The X-Files: The Erlenmeyer Flask Rewatch
March 20, 2020 9:06 PM - Season 1, Episode 24 - Subscribe
In the season one finale, Deep Throat calls Mulder to advise him to watch channel 8, which is broadcasting a news item about a man who managed to escape the police after first leading them on a car chase, and then being beaten with a nightstick, tasered, and shot.
So, two new nucleotides in a DNA sequence is a big deal, especially if it could be irrefutably demonstrated as coming from a living organism (qv. that debacle with mountaintop lake bacteria that used Arsenic instead of Phosphate for their DNA backbone or something - it was shown to be a contaminant).
However, back in '93 (or now for that matter, with Sanger/ amplification-based sequencing), they would have simply failed to amplify for sequencing - not seeing "gaps." Obvious culprits would be a "pcr inhibitor" in the sample or that none of the commonly used primers (you have to start the amplification for sequencing somewhere specific, there are sufficiently conserved sequences within different phylogenies that are used as a starting point) would prime to the DNA. To prove the latter would take weeks or months.
Only with today's specialist nanopore-type long-read sequencing would it - maybe, depends - read out as having gaps, and can work without primers.
If they suspected that there were nucleotides in the sequence not A, T, C, or G... and there's no reason to, it would probably be doable (probably through looking the sequence over for long-enough lengths to make a probe from, fragment the DNA sample, extract what the probe picks up, then run that through a tandem mass spectrophotometer (MS)/ high performance liquid chromatography (HPLC), then do nuclear magnetic resonance imaging (NMR) to figure out what the non-standard nucleotides are).
But it would take a lot of sample and be a months-long, if not longer, project if sufficient academic resources were thrown at it.
Modern tandem MS/HPLC is a helluva lot more efficient than those in '93 - if they existed outside of hand-built setups.
These days, synthetic non ATCG nucleotides are commonly used in lots of different specialist PCR applications, and nanopore type sequencing could help identify non-standard nucleotides more easily.
Knowing that there are non-standard nucleotides present makes it easier to diagnose and enable modifying the nanopore sequencing equipment to collect the novel nucleotides for NMR analysis and identification.
However, once you've characterized the novel nucleotides and could synthesize them in sufficient quantities (rather difficult in 93, a little less so by the late 90s) existing multi-lane sequencing equipment could handle the alien DNA as easily as earthling.
The Human Genome Project started in 1990 but didn't get completed until 2003 - and most of the gains started a lot closer to 2000 than 1990.
--
Now... the "cloned DNA" - does it contain the alien nucleotides? Aside from integration/ mosaicism (a whole other diatribe - qv gene therapy in general), earthlings don't have the synthase genes to make those alien nucleotides de novo so would need to have a diet(ary supplement) high in those alien nucleotides for cells to scavenge from to continue replicating the alien DNA sequences.
--
I always assumed that the Alien Conspiracy people (the Syndicate?) left Mulder and Scully as useful idiots/ misinformation vectors to further protect the conspiracy, and underestimated Mulder and Scully's competence and drive.
Was that the Alien Bounty Hunter?
As a season finale, this really sets up expectations for season 2. X-Files really had a solid premiere season.
posted by porpoise at 8:49 PM on March 28, 2020 [2 favorites]
However, back in '93 (or now for that matter, with Sanger/ amplification-based sequencing), they would have simply failed to amplify for sequencing - not seeing "gaps." Obvious culprits would be a "pcr inhibitor" in the sample or that none of the commonly used primers (you have to start the amplification for sequencing somewhere specific, there are sufficiently conserved sequences within different phylogenies that are used as a starting point) would prime to the DNA. To prove the latter would take weeks or months.
Only with today's specialist nanopore-type long-read sequencing would it - maybe, depends - read out as having gaps, and can work without primers.
If they suspected that there were nucleotides in the sequence not A, T, C, or G... and there's no reason to, it would probably be doable (probably through looking the sequence over for long-enough lengths to make a probe from, fragment the DNA sample, extract what the probe picks up, then run that through a tandem mass spectrophotometer (MS)/ high performance liquid chromatography (HPLC), then do nuclear magnetic resonance imaging (NMR) to figure out what the non-standard nucleotides are).
But it would take a lot of sample and be a months-long, if not longer, project if sufficient academic resources were thrown at it.
Modern tandem MS/HPLC is a helluva lot more efficient than those in '93 - if they existed outside of hand-built setups.
These days, synthetic non ATCG nucleotides are commonly used in lots of different specialist PCR applications, and nanopore type sequencing could help identify non-standard nucleotides more easily.
Knowing that there are non-standard nucleotides present makes it easier to diagnose and enable modifying the nanopore sequencing equipment to collect the novel nucleotides for NMR analysis and identification.
However, once you've characterized the novel nucleotides and could synthesize them in sufficient quantities (rather difficult in 93, a little less so by the late 90s) existing multi-lane sequencing equipment could handle the alien DNA as easily as earthling.
The Human Genome Project started in 1990 but didn't get completed until 2003 - and most of the gains started a lot closer to 2000 than 1990.
--
Now... the "cloned DNA" - does it contain the alien nucleotides? Aside from integration/ mosaicism (a whole other diatribe - qv gene therapy in general), earthlings don't have the synthase genes to make those alien nucleotides de novo so would need to have a diet(ary supplement) high in those alien nucleotides for cells to scavenge from to continue replicating the alien DNA sequences.
--
I always assumed that the Alien Conspiracy people (the Syndicate?) left Mulder and Scully as useful idiots/ misinformation vectors to further protect the conspiracy, and underestimated Mulder and Scully's competence and drive.
Was that the Alien Bounty Hunter?
As a season finale, this really sets up expectations for season 2. X-Files really had a solid premiere season.
posted by porpoise at 8:49 PM on March 28, 2020 [2 favorites]
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Poor Mulder always finds something amazing only to wind up with nothing to show for it. This was back in the day when one couldn't take photos with one's cellphone, of course, but you'd think he'd learn to carry a camera around with him.
That's the end of Deep Throat. Not that I mind. I found his smoke and mirrors game annoying anyway. But it doesn't make much sense that the alien conspiracy people would kill the scientist and Deep Throat and let Scully and Mulder live.
posted by orange swan at 5:04 PM on March 21, 2020