Arthur Schopenhauer and the Current Conception of the Origin of Species: What Did the Philosopher Anticipate?

Arthur Schopenhauer (1788-1860) was deeply influenced by Plato and conceived each species as an Idea, whose shape is essentially and permanently predetermined. He rejected Lamarck’s proposal of organ’s use/disuse as a source of evolution, but he was close to the orthogenetic movement that developed after his death. The philosopher did not conceive biological individual variability as a source for evolution, mathematical population analysis, and gradual evolution; he even imagined an ultra-rapid saltatory model in “higher forms.” Moreover, he conceived a metaphysically based coupling among all phenomena which resembles the contemporary model of natural drift of evolution. Hence, Schopenhauer did not strictly anticipate Darwin’s model of natural selection. However, he expressed in his own words competition and struggle for life. The philosopher thus anticipated more the orthogenesis and natural drift and less the Darwinian’s mechanisms of evolution than what is generally alleged. His work is a valuable philosophical source in the contemporary search for a new synthesis in evolutionary thought.

Download Full-text

Human pharmacokinetic (PK) characterization of the novel dual-action anti-HER3/EGFR antibody MEHD7945A (MEHD) in patients with refractory/recurrent epithelial tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.2567 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 2567-2567 ◽

Cited By ~ 1

Author(s):

Manuel Hidalgo ◽

Antonio Calles ◽

Dejan Juric ◽

Rodrigo Dienstmann ◽

Desamparados Roda Perez ◽

...

Keyword(s):

Phase I ◽

Phase I Study ◽

Population Analysis ◽

Demographic Data ◽

Single Agent ◽

Compartment Model ◽

Individual Variability ◽

Study Patient ◽

Epithelial Tumors ◽

Dual Action

2567 Background: MEHD is a novel dual-action human IgG1 antibody that blocks ligand binding to HER3 and EGFR, and elicits antibody-dependent cell-mediated cytotoxicity (ADCC). MEHD demonstrates single-agent activity in a broad panel of tumor models, including models resistant to anti-HER3 or anti-EGFR treatment alone. The objective of this analysis was to characterize the PK of MEHD associated with body weight (BW)-based dosing used in a phase I study in patients with epithelial tumors and to evaluate the potential for using fixed dosing in future studies. Methods: Preliminary non-compartmental and population PK analyses were performed using patient data from the dose-escalation stage [1, 4, 10, 15, 22, and 30 mg/kg every two weeks (q2w)] and expansion stage (14 mg/kg q2w) of the phase I study. Patient demographic data and other relevant clinical covariates were evaluated in the population analysis. PK simulation of 1000 subjects with a log-normal BW distribution was performed to compare the inter-individual variability of MEHD exposure following fixed or BW-based dosing. Results: As expected,MEHD exhibited nonlinear PK. In the noncompartmenal analysis, the apparent clearance (CL) decreased in a dose-dependent fashion (about 40 to 9.9 mL/day/kg from 1 to 30 mg/kg) and approached linearity at doses >10 mg/kg (q2w). In the population analysis, the PK profile of MEHD was well described by a two compartment model with linear and nonlinear clearance. The target-mediated clearance was consistent with that of anti-EGFR antibodies. The nonspecific CL and central volume of distribution (V1) values were approximately 6 mL/day/kg and 52.4 mL/kg, respectively. BW had a moderate effect on V1, but not on CL. PK simulations suggest that, compared with BW-based dosing, fixed dosing would result in less inter-individual variability in MEHD exposure. Both 1100 mg q2w or 1650 mg q3w of MEHD achieve the targeted therapeutic exposure. Conclusions: The dual-action antibody MEHD demonstrated PK consistent with anti-EGFR antibodies. Fixed dosing of MEHD on an every 2 or 3 week schedule is supported.

Download Full-text

Revisiting FDA’s 1995 Guidance on Bioequivalence Establishment of Topical Dermatologic Corticosteroids: New Research Based Recommendations

Journal of Pharmacy & Pharmaceutical Sciences ◽

10.18433/jpps30021 ◽

2018 ◽

Vol 21 ◽

pp. 413-428 ◽

Cited By ~ 2

Author(s):

Deniz Ozdin ◽

Naveen Sharma ◽

Jorge Lujan-Zilbermann ◽

Philippe Colucci ◽

Isadore Kanfer ◽

...

