss of fitness due to Muller's ratchet. We now demonstrate that Muller's ratchet also operates when genetic bottleneck passages are carried out at 37 rather than 32 degrees C. Thus, these fitness losses do not depend on growth of temperature-sensitive (ts) mutants at lowered temperatures. We also demonstrate that during repeated genetic bottleneck passages, accumulation of deleterious mutations does occur in a stepwise (ratchet-like) manner as originally proposed by Muller. One selected clone which had undergone significant loss of fitness after only 20 genetic bottleneck passages was passaged again in clone-to-clone series. Additional large losses of fitness were observed in five of nine independent bottleneck series; the relative fitnesses of the other four series remained close to the starting fitness. In sharp contrast, when the same selected clone was transferred 20 more times as large populations (10(5) to 10(6) PFU transferred at each passage), significant increases in fitness were observed in all eight passage series. Finally, we selected several clones which had undergone extreme losses of fitness during 20 bottleneck passages. When these low-fitness clones were passaged many times as large virus populations, they always regained very high relative fitness. We conclude that transfer of large populations of RNA viruses regularly selects those genomes within the quasispecies population which have the highest relative fitness, whereas bottleneck transfers have a high probability of leading to loss of fitness by random isolation of genomes carrying debilitating mutations. Both phenomena arise from, and underscore, the extreme mutability and variability of RNA viruses.     

'Our load of mutation': reappraisal of an old problem.

H. J. Muller, in a paper in 1950 entitled 'Our load of mutation', predicted the genetic decay of the human species due to increasing mutation pressure combined with relaxation of natural selection. In the meantime, much information on spontaneous and induced mutations in humans has been accumulated, and a reappraisal of Muller's conclusions gives a much less gloomy overall picture. However, a certain increase of malformation and disease can be predicted as a result of ionizing radiation and chemical mutagens. On the other hand, genetic counselling and antenatal diagnosis of genetic anomalies may help to keep the genetic risks within tolerable limits. Research on the biological conditions for the untoward effects of mutagenic chemicals considered necessary for the wellbeing of humans may also help to reduce genetic risks. The extent and kind of the risks as well as possibilities for prevention are discussed with a few examples.     

Dobzhansky-Muller model of hybrid dysfunction supported by poor burst-speed performance in hybrid tiger salamanders

Speciation may result from 'complementary' genetic differences that cause dysfunction when brought together in hybrids despite having no deleterious effects within pure species genomes. The theory of complementary genes, independently proposed by Dobzhansky and Muller, yields specific predictions about the genetics of hybrid fitness. Here, I show how alternative models of hybrid dysfunction can be compared using a simple multivariate analysis of hybrid indices calculated from molecular markers. I use the approach to fit models of hybrid dysfunction to swimming performance in hybrid tiger salamander larvae. Poor burst-speed performance is a dysfunction suggesting low vigour and could translate directly into low survival. My analyses show that the Dobzhansky-Muller model fits these data better than heterozygote disadvantage. The approach demonstrated here can be applied to a broad array of nonmodel species, potentially leading to important generalizations about the genetics of hybrid dysfunction.