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4 Evaluating Plasma GFAP for the Detection of Alzheimer’s Disease Dementia
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Ann C. McKee, Thor D. Stein, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Michael L. Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 408-409
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Objective:
Blood-based biomarkers represent a scalable and accessible approach for the detection and monitoring of Alzheimer’s disease (AD). Plasma phosphorylated tau (p-tau) and neurofilament light (NfL) are validated biomarkers for the detection of tau and neurodegenerative brain changes in AD, respectively. There is now emphasis to expand beyond these markers to detect and provide insight into the pathophysiological processes of AD. To this end, a reactive astrocytic marker, namely plasma glial fibrillary acidic protein (GFAP), has been of interest. Yet, little is known about the relationship between plasma GFAP and AD. Here, we examined the association between plasma GFAP, diagnostic status, and neuropsychological test performance. Diagnostic accuracy of plasma GFAP was compared with plasma measures of p-tau181 and NfL.
Participants and Methods:This sample included 567 participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC) Longitudinal Clinical Core Registry, including individuals with normal cognition (n=234), mild cognitive impairment (MCI) (n=180), and AD dementia (n=153). The sample included all participants who had a blood draw. Participants completed a comprehensive neuropsychological battery (sample sizes across tests varied due to missingness). Diagnoses were adjudicated during multidisciplinary diagnostic consensus conferences. Plasma samples were analyzed using the Simoa platform. Binary logistic regression analyses tested the association between GFAP levels and diagnostic status (i.e., cognitively impaired due to AD versus unimpaired), controlling for age, sex, race, education, and APOE e4 status. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate diagnostic groups compared with plasma p-tau181 and NfL. Linear regression models tested the association between plasma GFAP and neuropsychological test performance, accounting for the above covariates.
Results:The mean (SD) age of the sample was 74.34 (7.54), 319 (56.3%) were female, 75 (13.2%) were Black, and 223 (39.3%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having cognitive impairment (GFAP z-score transformed: OR=2.233, 95% CI [1.609, 3.099], p<0.001; non-z-transformed: OR=1.004, 95% CI [1.002, 1.006], p<0.001). ROC analyses, comprising of GFAP and the above covariates, showed plasma GFAP discriminated the cognitively impaired from unimpaired (AUC=0.75) and was similar, but slightly superior, to plasma p-tau181 (AUC=0.74) and plasma NfL (AUC=0.74). A joint panel of the plasma markers had greatest discrimination accuracy (AUC=0.76). Linear regression analyses showed that higher GFAP levels were associated with worse performance on neuropsychological tests assessing global cognition, attention, executive functioning, episodic memory, and language abilities (ps<0.001) as well as higher CDR Sum of Boxes (p<0.001).
Conclusions:Higher plasma GFAP levels differentiated participants with cognitive impairment from those with normal cognition and were associated with worse performance on all neuropsychological tests assessed. GFAP had similar accuracy in detecting those with cognitive impairment compared with p-tau181 and NfL, however, a panel of all three biomarkers was optimal. These results support the utility of plasma GFAP in AD detection and suggest the pathological processes it represents might play an integral role in the pathogenesis of AD.
5 Antemortem Plasma GFAP Predicts Alzheimer’s Disease Neuropathological Changes
- Madeline Ally, Henrik Zetterberg, Kaj Blennow, Nicholas J. Ashton, Thomas K. Karikari, Hugo Aparicio, Michael A. Sugarman, Brandon Frank, Yorghos Tripodis, Brett Martin, Joseph N. Palmisano, Eric G. Steinberg, Irene Simkina, Lindsay Farrer, Gyungah Jun, Katherine W. Turk, Andrew E. Budson, Maureen K. O’Connor, Rhoda Au, Wei Qiao Qiu, Lee E. Goldstein, Ronald Killiany, Neil W. Kowall, Robert A. Stern, Jesse Mez, Bertran R. Huber, Ann C. McKee, Thor D. Stein, Michael L. Alosco
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- Journal:
- Journal of the International Neuropsychological Society / Volume 29 / Issue s1 / November 2023
- Published online by Cambridge University Press:
- 21 December 2023, pp. 409-410
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Objective:
Blood-based biomarkers offer a more feasible alternative to Alzheimer’s disease (AD) detection, management, and study of disease mechanisms than current in vivo measures. Given their novelty, these plasma biomarkers must be assessed against postmortem neuropathological outcomes for validation. Research has shown utility in plasma markers of the proposed AT(N) framework, however recent studies have stressed the importance of expanding this framework to include other pathways. There is promising data supporting the usefulness of plasma glial fibrillary acidic protein (GFAP) in AD, but GFAP-to-autopsy studies are limited. Here, we tested the association between plasma GFAP and AD-related neuropathological outcomes in participants from the Boston University (BU) Alzheimer’s Disease Research Center (ADRC).
