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BCB HomeResearch AreasFaculty ProfilesPaul M. Bingham

Paul M. Bingham

PhotoAssociate Professor Emeritus
Department of Biochemistry and Cell Biology

E-mail: paul.bingham@stonybrook.edu

  • Research Description

    Overview of Research History

    After completing a PhD in Biochemistry and Molecular Biology at Harvard in 1980, Paul spent two years at the NIH branch in Research Triangle Park before jointing the faculty of the School of Medicine at Stony Brook University where he has worked for the last 43 years. Paul’s research interests are diverse.  His early work focused on  metazoan molecular genetics.  Among his many contributions are discovery of the P element transposon (in collaboration with Margaret Kidwell and Gerry Rubin; Bingham, et al., 1982), development of the P element transposon tagging cloning strategy (in collaboration with Arno Greenleaf’s group; Searles, et al., 1982) discovery of novel mechanisms of transcriptional enhancer function (in collaboration with Zuzana Zachar; Bingham and Zachar, 1985), discovery of novel forms of post-transcriptional regulation (in collaboration with Tze-bin Chou, Zuzana Zachar and Debbie Spikes; Chou, et al., 1987; Zachar, et al., 1987; Spikes, et al., 1994) and discovery of fundamental mechanisms of intra-nuclear molecular transport (in collaboration with Joe Kramer and Zuzana Zachar; Zachar, et al., 1993).

    Paul has also made major contributions to understanding human evolution, including the development of the first complete, coherent theory of human origins, behavior, and history we have ever had (reviewed in Bingham and Souza, 2009). See below for more detail.

    In recognition of his diverse research and service contributions, Paul received an honorary doctorate from his alma mater, Blackburn College, in May of 2006.

    Current Research

    Current Research

    More recently Paul’s research has focused on two areas.

                First, in collaboration with Prof. Zuzana Zachar (shown at right), Paul has been pursuing a novel approach to cancer chemotherapy.  This approach exploits the increasingly well-characterized differences in patterns of metabolism between tumor cells and normal cells (including normal growing stem cell populations). Lipoic acid is both a catalytic component of the two enzymes through which almost all carbon enters tumor cell mitochondria as well as the source of regulatory signals that control this carbon flux and tumor cell mitochondrial metabolism more generally. Zuzana and Paul have shown that these regulatory signals and their targets are so extensively different in tumor and normal cells that properly designed lipoate analogs – mis-informing these regualtory processes - can be used to selectively kill tumor cells, through catastrophic inhibition of tumor mitochondrial metabolism. The first of our lipoate analogs to be subjected to clinical trial is designated CPI-613 or devimistat.

    The crucial feature of this approach is that it apparently allows the killing of tumor cells without killing growing normal cells in vivo. The therapeutic index of these lipoate analog drugs in human tumor animal models can be as high as two-three orders of magnitude as a result of these properties. This is essentially unprecedented among cancer chemotherapeutic agents. Virtually all chemotherapeutic approaches currently in wide use kill normal cells with appreciable frequency – resulting in side-effect toxicity that is often quite severe (occassionally even fatal).

                This approach was originally developed by Zuzana and Paul and Stony Brook University holds a patent on these agents. Liscensing of these patents led the first major clinical trials, from which we learned an enormous about about the behavior of these drugs (Alistar, et al., 2017). On the basis of these results we have carried out an additional major body of basic preclinical work on the molecular/cellular mechanims of CPI-613 tumor resistance (Guardado Rivas, et al., 2022; Bingham and Zachar, 2023). We are now developing a second generation of molecules from this family designed to overcome clinical resistance (our unpublished work in progress).

                In recognition of their research contributions Paul and Zuzana received the Michael Maffetone Award for Cancer Research by the Carol M. Baldwin Breast Cancer Research Fund in the Fall of 2008 (see picture below from the award ceremony; Pictured, from left, are: Dawn Maffetone, Carol M. Baldwin, Paul, Zuzana, Billy Baldwin, and John Stoerback, Board President, Carol M. Baldwin Research Fund).

    group

    Second, Paul has developed a fundamentally new theory of the origin of humans as a unique species with diverse, unprecedented properties (Bingham, 1999 and 2000). This novel approach has subsequently been extensively refined in collaboration with economist Daijiro Okada (Okada and Bingham, 2008) and pschologist Joanne Souza (Bingham and Souza, 2009, 2011)(see pictures of Joanne and Daijiro on next page). This theory proposes that unique human properties (includuing complex language, enlarged brains and cognitive virtuosity, complex ethical/political psychology and vast ecological dominance) are all results or features of a single, underlying adaptation – vastly expanded, unprecedented social cooperation independent of close genetic kinship. Non-human animals never display this pattern of social behavior.

