Metaphysics and population genetics: Karl Pearson and the background to Fisher's multi-factorial theory of inheritance

This paper traces the background to R. A. Fisher's multi-factorial theory of inheritance. It is argued that the traditional account is incomplete, and that Karl Pearson's well-known pre-Fisherian objections to the theory were in fact overcome by Pearson himself. It is further argued that Pearson's stated reasons for not accepting his own achievement has to be seen as a rationalization, standing in for deeper-seated metaphysical objections to the Mendelian paradigm of a type not readily discussed in a formal scientific paper. The apparent, post-Fisherian, continued acceptance of Pearson's objections is presented as an interesting problem for the historian and sociologist.     

Hashish VI1: Conversion of (-)-Δ 1(6)-Tetrahydrocannabinol to (-)-Δ 1(7)-Tetrahydrocannabinol. Stability of (-)-Δ 1 and (-)-Δ 1(6)-Tetrahydrocannabinols

Zusammenfassung Die Synthese von (—)-¹⁽⁷⁾-Tetrahydrocannabinol (THC) auf (—)-¹⁽⁶⁾ wird beschrieben. Das Hauptprodukt der oxidativen Zerstörung von (—)-¹-THC ist Cannabinol. Beschleunigte Versuche der Luftoxidation von (—)-¹-THC und (—)-¹⁽⁶⁾-THC haben gezeigt, dass das letztere beständiger ist. Dieser Unterschied kann mit der Reaktivität des C₃-benzylisch-allylischen Wasserstoffes in (—)-¹-THC erklärt werden.     

A one-step synthesis of (-)-Δ1-Tetrahydrocannabinol from chrysanthenol

Zusammenfassung Eine Einschritt-Synthese von (—)-Tetrahydrocannabinol¹ (THC) ausgehend von Chrysanthenol mit möglichen biogenetischen Folgerungen wird beschrieben.     

Structure of albizziine [L(-)-2-amino-3-ureidopropionic acid], an amino acid from higher plants(Mimosaceae)

Zusammenfassung Eine neue Aminosäure, Albizziin, wurde durch chemische Verknüpfung zwischen N-Benzoylalbizziinmethylester undl-2-Benzamido-3-ureidopropionsäuremethylester (III) alsl-2-Amino-3-ureidopropionsäure (I) identifiziert. Die Synthese vonl-2-Ureido-3-aminopropionsäure (II) wird beschrieben.     

Philosophy in the trenches: from naturalized to experimental philosophy (of science)

Recent years have seen the development of an approach both to general philosophy and philosophy of science often referred to as ‘experimental philosophy’ or just ‘X-Phi’. Philosophers often make or presuppose empirical claims about how people would react to hypothetical cases, but their evidence for claims about what ‘we’ would say is usually very limited indeed. Philosophers of science have largely relied on their more or less intimate knowledge of their field of study to draw hypothetical conclusions about the state of scientific concepts and the nature of conceptual change in science. What they are lacking is some more objective quantitative data supporting their hypotheses. A growing number of philosophers (of science), along with a few psychologists and anthropologists, have tried to remedy this situation by designing experiments aimed at systematically exploring people’s reactions to philosophically important thought experiments or scientists’ use of their scientific concepts. Many of the results have been surprising and some of the conclusions drawn from them have been more than a bit provocative. This symposium attempts to provide a window into this new field of philosophical inquiry and to show how experimental philosophy provides crucial tools for the philosopher and encourages two-way interactions between scientists and philosophers.     

Antihypertensive and other cardiovascular effects of 2-(3-pyridyl)- and 2-(4-pyridyl)-4-trifluoromethylimidazoles

Summary 2 new 4-trifluoromethylimidazole derivatives were found which lowered mean arterial pressure in renal and spontaneously hypertensive (SH) rats by the oral route. In SH rats, compounds A and B were 0.1 and 0.3 times, respectively, as potent as hydralazine. No tolerance development was observed in SH rats with either compound over a 1-week period. In anesthetized dogs, both compounds lowered arterial pressure and peripheral vascular resistance but increased cardiac output. By intraarterial administration, both compounds increased femoral arterial blood flow. These findings represent discovery of a new class of vasodilator drugs.Deceased, May 31, 1978.     