Participants and Methods:This sample included 45 participants from the BU ADRC who had a plasma sample within 5 years of death and donated their brain for neuropathological examination. Most recent plasma samples were analyzed using the Simoa platform. Neuropathological examinations followed the National Alzheimer’s Coordinating Center procedures and diagnostic criteria. The NIA-Reagan Institute criteria were used for the neuropathological diagnosis of AD. Measures of GFAP were log-transformed. Binary logistic regression analyses tested the association between GFAP and autopsy-confirmed AD status, as well as with semi-quantitative ratings of regional atrophy (none/mild versus moderate/severe) using binary logistic regression. Ordinal logistic regression analyses tested the association between plasma GFAP and Braak stage and CERAD neuritic plaque score. Area under the curve (AUC) statistics from receiver operating characteristics (ROC) using predicted probabilities from binary logistic regression examined the ability of plasma GFAP to discriminate autopsy-confirmed AD status. All analyses controlled for sex, age at death, years between last blood draw and death, and APOE e4 status.
Results:Of the 45 brain donors, 29 (64.4%) had autopsy-confirmed AD. The mean (SD) age of the sample at the time of blood draw was 80.76 (8.58) and there were 2.80 (1.16) years between the last blood draw and death. The sample included 20 (44.4%) females, 41 (91.1%) were White, and 20 (44.4%) were APOE e4 carriers. Higher GFAP concentrations were associated with increased odds for having autopsy-confirmed AD (OR=14.12, 95% CI [2.00, 99.88], p=0.008). ROC analysis showed plasma GFAP accurately discriminated those with and without autopsy-confirmed AD on its own (AUC=0.75) and strengthened as the above covariates were added to the model (AUC=0.81). Increases in GFAP levels corresponded to increases in Braak stage (OR=2.39, 95% CI [0.71-4.07], p=0.005), but not CERAD ratings (OR=1.24, 95% CI [0.004, 2.49], p=0.051). Higher GFAP levels were associated with greater temporal lobe atrophy (OR=10.27, 95% CI [1.53,69.15], p=0.017), but this was not observed with any other regions.
Conclusions:The current results show that antemortem plasma GFAP is associated with non-specific AD neuropathological changes at autopsy. Plasma GFAP could be a useful and practical biomarker for assisting in the detection of AD-related changes, as well as for study of disease mechanisms.
Reliability of the Clinician’s Tardive Inventory (CTI)
- Richard M. Trosch, Cynthia L. Comella, Stanley N. Caroff, William G. Ondo, Alicia C. Shillington, Brandon J. LaChappelle, Robert A. Hauser, Christof U. Correll, Joseph H. Friedman
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- Journal:
- CNS Spectrums / Volume 28 / Issue 2 / April 2023
- Published online by Cambridge University Press:
- 14 April 2023, p. 219
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Objectives
Currently utilized clinician-rated symptom scales for tardive dyskinesia (TD) have not kept up with the expanding spectrum of TD phenomenology. The objective of this study was to develop and test the reliability of a new instrument, the CTI.
MethodsA movement disorder neurologist devised the outline of the scale. A steering committee (four neurologists and two psychiatrists) provided revisions until consensus was reached. The resulting instrument assesses frequency of abnormal movements of the eye/eyelid/face, tongue/mouth, jaw, limb/trunk, complex movements (e.g., handwringing, self-caressing), and vocalizations. The CTI rates symptoms from 0–3 with 0 = absent, 1 = infrequent/intermittent or only present with activating maneuvers, 2 = frequent intermittent, brief periods without movements, 3 = constant or nearly constant. Functional impairments including activities of daily living (ADL), social impairment, symptom bother, and harm are rated 0–3 with 0 = patient is unaware or unaffected, 1 = symptoms mildly impact patient, 2 = symptoms moderately impact patient, 3 = symptoms severely impact patient. Following institutional review board approval, the CTI underwent inter-rater and test-retest reliability testing. Videos of patient TD examinations were obtained and reviewed by two movement disorder specialists to confirm the diagnosis of TD by consensus and the adequacy to demonstrate a TD-consistent movement. Vignettes were created to include patients’ symptom descriptions and functional, social, or occupational impairments/limitations. Four clinicians rated each video/vignette. Selected videos/vignettes were also subject to an intra-rater retest. Interrater agreement was analyzed via 2-way random-effects interclass correlation (ICC) and test-retest agreement assessment utilizing Kendall’s tau-b.
Results45 video/vignettes were assessed for interrater reliability, and 16 for test-retest reliability. ICCs for movement frequency were as follows: abnormal eye movement .89; abnormal tongue/mouth movement .91; abnormal jaw movement .89; abnormal limb movement .76; complex movement .87; abnormal vocalization .77; and functional impairments including harm .82; social embarrassment .88; ADLs .83; and symptom bother .92. Retests were conducted on mean (SD) 15 (3) days later with scores ranging from .66–.87.
ConclusionsThe CTI is a new instrument with good reliability in assessing TD symptoms and functional impacts. Future validation study is warranted.
FundingNeurocrine Biosciences
The Missing Two-Thirds of Evolutionary Theory
- Robert N. Brandon, Daniel W. McShea
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- Published online:
- 25 February 2020
- Print publication:
- 26 March 2020
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- Element
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In this Element, we extend our earlier treatment of biology's first law. The law says that in any evolutionary system in which there is variation and heredity, there is a tendency for diversity and complexity to increase. The law plays the same role in biology that Newton's first law plays in physics, explaining what biological systems are expected to do when no forces act, in other words, what happens when nothing happens. Here we offer a deeper explanation of certain features of the law, develop a quantitative version of it, and explore its consequences for our understanding of diversity and complexity.
