The premise of Back-Alley Doctor Gleen is quickly told. An anti-hero physician is asked to cure an incurable disease. He succeeds. What is interesting though is the disease itself. It's called 'crystallization' and manifests itself by turning a person into crystal. It starts at the extremities like the hands or feet, but the organic conversion process doesn't stop and after about a month, it reaches the heart and the patient dies. And about the crystal - it's pretty much spelled out that it's either Septium or a material very similar to Septium. In case of the patient who is an aspiring violinist, his hands have been turned to Esmelas. The underlying cause of the crystallization is revealed during the story: a tumor-like growth that fuses with the heart and pumps toxins through the bloodstream, which in turn causes organic matter to turn into Septium. Once the toxin-producing tumor is removed, the converted tissue reverts back to its original composition.

Now going from here, let's ask the following questions. What if this phenomenon of turning normal matter into Septium Crystal is far more common than a medical curiosity? It is after all the first time we witness the creation of Septium, its genesis in any kind, shape or form. What if all the Septium that is the key ressource of the Orbal Revolution has once been matter that could be found on the Periodic Table of Elements? But through some kind of unknown 'growth', it has been turned into the magical crystals of the Kiseki setting?

U-Material

For a series with such painstaking worldbuilding, where pretty much every item in your inventory is integrated into the setting, the U-Material sticks out like a sore thumb. Since the Cold Steel Arc, the player even knows the background of the mysterious Zemurian Ore, but the U-Material is still treated as an unknown despite it's multitude of uses. Most readers can already see where I'm going with this. If we assume that the U-Material's identity is this dark tumor from the Doctor Glenn novel, or at least something similar, a lot of things fall into place. Zero no Kiseki is also the first game where the stuff appears. The same game as the Dr Glenn novel. Coincidence?

The most common source of U-Material are monster drops, in other words organic matter. There's of course the question why monsters doesn't succumb to crystallization, but we know from game lore that monsters were once naturally occuring wildlife that have mutated through the influence of ingested Septium. Mutations are a crucial part of biological evolution and Septium is implied to accelerate it. It wouldn't be strange to assume that the monsters we encounter and do drop U-Material are the ones whose bodies adapted to the potentially fatal effect of such a tumor. This is after all natural selection. 

Of course, natural selection implies that a lot of lifeforms or biological species didn't make the cut. But then again, Doctor Glenn implies that an untreated patient's body turns almost entirely into Septium. And all the deposits that are mined to keep the Orbal Revolution going have to come from somewhere. If we think of fossil fuels in real life, my above theory shouldn't be that outlandish. They are made of converted biological matter after all. 

Now let's see what U-Material does for our heroes: It upgrades equipment, accessories and Quartz. Now, if we assume that one key reason why characters like Rean can perform flaming slashes is due to their weapons containing septium parts, the U-Material might be used to either purify existing Septium parts on the weapon or give a steel blade some kind of alternating Septium-metal structure that would be too difficult to create by using traditional smithing methods. This part of my argument assumes that this unknown 'growth' can convert other elements beside carbon, oxygen, nitrogen as well as hydrogen into Septium. (I won't bother listing trace elements that are found in the human body like Edward Eldric from FMA does.)

Septium Veins

Here is where we enter into really cracky territory. While my current argument might explain the mundane Septium occurences, the Septium Veins are another matter entirely. While we aren't given exact details of their scale, they are implied to be gigantic. There's another point that makes it unlikely that they were formed from converted lifeforms. They possess a multitude of powerful magical functions which implies that their formation and structure obeys certain laws or some kind of internal logic/order. Randomly accumulated Septium certainly doesn't allow the heroes to use a Spirit Path or cultivate Pleroma Flowers with all the creepy functionality that they bring to the table. So why do they exist?

