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From screening to clinical research: the cure of leukemia and the early development of the cooperative oncology groups, 1955-1966.

Recent work in the history and sociology of biomedicine has emphasized the novelty of the biomedical enterprise as a distinctive institutional, material, and epistemological configuration. Since World War II, biology and medicine have become such tightly intertwined research enterprises that those working in biomedicine cannot predict whether a particular research project, clinical investigation, or even clinical intervention will result in biological or medical facts. In this paper, we examine part of the process of the emergence of biomedicine by focusing on the development of clinical cancer trials in the United States in the years 1955-66, a period during which the clinical trials program run by the National Cancer Institute became autonomous from the Institute's screening program for anticancer compounds. We examine in particular the work carried out by the cooperative groups and the Acute Leukemia Task Force to which they belonged, analyzing the evolution of the relations between screening, chemotherapy, clinical trials, and clinical research.

Clinical Trials as Topic↗

Morphological evolution of athletes over the 20th century: causes and consequences.

Over the course of the past century it has become increasingly difficult to find athletes of the size and shape required to compete successfully at the highest level. Sport is Darwinian in that only the 'fittest' reach the highest level of participation. Not every physical characteristic could be expected to play a role in this selection process, but two that are important and for which substantial data assemblies exist, are height and mass. Measurements of elite athlete sizes were obtained from a variety of sources as far back as records allowed. We charted the shift in these anthropometric characteristics of elite sportspeople over time, against a backdrop of secular changes in the general population. Athletes in many sports have been getting taller and more massive over time; the rates of rise outstripping those of the secular trend. In open-ended sports, more massive players have an advantage. Larger players average longer careers and obtain greater financial rewards. In some sports it is equally difficult to find athletes small enough to compete. In contrast, there are sports that demand a narrow range of morphological characteristics. In these sports the size of the most successful athletes over the century has remained constant, despite the drift in the population characteristics from which they are drawn. A number of social factors both drive and are driven by the search for athletes of increasingly rare morphology. These include globalisation and international recruitment, greater financial and social incentives, and the use of special training methods and artificial growth stimuli. In many sports the demand for a specific range in body size reinforces the need to adopt questionable and illegal behaviours to reach the required size and shape to compete at the top level. Future scenarios also include 'gene-farming' through assortative mating and athlete gamete banks.

Biological Evolution↗

[The evolution of zoonoses].

Firstly, the author describes the evolution of the epidemiology of zoonoses, using examples of decreases and increases in incidence and of the probable 'birth' of zoonoses. Secondly, an analysis is presented of the main factors that may influence one of the components of a zoonosis (receptive animal populations, pathogens, external environment and humans), in addition to those factors responsible for changes in the epidemiology of zoonoses. Finally, a description is given of the main measures which can be applied within a given country or through international co-operation, to limit the development of zoonoses.

Animals↗

Electron beam treatment for cutaneous T-cell lymphoma.

Total skin electron radiation has proven efficacy in treating MF. It is a complex technique that requires a dedicated radiation team, involving physicists, radiotherapists, and radiation oncologists. A center must treat a sufficiently high volume of patients to justify the development of TSE, with appropriate organization, time, and expense. The radiation team should be an integral part of a multidisciplinary clinical group, including medical oncologists, dermatologists, pathologists, and nurses. In these contexts, TSE has appropriately been developed in a limited number of centers. Cooperation between these centers is essential for further refinement of TSE techniques and for evolution of the role of TSE in the management of most patients with MF.

Combined Modality Therapy↗

Evolution without speciation but with selection: LUCA, the Last Universal Common Ancestor in Gilbert's RNA world.

