Models in Systems Biology: the Parameter Problem and the Meanings of Robustness

I co-teach a graduate course at Harvard called “An Introduction to Systems Biology”. It covers some of the mathematical methods used to build mechanistic models of molecular and cellular systems. Beginning students tend to ask twokinds of questions. Those with a biological background say “Why do I need to use mathematical models? What can they tell me that conventional biological methods cannot?”, while those from the physical sciences (mathematics, physics, engineering) or computer science say“I knowhow tomodel. Why is biologyanydifferent fromphysics or engineering?”. Broadly speaking, everyone wants to know, from very different perspectives, “How do I do systems biology?”. Students are usually under the misapprehension that the person standing in front of them knows the answers to such questions. In my case, I was only marginally less ignorant than the students themselves. It was their curiosity