Paracelsus (1493-1541) was the first physician to understand this concept based on his experiments, "All substances are poisons; there is none that is not a poison. The right dose differentiates a poison, and a remedy." In his experiments, he plotted what we call today "dose-response relationships." Such experiments determine the percentage of organisms or systems that respond to chemicals at increasingly higher doses. Below a certain threshold dose, no adverse effects or therapeutic effects are observed.
The existence of a dose-response relationship strengthens the evidence for a causal relationship between the chemical and the disease. This is fairly simple to do for acute effects like carbon monoxide poisoning. With increasing doses above the threshold dose, increasing number of experimental animals have adverse effects. The dose-response relationship is also important in determining causality in chronic diseases, for example, the fact that moderate smokers have intermediate risks for lung cancer compared with nonsmokers and heavy smokers.
