What's the difference between heirloom and direct-set yogurt cultures? Yogurt cultures seem to come in two varieties: heirloom and direct-set. 

The difference between the varieties is that one is a carefully selected mix of bacterial strains (direct-set), and the other is a "mother" that's been cultivated and sustained over generations (heirloom). 

Most direct-set culture will specify that the culture cannot be reused. This means that once the yogurt is done culturing, one should not use a part of that yogurt to culture more milk.

On the other hand, heirloom cultures are specifically meant to be reused and sustained. 

Where does the difference lie? 

My guess is that the direct-set is not a "stable" symbiotic mixture of microbes, so the fear is that if one reuses that yogurt AFTER it's been sitting in the fridge, it'll have some additional microbes it may have picked up in it, which may foul the next batch.

The heirloom variety may be more "stable" in some way, so any additional microbes may be out-competed and won't survive into the next batch.

Another question is: if contamination is the only worry in direct-set cultures, could one immediately freeze direct-set yogurt (to avoid contamination) and then reuse it to get similar results?
It's simple. Heirlooms will produce expected results no matter how many times you reinoculate your culture. Direct set is a blend of species and eventually only the strongest strain will remain and it may not create anything you want to eat. I never bought cultures, I just buy plain or vanilla yogurt, eat it and use what's left behind to make another batch.

Remember the single most important part of yogurt making is hygiene. I can't stress this enough. Yogurt won't always tell you it's bad until it's too late and you eat it and get very very sick. Trust me on this from experience. With yogurt HYGIENE is the most important part of the process.!!!