Darkness in El Dorado: Human genetics on trial

A recent book by a freelance journalist makes major accusations against genetic studies by J. V. Neel in the Amazon a generation ago. Contrary to these charges, there was no connection of Neel’s work with human experiments conducted by the Rochester Manhattan Project twenty years earlier, nor did the studies serve as a control for survivors of the atomic bombs in Japan. Neel was not a eugenicist. His program of measles vaccination reduced mortality, and was not in any sense an experiment. Given the passage of time and lack of supporting evidence, further investigation of these charges is pointless. However, the political climate in which human populations are studied has changed dramatically over the last generation. Unless guidelines reflect an international consensus, the benefits of population studies to human welfare and science will be jeopardized. The World Health Organization guidelines should be extended to cover current research.     

Fission-fusion and lineal effect: aspects of the population structure of the Semai Senoi of Malaysia.

Analysis of histories and genealogies from seven relatively unacculturated, swidden-farming Semai settlements shows that the composition of local groups fluctuates through time. This instability is similar to a pattern which Neel and his colleagues have suggested is typical of primitive society, the fission-fusion model. In addition, the individuals comprising Semai fission groups are kinsmen which implies that the number of independent genomes represented is markedly less than the number of individual migrants (the lineal effect). Fission groups may form new villages or fuse with an established settlement. In either case, the genetic effects of such migration are more pronounced than would be expected on the basis of founder effect or random migration. Despite several conspicuous differences in social organization between the Semai and the South American Indians (e.g., bilateral vs. unilineal descent) whose population structure provided the empirical basis for the fission-fusion, lineal effect model, the basic similarities are striking. The Semai case thus lends support to the proposition that this pattern may be of some generality in technologically primitive populations.     

James Neel and the doubling dose concept

The doubling dose (DD) is a very valuable concept in attempts to assess the genetic risks of radiation in man. It was long thought that the value of the doubling dose obtained from specific locus experiments in mice could be applied to man. James Neel, as a result of his studies on the offspring of atomic bomb survivors, showed that this was not so, but that different doubling doses could be inferred from different endpoints.     

Molecular epidemiology: potential impacts on the assessment of public health

In trying to decide what type of scientific paper I could prepare as a tribute to Jim Neel, I thought back over the discussions that we had over some 25 years. Sometimes these discussions were on specific topics such as how to extrapolate from mutation data in mice to those for humans following radiation or chemical exposures. On other occasions, our discussions were of a more philosophical nature, particularly on where the field of epidemiology might or needed to go. For example, what types of data are needed for assessing the public health impact of exposure to environmental agents. Perhaps because I enjoyed these discussions so much, I have chosen to take a look from a current perspective at the field of molecular epidemiology. Jim Neel would have loved to have entered into this discussion; he would have enhanced it in is own inimitable way.     

A Critique of R.D. Alexander's Views on Group Selection

Group selection is increasingly being viewed as an important force in human evolution. This paper examines the views of R.D. Alexander, one of the most influential thinkers about human behavior from an evolutionary perspective, on the subject of group selection. Alexander's general conception of evolution is based on the gene-centered approach of G.C. Williams, but he has also emphasized a potential role for group selection in the evolution of individual genomes and in human evolution. Alexander's views are internally inconsistent and underestimate the importance of group selection. Specific themes that Alexander has developed in his account of human evolution are important but are best understood within the framework of multilevel selection theory. From this perspective, Alexander's views on moral systems are not the radical departure from conventional views that he claims, but remain radical in another way more compatible with conventional views.     

Types Distinct from Our Own: Franz Boas on Jewish Identity and Assimiliation

Boas's published writings on assimilation were deeply influenced by his German Jewish background. In particular, his unwillingness to recognize Jewish cultural identity as a reality was central to his persistent emphasis on human plasticity and his insistence that people not be "classified" in groups. In support of this argument, 19th-century German and German Jewish history is reviewed, focusing on the relation between Kultur ideology and anti-Semitism. It is suggested that this approach to Boas's statements offers fresh perspective on some of the apparent confusion in his ideas about culture and assimilation.     