Keyword(s):

Normal Distribution ◽

Population Analysis ◽

Population Modeling ◽

Individual Variability ◽

Mixed Effect ◽

Pilot Studies ◽

Fda Guidance ◽

Emax Model ◽

New Research ◽

The Impact

Purpose: As per the US FDA guidance issued on June 2, 1995, the establishment of bioequivalence for topical dermatologic corticosteroids is based on comparing the pharmacodynamic (PD) effects of Test and Reference products at the dose duration corresponding to the population ED50, determined either by naïve pooled data or nonlinear mixed effect modeling (NLME). The guidance was introduced using a study case example where the expectation maximization (EM) NLME algorithm, as implemented in P-PHARM®, was used. Although EM methods are relatively common, other methods such as the First-Order Conditional Estimation (FOCE) as implemented in the NONMEM® software are even more common. The objective of this study was to investigate the impact of using different parametric population modeling/analysis methods and distribution assumptions on population analysis results. Methods: The dose duration-response data from 11 distinct skin blanching blinded pilot studies were fitted using FOCE (NONMEM®) and an EM algorithm (ADAPT5® (MLEM)). Three different Emax models were tested for each method. Population PD estimates and associated CV%, and the agreement between model predicted values and observed data were compared between the two methods. The impact of assuming different distributions of PD parameters was also investigated. Results: The simple Emax model, as proposed in the FDA guidance, appeared to best characterize the data compared to more complex alternatives. The MLEM method in general appeared to provide better results than FOCE; lower population PD estimates with less inter-individual variability, and no variance shrinkage issues. The results also favored ln-normal versus normal distribution assumptions. Conclusions: The population ED50 estimates were influenced by both the type of population modeling methods and the distribution assumptions. We recommend updating the FDA guidance with more specific instructions related to the population approach to be used (EM-like versus FOCE-like methods) and to the normality assumptions that need to be set (ln-normal versus normal distribution).

Download Full-text

Social Behavior and Evolutionary Thought

Social Evolution and Inclusive Fitness Theory ◽

10.23943/princeton/9780691161563.003.0001 ◽

2015 ◽

Author(s):

James A.R. Marshall

Keyword(s):

Natural Selection ◽

Mathematical Theory ◽

Group Selection ◽

Inclusive Fitness ◽

Price Equation ◽

Inclusive Fitness Theory ◽

Evolutionary Thought ◽

Multilevel Selection Theory ◽

The Individual ◽

Evolutionary Explanations

This book demonstrates the generality of inclusive fitness theory, with particular emphasis on its fundamental evolutionary logic. It presents the basic mathematical theory of natural selection and shows how inclusive fitness theory deals with more complicated social scenarios. Topics include the Price equation, Hamilton's rule, nonadditive interactions, conditional behaviors, heritability, and maximization of inclusive fitness. This chapter provides a brief historical introduction to the problem of apparent design in biology, evolutionary explanations of this, and in particular, evolutionary explanations of individual behaviors that appear designed to benefit not the individual themselves, but other members of their species. It examines how social behaviors can be shaped by natural selection and discusses the problem of providing an evolutionary explanation of self-sacrifice by individuals, altruism in group selection, and multilevel selection theory.

Download Full-text

Wallace, Alfred Russel (1823–1913)

Routledge Encyclopedia of Philosophy ◽

10.4324/9780415249126-q110-1 ◽

2018 ◽

Cited By ~ 1

Author(s):

Barbara G. Beddall

Keyword(s):

Natural Selection ◽

Geographical Distribution ◽

Charles Darwin ◽

South American ◽

Malay Archipelago ◽

Evolutionary Thought

Co-discoverer with Charles Darwin of the theory of natural selection, Wallace travelled to the Amazon in 1848. Four years of collecting specimens there for sale in Europe revealed patterns of geographical distribution among animals. Unfortunately, much of his South American collection was lost in a fire at sea during the voyage home, which forced him to begin his collecting anew. This led to eight more years of travel (1854–62), this time in the Malay Archipelago, where he made his own momentous discovery of the theory of natural selection in 1858. An exceptionally clear thinker, he made many valuable contributions to evolutionary thought.

Download Full-text

Selección natural y construcción de nicho: una ¿dialéctica? evolucionista

Contrastes Revista Internacional de Filosofía ◽

10.24310/contrastescontrastes.v0i0.1177 ◽

2013 ◽

Author(s):

Juan R. Álvarez

Keyword(s):

Natural Selection ◽

Niche Construction ◽

Human Sciences ◽

Construction Technology ◽

Selection Theory ◽

Niche Construction Theory ◽

Evolutionary Thought ◽

Transformation Processes ◽

Natural Selection Theory

RESUMENEn el marco del pensamiento evolucionista de los últimos treinta años, la teoría de construcción de nicho ha ido abriéndose paso como una perspectiva opuesta a y complementaria de la teoría de la selección natural en la explicación del proceso evolutivo. El planteamiento que sigue aborda su oposición como un proceso de combinación de principios ecológicos (restrictivos) y técnicos (transformadores) que tienden un puente entre ciencias biológicas y ciencias humanas, basado en una analogía de la técnica que se naturaliza en procesos de trasformación en que los organismos «se trabajan» sus ambientes.PALABRAS CLAVECONSTRUCCIÓN DE NICHO, DIALÉCTICA, ECOLOGÍA, TÉCNICA, SELECCIÓN NATURALABSTRACTWithin the frame of evolutionary thought during the last thirty years, niche construction theory has been gaining ground as an opposed and complementary outlook regarding natural selection theory in the explanation of evolution. The following approach construes their opposition as a combination of ecologic (restrictive) and technologic (transformational) principles that serve as a bridge between biological and human sciences, based on an analogy with technology that is naturalized in terms of transformation processes wherein organisms «do their work on» their environments.KEYWORDSDIALECTICS, ECOLOGY, NATURAL SELECTION, NICHE CONSTRUCTION, TECHNOLOGY