                Moreover, this uniquely human social adaptation, in turn, has a single, simple underlying cause – unprecedented access to inexpensive social coercion (and coercive threat). This novel capacity makes “law enforcement” a co

    herent Darwinian adaptation only in humans among all terrestrial animals. This unique access to coercion initially developed through the evolution of the uniquely human capacity for elite aimed throwing (allowing cost-effective social coercive threat).  As a result, humans have an ~two million year history of exquisite adaptation to the use of social coercion to sustain vast, productive social cooperation.  As we humans have developed ever newer coercive technologies we have continued to deploy them to sustain this cooperation on ever larger scales. As a result of these features, this approach as come to be called “social coercion theory.”

                Social coercion theory is unprecedented in its simplicity, on the one hand, and its predictive power, on the other.  These features, collectively, constitute parsimony – a property of all strong, useful theories.

    This theory has novel power to predict all the diverse features of the fossil record of human origins (including the recent, exciting findings emerging for the Dmanisi dig in former Soviet Republic of Georgia, for example) and the origin and details of individual human properties (including language, brain expansion, cognitive virtuosity and sexual/child-rearing behaviors).  Moreover, this approach inevitably contains within it a theory of history of unprecedented detail and completeness – able to predict the salient details of the behaviorally modern human revolution, the agricultural revolutions and the rise of the archaic and modern

    states, for example.

    Joanne SouzaPaul and collaborator, Joanne Souza, have recently published a book-length treartment of the diverse implications of the theory (Bingham and Souza, 2009, 2011). More recently Joanne and Paul continue topublish refinements and developments of the theory (see publications below). They organized and chaired a Symposium at the National meeting of the Society for American Archaeology on the role of the bow in driving the prehistoric North American Neolithic revolutions, culminating in a dedicated issue of Evolutionary Anthropology (May/June 2013). Joanne and Paul continue to give public lectures in diverse setting, bringing social coercion theory to the various subcultures withing the human sciences.

    Paul was part of a panel presentation/discussion of theories of human uniqueness hosted by the pretigious World Science Festival entitled “Planet of the Humans” together with fellow participants on May 29, 2015 (l to r in image below; moderator Brian Lehrer; prominent human evolutionary scientists, Dean Falk, Steve Pinker, PMB, and Lee Berger). The session was delivered in front of a live audience of ~1000 and simultaneously streamed to a global audience

    Paul Bingham and collaborator

     (https://www.youtube.com/watch?v=V3IlnuMG39U).

    Paul and Joanne continue to work on development of an enhanced understanding of human behavior and the human future, including a new book and several other publications. This work is especially important in view of the increasing dysfunction of contemporary political systems.

  • Current Teaching and Services
     

    Wold Science Festival PannelPaul’s theoretical work on human origins, properties and history have lead to a variety of ongoing educational projects.

    First, in collaboration with Joanne Souza, Paul developed and teaches a large, successful Stony Brook University course on biological theories of human origins, properties and history  (BIO358), reaching over 10,000 students. Our approach to the course has taken on a new level of sophistication as we have expanded our pedgogical and technical capabilities, on pace with the evocative, important course content.  This course is a vigorous, exciting exploration of the crucial issues in this area.  Students emerge with an entirely new perspective on themselves and on what it means (and has meant) to be human. 

    Second, in collaboration with Joanne, Paul has developed a state-of-the-art online version of this course (BIO358 online). This online course has been successfully delivered to a large group of Stony Brook students over the last ten years. This is an exciting experiment with great potential to enrich the educational experiences of our students. In the course of this project, we developed world-class expertise in online instruction.

    Third, our courses were structured to provide a uniquely powerful educational research environment. They provide enormous sample sizes for robust evaluation of new pedagogical practices and techniques and for the comparison of traditonal live teaching with online instruction. Our twenty years of research in this environment have allowed us to make dramatic, demonstrable progress in diverse areas such as improved quality of instruction and breaking the size barrier in online instruction (allowing a few faculty to teach hundreds of student well online).

