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Post by sgamer82 on Feb 24, 2016 3:06:23 GMT
This is a theory I've had for a while, even posted it on TV Tropes "Wild Mass Guessing" section, and didn't see elsewhere on the board, so thought I'd toss it out.
The theory regards the shrinking effect of APTX-4869. Is it truly just a million to one chance? Or is there some specific trigger to the effect? My theory is that there is a rare trait or quality, likely genetic, that reacts with APTX-4869 to cause the shrinking effect. Those who have this trait are also prone to high intellect.
The trigger has to be something rare for the simple reason that the poison has been used multiple times and we only have three confirmed instances of shrinking: Shinichi, Haibara, and one of Haibara's lab mice back when she was Sherry.
While obviously we can't know about the mouse, we do know that one thing that Shinichi and Ai have in common is high intelligence. Shinichi has been reading Arthur Conan Doyle since at least preschool, while Haibara was by all indications an accredited scientist by the time she was middle school age. Their intellect is focused in different areas, but it's undeniably there.
Then we have two cases that are less certain, but could be inferred to be affected by the drug: Vermouth and Mary, the Mysterious Child.
Vermouth has been specifically noted by both Jodie Starling and Yukiko Kudo to have not aged or, at least, look much younger than she should. she is also a highly skilled actress and master of disguise, as well as a skilled field operative for the Organization.
While we don't know enough about Mary to fully gauge her intellect, if she is related to Masumi Sera and Shuichi Akai, we can assume she's likely more intelligent than average. Mary is also shown to follow Shogi and apparently speak in a manner more adult than her physical age would suggest.
A minor side theory, since I mention Vermouth, is that APTX-4869 does not just reverse aging in those it effects, but also halts it. If true, this could have interesting implications for Conan and Ai down the line.
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Post by ichthyophobia on Feb 24, 2016 7:06:03 GMT
I have to wonder if the high intellect is actually associated with survival of the drug, or if it's partially to do with just who's given the drug in the first place. An untraceable poison is something that really only needs to be used for high profile murders, where signficant tox screens are going to be carried out in the first place. And high profile murders do not tend to be carried out on stupid people - if you've got someone with all the brains of a brick you might as well make it out as an accident, since they'll probably fall for whatever it is. As far as in-story evidence goes, though, it makes sense. Everyone who survives seems to have been extraordinary to start with - though that might just be plot convenience. Biochemically, though (BEWARE: HUGE NERD) I don't see how it would work. There's been a lot of studies carried out to see if extremely smart people actually have different biochemistry going on in their bodies and brains than the rest of us plebeians, and the answer so far has been no. Though it's admittedly a hard thing to study, since brain biopsies are not something one does casually or usually consents to without very good reason. There hasn't been a single structure or chemical concentration or even total brain mass that's come up as being associated with intelligence. That's not to say that one isn't there - just that we haven't found one. But if there isn't anything chemically different about an intelligent person's brain, (or, as I think may be more important, the blood brain barrier) then there isn't anything there to make a difference to whether or not someone lives when exposed to a chemical that could attack it. Diffusion and enzyme activities cannot be blocked or changed by sheer force of mind. I think it might just be random chance. We don't know anything about the actual structure of APTX, so anything I could guess at as to its metabolic pathway would be a total shot in the dark. It could just be that Shinichi and Haibara have a specific decreased enzyme activity or a very slightly changed active site on whatever protein usually starts the signalling cascade for apoptosis. Protein activity is largely based on shape and charge; the substrate has to fit into the active site like a puzzle piece. If the active site just bent enough to still allow the natural substrate in without fully allowing the APTX to bind as well, it could slow the action of the poison just enough for the immune system to have time to respond, and hence make what would be entirely deadly not as deadly as it would otherwise be. Sort of like the dioxins that don't quite fit into cytochrome P450 aren't quite as toxic as the ones that do. Or more accurately, like how people with one very specific cholesterol transporter that's mutated are immune to ebola - because what the poison/virus would usually use to get into the cell becomes slow or nonresponsive to let it into the cell. Something else to consider, though: Despite the knock Shinichi took, both he and Haibara were conscious when they were given the drug, and for large parts of their transformation. It could be that firing action of the neurons is what protects the brain and intelligence during the shrinking process - though as not every neuron fires at once, the whole brain would not have been protected. I personally think it's more likely that APTX is a larger molecule or protein that just can't pass the blood brain barrier. I actually have loads of very complex theories about how APTX actually works (and why, if Vermouth isn't aging, I'm convinced that outside of fictionland it would *have* to be a different drug that she took) and, given the explanations we've been given in canon, what its victims would usually die of, but that's probably a post for some time other than midnight.
