Paul M. Bingham, Ph.D. Associate Professor Department of Biochemistry and Cell Biology Faculty Director, College of Human Development Life Sciences Building Stony Brook University Stony Brook, NY 11794-5215 Office telephone: 631-632-8548 E-mail: pbingham@notes.cc.sunysb.edu
Research Description

Paul’s long scientific career has been unusual. He has consistently pursued the most important scientific questions available to be answered rather than narrowly specializing, as most professional scientists do.

By the end of the 1960’s the basic molecular biology of Earth’s organisms had been defined. Paul trained as a young investigator with the makers of this first “molecular revolution” – completing a PhD in Biochemistry and Molecular Biology at Harvard with Matt Meselson in 1980. Beginning his own career, Paul pursued the next great series of questions in biology – how genes build complex organisms.

In the late 1970’s Paul was among the small avante garde who moved into new experimental systems, helping to build our contemporary picture of how genomes build creatures. Among his many earlier contributions are the following:

• Organized the discovery of the P element transposon (recruiting collaborators Margaret Kidwell and Gerry Rubin; Bingham, et al., 1982, see references below).
• Developed the cloning strategy of P element transposon tagging (recruiting collaborators Arno Greenleaf and Bob Voelker to demonstrate its effectivness; Searles, et al., 1982).
  
  These two contributions revolutionized the molecular cloning of genes in animals and helped drive the intellectual revolutions of the 80’s and 90’s in biology.
  
  These two contributions also revolutionized our understanding of the fundamental logic of genetic design information as “self-interested”. Paul and colleagues (including his long time friend, the late Barbara McClintoc) refined our understanding of the interface between molecular and evolutionary biology as a result.
• Dicovered the unexpected molecular basis of the mutations used in the development of classical genetics in Drosophila in the early 20 th Century (in collaboration with Zuzana Zachar; Zachar and Bingham, 1982).
  
  These insights (together with Welcome Bender’s contemporary studies at the biothorax complex) profoundly reshaped the way we look at mutation and molecular evolution in multicellular animals.
• Discovered novel mechanisms of regulation (and evolution) of animal gene expression at the transcription level (in collaboration with Zuzana Zachar; Bingham and Zachar, 1985).
  
  These observations were an element of the revolution in understanding how “transcription enhancers” (and related elements) work in animal genomes – so differently than the regulatory elements then known from bacterial systems.
• Discovered novel forms of post-transcriptional regulation at the level of pre-mRNA splicing (in collaboration with Tze-bin Chou, Zuzana Zachar and Debbie Spikes; Chou, et al., 1987; Zachar, et al., 1987; Spikes, et al., 1994).
  
  As reviewed in Bingham et al. (1988) these observations (together with two other contemporary studies) introduced the novel, then-unexpected mode of on/off regulation of gene expression at the level of contingent processing of pre-mRNA. This area of investigation continues to generate new insight through the present.
• Made important contributions to our undertanding of the inner workings of the nuclei of animal cells (in collaboration with Joe Kramer, Hao Li and Zuzana Zachar; Zachar, et al., 1993 and Li and Bingham, 1991).

Current Research

In the past decade Paul has continued his focus on the most important accessible scientific objectives. This has taken him in two important new directions.

First, the revolution in our understanding of how genes build animals (above) has put us in the position to attack human health problems with entirely new power. In collaboration with Prof. Zuzana Zachar (shown at right), Paul has pursued this new opportunity to develop a fundamentally novel approach to cancer chemotherapy. This approach exploits the now-well-characterized differences in patterns of metabolism between tumor cells and normal cells (including normal growing stem cells).

Crucially, this approach attacks tumor cells without killing growing normal cells. This is essentially unprecedented. Virtually all other chemotherapeutic agents currently in wide use kill normal cells with appreciable frequency – resulting in side-effect toxicity that is often quite severe (occassionally even fatal).

This novel approach was developed by Zuzana and Paul in the late 1990’s and Stony Brook University holds a patent on these agents. An exclusive, world-wide liscense has now been taken on this patent by Cornerstone Pharmaceuticals (http://www.cornerstonepharma.com/). Zuzana and Paul are working with the regulatory and drug development experts at Cornerstone to bring this approach into human clinical trials in the near future.

Second, the revolutions in molecular biology of the last century (above) were paralleled by quieter (but equally important) revolutions in our understanding of the logic of evolution by natural selection. Evolutionary biology has always been another of Paul’s major scientific interests. Building on 20 th Century insights, he developed a fundamentally new, powerful theory of the origin of humans as a qualitatively unique species (Bingham, 1999 and 2000). This theory also accounts for all the unprecedented human properties (includuing complex language, large brains and cognitive virtuosity, complex ethical/political psychology and vast ecological dominance). Finally, this theory of human origins implies a fundamentally new theory of history of unprecedented scope – accounting economically for all the salient events of the human story from our origins 2 million years ago through the present.

This large project is currently being developed into a monograph directed at a global audience in collaboration with Joanne Souza (below left). This project continues to grow, including field research (see Paul at a pre-contact Native American site in Chaco Canyon, New Mexico below center) and a collaborative project with Rutgers economist Prof. Daijiro Okada (Daijiro and Paul are shown below right).

In pursuit of the human uniqueness work Paul has developed relationships and collaborations with a diverse group of investigators and thinkers in the human sciences, social sciences and humanities around the world.

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