Back to Mr. Richardson:
Set up lines:
Use no more than one or two lines (sentences) to set up a joke.
These set up lines must give the audience all the information they need to get the joke in as few words as possible.
So, you don't want the setup to be too long, or the audience loses interest. At the same time, you need to give them the information they need to understand and appreciate the joke.
Is this funny?
Probably not.
And if you do not know what DNA or genes are, definitely not. In order to understand, and appreciate, the joke, you must know:
that DNA are the long, twisted strings of genes,
that DNA strands are a double row that look like a twisted ladder,
that helicase is a chemical used by scientists to untwist and split the double row, like cutting the ladder rungs in half,
that this splitting and untwisting is called unzipping the DNA strand,
and that biological genes and the type of pants, jeans, which have zippers that people sometimes forget to pull up after using the bathroom, sound the same despite being spelled differently.
Now that I explained all that, the joke is funny, right?
Still probably not. Explaining the information afterwards ruins the joke. That is why you need to give your audience the information they need in the set up. At the same time, you want to keep it as short as you can. Give the audience the information they need, but nothing more. And different audiences don't necessarily need the same things.
No one said it was easy.
If Scott Adams had spent a paragraph explaining what a Disaster Recovery Plan means and what a legitimate plan would contain, this would not be as funny. It is funny because you can figure out what it should be and why this isn't it.
So, the setup should be direct, short, and get as broad an audience as possible to the point where they can enjoy the punchline.
But first, by the teachers' code I am required to make you answer some questions:
1) Think of an everyday situation when you thought something was funny? For example try remembering a scene when you were talking with your friends about your lives and ended up laughing? What made you laugh? What was funny?
2) Think of a serious situation that you have encountered or encounter daily? Now try to reframe it in a way as to make it funny. What is absurd about that serious situation?
Comics are great because they can convey the set up through the image, giving a lot of information very quickly. Gary Larson is a master at this in his Far Side comics:
Sometimes the humor of a joke comes from intentionally breaking the rules to an absurd degree. Here is an example. The joke is almost 4 minutes long. Notice how much he adds after the punchline. (Also, notice the smaller jokes within the joke, but that is another story...)