In ancient Greece between the fifth and first centuries BC, several philosophers --Leucippus, Democritus, Epicurus, and then Lucretius -- speculated that all things were comprised of something a single fundamental --and invisible- entity, which they called "atom" (in Greek, "indivisible").
This amazing insight was certainly improbable in ancient Greece. But it was not accepted by most of the philosophers familiar with the concept. Crucially, Aristotle rejected the notion of the atom completely, and it was Aristotle's ideas that became the basis of European thought beginning in the medieval era and continuing for centuries. Although most of Aristotle's ideas were wrong, his concepts were congenial to the teachings of the Church. For this reason many scientific discoveries were blocked.
Early in the twentieth century the idea of the atom was revived, especially by the brilliant Austrian physicist, Ludwig Boltzmann. However, when Boltzmann suggested that all matter was composed of invisible, indivisible structures, he was widely ridiculed. Boltzmann's atom of course offended religious authorities, but it also contradicted the favored scientific theory of the time, which proposed energy as the most fundamental component of matter. Few scientists were prepared to consider an invisible structure (the atom) as the basis of matter. One of Boltzmann's harshest critics was Ernst Mach, a leading physicist of the late nineteenth-early twentieth centuries. Mach's prejudice that what was real must also be observable was typical of the period. An invisible reality suggested mysticism.
Ultimately, it was the young Albert Einstein who vindicated Boltzmann. In 1905, Einstein proved that the enigma known as Brownian motion was caused by the random movement of atoms. Brownian motion was first observed in the jiggling of pollen grains in still water, but remained an unexplained phenomenon until Einstein realized that it was the motion of invisible atoms that caused the movement of grains. This proved Boltzmann correct: atoms existed. Unfortunately, Einstein's discovery did not not reach Boltzmann in time. In 1906 Boltzmann committed suicide. But Einstein's proof demonstrated that atoms were the building blocks of matter. It was some time, of course, before the structure of the atom itself was understood. And as that structure was unraveled an even more fundamental level -the subatomic level- was discovered, and a whole new field of physics developed.