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Post by dragonsandmagic on Feb 24, 2016 7:28:25 GMT
Idk Ichthy, I'm quite liking your ramblings at midnight, just sayin'. Not that I can really understand them or make a suggestion on the chemical side of things and how they would/might work, but I still think it's incredibly fascinating to read what happens anyway. I can at least understand the basics of what you're saying, so huzzah for rudimentary high school science that actually stuck! (And doesn't that say enough about the American education system.)Just to pop another theory out there (and mild When Pandora's Box Is Opened spoilers ahead if you haven't read the fic by mangaluva you totally should) but I wonder if the idea that she came up in that could potentially have any sustenance to it? If you haven't read it and don't mind the spoiler, they discover that the apoptoxin de-ages people below a certain age threshold due to some sort of chemical in the brain that children have that adults don't. Or at least I'm fairly certain I'm attaching the correct theory to the correct fanfiction, it has been a while since I read it. A~nyway. I'm not sure if logically/chemically that would cause that sort of a reaction in the real world, but it's certainly an idea. We haven't been given any other victims ages/sex/profession or any details at all, really, so it's hard to come up with theories when we don't have a pool of information to find a common factor in. Still, I enjoy thinking of different ideas anyway. Makes it interesting.
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doublexxcross
Junior Member
Yes, and on this night I will again visit a most resplendent gem...
Posts: 63
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Post by doublexxcross on Feb 24, 2016 11:28:43 GMT
To throw a bad and related theory out there: {Spoiler: Click to view/hide}We were recently reminded that the drug Haibara made is not the same as her parents' drug, but a recreation based on faulty data recovered from a fire. Haibara has also lost the data pertaining to her own version and only remembers the major mechanics (the targeted cell death and restoration).
This makes another thing interesting, namely that - unless I'm very wrong, and unless we suddenly find out that Mary is Kouji - the only survivors we've seen that were confirmed to be APTX victims all survived from the second version: the mouse, Shin'ichi, and Haibara. We don't actually know the full extent of the second drug's survival ratio, either. We know Haibara as Sherry was still testing it in the lab until very recently, we know Gin said the APTX was being field-tested on Shin'ichi, and we know the tiny sliver of the victim list we've seen is actually comprised of both drugs with the results jumbled into an unknown order.
Vermouth is often suspected of also being a 'victim', or of taking the drug willingly, but we have no reference for her dramatically de-ageing and especially not to the extent that Haibara describes APTX4869 as doing (which was 'to the state of a child' specifically, not just 'ten years younger' and lines up with the whole body-wide atrophy thing implied by the name). We only know that she's the same as she was twenty years ago - and that twenty years ago is long before the current form existed.
As the Organisation's most public figure there would be a lot of trouble if she actually shrunk, so in all likelihood she wouldn't risk that transformation. I doubt she'd risk taking an APTX in general given how likely it supposedly is to kill one, as well. So I doubt her drug was APTX, and definitely not the second version.
