Medical ethics in the wake of the Holocaust: departing from a postwar paper by Ludwik Fleck

In 1948 Ludwik Fleck published a paper in Polish discussing the use of humans in medical experiments, thereby addressing his peers. Though the paper has so far not been translated or studied, it has been taken to indicate Fleck's deep commitment to ethical questions, notably the question of informed consent. In being written by a former victim of the Nazi policy and a survivor of the Holocaust also acting as an expert witness in the trial of the IG Farben in Nuremberg, the paper is of interest. A scrutiny of Fleck's text and related sources discloses, however, not only the complexity of the issue at the centre of the Nuremberg trial, but also Fleck's unexpected stance in seemingly adducing his arguments from both the German defendants and the prosecution, heavily informed by US scientists. Further, the contentious discussion of the past in Fleck's paper reveals its links to modern bioethical discussion. Though sometimes oblivious of that past, it still faces the same questions.     

Ludwik Fleck and the causative agent of syphilis: sociology or pathology of science? A rejoinder to Jean Lindenmann

In 1905 two different microbes were proposed to fill the vacant role of etiologic agent for syphilis, one, the Cytorrhyctes luis, by John Siegel, the other, Spirochaeta pallida, by Fritz Schaudinn. After gathering and reviewing the evidence the majority of medical scientists decided in favor of Schaudinn’s candidate. In a previous issue Jean Lindenmann challenged Ludwik Fleck’s suggestion that under suitable social conditions Siegel’s candidate could just as well have won acceptance by the scientific community (Lindenmann, 2001). To refute this counterfactual thesis, Lindenmann presented an asymmetric account of the dispute over the etiology of syphilis. He adopted the view of the proponents that Schaudinn’s spirochete had already been there in syphilitic lesions for centuries, only awaiting the discovery of an appropriate staining technique to be revealed. Here a more symmetric analysis of the episode will be attempted, paying serious attention to the arguments put forward by the spirochete’s opponents, who expatiated on the many possibilities of inadvertently creating artifacts through microscopic preparation and staining. The symmetric account that is presented in this rejoinder thus aims to trace the simultaneous construction of facts and artifacts. It will not, however, resurrect Fleck’s counterfactual thesis.     

The origins of gestures and language: history,current advances and proposed theories

Investigating in depth the mechanisms underlying human and non‐human primate intentional communication systems (involving gestures, vocalisations, facial expressions and eye behaviours) can shed light on the evolutionary roots of language. Reports on non‐human primates, particularly great apes, suggest that gestural communication would have been a crucial prerequisite for the emergence of language, mainly based on the evidence of large communication repertoires and their associated multifaceted nature of intentionality that are key properties of language. Such research fuels important debates on the origins of gestures and language. We review here three non‐mutually exclusive processes that can explain mainly great apes' gestural acquisition and development: phylogenetic ritualisation, ontogenetic ritualisation, and learning via social negotiation. We hypothesise the following scenario for the evolutionary origins of gestures: gestures would have appeared gradually through evolution via signal ritualisation following the principle of derived activities, with the key involvement of emotional expression and processing. The increasing level of complexity of socioecological lifestyles and associated daily manipulative activities might then have enabled the acquisition and development of different interactional strategies throughout the life cycle. Many studies support a multimodal origin of language. However, we stress that the origins of language are not only multimodal, but more broadly multicausal. We propose a multicausal theory of language origins which better explains current findings. It postulates that primates' communicative signalling is a complex trait continually shaped by a cost–benefit trade‐off of signal production and processing of interactants in relation to four closely interlinked categories of evolutionary and life cycle factors: species, individual and context‐related characteristics as well as behaviour and its characteristics. We conclude by suggesting directions for future research to improve our understanding of the evolutionary roots of gestures and language.     

The early history of estriol

The early history of estriol is reviewed with special emphasis on its isolation, identification, quantitation in tissues and body fluids and its unique biogenesis in the human feto-placental unit. The relationship to epimeric estriols and acidic estrogens and the pharmacokinetic and pharmacodynamic properties which led to a widespread therapeutic use of this compound are also discussed.     