Contributors
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- By Magdalena Anitescu, Charles E. Argoff, Arash Asher, Nyla Azam, Nomen Azeem, Sachin K. Bansal, Jose E. Barreto, Rodrigo A Benavides, Niteesh Bharara, Justin B. Boge, Robert B. Bolash, Thomas K. Bond, Christopher Centeno, Zachariah W. Chambers, Jonathan Chang, Grace Chen, Hamilton Chen, Jeffry Chen, Jianguo Cheng, Natalia Covarrubias, Claire J. Creutzfeldt, Gulshan Doulatram, Amirpasha Ehsan, Ike Eriator, Jeff Ericksen, Mark Etscheidt, Frank J. E. Falco, Jack Fu, Timothy Furnish, Annemarie E. Gallagher, Kingsuk Ganguly, Eugene Garvin, Cliff Gevirtz, Scott E. Glaser, Brandon J. Goff, Harry J. Gould, Christine Greco, Jay S. Grider, Maged Guirguis, Qiao Guo, Justin Hata, John Hau, Garett J. Helber, Eric R. Helm, Lori Hill Marshall, Dean Hommer, Jeffrey Hopcian, Eric S. Hsu, Jakun Ing, Tracy P. Jackson, Gaurav Jain, Chrystina Jeter, Alan David Kaye, James Kelly, Soorena Khojasteh, Ankur Khosla, Daniel Krashin, Monika A. Krzyzek, Prasad Lakshminarasimhiah, Steven Michael Lampert, Garrett LaSalle, Quan D. Le, Ankit Maheshwari, Edward R. Mariano, Joaquin Maury, John P. McCallin, John Michels, Natalia Murinova, Narendren Narayanasamy, Rebekah L. Nilson, Elliot Palmer, Vikram B. Patel, Devin Peck, Donald B. Penzien, Danielle Perret Karimi, Tilak Raj, Michael R. Rasmussen, Mohit Rastogi, Rahul Rastogi, Nashaat N. Rizk, Rinoo V. Shah, Paul A. Sloan, Julian Sosner, A. Raj Swain, Minyi Tan, Natacha Telusca, Santhosh A. Thomas, Andrea Trescot, Michael Truong, Jason Tucker, Richard D. Urman, Brandon A. Van Noord, Nihir Waghela, Irene Wu, Jiang Wu, Jijun Xu, Jinghui Xie, William Yancey
- Edited by Alan David Kaye, Louisiana State University, Rinoo V. Shah
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- Book:
- Case Studies in Pain Management
- Published online:
- 05 October 2014
- Print publication:
- 16 October 2014, pp xi-xv
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- By Syed S. Ali, Nathan Allen, John E. Arbo, Elizabeth Arrington, Ani Aydin, Kenneth R. L. Bernard, Amy Caggiula, Nolan Caldwell, Jennifer L. Carey, Jennifer Carnell, Jayaram Chelluri, Michael N. Cocchi, Cristal Cristia, Vishal Demla, Bram Dolcourt, Andrew Eyre, Shawn Fagan, Brandy Ferguson, Sarah Fisher, Jonathan Friedstat, Brian C. Geyer, Brandon Godbout, Jeremy Gonda, Jeremy Goverman, Ashley L. Greiner, Casey Grover, Carla Haack, Abigail Hankin, John W. Hardin, Katrina L. Harper, Gregory Hayward, Stephen Hendriksen, Daniel Herbert-Cohen, Nadine Himelfarb, Calvin E. Hwang, Jacob D. Isserman, Joshua Jauregui, Joshua W. Joseph, Elena Kapilevich, Feras H. Khan, Sarvotham Kini, Karen A. Kinnaman, Ruth Lamm, Calvin Lee, Jarone Lee, Charles Lei, John Lemos, Daniel J. Lepp, Elisabeth Lessenich, Brandon Maughan, Julie Mayglothling, Kevin McConnell, Laura Medford-Davis, Kamal Medlej, Heather Meissen, Payal Modi, Joel Moll, Jolene H. Nakao, Matthew Nicholls, Lindsay Oelze, Carolyn Maher Overman, Viral Patel, Timothy C. Peck, Jeffrey Pepin, Candace Pettigrew, Byron Pitts, Zubaid Rafique, Chanu Rhee, Jonathan C. Roberts, Daniel Rolston, Steven C. Rougas, Benjamin Schnapp, Kathryn A. Seal, Raghu Seethala, Todd A. Seigel, Navdeep Sekhon, Kaushal Shah, Robert L. Sherwin, Kirill Shishlov, Ashley Shreves, Sebastian Siadecki, Jeffrey N. Siegelman, Liza Gonen Smith, Ted Stettner, Marie Carmelle Tabuteau, Joseph E. Tonna, N. Seth Trueger, Chad Van Ginkel, Bina Vasantharam, Graham Walker, Susan Wilcox, Sandra J. Williams, Matthew L. Wong, Nelson Wong, Samantha Wood, John Woodruff, Benjamin Zabar
- Edited by Kaushal Shah, Jarone Lee, Kamal Medlej, American University of Beirut, Scott D. Weingart
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- Book:
- Practical Emergency Resuscitation and Critical Care
- Published online:
- 05 November 2013
- Print publication:
- 24 October 2013, pp xi-xx