But maybe, what if Vermouth's drug was not an APTX, and was instead a separate project of the Miyano family's that was confused with the APTX research during the recovery of files after the fire? And as a result this has glitched the second APTX?
and also it's the matrix lol
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Post by sgamer82 on Feb 24, 2016 13:22:01 GMT
Working my way through replies but one thing I did want to hit on real quick was that my theory wasn't so much that intelligent people are more likely to survive so much as whoever has that particular trait I suggested is also highly intelligent. An intelligent person without the trait would die like anyone else. It could also be the trait caused the lower enzyme or protein activity that Icthy mentioned. Main point was that the high intellect is a side effect of possessing this quality.
I do like the suggestion that being conscious at the time could also be a deciding factor. The only issue there is we don't know how it was administered to prior victims.
I'd also forgotten that Haibara's aptx isn't necessarily the same thing as her parents' Silver Bullet. If we're right about Vermouth taking some kind of drug to stay youthful that would explain it and also why no one else in the Organization seems to know about the regression effect.
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Post by presumenothing on Feb 24, 2016 15:33:28 GMT
Don't really have any concrete thoughts on this, but some relevant points we've learned/been reminded of from the latest files: {Spoiler: file 948} regarding the Miyano parents' drug: seems to have already existed 17 years ago, and the cause of death appears unknown in its victims (as assumed to be the case for Kouji and Amanda)
regarding APTX4869, as made by Haibara: recreation of above drug from burned remains of data, though the Org seems to have wanted Haibara to make some other drug
possibly regarding both: something about the drug(s?) may be related to blood type (948, p3: Haibara says that whoever was in charge of the data may have arranged it by blood type instead of chronological order – unless, of course, this is a throwaway/insignificant line)
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Cesela
Senior Member
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Post by Cesela on Feb 24, 2016 15:49:01 GMT
It could also be as simple as a mutation in their genetics. There has been some speculations as to whether or not Yukiko is half-American. The combination of Japanese and (I assume western) genes could have created a mutation in their mtDNA. Consider this. Most currently living in Europa have between 3 and 5% of their genes from the Neanderthals. Asians on the other hand, are descendants of Homo Erectus and Homo Sapiens Sapiens (as well as a couple of other variation but I shan’t go into that). A sudden mixture in the population in our modern history can have created a mutation that somehow protects them from the toxins. The fact is, you can easily pinpoint someone’s ethnic origin just by mapping ones genes. Even without any knowledge of the person in the first hand. If I had access to your mtDNA I could pinpoint which country your genetic mapping belongs to. Even over smaller scale as to see the difference between Portugal and Spain. So if both Shiho and Shinichi are in fact half-Japanese, half-American, this theory could hold some credits. And they probably used thousands of mice, that one mouse would have the same genetic mutation is not farfetched. And regarding to at least Vermouth and Mary, one cannot rule out the possibility of the same mutation showing up in other areas. Looking at your own theory, maybe this mutation gives the barer a high intelligent? Not entirely implausible.
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Post by sgamer82 on Feb 24, 2016 17:17:56 GMT
A mutation of some kind would probably be a good fictionland way of explaining away any reasons this theory or its logic wouldn't work in real life. Also something like that would be just uncommon enough, especially if it occurs specifically in people of mixed heritage, would explain its rarity, too.
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Post by ichthyophobia on Feb 24, 2016 20:20:53 GMT
Cesela, I really doubt it has anything to do with mitochondrial DNA. In any other part of the DNA, I would say sure, why not, a combination of two recessive genes could play off each other to amplify or suppress something that has to do with the toxin response. But mitochondrial DNA *doesn't mix*. You get it all from your mom - that's why it's so useful for tracking lineages, because it's essentially identical along the maternal line. And because it doesn't have the same set of repair and spellcheck mechanisms during replication that DNA in the nucleus does, non-damaging mutations persist and can be tracked. When you see those gene tests that say someone is like, 25% irish or whatever, those are more typically tracking SNPs, single nucleotide polymorphisms - known points along the genome where a single DNA base has been changed that are more common in some population groups than in others.