This is not an attempt to analyze the Last Universal Common Ancestor (LUCA) to understand the origin of living systems. We do not know what came before Gilberts' RNA world. Our analysis starts with the RNA world and with genes (biological replicators alla Dawkings) made up of RNA proteins with enzymatic catalytic functions within units that are not yet modern cells. We offer a scenario where cellular entities are very simple and without individuality; they are only simple primary units of selection (the first level of selection) in which replicators compete in the most Darwinian manner, totally deprived of cooperation and interactions among genes. The information processing system of this RNA world is inaccurate and inefficient when compared to that found in organisms that came later. Among the "genes" and the entities that harbor them, high mutation rate was the most prevalent source of variability and the only inheritance was through lateral gene transfer of mobile elements. There were no chromosomes or any other genomic organization. As millions of years accumulated, complex and organized biological structures and processes evolved thanks to the variability mustered up mostly by lateral gene transfers and mutations. With micro- and mini-satellites, lateral gene transfers became indispensable devices of selection to mold variability. Competition and Darwinian selection gave way to a new transition in evolution, one I consider ineluctable, in which cooperation among interactive genes prevailed for the sake of higher fitness. Compartmentalization constituted a major transition in evolution that spurted new types of genome organization. Minichromosomes is one of these; cellular membranes and cytoplasmic structures completed the picture of the primitive cell. However, the much talked about phylogenetic tree does not exit in that ancient LUCA. The tree has no organism at its base; only clusters of genes evoke a fragile beginning for the increasingly complex cell types that were to emerge later.

Animals↗

DNA fingerprinting analysis of parent-offspring conflict in a bee.

Demonstrating the importance of haplodiploidy in the evolution of eusociality among the Hymenoptera (bees, wasps, and ants) requires estimation of four parameters: relatedness between cooperating individuals, effective mating frequency, sex ratio, and rates of worker reproduction. Multilocus DNA fingerprinting techniques permitted the precise determination of these parameters for the primitively eusocial bee Augochlorella striata (Halictidae). DNA fingerprints revealed an unprecedented resolution of genetic relationships within colonies, detecting factors such as intraspecific nest parasitism and diploid males that confounded estimates of relatedness and sex ratio, respectively. Parameter estimates (i) corroborate recent evidence for queen-worker conflict over the sex ratio and (ii) implicate the role of haplodiploidy in the evolution of worker behavior.

Animals↗

Escape from Prisoner's Dilemma in RNA phage phi6.

We previously examined competitive interactions among viruses by allowing the RNA phage phi6 to evolve at high and low multiplicities of infection (ratio of infecting viruses to bacterial cells). Derived high-multiplicity phages were competitively advantaged relative to their ancestors during coinfection, but their fixation caused population fitness to decline. These data conform to the evolution of lowered fitness in a population of defectors, as expected from the Prisoner's Dilemma of game theory. However, the generality of this result is unknown; the evolution of viruses at other multiplicities may alter the fitness payoffs associated with conflicting strategies of cooperation and defection. Here we examine the change in matrix variables by propagating the ancestor under strictly clonal conditions, allowing cooperation the chance to evolve. In competitions involving derived cooperators and their selfish counterparts, our data reveal a new outcome where the two strategies are predicted to coexist in a mixed polymorphism. Thus, we demonstrate that the payoff matrix is not a constant in phi6. Rather, clonal selection allows viruses the opportunity to escape the Prisoner's Dilemma. We discuss mechanisms that may afford selfish genotypes an advantage during intrahost competition and the relevance in our system for alternative ecological interactions among viruses.

Bacteriophage phi 6↗

Linear and cyclic aliphatic carboxamides of the Murchison meteorite: hydrolyzable derivatives of amino acids and other carboxylic acids.

Analyses of fractionated aqueous extracts of the Murchison meteorite by gas chromatography-mass spectrometry after silylation with N-methyl-N (tert-butyldimethylsilyl) trifluoroacetamide have revealed an extensive series of linear and cyclic aliphatic amides. These include monocarboxylic acid amides, dicarboxylic acid monoamides, hydroxy acid amides, lactams, carboxy lactams, lactims, N-acetyl amino acids, and substituted hydantoins. Numerous isomers and homologues through at least C8 were observed in all cases, except for the N-acetyl amino acids and hydantoins. Carboxy lactams, lactams, hydantoins, and N-acetyl amino acids are converted to amino acids by acid hydrolysis, thus, these compounds qualitatively account for the earlier observation of acid-labile amino acid precursors in meteoritic extracts. Laboratory studies of the spontaneous decomposition of N-carbamyl-alpha-amino acids and their dehydration products, the 5-substituted hydantoins, have led to the recognition of a series of aqueous phase reactions by which amino acids and cyanic acid/cyanate ion in the primitive parent body might have given rise to several of the observed classes of amides, as well as to monocarboxylic acids, dicarboxylic acids, and hydroxy acids. A previously undescribed reaction of 5-substituted hydantoins with cyanic acid/cyanate ion to give carboxamides of the 5-substituent groups was observed in the course of these studies. The presence of an extensive suite of amides in a CM chondrite appears to be consistent with the interstellar-parent body formation hypothesis for the organic compounds of these meteorites. The presence of carboxy lactams and lactams along with free amino acids suggests the possibility of further chemical evolution of meteorite amino acids by thermal polymerization. The cyclic amides, given their potential for hydrogen-bonded pair formation, might be considered candidate bases for a primitive sequence coding system.