Arteria

Falcom recently published a map of the full Zemurian continent, although most of the locations that the games didn't visit are covered under a fog of war. What a lot of people noticed was the relative location of the Holy City Arteria, right in the heart of the Zemurian landmass. But what if Arteria's location at the heart of the continent isn't merely a figure of speech? Our Dominions, tight lipped as they are, still dropped some interesting bits of lore throughout the games. We know from Kevin that the Primal Ground under Grancel Cathedral is a replica of the original Primal Ground in Arteria. We can infer further that the Primal Ground under Heimdallr Cathedral that was moved under Carel Imperial Villa is a similar case. We also know from Ao no Kiseki and Wazy that the Arterian Primal Ground is connected to the Septium Veins. That of course explains why the Curse of Erebonia was so quickly spread along the Septium Veins, once the Sacred Beast was slain in CS3. So let us go back to our little novel of Doctor Glenn which states that the Septium Conversion originates from an unknown growth in the heart. Arteria's name itself refers to arteries and veins are just the flip side of arteries in a blood circulatory system. Does that mean that there is some unknown entity located inside the Arterian Primal Ground? A kind of growth that is many orders of magnitude more potent than the U-Material and pumps toxins through the arteries (or veins) of the Earth, converting natural matter into Septium on a large scale?

Ley-Lines. 

A lot of fantasy settings use Ley Lines, which is a concept that also exists in real world spiritual and religious traditions. They are thought of as paths of spiritual power that persons with the right training and esoteric knowledge can channel to perform miracles or great feats of magic. Important historical buildings or monuments of old were often build on top of such Ley Lines which was said to bring fortune and blessings. I thought for the longest time that the Septium Veins were simply Falcom's personal twist on this Ley-Line trope or idea. The Septian Church Cathedrals above the Primal Grounds alone already overlap with the real world practice of erecting important buildings above a Ley-Line or Dragon Stream as they are called in East Asia. But what if the curse unleashed in CS3, or in fact all the Ouroboros shenanigans to disturb the Septium Veins were a misdirection in a way? The Septium Veins were 'infected' with the curse and once the heroes go to remove said curse, the dark taint is purged, restoring the spiritual network beneath the Zemurian ground to it's 'healthy' state.
It's a natural assumption to make and a very good measure to conceal the fact that the Septium Veins were never healthy to begin with, that they are in fact the symptoms of a disease.
I propose that the natural Zemurian continent once possessed a Ley-Line system like any other vanilla fantasy setting. Given that we know Pre-Collapse society and the Septerrion to utilize Septium Veins, the conversion of the Ley-Lines was most likely a deliberate act (just like present day Zemurian engineers deliberately use U-Material). A reason could be because Septium Veins allowed for more powerful techniques to be utilized, like long distance teleportation or the accruing of orbal energy to form Zemurian Ore. Things that the vanilla Ley-Lines didn't offer. After the Collapse, the Church discovered it, but recognized some kind of danger or negative cost. They built Arteria with the dual purpose of concealing as well as containing the growth. The desertification that is mentioned by Yun-Ka Fai or Angelica might be a sign that the containment is slipping. It wouldn't be the first time. We need only look at the case of Zoro-Agruga.

Additional comments

As mentioned above the Dr Glenn Novel says that the Conversion process is reversible once the growth is cut out. Now one could argue that this disease defeats it's own effect by stopping the heart once it's crystallized, therefore stopping the distribution of the toxins, so the dead body reverses back to its original form. The only somehow vague counter-argument I have is that for organic tissue to revert back, the organism has to be alive.

Another way for the really big Septium deposits to form, like the Malga Mine in Liberl or the Mainz Mine in Crossbell is through metastasis. The unknown growth is specifically stated in the novel to be a tumor and we know from real-life cancer how it behaves late-stage. I already noted that elements outside from those found in organic matter can be converted, so there is the possibility that the main 'tumor' in Arteria metastized and threw out flecks of lesser U-Material through the Septium Veins to infect part of Zemurian earth crust to convert it into Septium.The Nature of Septium. 

An interesting quirk is that while Spirit Veins get referred to with the Ley Line furigana in Japanese, when Valimar opens the Spirit Path to get himself and the Soldats into the Grail, in Japanese the term gets furigana indicating the word is meant to be read as 'Ether Line'. It hadn't previously gotten furigana, so two terms related to the Veins got 'official' names within the same game. This was one of the terms that didn't make it into the localization, probably because Spirit Path was well established and it's hard to pull the kind of 'this expression has two readings' thing with English.