Population regulation and the life history studies of LaMont Cole

Transformative changes marked the growth of mid-twentieth century American ecology. This included redirection of the scholarly focus of the discipline, especially on the role evolutionary theory and "levels of selection", and increased visibility of ecologist as public figures in the environmental movement with special knowledge of how natural systems work. Cornell ecologist LaMont Cole is an important figure to examine both of these trends. Like many of his contemporaries, Cole was devoted to a perspective on natural selection operating at levels above the individual. However, because of his influential mathematical treatment of animal demography he has been historically subsumed into a group of scholars that views the events in the life course as adaptations to the maximization of individual fitness--life history theory. Cole's popular writings and lectures, which consumed his later career, extend his scholarly portrayal of natural populations as tending toward stable and homoeostatic equilibrium, with the goal of drawing contrasts with the deviance of rapid human population growth. In both regards, Cole serves as a topical and temporal extension of the well-documented and analyzed ecology of his mentors--Alfred Emerson, Thomas Park, and Warder Allee--in the University of Chicago Zoology Department.     

Recollections of James Neel

In his long and influential career Neel contributed to almost all aspects of genetic epidemiology from mutation to ethical and philosophical issues. His research spanned North America, Japan, Africa, and Latin America in a fascinating equipoise among clinical, biochemical, epidemiological, and molecular studies that have stimulated hundreds of researchers who enjoyed the controversies he generated as much as the insights he provided. Without exception, we treasure recollections of a high-principled and warm-hearted colleague whose field studies were a model for their generation.     

Cell replication and aging: in vitro and in vivo studies.

The relationship between human aging and cell replication has been investigated using two complementary approaches: in vitro studies of human fibroblasts derived from young and old volunteer members of the Baltimore Longitudinal Study and in vivo examinations of bone marrow cell populations from young and old mice and rats. Total proliferative capacity measured as either the onset of cell culture senescence or as in vitro life span was significantly diminished in cell cultures derived from old human donors when compared to parallel cultures established from young donors. Acute replicative abilities as measured by percent replicating cells, cell pupulation doubling time, cell number at confluency, and colony size distribution were also significantly decreased in human old cell populations. An in vivo cytogenetic technique for measuring cell replication was developed utilizing the differential staining properties of metaphase chromosomes of cells that have replicated in the presence of bromodeoxyuridine. With this technique, cell cycle times have been derived in vivo as well as in vitro. Preliminary in vivo results in both mice and rats indicate that cell replication is slowed in old animal cell populations. Further research will be directed both in vitro and in vivo at discerning the mechanisms for this impairment of cellular replication with aging.     

Darwin and the linguists: the coevolution of mind and language, Part 1. Problematic friends

In his book The descent of man (1871), Charles Darwin paid tribute to a trio of writers (Hensleigh Wedgwood, F. W. Farrar, and August Schleicher) who offered naturalistic explanations of the origin of language. Darwin's concurrence with these figures was limited, however, because each of them denied some aspect of his thesis that the evolution of language had been coeval with and essential to the emergence of humanity's characteristic mental traits. Darwin first sketched out this thesis in his theoretical notebooks of the 1830s and then clarified his position in Descent, where he argued that mind-language coevolution had occurred prior to the rise of distinct racial groups. He thus opposed the view of August Schleicher and Ernst Haeckel, who (along with Alfred Russel Wallace) taught that speech had originated subsequent to the geographical and racial dispersion of humanity's ancestors. As Darwin argued in Descent, this quasi-polygenetic version of coevolution was unable to explain primeval man's initial dominance over rival ape-like populations. Drawing inspiration from British anthropologists, Darwin made the early development of language, hence mental monogenesis, central to his account of human evolution.     

The frequency of private electrophoretic variants in Australian aborigines and indirect estimates of mutation rate.