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- By Ioannis P. Androulakis, Djillali Annane, Gérard Audibert, Lisa L. Barnes, Paolo Bartolomeo, Walter S. Bartynski, David A. Bennett, Nicolas Bruder, Nathan E. Brummel, Steve E. Calvano, Alain Cariou, F. Chretien, Jan Claassen, Colm Cunningham, Souhayl Dahmani, Robert Dantzer, Dimitry S. Davydow, Sanjay V. Desai, E. Wesley Ely, Frédéric Faugeras, Karen J. Ferguson, Brandon Foreman, Sadanand M. Gaikwad, Rebecca F. Gottesman, Maura A. Grega, Richard D. Griffiths, Marion Griton, Stefan D. Gurney, Hebah M. Hefzy, Michael T. Heneka, Dustin M. Hipp, Ramona O. Hopkins, Christopher G. Hughes, James C. Jackson, Christina Jones, Peter W. Kaplan, Keith W. Kelley, Raymond C. Koehler, Matthew A. Koenig, Jan Pieter Konsman, Felix Kork, John P. Kress, Stephen F. Lowry, Alawi Luetz, David Luis, Alasdair M. J. MacLullich, Guy M. McKhann, Jean Mantz, Panteleimon D. Mavroudis, Mervyn Maze, Bruno Mégarbane, Lionel Naccache, Dale M. Needham, Pratik P. Pandharipande, Jean-Francois Payen, V. Hugh Perry, Margaret Pisani, C. Rauturier, Benjamin Rohaut, Jennifer Ryan, Robert D. Sanders, Jeremy D. Scheff, Frederic Sedel, Ola A. Selnes, Tarek Sharshar, Martin Siegemund, Yoanna Skrobik, Jamie W. Sleigh, Romain Sonneville, Claudia D. Spies, Luzius A. Steiner, Robert D. Stevens, Raoul Sutter, Fabio Silvio Taccone, Richard E. Temes, Willem A. van Gool, Christel C. Vanbesien, F. Verdonk, Odile Viltart, Julia Wendon, Catherine N. Widmann, Robert S. Wilson
- Edited by Robert D. Stevens, Tarek Sharshar, E. Wesley Ely, Vanderbilt University, Tennessee
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- Book:
- Brain Disorders in Critical Illness
- Published online:
- 05 October 2013
- Print publication:
- 19 September 2013, pp viii-xii
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A Non-Newtonian Newtonian Model of Evolution: The ZFEL View
- Robert N. Brandon
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- Journal:
- Philosophy of Science / Volume 77 / Issue 5 / December 2010
- Published online by Cambridge University Press:
- 01 January 2022, pp. 702-715
- Print publication:
- December 2010
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Recently philosophers of biology have argued over whether or not Newtonian mechanics provides a useful analogy for thinking about evolutionary theory. For philosophers, the canonical presentation of this analogy is Sober's. Matthen and Ariew and Walsh, Lewins, and Ariew argue that this analogy is deeply wrong-headed. Here I argue that the analogy is indeed useful, however, not in the way it is usually interpreted. The Newtonian analogy depends on having the proper analogue of Newton's First Law. That analogue is what McShea and Brandon call the Zero Force Evolutionary Law (ZFEL). According to the ZFEL, change, not stasis, is the default state of evolutionary systems.
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- By Rose Teteki Abbey, K. C. Abraham, David Tuesday Adamo, LeRoy H. Aden, Efrain Agosto, Victor Aguilan, Gillian T. W. Ahlgren, Charanjit Kaur AjitSingh, Dorothy B E A Akoto, Giuseppe Alberigo, Daniel E. Albrecht, Ruth Albrecht, Daniel O. Aleshire, Urs Altermatt, Anand Amaladass, Michael Amaladoss, James N. Amanze, Lesley G. Anderson, Thomas C. Anderson, Victor Anderson, Hope S. Antone, María Pilar Aquino, Paula Arai, Victorio Araya Guillén, S. Wesley Ariarajah, Ellen T. Armour, Brett Gregory Armstrong, Atsuhiro Asano, Naim Stifan Ateek, Mahmoud Ayoub, John Alembillah Azumah, Mercedes L. García Bachmann, Irena Backus, J. Wayne Baker, Mieke Bal, Lewis V. Baldwin, William Barbieri, António Barbosa da Silva, David Basinger, Bolaji Olukemi Bateye, Oswald Bayer, Daniel H. Bays, Rosalie Beck, Nancy Elizabeth Bedford, Guy-Thomas Bedouelle, Chorbishop Seely Beggiani, Wolfgang Behringer, Christopher M. Bellitto, Byard Bennett, Harold V. Bennett, Teresa Berger, Miguel A. Bernad, Henley Bernard, Alan E. Bernstein, Jon L. Berquist, Johannes Beutler, Ana María Bidegain, Matthew P. Binkewicz, Jennifer Bird, Joseph Blenkinsopp, Dmytro Bondarenko, Paulo Bonfatti, Riet en Pim Bons-Storm, Jessica A. Boon, Marcus J. Borg, Mark Bosco, Peter C. Bouteneff, François Bovon, William