The early history of polyamine research

In 1678 Antonie van Leeuwenhoek identified crystalline substances in human semen. The structure of these crystals, named “spermine”, was not elucidated by Rosenheim until 250 years later. Subsequently a triamine (spermidine) and a diamine (putrescine; 1,4-diaminobutane) were isolated from prokaryotic and eukaryotic systems. Soon it became apparent that polyamines can promote the growth of fastidious bacteria. Subsequently a group in Helsinki studied the accumulation of polyamines in regenerating rat liver, while Caldarera and his group studied polyamine synthesis in the developing chick embryo. These investigations led to metabolic studies. Ornithine decarboxylase was identified as a key enzyme in polyamine biosynthesis, while polyamine and diamine oxidations were studied by Mondovì. α-Diflouromethylornithine (DFMO) was synthesized by Merrell-Dow and became a potent inhibitor of ornithine decarboxylase. The findings of Russell that polyamines are excreted in the urine of cancer patients drew the attention of oncologists, who attempted the use new technologies for the detection of cancer and improving therapy. With the advance of molecular biology the structure of polyamine-biosynthetic enzymes was elaborated. Plants served as another important tool to study the physiological functions of polyamines. Bagni and his group at Bologna were pioneers in that field and for more than forty-six years set the foundation of a most interesting discipline.     

A conserved chromatin architecture marks and maintains the restricted germ cell lineage in worms and flies

In C. elegans, mRNA production is initially repressed in the embryonic germline by a protein unique to C. elegans germ cells, PIE-1. PIE-1 is degraded upon the birth of the germ cell precursors, Z2 and Z3. We have identified a chromatin-based mechanism that succeeds PIE-1 repression in these cells. A subset of nucleosomal histone modifications, methylated lysine 4 on histone H3 (H3meK4) and acetylated lysine 8 on histone H4 (H4acetylK8), are globally lost and the DNA appears more condensed. This coincides with PIE-1 degradation and requires that germline identity is not disrupted. Drosophila pole cell chromatin also lacks H3meK4, indicating that a unique chromatin architecture is a conserved feature of embryonic germ cells. Regulation of the germline-specific chromatin architecture requires functional nanos activity in both organisms. These results indicate that genome-wide repression via a nanos-regulated, germ cell-specific chromatin organization is a conserved feature of germline maintenance during embryogenesis.     

A history of theories of acquired immunity

Alloimmune mouse spleen cells are capable of carrying out nonspecific cell-mediated cytolysis of syngeneic target cells when incubated in the presence of lectins such as Con A or PHA (lectin-dependent cell-mediated cytotoxicity). In the present study plant lectins from a variety of sources were examined for their ability to participate in alloimmune-LDCC. Reactivity was then compared to mitogenic activity and the ability to activate cytotoxic effector cells in vitro. Of the lectins tested only those reported to be T-cell mitogens were capable of participating in alloimmune-LDCC. Agglutinating but nonmitogenic lectins (e.g., WGA) or mitogens such as LPS or PWM failed to yield positive LDCC. Of the T-cell mitogens demonstrating positive reactivity in the alloimmune-LDCC assay, only a portion were able to generate cytolytic activity when incubated with normal spleen cells in vitro (Con A, GPA, lentil). Crude PHA, purified erythroagglutinin, or leukagglutinin failed to generate cytotoxic effector cells in this system even though these were mitogenic and demonstrated positive alloimmune-LDCC. The results suggest that T-cell mitogens interact with cytotoxic effector cells in a manner which specifically triggers cytolysis. The relationship of this interaction to other lymphocyte-lectin interactions is discussed.     

The origin and early evolutionary history of amniotes

Recent phylogenetic analyses of Paleozoic tetrapods have yielded startling new insights into the origin and early evolutionary history of amniotes. The origin of this successful group involves evolutionary innovations that are associated with the development of the cleidoic egg and related reproductive strategies, and are therefore not represented directly in the fossil record. Despite this obvious difficulty, recent studies have been able to distinguish Paleozoic amniotes from their anamniotic tetrapod relatives to determine major patterns of interrelationships.     

Nucleotide excision repair of DNA: The very early history

This article, taken largely from the book Correcting the Blueprint of Life: An Historical Account of the Discovery of DNA Repair Mechanisms, summarizes the very early history of the discovery of nucleotide excision repair.