Acetamides↗

Selfish sentinels in cooperative mammals.

Like humans engaged in risky activities, group members of some animal societies take turns acting as sentinels. Explanations of the evolution of sentinel behavior have frequently relied on kin selection or reciprocal altruism, but recent models suggest that guarding may be an individual's optimal activity once its stomach is full if no other animal is on guard. This paper provides support for this last explanation by showing that, in groups of meerkats (Suricata suricatta), animals guard from safe sites, and solitary individuals as well as group members spend part of their time on guard. Though individuals seldom take successive guarding bouts, there is no regular rota, and the provision of food increases contributions to guarding and reduces the latency between bouts by the same individual.

Animals↗

Ontogeny recapitulates phylogeny: comparative immunology in Germany.

The innate immune system is in the spot light of modern immunology. Whenever protists, invertebrates and vertebrates are threatened by pathogens, they rapidly activate highly effective antimicrobial defense reactions. Because this young field develops very dynamically, it is important to ask what we really know about the mechanisms governing the innate immune defense system. This was the topic of a recent meeting entitled 'The Evolution of the Immune System', held at the Friedrich Schiller University in Jena, Germany. Leading scientists in the field of innate immunity presented their latest data in a historical and friendly setting.

Allergy and Immunology↗

Tug-of-war over reproduction in a social bee.

One of the main transitions in evolution is the shift from solitary organisms to societies with reproductive division of labour. Understanding social evolution requires us to determine how ecological, social and genetic factors jointly influence group stability and partitioning of reproduction between group members. Here we test the role of the three key factors predicted to influence social evolution by experimentally manipulating them in a social allodapine bee. We show that increased relatedness between nestmates results in more even reproduction among group members and a greater productivity per individual. By contrast, the degree of reproductive skew is not influenced by the opportunity for solitary breeding or by the potential benefits of cooperation. Relatedness also has a positive effect on group stability and overall productivity. These findings are in line with predictions of the tug-of-war models, in which the degree of reproductive division of labour is determined primarily by selfish competition between group members. The alternative view, where the degree of reproductive skew is the outcome of a social contract between potential breeders, was not supported by the data.

Animals↗

The evolution of alpha-fetoprotein and albumin. I. A comparison of the primary amino acid sequences of mammalian alpha-fetoprotein and albumin.

The amino acid sequence of mouse alpha-fetoprotein has been deduced from the nucleotide sequence of its mRNA and three chimeric plasmids containing overlapping segments of its cDNA. A comparison of the amino acid sequence with that of either human and bovine albumin reveals in each case a 32% conservation of primary sequence. In addition, using the regularly spaced positions of cystine bridges, a 2-dimensional structure was generated, which revealed the presence of 3 closely related domains within alpha-fetoprotein. The structures of these domains are identical with the triplicated domains previously observed in several mammalian albumins. These homologies lend strong circumstantial evidence to the proposal that these two proteins arose in evolution as the consequence of a duplication in a common tripartite ancestral gene.

Albumins↗

Recombination in primeval genomes: a step forward but still a long leap from maintaining a sizable genome.

A stubborn question in early molecular evolution is how to sustain the "minimum" informational length required for the basic features of life with a putative low-copying fidelity RNA polymerase ribozyme. Proposals to circumvent the information crisis have primarily focused on networks of cooperative molecules or compartmentalization of non-cooperative unlinked templates, but success has been very limited so far. Lehman (2003) has recently suggested that recombination--a frequently ignored player in early evolution--could have been crucial to building up primeval genomes of sizable length. Here we investigate this claim by assuming (without loss of generality) that genes were already enclosed in a compartment (vesicle, protocell). The numerical results show a quite intricate interplay among mutation, recombination, and gene redundancy. Provided that the minimum number of gene copies per protocell was enough for recombination to recreate wildtype templates--but not too high to impose an unbearable burden of mutants--informational content could have increased by at least 25% by keeping the same mutational load as that for a population without recombination. However, the upper bound of informational length would still be far from the "minimal life" provisions.

Chromosome Positioning↗