Potentiation of ocular response to adrenaline by 3,3-dimethyl-1-[3-methylaminopropyl]-1-phenylphthalan (Lu 3-010) and a thiophthalan analogue (Lu 5-003): Blockers of catecholamine uptake

Résumé Concernant la durée de l'effet du traitement, le composé Lu 3-010 en combinaison avec l'adrenaline est semblable à la protriptyline, et il est plus actif que Lu 5-003 en ce qui concerne la potentiation de la reaction oculaire provoquée par l'adrenaline. Administrés séparement, les composés Lu 3-010 et Lu 5-003 ont des effets semblables, tandis que la protriptyline est le composé le plus actif. L'accroissement de l'efficacité de ces composés résulte probablement de leur abilité à bloquer le mécanisme de l'incorporation de la catecholamine.

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The author acknowledges the technical assistance of Mrs.S. Schaal, Mrs.C. Wood, MissB. Kawchak and Mrs.B. Sumner. The Lu compounds were gifts from H. Lundbeck and Co. Ltd.     

Disappearance of radioactivity from plasma following intravenous administration of tritiated thyrotrophin-releasing hormone (Ro 8-6270) to man

Zusammenfassung Nach i. v. Verabreichung von Thyrotrophin-releasing Hormonen an Versuchspersonen ergibt sich eine biphasische Kurve für den Abfall der Tritiumaktivität im Plasma mit einer Exkretions-Halbwertszeit von 3 h.

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Acknowledgements. The authors wish to express their gratitude to Hoffmann-La Roche and Co. AG, Basel for the research funds which supported this work. We are indebted to Dr.C. Metzler, Upjohn Co., Kalamazoo for a gift of the NON-LIN computer programme.     

Interaction of N-(DL-seryl)N′-(2,3,4-trihydroxybenzyl)-hydrazine with L-Dopa decarboxylase from pig kidney

Summary Interaction of seryl trihydroxy-benzyl-hydrazine with a highly purified preparation of Dopa decarboxylase from pig kidney has been studied. This compound was found not to be a powerful inhibitor in vitro. Kinetic and spectral data suggest some possibilities on the binding nature of the inhibitor and substrates.     

Stereospecific reduction of geraniol to (R)-(+)-citronellol bySaccharomyces cerevisiae

Summary (R)-(+)-citronellol, a useful C₁₀ chiral synthon for natural terpenoid products, can be obtained in enantiomerically pure form and satisfactory yield by yeast reduction of geraniol.     

Pharmacological studies of a new analgesic,dl-erythro-1-phenyl-2-(o-chlorophenyl)-2-[4-(p-methoxybenzyl)-1-piperazinyl] ethanol dihydrochloride,in experimental animals

Summary dl-Erythro-1-phenyl-2-(o-chlorophenyl)-2-[4-(p-methoxybenzyl)-1-piperazinyl] ethanol dihydrochloride showed orally a definite analgesic activity, without producing the significant morphine-like physical dependence liability, and its analgesic potency was about a half that of codeine and far superior to aminopyrine in experimental animals.     

Marine eicosanoids: Occurrence of 8-(R)-HETE in the starfishPatiria miniata

Summary The first isolation of 8-(R)-hydroxy-5Z, 9E, 11Z, 14Z-eicosatetraenoic acid [8-(R)-HETE] from a marine source, the pacific starfishPatiria miniata, is reported. 8-(R)-HETE occurs together with 8-(R)-hydroxy-5Z, 9E, 11Z, 14Z, 17Z-eicosapentaenoic acid.     

Anti-arrhythmic properties of 1,5-dimorpholino-3-(1-Naphthyl)-pentane: DA 1686

Riassunto Il DA 1686, corrispondente al 1,5-dimorfolino-3-(1-naftil) pentano, è un derivato della naftalina ad attività antiaritmica come risulta dalle prove in vitro (orecchiette isolate di cavia) e in vivo (cani, conigli, cavie e ratti). Il composto è ben assorbito dopo somministrazione orale e viene escreto nelle urine non metabolizzato.     