The number of "private" electrophoretic variants of enzymes controlled by 25 loci has been used to obtain estimates of mutation rate in Australian Aborigines. Three different methods yield values of 6.11 X 10(-6), 2.78 X 10(-6), and 12.86 X 10(-6)/locus per generation for the total sample of Aborigines. One tribal population of Waljbiri in central Australia gives values of 2.99 X 10(-6) and 2.04 X 10(-6) for two of the methods, the third being unapplicable. The mean mutation rate for the total Aboriginal sample of 7.25 X 10(-6) is very similar to the value obtained by Neel and his colleagues for Amerindians in South America.     

The human microbiome in evolution

The trillions of microbes living in the gut—the gut microbiota—play an important role in human biology and disease. While much has been done to explore its diversity, a full understanding of our microbiomes demands an evolutionary perspective. In this review, we compare microbiomes from human populations, placing them in the context of microbes from humanity’s near and distant animal relatives. We discuss potential mechanisms to generate host-specific microbiome configurations and the consequences of disrupting those configurations. Finally, we propose that this broader phylogenetic perspective is useful for understanding the mechanisms underlying human–microbiome interactions.     

Mysteries of attraction: Giovanni Pico della Mirandola,astrology and desire

Although in his later years Giovanni Pico della Mirandola (1463–1494) vehemently rejected astrology, he earlier used it in a variety of ways, but primarily to provide further evidence for positions to which he had arrived by other means. One such early use appears in his commentary on his friend Girolamo Benivieni’s love poetry, the Canzone d’amore, of 1486–1487. In the passages discussed here, Pico presents an intensive Platonic natural philosophical analysis based on a deep astrologically informed understanding of human nature as he attempts to explain a perennial question, namely, why one person is attracted to a certain person (or people), and another to others. I will place this discussion of the mysteries of attraction and desire in historical perspective by tracing Pico’s changing relationship to astrology during the course of his short but passionate life, and in historiographic perspective by revising Frances Yates’s still influential views concerning Pico’s contribution to Renaissance thought and his relationship with Marsilio Ficino.     

Shifting trends in pathogen dynamics on a changing planet

In this perspective we offer views on how microbial activities may change in response to the impact of human activities and an increasing human population. New knowledge is forthcoming in microbiology and immunology on the biology of emerging pathogens. With the exposure of human populations to changing environments, through climate change and human encroachment into previously unpopulated areas, there is likely to be increased incidences of diseases caused by existing, emerging and previously unrecognised pathogens.     

Normal human endometrium in cell culture

Summary Separation of human endometrium into its epithelial and stromal components has been achieved through collagenase digestion and has permitted a study of these two cell populations under specific experimental culture conditions. The stromal cell populations showed a progesterone response, were easily handled in culture, and displayed a limited in vitro life span typical of human diploid fibroblasts. In contrast, epithelium only survived in shortterm primary culture and showed no clear hormone response. High-density epithelial cultures remained viable for longer periods in culture. Comparisons between resurfacing endometrial epithelial cells in vivo and epithelial cells migrating from explants in vitro suggested that this initial epithelial migration in vitro was the counterpart of the repair response in vivo. We are much in debt to Dr. R. C. Hallowes (Department of Pathology, Imperial Cancer Research Fund) for his guidance and encouragement throughout the course of this work. We also gratefully acknowledge Dr. P. N. Riddle (Time-Lapse Cinematography Unit, Imperial Cancer Research Fund) for carrying out the time-lapse cinematography; Mrs. Lyn Rolph (Stereoscan Unit, Bedford College, University of London) for assisting with the SEM; and Mr. G. D. Leach for his competent help with the photography.     