D. Bowman, Paul S. Boyer, David Brakke, Richard E. Brantley, Marcus Braybrooke, Ian Breward, Ênio José da Costa Brito, Jewel Spears Brooker, Johannes Brosseder, Nicholas Canfield Read Brown, Robert F. Brown, Pamela K. Brubaker, Walter Brueggemann, Bishop Colin O. Buchanan, Stanley M. Burgess, Amy Nelson Burnett, J. Patout Burns, David B. Burrell, David Buttrick, James P. Byrd, Lavinia Byrne, Gerado Caetano, Marcos Caldas, Alkiviadis Calivas, William J. Callahan, Salvatore Calomino, Euan K. Cameron, William S. Campbell, Marcelo Ayres Camurça, Daniel F. Caner, Paul E. Capetz, Carlos F. Cardoza-Orlandi, Patrick W. Carey, Barbara Carvill, Hal Cauthron, Subhadra Mitra Channa, Mark D. Chapman, James H. Charlesworth, Kenneth R. Chase, Chen Zemin, Luciano Chianeque, Philip Chia Phin Yin, Francisca H. Chimhanda, Daniel Chiquete, John T. Chirban, Soobin Choi, Robert Choquette, Mita Choudhury, Gerald Christianson, John Chryssavgis, Sejong Chun, Esther Chung-Kim, Charles M. A. Clark, Elizabeth A. Clark, Sathianathan Clarke, Fred Cloud, John B. Cobb, W. Owen Cole, John A Coleman, John J. Collins, Sylvia Collins-Mayo, Paul K. Conkin, Beth A. Conklin, Sean Connolly, Demetrios J. Constantelos, Michael A. Conway, Paula M. Cooey, Austin Cooper, Michael L. Cooper-White, Pamela Cooper-White, L. William Countryman, Sérgio Coutinho, Pamela Couture, Shannon Craigo-Snell, James L. Crenshaw, David Crowner, Humberto Horacio Cucchetti, Lawrence S. Cunningham, Elizabeth Mason Currier, Emmanuel Cutrone, Mary L. Daniel, David D. Daniels, Robert Darden, Rolf Darge, Isaiah Dau, Jeffry C. Davis, Jane Dawson, Valentin Dedji, John W. de Gruchy, Paul DeHart, Wendy J. Deichmann Edwards, Miguel A. De La Torre, George E. Demacopoulos, Thomas de Mayo, Leah DeVun, Beatriz de Vasconcellos Dias, Dennis C. Dickerson, John M. Dillon, Luis Miguel Donatello, Igor Dorfmann-Lazarev, Susanna Drake, Jonathan A. Draper, N. Dreher Martin, Otto Dreydoppel, Angelyn Dries, A. J. Droge, Francis X. D'Sa, Marilyn Dunn, Nicole Wilkinson Duran, Rifaat Ebied, Mark J. Edwards, William H. Edwards, Leonard H. Ehrlich, Nancy L. Eiesland, Martin Elbel, J. Harold Ellens, Stephen Ellingson, Marvin M. Ellison, Robert Ellsberg, Jean Bethke Elshtain, Eldon Jay Epp, Peter C. Erb, Tassilo Erhardt, Maria Erling, Noel Leo Erskine, Gillian R. Evans, Virginia Fabella, Michael A. Fahey, Edward Farley, Margaret A. Farley, Wendy Farley, Robert Fastiggi, Seena Fazel, Duncan S. Ferguson, Helwar Figueroa, Paul Corby Finney, Kyriaki Karidoyanes FitzGerald, Thomas E. FitzGerald, John R. Fitzmier, Marie Therese Flanagan, Sabina Flanagan, Claude Flipo, Ronald B. Flowers, Carole Fontaine, David Ford, Mary Ford, Stephanie A. Ford, Jim Forest, William Franke, Robert M. Franklin, Ruth Franzén, Edward H. Friedman, Samuel Frouisou, Lorelei F. Fuchs, Jojo M. Fung, Inger Furseth, Richard R. Gaillardetz, Brandon Gallaher, China Galland, Mark Galli, Ismael García, Tharscisse Gatwa, Jean-Marie Gaudeul, Luis María Gavilanes del Castillo, Pavel L. Gavrilyuk, Volney P. Gay, Metropolitan Athanasios Geevargis, Kondothra M. George, Mary Gerhart, Simon Gikandi, Maurice Gilbert, Michael J. Gillgannon, Verónica Giménez Beliveau, Terryl Givens, Beth Glazier-McDonald, Philip Gleason, Menghun Goh, Brian Golding, Bishop Hilario M. Gomez, Michelle A. Gonzalez, Donald K. Gorrell, Roy Gottfried, Tamara Grdzelidze, Joel B. Green, Niels Henrik Gregersen, Cristina Grenholm, Herbert Griffiths, Eric W. Gritsch, Erich S. Gruen, Christoffer H. Grundmann, Paul H. Gundani, Jon P. Gunnemann, Petre Guran, Vidar L. Haanes, Jeremiah M. Hackett, Getatchew Haile, Douglas John Hall, Nicholas Hammond, Daphne Hampson, Jehu J. Hanciles, Barry Hankins, Jennifer Haraguchi, Stanley S. Harakas, Anthony John Harding, Conrad L. Harkins, J. William Harmless, Marjory Harper, Amir Harrak, Joel F. Harrington, Mark W. Harris, Susan Ashbrook Harvey, Van A. Harvey, R. Chris Hassel, Jione Havea, Daniel Hawk, Diana L. Hayes, Leslie Hayes, Priscilla Hayner, S. Mark Heim, Simo Heininen, Richard P. Heitzenrater, Eila Helander, David