A Proposed Explanation of The Bree Solution

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TOSG
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A Proposed Explanation of The Bree Solution

Post by TOSG »

Hey Spencer, after a lot of work, I think that we've finally been able to make some sense of your father's research. Let us know what you think!



So, there has been a lot of awesome work done deciphering the words that have been water-damaged. What’s missing from a lot of this effort, though, is a cohesive theory making sense of the document. Below, I present a theory, developed in collaboration with marlasinger (lovely diagrams courtesy of her, too!), regarding the meaning and significance of the document’s contents.


So, Bree’s blood contains a ribozyme that has a special activity that is unique only to her (Given Fact #1). The gene coding for this ribozyme (in everyone, not just Bree), has a regulatory element that is prone to hypermutation – that is to say, a regulatory portion of the gene mutates frequently (Given Fact #2). We propose that this regulatory element is controlling the correct synthesis of the RNA strand that is complementary to the active coding strand. Put more simply, the coding strand specifies a RNA molecule that is “active” – it is the functional ribozyme that resides in Bree’s blood. Each Hymn of One girl has this gene (Given Fact #3). HOWEVER, each of them also synthesizes the RNA strand that is complementary to this active molecule. This complementary strand binds to the ribozyme, rendering it inactive.

Figure 1.0 – ribozyme; inactive with complementary RNA strand binding to active RNA strand:
Image
Note – complementary colors indicate where strands bind.

But, what makes Bree special is this – the regulatory element has mutated, such that it prevents the correct synthesis of the complementary RNA strand! Thus, the complementary strand is not made, and cannot bind to the active strand – the active strand remains active. Given the interpretation that Given Fact #4 says “this portion (the active strand) still functions, but you cannot block it because the complementary strand won’t copy,” this makes perfect sense. Without the complementary strand to “occlude the activity” of the active strand (Theoretical Solution #3), Bree’s ribozyme remains active.

Figure 1.1 – active strand: normal gene sequence
Image


Figure 1.2 – complementary strand: gene sequence including regulatory gene portion, inhibiting complementary strand synthesis (note: the regulatory element is likely also located on the coding strand, but it is depicted on the complementary strand to reinforce that is where it has its effect).
Image
Note – complementary colors indicate where strands bind.



So, this explains all of the “Given Facts,” but it goes even further – in this context, the treatment makes perfect sense. A blood sample must be taken from Bree, and the active ribozyme isolated. The ribozyme can then be sequenced – once its sequence is known, the sequence of the complementary strand will also be revealed, as in RNA, base A binds with base U on the complementary strand (and vice versa), and base G binds with base C (and vice versa). This complementary strand can be synthesized, and injected into Bree. Bree’s mutated regulatory element renders her unable to make the complementary strand, but once this strand is injected into her, it will bind to her active ribozyme and inactivate it, just as it does in everyone else who naturally synthesizes the complementary strand in their bodies. Given the text that Kellylen, Marla, myself, and others have decoded, this theory explains the proposed treatment as well!

And, this theory may even suggest a reason for the purity bond. As noted in Given Fact #2, the mutation in the regulatory element changes with every generation – it may be possible that if Bree were to have children, the ribozyme would be further destabilized, perhaps becoming uncontrollably active. Because we do not know the function of the ribozyme, we do not know what the consequences of this would be, but given its importance to the Hymn of One, the danger could be vast.

So, in the context of this theory, the pieces of this puzzle – and its solution – begin to assemble together.
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Post by allie »

nice work guys =)
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Post by Sheqinah »

I almost understand it :-k
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Post by Aponi »

See I tried making sense of this last night but it was already 3am and it just wasn't happening.

I can get this easily now, but one question. It might be stupid.

This sounds pretty easy (well, in theory), so why was Bree getting multiple injections? This sounds like you just need one.

Or was that maybe some different treatment until they ironed out a full solution?
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Post by TOSG »

Aponi wrote: This sounds pretty easy (well, in theory), so why was Bree getting multiple injections? This sounds like you just need one.

Or was that maybe some different treatment until they ironed out a full solution?
Unclear - previously, we thought that it was just Epogen, but given what we know now, it was probably the complementary strand.

But, it's expected that she would need multiple injections...biomolecules do not last forever inside the body - she would eventually degrade the inactivated ribozyme (and keep making active ones). In fact, it's possible that she would need "booster" shots occasionally for the rest of her life (or at least until she is no longer a ceremony candidate).

I guess you can think of it like this - if you have an infection, you can't cure it just by taking one dose of antibiotics.
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Post by Aponi »

That helps TOSG thanks!

Spencer, I think you might have to piggyback off your dad's research to make something long-term. This way the Order will always be after her.
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Post by kellylen »

maybe the epogen was the medium needed to inject the complementary strand with
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Post by TOSG »

kellylen wrote:maybe the epogen was the medium needed to inject the complementary strand with
I don't see any reason to suspect that.

Epogen increases red blood cell count, though - if the ribozyme is located in red blood cells (we know that it's somewhere in the blood), then there could definitely be a connection. Maybe the complementary strand can only enter immature, newly-formed red blood cells? Just speculation.
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Post by kellylen »

well if the strand enters the blood straight it will get killed. so doesnt it need a medium to help it enter?

it would also need to enter cell nuclei in order to work on the DNA and RNA synthesis. so maybe something in the solution can help it do that.
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Post by Aponi »

Actually Kelly that makes sense to me.

Bree had also said the shots didn't leave her feeling good, and I know Epogen had some icky side effects. I don't think just injecting her with rna would give any side effects (I could be wrong).
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Post by wordfish »

what i want to know is: Why are the genes of the HoO girls different from other people's??
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Post by kellylen »

no her immune system would be down if they were just injecting her with rna. becuase her body would be fighting it off. but still. it needs SOME way to get inside the cell. and i think since the epogen makes more red blood cells that it gets inside and allows cells to replicate more quickly. which involves DNA and stuff so maybe the rna would travel on it
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Post by TOSG »

kellylen wrote:well if the strand enters the blood straight it will get killed. so doesnt it need a medium to help it enter?

it would also need to enter cell nuclei in order to work on the DNA and RNA synthesis. so maybe something in the solution can help it do that.
Sure, it needs some kind of medium, but epogen is a hormone, not a buffer or vector.

And:
1) Red blood cells don't have nuclei.
2) Ribozymes are not generally located in the nucleus (at least not exclusively). So, there's no reason to assume that the strand needs to enter the nucleus. Just think of it as a macromolecular inhibitor, acting on a ribozyme that is probably cytoplasmic (or membrane bound?).
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Post by marlasinger »

depends on what that rna is inhibiting/activating, aponi - we're still not sure what the trait actually is, and whether it has physical or noticeable symptoms.

for all we know, it could be asymptomatic?
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Post by marlasinger »

wordfish, it is apparently genetic - and i'd think of it not so much as the ORDER babies being different, but rather as the Order CHOOSING the different babies out of the public. Know what I mean?
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