Challenges for epidemiologic research on the verge of a new era

Although risk factor epidemiology has achieved much, it has its limitations (e.g., a failure to reveal causal mechanisms at multiple levels). To illustrate contemporary challenges for epidemiological research, we present a dialog with examples and argue for incorporating a "systems thinking through a life course" paradigm in epidemiological research. There is an increasing interest in moving part of public health from a discipline concerned primarily with risk factors at the individual level toward one concerned with complex causal patterns which often operate across different levels in time and space (e.g., from the molecular to the population, from the past to the future, and from the distal to the proximal). However, the methodology for discovering these complex and dynamic relationships remains to be improved. We propose strategies for taking up this challenge.