"For you are dust, and to dust you shall return."
--Hebrew Bible, Genesis, 3:19b
In this passage, God speaks very reductively about living humans! Does he say here "you are made of living tissue" or "you are evolved from other animals"? No, people are just terrestrial minerals, which is to say simple inorganic and organic compounds. God looks very much like a reductionist here, if not an outright eliminativist about categories such as life and consciousness. Humans are just rearranged physical stuff, and they return to the basic forms of the same physical stuff, God says here. (And yes, it is also in a very negative context, about human mortality).
So, if God can be a reductionist about human existence in some contexts, why can't we be so also? There are many scientific virtues to considering real substance and essence to be things which are very relative to context.
The human organism is a part of a larger culture, and our culture exists as part of the planet earth. On one level, we are but a part of a whole, life on Earth, which is the substance created in the Genesis stories. On another level, our organs and their systems are the substance, made of cells.
In the past century, medical science has had its greatest successes via investigations which treat animals and humans as systems of organs, not as persons, and not as cultures. This lack of holism can be seen as a limitation of much of current medicine, yet without the reductionist's ability to target substances at the level of the body's systems and organs, most medical technology would fail.
Some of our best diagnostic tests work at the level of organic and inorganic molecules (laboratory science) and atoms (CT and MRI scans). Without considering the body as mere well hydrated, structured dust, our imaging systems could not have been invented.
Pragmatically then, what is a substance? It is whatever form and whatever matter we need to understand in our chosen context. Form and matter are related like layers in a cake: one layer's matter is the next layer lower down's form! Where do those shrinking layers bottom out? Well below the granularity seen by quantum mechanics, perhaps?