Hempton, Scott H. Hendrix, Jan-Olav Henriksen, Gina Hens-Piazza, Carter Heyward, Nicholas J. Higham, David Hilliard, Norman A. Hjelm, Peter C. Hodgson, Arthur Holder, M. Jan Holton, Dwight N. Hopkins, Ronnie Po-chia Hsia, Po-Ho Huang, James Hudnut-Beumler, Jennifer S. Hughes, Leonard M. Hummel, Mary E. Hunt, Laennec Hurbon, Mark Hutchinson, Susan E. Hylen, Mary Beth Ingham, H. Larry Ingle, Dale T. Irvin, Jon Isaak, Paul John Isaak, Ada María Isasi-Díaz, Hans Raun Iversen, Margaret C. Jacob, Arthur James, Maria Jansdotter-Samuelsson, David Jasper, Werner G. Jeanrond, Renée Jeffery, David Lyle Jeffrey, Theodore W. Jennings, David H. Jensen, Robin Margaret Jensen, David Jobling, Dale A. Johnson, Elizabeth A. Johnson, Maxwell E. Johnson, Sarah Johnson, Mark D. Johnston, F. Stanley Jones, James William Jones, John R. Jones, Alissa Jones Nelson, Inge Jonsson, Jan Joosten, Elizabeth Judd, Mulambya Peggy Kabonde, Robert Kaggwa, Sylvester Kahakwa, Isaac Kalimi, Ogbu U. Kalu, Eunice Kamaara, Wayne C. Kannaday, Musimbi Kanyoro, Veli-Matti Kärkkäinen, Frank Kaufmann, Léon Nguapitshi Kayongo, Richard Kearney, Alice A. Keefe, Ralph Keen, Catherine Keller, Anthony J. Kelly, Karen Kennelly, Kathi Lynn Kern, Fergus Kerr, Edward Kessler, George Kilcourse, Heup Young Kim, Kim Sung-Hae, Kim Yong-Bock, Kim Yung Suk, Richard King, Thomas M. King, Robert M. Kingdon, Ross Kinsler, Hans G. Kippenberg, Cheryl A. Kirk-Duggan, Clifton Kirkpatrick, Leonid Kishkovsky, Nadieszda Kizenko, Jeffrey Klaiber, Hans-Josef Klauck, Sidney Knight, Samuel Kobia, Robert Kolb, Karla Ann Koll, Heikki Kotila, Donald Kraybill, Philip D. W. Krey, Yves Krumenacker, Jeffrey Kah-Jin Kuan, Simanga R. Kumalo, Peter Kuzmic, Simon Shui-Man Kwan, Kwok Pui-lan, André LaCocque, Stephen E. Lahey, John Tsz Pang Lai, Emiel Lamberts, Armando Lampe, Craig Lampe, Beverly J. Lanzetta, Eve LaPlante, Lizette Larson-Miller, Ariel Bybee Laughton, Leonard Lawlor, Bentley Layton, Robin A. Leaver, Karen Lebacqz, Archie Chi Chung Lee, Marilyn J. Legge, Hervé LeGrand, D. L. LeMahieu, Raymond Lemieux, Bill J. Leonard, Ellen M. Leonard, Outi Leppä, Jean Lesaulnier, Nantawan Boonprasat Lewis, Henrietta Leyser, Alexei Lidov, Bernard Lightman, Paul Chang-Ha Lim, Carter Lindberg, Mark R. Lindsay, James R. Linville, James C. Livingston, Ann Loades, David Loades, Jean-Claude Loba-Mkole, Lo Lung Kwong, Wati Longchar, Eleazar López, David W. Lotz, Andrew Louth, Robin W. Lovin, William Luis, Frank D. Macchia, Diarmaid N. J. MacCulloch, Kirk R. MacGregor, Marjory A. MacLean, Donald MacLeod, Tomas S. Maddela, Inge Mager, Laurenti Magesa, David G. Maillu, Fortunato Mallimaci, Philip Mamalakis, Kä Mana, Ukachukwu Chris Manus, Herbert Robinson Marbury, Reuel Norman Marigza, Jacqueline Mariña, Antti Marjanen, Luiz C. L. Marques, Madipoane Masenya (ngwan'a Mphahlele), Caleb J. D. Maskell, Steve Mason, Thomas Massaro, Fernando Matamoros Ponce, András Máté-Tóth, Odair Pedroso Mateus, Dinis Matsolo, Fumitaka Matsuoka, John D'Arcy May, Yelena Mazour-Matusevich, Theodore Mbazumutima, John S. McClure, Christian McConnell, Lee Martin McDonald, Gary B. McGee, Thomas McGowan, Alister E. McGrath, Richard J. McGregor, John A. McGuckin, Maud Burnett McInerney, Elsie Anne McKee, Mary B. McKinley, James F. McMillan, Ernan McMullin, Kathleen E. McVey, M. 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Yee, Viktor Yelensky, Yeo Khiok-Khng, Gustav K. K. Yeung, Angela Yiu, Amos Yong, Yong Ting Jin, You Bin, Youhanna Nessim Youssef, Eliana Yunes, Robert Michael Zaller, Valarie H. Ziegler, Barbara Brown Zikmund, Joyce Ann Zimmerman, Aurora Zlotnik, Zhuo Xinping
- Edited by Daniel Patte, Vanderbilt University, Tennessee
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- The Cambridge Dictionary of Christianity
- Published online:
- 05 August 2012
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- 20 September 2010, pp xi-xliv
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4 - What’s Wrong with the Emergentist Statistical Interpretation of Natural Selection and Random Drift?