    Fourth, Paul has supported Joanne Souza’s important work in brining new strategies for online education to teaching in Undergraduate Biology more generally. This collaborative project has the potential to revolutionize the teaching of biology at Stony Brook.

    Fifth, Paul invested extensively in University service. He served on the CAPRA subcommittee of the University Senate for over eight years, contributing to this important committee’s ongoing work in diverse ways.

    Finally, Paul’s longstanding belief in the crucial interconnection between high quality research and undergraduate teaching have led to a variety of further important educational projects.  In addition to the human origins courses mentioned above,  Paul served for four years as the founding Faculty Director for one of the new Undergraduate Colleges at Stony Brook – in collaboration with Joanne Souza. In building the College of Human Development Joanne and Paul initiated a number of new programs and features designed to help students (especially incoming freshman and sophomores) to access the vast opportunities presented by the large, rich faculty of this major research university. Many of these innovations persist in use today.

  • Selected Publications

    Bingham, P. M., & Zachar, Z. (2023). Toward a unifying hypothesis for redesigned lipid catabolism as a clinical target in advanced, treatment-resistant carcinomas. International Journal of Molecular Sciences, 24(18). doi:10.3390/ijms241814365

     

    Guardado-Rivas, M. O., Stuart, S. D., Thach, D., Dahan, M., Shorr, R., Zachar, Z., & Bingham, P. M. (2022). Evidence for a novel, effective approach to targeting carcinoma catabolism exploiting the first-in-class, anti-cancer mitochondrial drug, CPI-613. Plos One, 17(6). doi:10.1371/journal.pone.0269620

     

    Souza, J and Bingham PM (2019). The new human science: sound, new evolutionary theory gives us ultimate causal understanding of human origins, behavior, history, politics, and economics. in Evolutionary Studies: Darwin’s Roadmap to the Curriculum. Oxford University Press.

     

    Alistar, A….Bingham, PM….et al. (2017) Safety and tolerability of the first-in-class agent CPI-613 in combination with modified FOLFIRINOX in patients with metastatic pancreatic cancer: a single-centre, open-label, dose-escalation, phase 1 trial. Lancet Oncology S1470-2045(17)30314-5  http://dx.doi.org/10.1016/

     

    Bingham, PM, Stuart, SD and Zachar, Z. (2014) Lipoic acid and lipoic acid analogs in cancer metabolism and chemotherapy. Expert Review of Clinical Pharmacology, 7, 837-846.

     

    Stuart, SD, Schauble, A, Gupta, S, Kennedy, AD,  Keppler, BR, Bingham, PM, Zachar, Z. (2014) A strategically designed small molecule attacks alpha-ketoglutarate dehydrogenase in tumor cells through a redox process. Cancer & Metabolism2,4.

     

    Bingham, PM, Stuart, SD and Zachar, Z. (2014)Cancer metabolism: a nexus of matter, energy, and reactive oxygen species. pgs.7-28  in Tumor Metabolome Targeting and Drug Development. eds. Steven Kanner (Arrowhead Research) and Beverly A. Teicher (NCI). Springer, New York.

     

    Souza, J. & Bingham P. M. (2014). Disciplinary unification of the natural sciences, the humanities, and the social sciences: Adapted minds and strategic approaches to consilience in the academy. EvoS Journal: The Journal of the Evolutionary Studies Consortium, 6(1), 51-62.

    http://evostudies.org/wp-content/uploads/2014/01/Souza-Bingham_Vol6Iss1.pdf

     

    Bingham PM, Souza J. Theory testing in prehistoric North America: Fruits of one of the world's great archeological natural laboratories. Evolutionary Anthropology. 2013;22(3):145-53.

     

    Bingham PM, Souza J, Blitz JH. Social complexity and the bow in the prehistoric North American record. Evolutionary Anthropology. 2013;22(3):81-8.

     

    Bingham PM, Souza J. The evolved apprentice: how evolution made humans unique. (book review) American Journal of Human Biology. 2012;24(6):871-2.

     

    Bingham, P.M. and Souza, J. (2012). Ultimate causation in evolved human political psychology: implications for public policy. Journal of Social, Evolutionary, and Cultural Psychology. 6(3):360-83.