Download Full-text

Adaptation and Natural Selection: A Critique of Some Current Evolutionary Thought. George C. Williams

Philosophy of Science ◽

10.1086/288332 ◽

1970 ◽

Vol 37 (4) ◽

pp. 620-623 ◽

Cited By ~ 4

Author(s):

William C. Wimsatt

Keyword(s):

Natural Selection ◽

Evolutionary Thought

Download Full-text

Effects of intrinsic environmental predictability on intra-individual and intra-population variability of plant reproductive traits and eco-evolutionary consequences

Annals of Botany ◽

10.1093/aob/mcaa096 ◽

2020 ◽

Author(s):

Martí March-Salas ◽

Guillermo Fandos ◽

Patrick S Fitze

Keyword(s):

Natural Selection ◽

Individual Variation ◽

Reproductive Traits ◽

Individual Variability ◽

Population Variability ◽

Population Variation ◽

Stabilizing Selection ◽

Environmental Predictability ◽

Developmental Noise ◽

Evolutionary Consequences

Abstract Background and Aims It is widely accepted that changes in the environment affect mean trait expression, but little is known about how the environment shapes intra-individual and intra-population variance. Theory suggests that intra-individual variance might be plastic and under natural selection, rather than reflecting developmental noise, but evidence for this hypothesis is scarce. Here, we experimentally tested whether differences in intrinsic environmental predictability affect intra-individual and intra-population variability of different reproductive traits, and whether intra-individual variability is under selection. Methods Under field conditions, we subjected Onobrychis viciifolia to more and less predictable precipitation over 4 generations and 4 years. We analysed effects on the coefficient of intra-individual variation (CVi-i) and the coefficient of intra-population variation (CVi-p), assessed whether the coefficients of intra-individual variation (CsVi-i) are under natural selection and tested for transgenerational responses (ancestor environmental effects on offspring). Key Results Less predictable precipitation led to higher CsVi-i and CsVi-p, consistent with plastic responses. The CsVi-i of all studied traits were under consistent stabilizing selection, and precipitation predictability affected the strength of selection and the location of the optimal CVi-i of a single trait. All CsVi-i differed from the optimal CVi-i and the maternal and offspring CsVi-i were positively correlated, showing that there was scope for change. Nevertheless, no consistent transgenerational effects were found in any of the three descendant generations, which contrasts with recent studies that detected rapid transgenerational responses in the trait means of different plant species. This suggests that changes in intra-individual variability take longer to evolve than changes in trait means, which may explain why high intra-individual variability is maintained, despite the stabilizing selection. Conclusions The results indicate that plastic changes of intra-individual variability are an important determinant of whether plants will be able to cope with changes in environmental predictability induced by the currently observed climatic change.

Download Full-text

Arthur James Cain. 25 July 1921 — 20 August 1999

Biographical Memoirs of Fellows of the Royal Society ◽

10.1098/rsbm.2007.0034 ◽

2008 ◽

Vol 54 ◽

pp. 47-57

Author(s):

Bryan C. Clarke

Keyword(s):

Natural Selection ◽

Evolutionary Thought ◽

The 1950S

Arthur Cain was a polymath, and one of Britain's leading evolutionary biologists. A strong believer in, and advocate for, the importance of natural selection, he greatly influenced evolutionary thought during the period from the 1950s to the 1980s. He wrote important papers in many areas of biology, and he was a noted historian of science.

Download Full-text

Yan Fu's Unfaithful Translation of Thomas Huxley's 'Evolution and Ethics'

Linguaculture ◽

10.47743/lincu-2021-2-0206 ◽

2021 ◽

Vol 12 (2) ◽

pp. 163-174

Author(s):

Qi Yuhan

Keyword(s):

Natural Selection ◽

Late Nineteenth Century ◽

Chinese People ◽

Theory Of Evolution ◽

National Crisis ◽

Evolutionary Thought ◽

Yan Fu ◽

Late Nineteenth ◽

Key Terms ◽

The Relationship

This paper analyses Yan Fu’s translation of the title and the key terms in Thomas Huxley’s Evolution and Ethics and shows that his unfaithfulness was mainly due to his personal intention to inspire the Chinese people to fight against foreign enemies and the feudal system in late nineteenth-century China. In his famous The Heavenly Theory of Evolution, the translation of Evolution and Ethics, Yan Fu added the traditional Chinese value of ‘heaven’ by translating ‘evolution’ as ‘heavenly evolution’ in order to make Darwin’s theory more acceptable and easier to understand by target readers. When he translated terms such as ‘competition’ and ‘natural selection’, Yan Fu borrowed the slogan of the Westernizing reform to explain the relationship linking evolution, competition and selection. Yan Fu wanted to arouse people’s attention to the theory of evolution and hoped they would use evolutionary thought as a theoretical weapon to save themselves and the country from a national crisis. His unfaithful translation appealed to the scholars to make them spread the theory through their social influence.

Download Full-text