- Edited by David L. Hull, Northwestern University, Illinois, Michael Ruse, Florida State University
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- The Cambridge Companion to the Philosophy of Biology
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- 28 April 2008
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- 01 October 2007, pp 66-84
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Summary
Population-level theories of evolution - the stock and trade of population genetics - are statistical theories par excellence. But what accounts for the statistical character of population-level phenomena? One view is that the population-level statistics are a product of, are generated by, probabilities that attach to the individuals in the population. On this conception, population-level phenomena are explained by individual-level probabilities and their population-level combinations. Another view, which arguably goes back to Fisher (1930) but has been defended recently, is that the population-level statistics are sui generis, that they somehow emerge from the underlying deterministic behavior of the individuals composing the population. Walsh, Lewens, and Ariew (2002) label this the statistical interpretation. We are not willing to give them that term, since everyone will admit that the population-level theories of evolution are statistical, so we will call this the emergentist statistical interpretation (ESI). Our goals are to show that (1) this interpretation is based on gross factual errors concerning the practice of evolutionary biology, concerning both what is done and what can be done; (2) its adoption would entail giving up on most of the explanatory and predictive (i.e., scientific) projects of evolutionary biology; and finally (3) a rival interpretation, which we will label the propensity statistical interpretation (PSI), succeeds exactly where the emergentist interpretation fails.
The Empirical Nonequivalence of Genic and Genotypic Models of Selection: A (Decisive) Refutation of Genic Selectionism and Pluralistic Genic Selectionism
- Robert N. Brandon, H. Frederik Nijhout
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- Journal:
- Philosophy of Science / Volume 73 / Issue 3 / July 2006
- Published online by Cambridge University Press:
- 01 January 2022, pp. 277-297
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- July 2006
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Genic selectionists (Williams 1966; Dawkins 1976) defend the view that genes are the (unique) units of selection and that all evolutionary events can be adequately represented at the genic level. Pluralistic genic selectionists (Sterelny and Kitcher 1988; Waters 1991; Dawkins 1982) defend the weaker view that in many cases there are multiple equally adequate accounts of evolutionary events, but that always among the set of equally adequate representations will be one at the genic level. We describe a range of cases all involving stable equilibria actively maintained by selection. In these cases genotypic models correctly show that selection is active at the equilibrium point. In contrast, the genic models have selection disappearing at equilibrium. For deterministic models this difference makes no difference. However, once drift is added in, the two sets of models diverge in their predicted evolutionary trajectories. Thus, contrary to received wisdom on this matter, the two sets of models are not empirically equivalent. Moreover, the genic models get the facts wrong.
Characterization and Applications of Modulated Optical Nanoprobes (MOONs)
- Jeffrey N. Anker, Caleb J. Behrend, Brandon H. McNaughton, Teresa Gail Roberts, Murphy Brasuel, Martin A. Philbert, Raoul Kopelman
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- MRS Online Proceedings Library Archive / Volume 790 / 2003
- Published online by Cambridge University Press:
- 01 February 2011, P4.1
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- 2003
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Modulated optical nanoprobes (MOONs) are microscopic (spherical and aspherical) particles designed to emit different fluxes of light in a manner that depends on particle orientation. When particle orientation is controlled remotely using magnetic fields (MagMOONs) it allows modulation of fluorescence intensity in any selected pattern including square and sinusoidal waves. The broad range of sizes over which MOONs can be prepared allows them to be tailored to applications from intracellular sensors using submicron MOONs to immunoassays using larger MOONs (1–10μm). In the absence of external fields, or material that responds to external fields, the particles tumble erratically due to Brownian thermal forces. These erratic changes in orientation cause the MOONs to blink. The temporal pattern of blinking contains information about the local rheological environment and any forces and torques acting on the MOONs.
Does Biology Have Laws? The Experimental Evidence
- Robert N. Brandon
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- Journal:
- Philosophy of Science / Volume 64 / Issue S4 / 1997
- Published online by Cambridge University Press:
- 01 April 2022, pp. S444-S457
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- 1997
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In this paper I argue that we can best make sense of the practice of experimental evolutionary biology if we see it as investigating contingent, rather than lawlike, regularities. This understanding is contrasted with the experimental practice of certain areas of physics. However, this presents a problem for those who accept the Logical Positivist conception of law and its essential role in scientific explanation. I address this problem by arguing that the contingent regularities of evolutionary biology have a limited range of nomic necessity and a limited range of explanatory power even though they lack the unlimited projectibility that has been seen by some as a hallmark of scientific laws.
