I think there must be a gene for it: the innate ability to think about biological cause-and-effect as an abstract pathway instead of as concrete machinery. Classical geneticists do it effortlessly. Their vocabulary is old and rich: synthetic lethal; partial rescue; incomplete penetrance. And these phrases evoke a time when biology was all smooth and wrinkled peapods, ochre- or amber-eyed fruit flies, striped petunias.
In the minds of true geneticists, genes enhance and suppress, and exert their effects upstream and downstream of other genes. And thought processes are unsullied by the need to picture what the gene products are actually doing. Proteins binding, proteins being modified, proteins translocating to the nucleus – it can all be irrelevant, if you just let it wash over you. Of course many geneticists nowadays can and do care about proteins, but they still retain this enviably breezy grasp of the almost ghostly conceptual scaffold that can be placed around them.
If there is a gene for the geneticist mindset, then I am surely a homozygous null mutant. Of course certain thought experiments are easy. In the following example,
A –> B –> C –> Effect
it’s pretty straightforward: A activates B which activates C which leads to a perceptible manifestation. These could be a chain reaction of kinases, say, leading to the onset of mitosis. Knock out B and mitosis no longer occurs: but knock out B while simultaneously adding a dose of exogenous C and mitosis is rescued. If you hadn’t already known that this pathway unfolded in that order, an epistasis experiment like this could help you to sort it out.
It all gets a bit sticky when your hypothesized pathway is more complicated, as in
A –| B –| C –> D –| Effect
that is, when your players are inhibiting as well as activating. And when you start knocking down multiple genes at once to get a feel for the order, it begins to seem, qualitatively, like one of those drunken sentences: “It isn’t that I don’t not dislike you, but…”
Fortunately, it’s nothing that an intense session with pen, paper, salted cashews and a few cocktails down at Henry’s Bar with a good friend can’t clear up. After a few Cosmopolitans, this genetics thing is doddle.