This presentation opened a two-day symposium held at Cornell University in September 2003 to explore how biological and social factors are intertwined in the development of and response to environmental and health risks. The presentation explores the roles of biophysical and social factors in the construction of risk and the assessment of risk issues. It looks at how cross-disciplinary bridges, networks and communication between biologists and physical scientists, on the one hand, and social scientists, on the other, can be strengthened to carry out the outreach and research missions of the Land Grant Universities. The disease smallpox is used as the case example because the fear and reality of smallpox has affected and been affected by the course of wars, economic power, political dominance and subjugation, civil liberties, social cohesion, trust, mental health, and the quality of life in families and communities. Biological and social factors have been intertwined throughout history in setting and responding to the course of this disease.