However, the mitochondria in general are a very likely target for APTX in general; they're enormously important in the normal process of apoptosis. What normally happens is once the cell receives the signal to begin apoptosis, certain proteins open up holes in the outer membrane of the mitochondria. I don't know how much cell biology y'all know, but because of how mitochondria work, that whole area's filled with protons at really high concentrations. So it essentially starts leaking acid and electron transporters such as Cytochrome C into the rest of the cell. The acid starts changing protein configurations that are sensitive to pH (so like... all of them) and cytochrome C starts signalling other crud to start breaking the cell down into nice easily-swept-up bits for the immune system once it comes by later to clean up. I sincerely doubt that APTX could make it into the cell to directly activate those hole-making complexes, because those need a fair amount of signal amplification to function, and if APTX is a larger molecule (or a polar molecule, which is likely) it would need a transporter to get into the cell in the first place. So a mutation in the mitochondrial DNA (and hence the mitochondrial proteins) COULD protect someone from APTX, yeah... I just don't think that it's a likely mechanism of action in the first place.
However! Since mitochondrial DNA and mitochondria in general are inherited maternally, that could make that "Two mothers are sisters" theory (that I never understood and thus will not get into) much more relevant, if this does turn out to be the case.
I personally think APTX would have to mimic the "death factor" signalling molecule, because that way it wouldn't need a way into the cell (the receptor complex for that is on the surface of the outer membrane) and it could at that point detach and go on to signal destruction to another cell. Because we know that it can destroy a lot of cells with a relatively small dose, and we know it persists in the body. And a non-permanent attachment to the signalling complex makes the most sense for both of those, in my mind.
That said... This whole thing might eventually (long past the course of the series, but eventually) really suck for Shinichi and Haibara. Because you know how we know so much about the apoptotic pathway? Because cancer. Any mutations anywhere involved with apoptosis tend to make a person way more likely to develop cancers, since the cells won't respond to the normal apoptosis signals. They essentially refuse to die. And that's how tumors get started.
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Wyz
New Member
Dying inside because of calc 2
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Post by Wyz on Aug 4, 2017 22:46:54 GMT
Going off of what ichthyophobia was saying, perhaps the whole reason as to why Shinichi and Haibara were able to survive the APTX because they were already susceptible to developing cancer, which would, in turn, counteract the effects of the APTX in the first place. I would think that Haibara would start her initial tests with cells in vitro (on a cell culture plate or something similar), and those are typically already cancer cells (because non-cancerous cells don't do well in an in vitro environment), which would mean that cancer cells are just as susceptible to the APTX, but maybe there are certain variations that are resistant
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Post by ichthyophobia on Nov 3, 2017 4:03:42 GMT
Resurrecting what may be a dead conversation here, but not all cell lines are cancer cells, actually! You're right, most of them are because cancer cells are much easier to work with - they don't want to die. But if you want to simulate healthy cells, or you know you may be looking at an apoptotic or mitochondrial mechanism that would be very likely to be mutated in a cancer line, it would be a lot more logical to use a stem cell line. And there are loads of them - they're a lot fussier than cancer lines, true, but even here in the US where stem cell research is stranglehold-regulated there are over 300 approved lines of stem cells in use. It's harder, it's more expensive, but there'd be really no other way to get good data in this kind of experiment.
Related, almost all the really exciting stem cell research right now, like the induced pluripotent cells and the grow-a-new-retina thing? All happening in Japan!
But in story terms, I wouldn't argue that any of them would be developing cancer already. If apoptosis isn't working at all, someone would be born with webbed fingers and toes at the very least, and probably wouldn't live very long due to their immune system being messed up to heck and back. But more specifically - APTX works off apoptosis, it's in the name. Cancer cells don't respond to apoptotic signals - that's what makes them cancer. So APTX would induce cell death broadly around the body except in the cancer cells. Which means everything but the cancer shrinks, and all of the tumors are suddenly much larger by comparison! Which sucks, because even a benign tumor can be really bad if it's pressing on an important nerve or blood vessel. So if either of them had active cancer - they would've noticed!
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