     

    Bingham, P.M. and Zachar, Z. (2012).  The pyruvate dehydrogenase complex in cancer: Implications for the transformed state and cancer chemotherapy. Chapter 3 In: Dehydrogenases”\ Canuto, RA ed. InTech Press.

    http://www.intechopen.com/articles/show/title/the-pyruvate-dehydrogenase-complex-in-cancer-implications-for-the-transformed-state-and-cancer-chemo   

     

    Zachar, Z, Marecek, J, Maturo, C., Gupta, S, Stuart S.D., Howell, K., Schauble, A., Lem, A., Piramzadian, A., Karnik, S., Lee, K., Rodriguez, R., Shorr, R. and Bingham, P.M. (2011). Non-redox-active lipoate derivates disrupt cancer cell mitochondrial metabolism and are potent anticancer agents in vivo. Journal of Molecular Medicine 89(11): 1137-1148. DOI 10.1007/s00109-011-0785-8

     

    Bingham P.M. and Souza, J. (2011). Death from a distance and the birth of the humane universe: Human evolution, history and your future. KINDLE EDTION. BookSurge, South Carolina

     

    Bingham P.M. and Souza, J. (2009). Death from a distance and the birth of the humane universe: Human evolution, history and your future. BookSurge, South Carolina.

     

    Bingham, PM, (2009).  On the evolution of language: Implications of a new and general theory of human origins, properties and history in: Larson, RK, Deprez, V, and Yamakido, H, (Eds.), The Evolution of Human Language: Biolinguistic Perspectives, Cambridge University Press., Cambridge, UK.

     

    Okada, D. and Bingham, P.M. (2008).  Human uniqueness - self-interest and social cooperation.  Journal of Theoretical Biology  253, 261– 270

     

    Bingham, P. M. (2000). Human evolution and human history: A complete theory. Evolutionary Anthropology 9(6): 248-257.

               

    Bingham, P. M. (1999). "Human uniqueness: A general theory."  Quarterly Review of Biology 74(2): 133-169.

               

    Bingham, P. M. (1997). Cosuppression comes to the animals. Cell 90(3): 385-387.

               

    Spikes, D. A., J. Kramer, et al. (1994). SWAP pre-messenger-RNA splicing regulators are a novel, ancient protein family sharing a highly conserved sequence motif with the prp21 family of constitutive splicing proteins. Nucleic Acids Research 22(21): 4510-4519.

     

    Kramer, J., Zachar, Z., Bingham, PM. (1994). Nuclear pre-mRNA metabolism: channels and tracks. Trends in Cell Biology4(2): p35–37.

     

    Zachar, Z., T. B. Chou, et al. (1994). Analysis of autoregulation at the level of pre-messenger-RNA splicing of the suppressor-of-white-apricot gene in Drosophila." Genetics 137(1): 139-150.

               

    Zachar, Z., J. Kramer, et al. (1993). Evidence for channeled diffusion of pre-messenger RNAs during nuclear-rna transport in metazoans. Journal of Cell Biology 121(4): 729-742.

               

    Spikes, D. and P. M. Bingham (1992). Analysis of spliceosome assembly and the structure of a regulated intron in Drosophila in vitro splicing extracts. Nucleic Acids Research 20(21): 5719-5727.

               

    Li, H. and P. M. Bingham (1991). arginine-serine-rich domains of the su(wa) and tra RNA processing regulators target proteins to a subnuclear compartment implicated in splicing. Cell 67(2): 335-342.

               

    Zachar, Z. and P. M. Bingham (1989). Suppressible insertion-induced mutations in Drosophila. Progress in Nucleic Acid Research and Molecular Biology 36: 87-98.

               

    Bingham, P. M., T. B. Chou, et al. (1988). On/off regulation of gene-expression at the level of splicing. Trends in Genetics 4(5): 134-138.

               

    Chou, T. B., Z. Z. Zachar, et al. (1987). Developmental expression of a regulatory gene is programmed at the level of splicing." EMBO Journal 6(13): 4095-4104.

               

    Zachar, Z. Z., T. B. Chou, et al. (1987). Evidence that a regulatory gene autoregulates splicing of its transcript." EMBO Journal 6(13): 4105-4111.

               

    Zachar, Z., D. Garza, et al. (1987). Molecular cloning and genetic analysis of the suppressor-of-white-apricot locus from Drosophila melanogaster. Molecular and Cellular Biology 7(7): 2498-2505.

               

    Zachar, Z., T. B. Chou, et al. (1987). suppressor-of-white-apricot is a post-transcriptionally autoregulated gene. Journal of Cellular Biochemistry: 31-31.