Evolutionary perspectives on human height variation

Human height is a highly variable trait, both within and between populations, has a high heritability, and influences the manner in which people behave and are treated in society. Although we know much about human height, this information has rarely been brought together in a comprehensive, systematic fashion. Here, we present a synthetic review of the literature on human height from an explicit evolutionary perspective, addressing its phylogenetic history, development, and environmental and genetic influences on growth and stature. In addition to presenting evidence to suggest the past action of natural selection on human height, we also assess the evidence that natural and sexual selection continues to act on height in contemporary populations. Although there is clear evidence to suggest that selection acts on height, mainly through life‐history processes but perhaps also directly, it is also apparent that methodological factors reduce the confidence with which such inferences can be drawn, and there remain surprising gaps in our knowledge. The inability to draw firm conclusions about the adaptiveness of such a highly visible and easily measured trait suggests we should show an appropriate degree of caution when dealing with other human traits in evolutionary perspective.     

Koch's postulates and the etiology of AIDS: an historical perspective.

This paper examines the debate over the human immunodeficiency virus (HIV) as the cause of acquired immunodeficiency syndrome (AIDS) from an historical perspective. The changing criteria for proving the link between putative pathological agents and diseases are discussed, beginning with Robert Koch's research on anthrax in the late nineteenth century. Various versions of 'Koch's postulates' are analyzed in relation to the necessity and sufficiency arguments of logical reasoning. In addition, alterations to Koch's postulates are delineated, specifically those required by the discovery of rickettsiae and viruses in the early twentieth century and by the immunological testing developed after mid-century to demonstrate the links between elusive viral agents and two diseases, hepatitis B and infectious mononucleosis. From this perspective, an examination of the AIDS debate is constructed. Molecular biologist Peter Duesberg's argument that HIV is not the cause of AIDS is analyzed in light of his contention that a version of Koch's postulates has not been satisfied. Additional research findings through 1990 relating to the etiology of AIDS are also noted.     

High levels of variation despite genetic fragmentation in populations of the endangered mountain pygmy-possum, Burramys parvus, in alpine Australia

In endangered mammals, levels of genetic variation are often low and this is accompanied by genetic divergence among populations. The mountain pygmy-possum (Burramys parvus) is an endangered marsupial restricted to the alpine region of Victoria and New South Wales, Australia. By scoring variation at eight microsatellite loci, we found that B. parvus populations exhibit high levels of genetic divergence and fall into three distinct groups from the northern, central and southern areas of the distribution of this species, consistent with previous assessments of mitochondrial DNA variation. F(ST) values between populations from these regions ranged from 0.19 to 0.54. Within the central area, there was further genetic fragmentation, and a linear association between genetic and geographical distance. This pattern is likely to reflect limited dispersal across barriers despite the fact that individual B. parvus can move several kilometres. Levels of genetic variation within populations were high with the exception of a southern population where there was evidence of inbreeding. From a conservation perspective, all three areas where B. parvus are found should be considered as separate gene pools; management of populations within these areas needs to take into account the low gene flow between populations, as well as threats posed by roads, resorts and other developments in the alpine region. The low genetic variability and inbreeding in the southern population is of particular concern given the high levels of variability in other B. parvus populations.     

Designing probiotics with respect to the native microbiome

It is now well known that genetic and environmental factors affect the intestinal microbiome in an individual's lifetime and thus, different individuals possess different intestinal microbiomes and microbial metabolomes. The intestinal microbiome has been shown to differ among individuals from the same sex, between sexes and between individuals of different ages. Different families and, from a larger perspective, different communities, possess different microbiomes, and thus corresponding metagenomes. Therefore, it can be deduced that each individual human being can be characterized by his/her own intestinal microbial fingerprint. This understanding may prove helpful in future individualized medicine. These microorganisms are natural beneficial symbionts of the GI tract, have adapted to their human host over million years of coevolution and are now regarded as the second human genome. The difference in intestinal microbiome of different populations may explain why the results from different clinical trials on probiotic efficacy do not match with each other. People pay much, but they benefit little. In this article, it is recommended to isolate probiotics from natives' microbiomes and in the interest of efficacy, to use them in the same population. This line of thought can be considered in future guidelines from the Food and Agriculture Organization and the WHO on evaluation of probiotics in foods.