Defensive secretions of Nematinae larvae (Symphyta - Tenthredinidae)

Summary The composition of the defensive secretion of larvae of 8 Nematinae species is reported. 7 derivatives have been identified: benzaldehyde, (E)-2-hexenol, (E)-2-hexenal, (E)-4-oxo-2-hexenal, geranial, neral andcis, trans-dolichodial.Maître de recherches du Fonds National de la Recherche Scientifique.We gratefully acknowledge the Fonds National de la Recherche Scientifique for financial support. We express our sincere thanks to Professor B. Zwanenburg and Dr J. M. J. Verlaak for helpful suggestions.     

Frederick Pavy (1829-1911) and his opposition to the glycogenic theory of Claude Bernard

For more than 50 years the Guy's Hospital physician Frederick Pavy (1829-1911) attempted to discredit the theory of his erstwhile teacher, Claude Bernard, that liver glycogen was broken down to supply sugar to the systemic circulation. His opposition was driven by his clinical perceptions and was based on two assumptions: the first was that the kidney was a simple filter through which small molecules would diffuse, so that sugar had to be prevented from reaching the systemic circulation. For Pavy, the liver was the barrier. The second was teleological: he could not believe that nature would operate in what he saw as a defective way, i.e. converting sugar into glycogen and then back again. At the beginning of his long working life Pavy regarded himself as a physiologist and was critical of the stagnancy of English physiology which was kept afloat by amateurs like himself in whatever time they could spare from busy private practice. At the end he came to see his own view of carbohydrate metabolism as symbolic of the schism between responsible clinicians (himself) and irresponsible daydreaming physiologists (his opponents).     

(E,E)-10,12-Hexadecadienal: A component of the female sex pheromone of the spiny bollworm,Earias insulana (Boisd.) (Lepidoptera: Noctuidae)

Summary (E,E)-10,12-Hexadecadienal has been identified as a component of the sex pheromone of the female spiny bollworm moth,Earias insulana, by gas-chromatographic, electroantennographic and microchemical studies of abdominal tip extracts and entrained volatiles from female moths.This work was carried out under Ministry of Agriculture, Fisheries and Food licence HH 11599/139, issued under the Destructive Pests and Diseases of Plants Order 1965.     

Inhibitors of the acrosomal proteinase acrosin: Human urinary trypsin inhibitor (UTI) and 4-(2-carboxyethyl) phenyl trans 4-aminomethylcyclohexanecarboxylate hydrochloride (DV-1006)

Summary Human urinary trypsin inhibitor (UTI) and (4-(2-carboxyethyl) phenyl trans 4-aminoethylcyclohexanecarboxylate hydrochloride (DV-1006) competitively inhibited the human acrosomal proteinase acrosin; Ki values were 1.2×10^–8M and 9.4×10^–7 M, respectively.     

ß-(p-hydroxyphenyl) ethanol in the chest gland secretion of a galago (Galago crassicaudatus)

Summary ß-(p-hydroxyphenyl)ethanol is present in the chest gland secretion of the galago Galago crassicaudatus.     

Antihypertensive and central nervous system depressant properties of 3-(γ-p-fluorobenzoyl propyl) 2,3,4,4a,5,6-hexahydro-1(H)-pyrazino(1,2-a) quinoline hydrochloride (compound 69-183, centpyraquin)

Zusammenfassung Centpyraquin (3-(-p-fluorobenzyl propyl) 2,3,4,4a,5,6-hexahydro-1(H)-pyrazino (1,2-a) quinoline hydrochloride) zeigte hypotensive Aktivität bei narkotisierten wie auch bei wachen Katzen. Es senkt auch den Blutdruck bei Ratten mit nephrogenem Hochdurck. Die Hypotension scheint auf einem peripheren Mechanismus zu beruhen.

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Thanks are due to Drs.M. L. Dhar andN. Anand for their interest in the work.

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Communication No. 1600 from the Central Drug Research Institute; Lucknow.