               

    Bingham, P. M. and C. H. Chapman (1986). Evidence that white-blood is a novel type of temperature-sensitive mutation resulting from temperature-dependent effects of a transposon insertion on formation of white transcripts. EMBO Journal 5(12): 3343-3351.

               

    Zachar, Z., C. H. Chapman, Bingham, P.M., et al. (1985). On the molecular-basis of transvection effects and the regulation of transcription." Cold Spring Harbor Symposia on Quantitative Biology 50: 337-346.

               

    Zachar, Z., T. B. Chou, et al. (1986). Developmental regulation of suppressor-of-white-apricot transcription. Journal of Cellular Biochemistry: 74-74.

               

    Zachar, Z., D. Davison, et al. (1985). A detailed developmental and structural study of the transcriptional effects of insertion of the copia transposon into the white locus of Drosophila melanogaster." Genetics 111(3): 495-515.

               

    Davison, D., C. H. Chapman, et al. (1985). Genetic and physical studies of a portion of the white locus participating in transcriptional regulation and in synapsis-dependent interactions in Drosophila adult tissues. Genetics 110(3): 479-494.

               

    Bingham, P. M. and Z. Zachar (1985). Evidence that 2 mutations, w(DZL) and z(1), affecting synapsis-dependent genetic behavior of white are transcriptional regulatory mutations." Cell 40(4): 819-825.

               

    Ginzburg, L. R., P. M. Bingham, et al. (1984). "On the theory of speciation induced by transposable elements." Genetics 107(2): 331-341.

               

    Searles, L. L., R. S. Jokerst, et al. (1982). Molecular cloning of sequences from a |Drosophila RNA polymerase-II locus by p-element transposon tagging. Cell 31(3): 585-592.

               

    Zachar, Z. and P. M. Bingham (1982). Regulation of white locus expression - the structure of mutant alleles at the white locus of Drosophila melanogaster. Cell 30(2): 529-541.

               

    Rubin, G. M., M. G. Kidwell, et al. (1982). "The molecular basis of PM hybrid dysgenesis - the nature of induced mutations." Cell 29(3): 987-994.

               

    Bingham, P. M., M. G. Kidwell, et al. (1982). The molecular-basis of PM hybrid dysgenesis - the role of the P-element, a P-strain-specific transposon family." Cell 29(3): 995-1004.

               

    Bingham, P. M. (1980). A Novel dominant mutant allele at the white locus of Drosophila melanogaster Is Mutable. Cold Spring Harbor Symposia on Quantitative Biology 45: 519-525.

               

    Bingham, P. M., R. Levis, et al. (1981). Cloning of DNA-sequences from the white locus of Drosophila-melanogaster by a novel and general method. Cell 25(3): 693-704.

               

    Bingham, P. M. and B. H. Judd (1981). "A copy of the copia transposable element is very tightly linked to the wa allele at the white locus of Drosophila melanogaster." Cell 25(3): 705-711.

               

    Bingham, P. M. (1980). The regulation of white locus expression - a dominant mutant allele at the white locus of Drosophila melanogaster. Genetics 95(2): 341-353.

               

    Wu, C., P. M. Bingham, et al. (1979). Chromatin structure of specific genes .1. evidence for higher-order domains of defined DNA sequence. Cell 16(4): 797-806.

               

    Bingham, P. M., R. H. Baltz, et al. (1976). Heat mutagenesis in bacteriophage-T4 - Transversion Pathway. Proceedings of the National Academy of Sciences of the United States of America 73(11): 4159-4163.

  • Education, Employment and Selected Honors
    • 1973 - BA, Biology Blackburn College
    • 1975 - MS, Microbiology University of Illinois
    • 1980 - PhD, Biochemistry and Molecular Biology, Harvard University
    • 1980 - 1982 Staff Fellow

       Laboratory of Genetics, NIEHS, Research Triangle Park, NC
    • 1982 - 1988 Assistant Professor, Department of Biochemistry

       State University of New York, Stony Brook, NY
    • 1988 - 2025 Associate Professor, Department of Biochemistry & Cell Biology - State University of New York, Stony Brook, NY
    • 2026 - Present Emeritus faculty, Department of Biochemistry & Cell Biology - State University of New York, Stony Brook, NY
    • 2006 Honorary doctorate, Blackburn College
    • 2008 Michael Maffetone Award for Cancer Research - Bestowed by the Carol M. Baldwin Breast Cancer Research Fund in recognition of our drug development work
  • Invited Lectures