The Indeterministic Character of Evolutionary Theory: No “No Hidden Variables Proof” But no Room For Determinism Either
- Robert N. Brandon, Scott Carson
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- Journal:
- Philosophy of Science / Volume 63 / Issue 3 / September 1996
- Published online by Cambridge University Press:
- 01 April 2022, pp. 315-337
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- September 1996
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In this paper we first briefly review Bell's (1964, 1966) Theorem to see how it invalidates any deterministic “hidden variable” account of the apparent indeterminacy of quantum mechanics (QM). Then we show that quantum uncertainty, at the level of DNA mutations, can “percolate” up to have major populational effects. Interesting as this point may be it does not show any autonomous indeterminism of the evolutionary process. In the next two sections we investigate drift and natural selection as the locus of autonomous biological indeterminacy. Here we conclude that the population-level indeterminacy of natural selection and drift are ultimately based on the assumption of a fundamental indeterminacy at the level of the lives and deaths of individual organisms. The following section examines this assumption and defends it from the determinists' attack. Then we show that, even if one rejects the assumption, there is still an important reason why one might think evolutionary theory (ET) is autonomously indeterministic. In the concluding section we contrast the arguments we have mounted against a deterministic hidden variable account of ET with the proof of the impossibility of such an account of QM.
Sober on Brandon on Screening-Off and the Levels of Selection
- Robert N. Brandon, Janis Antonovics, Richard Burian, Scott Carson, Greg Cooper, Paul Sheldon Davies, Christopher Horvath, Brent D. Mishler, Robert C. Richardson, Kelly Smith, Peter Thrall
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- Journal:
- Philosophy of Science / Volume 61 / Issue 3 / September 1994
- Published online by Cambridge University Press:
- 01 April 2022, pp. 475-486
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- September 1994
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Sober (1992) has recently evaluated Brandon's (1982, 1990; see also 1985, 1988) use of Salmon's (1971) concept of screening-off in the philosophy of biology. He critiques three particular issues, each of which will be considered in this discussion.
A Simple Theory of Evolution by Natural Selection
- Robert N. Brandon
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- Journal:
- Philosophy of Science / Volume 59 / Issue 2 / June 1992
- Published online by Cambridge University Press:
- 01 April 2022, pp. 276-281
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- June 1992
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Kary (1990) defends the view that evolution by natural selection can be adequately explained in terms of a theory incorporating only a single level of selection. Here I point out some of the inherent inadequacies of such a theory.
Grene on Mechanism and Reductionism: More Than Just a Side Issue
- Robert N Brandon
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- Journal:
- PSA: Proceedings of the Biennial Meeting of the Philosophy of Science Association / Volume 1984 / Issue 2 / 1984
- Published online by Cambridge University Press:
- 28 February 2022, pp. 344-353
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- 1984
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Two summers ago Marjorie Grene described a mutual acquaintance as a young fogy. That immediately suggested a fourfold classification: Young fogies, old fogies, young turks and old turks. Marjorie's place in this classification is obvious; moreover, it is relevant to today's session. Were she just out of graduate school we would wait awhile to honor her. Here she a fogy we wouldn't bother.
One of the ways Grene has expressed her anti-fogyism has been her consistent attacks on reductionism, especially reductionism in the philosophy of biology. In this paper I want to discuss the common association between ontological reductionism and a methodological position I will call mechanism. I wish to make three major points: (1) Mechanism (as I characterize it) is not to be identified with reductionism in any of its forms; in fact, mechanism leads to a nonreductionist ontology.
A Structural Description of Evolutionary Theory
- Robert N. Brandon
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- Journal:
- PSA: Proceedings of the Biennial Meeting of the Philosophy of Science Association / Volume 1980 / Issue 2 / 1980
- Published online by Cambridge University Press:
- 21 March 2022, pp. 427-439
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- 1980
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What is the structure of evolutionary theory? The question seems to presuppose a unique right answer. But the relevant notion of structure is highly relative to broad philosophic theories about scientific theories. At present no one such theory dominates. One once did. It went by the name ‘Logical Positivism’. During its heyday a unique right answer to our question might have been expected. There is no reason to expect one now.
Not only should one not suppose that there is a uniquely correct structural description of evolutionary theory, neither should one suppose that giving a structural description of evolutionary theory is essentially uncovering what is implicit in biological work. That approach is appropriate only when conceptual fossilization has occurred. In the case of evolutionary theory molding is more appropriate than uncovering.
‘Evolution’
- Robert N. Brandon
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- Journal:
- Philosophy of Science / Volume 45 / Issue 1 / March 1978
- Published online by Cambridge University Press:
- 01 April 2022, pp. 96-109
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- March 1978
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These days ‘evolution’ is usually defined as any change in the relative frequencies of genes in a population over time. This definition and some obvious alternatives are examined and rejected. The criticism of these definitions points out the need for a more holistic analysis of genotypes. I attempt such analysis by introducing measures of similarity of whole genotypes and then by grouping genotypes into similarity classes. Three sorts of measures of similarity are examined: a measure of structural similarity, a measure of functional similarity and one of relational or historical similarity. The functional approach is shown to be superior and a definition of ‘evolution’ is suggested.