When I learned about Pesach as a kid, I was taught that when flour and water are mixed together the mixture begins to rise after eighteen minutes, and this makes it chometz. The implication was that this was a physical change. Before eighteen minutes the dough had not yet begun to rise, and so it was still kosher l'Pesach. After eighteen minutes, it was chometz.
The problem here is that this isn't the way the world works. Yeast is a naturally-occurring parasite that lives on grains and other produce. When it is wet it metabolizes starches and sugar to make more of itself, giving off gasses in the process. It is these gasses that make bread rise. Eighteen is a magic number in Judaism, but yeast doesn't know that. Fermentation begins as soon as the water and flour are mixed together, not eighteen minutes later.
The problem can be solved by reclassifying chometz as a legal rather than a descriptive definition. Dough becomes chometz after eighteen minutes because that's the rule rather than because of some physical change. This sidesteps the empirical problem, but leaves two others.
The first is that this wasn't the original understanding. When the halacha was first formulated, people didn't know about microorganisms like yeast or how their lifecycles affect our baking. They just knew that if you mixed flour and water and left it alone long enough in a warm place, it would rise, and that by adding a bit of already-risen dough to a new batch, you could make it rise faster. Why this happened was a mystery. It wasn't until the invention of the microscope in the 1600s that it was discovered that there were tiny things on grain, and it wasn't until the mid-1800s that it was understood that these things were alive and were what made bread rise.
Given their lack of modern knowledge, it was reasonable for the formulators of the halachos of chometz to assume that it took some time for whatever it was that made bread rise to start working. If you watch a batch of dough, it certainly seems that it takes a while before anything happens. The importance of eighteen led them to use that number, and for millennia it was thought that dough doesn't begin to rise until eighteen minutes after the water and flour are mixed together. It is only in the last hundred and fifty years, when we learned how it really works, that it became necessary to reclassify chometz as a legal rather than a physical definition.
The second problem is that it makes the definition of chometz arbitrary. There is no discernible difference between a batch of dough that has been sitting for seventeen minutes and one that has been sitting for nineteen minutes. Instead of something real, chometz becomes a rule in a game we're playing called "Judaism." It's no longer that chometz is a different kind of thing than non-chometz, and we avoid that thing during Pesach because the nature of the holiday is such that chometz affects us differently than it does the rest of the year. Instead, chometz and non-chometz are separated only by the rules of the game. They are the same thing, but the rules say that after eighteen minutes we call dough "chometz" and treat it as if it were different than non-chometz.
Some try to save the sense of chometz and non-chometz really being different types of things by shunting the difference off into the metaphysical world. Although here, in the physical world, we don't see a difference, in the olam haemes there is a profound spiritual difference between them. Putting aside the oddity of people who decry the corrosive effects of "Greek wisdom" embracing a Platonic conception of the cosmos, this is obviously a post-hoc attempt to save the reality of the distinction between chometz and non-chometz. Right up until we knew differently, it was assumed that there was a real physical difference. As soon as we found out how fermentation really works, the difference was shunted off into an inaccessible metaphysical world where it is safe from empirical investigation.
One of the first major figures to change the underpinnings of halachos from physical to metaphysical was the Maharal, who lived through the beginning of the Scientific Revolution in the mid-1500s. That this trend emerged just as we began to discover how the world really works should make it obvious that it was not so much a revelation about the true nature of halacha as it was an attempt to keep halacha from becoming irrelevant as it's real-world justifications were cut out from under it.
For most of its history, the halachos of chometz were thought to rest on a real difference between chometz and non-chometz. They were different kinds of stuff, and so it made sense to treat them differently. As soon as it was discovered that's not so, chometz became just a rule in the Judaism game, weakly bolstered by the unknowable assertion that metaphysically, they really are different. This is the danger that science poses to religion. Rules that were once simply a reflection of reality become arbitrary, and those who want them to be more than that are left to petulantly insist that their game is real after all, in an inaccessible higher reality that small-minded materialists refuse to acknowledge just because there is no reason to posit its existence other than to keep religious rules from becoming arbitrary.