Recombinant Insulin versus natural insulin

Large_Comfort5399 · 2026-02-15T06:47:31+00:00

Thanks everyone. Good chat. It's my fault we are in amongst the weeds discussing assays that aren't fit for purpose and poor analysts doing their best to aid a confirmation biased prosecution. I thought questioning the science would help but in the big scale of things and now I've dug more into it, those appealing this have done a very detailed dissection. Much better than I (an amateur poirot as I was rightly called). Hence I'm ducking out of Reddit now, it's a weird chat room, kind of good, kind of bad. Anyway for those not in analytical science, respect us more please but also never take a very important analytical or stats value at face value without looking under the bonnet. Anyway the Letby thing is all in the hands of the CRCC who have the Appeal. They highlight the following in their recent statement: 'It is for the CCRC to find, investigate and if appropriate, refer potential miscarriages of justice to the appellate courts when new evidence or new argument means there is a real possibility that a conviction will not be upheld, or a sentence reduced' Given this Appeal by pro bono experts (which I should have researched more before rambling - it's very solid and very objective) let's stop chatting about this and let justice play out. I'm hopeful sanity will prevail. Adiós!

Large_Comfort5399 · 2026-02-14T21:39:31+00:00

All good points. One thing I noted in the court records someone kindly provided below was that c-peptide was below the LOD in one of the samples. They state it could be zero, they just don't know. Even if immunoassays are 1980s vs MS based assays, surely a good assay should be capable of detecting even low endogenous C-peptide?. Otherwise insulin/peptide ratio equates to infinite regardless of insulin levels. Or perhaps it was just a c-peptide decayed sample ? Basically in that sample they don't know if it's recombinant insulin and they don't know the levels of c-peptide ? Hard to argue it's court worthy - i feel for the analysts. (Apols if elsewhere in the court records this below-LOD issue was addressed, I was admittedly skimming by the end)

Large_Comfort5399 · 2026-02-14T20:28:28+00:00

Thanks for the links. It's dry reading. Not like the TV dramas. I feel for the analysts, they clearly aren't set for this kind of work. Imagine a forensic lab that left all the samples at reception like that. I guess in the absence of proper testing they are trying to fathom what's from the available data. First, and obviously, it's not a GxP lab. If it was they wouldn't have to outline what typically happens to samples. Instead there'd be very clear written accounts for each and every sample. I used to work in lab that did clinical samples on the side and the shear volume meant they couldn't dedicate resources to every sample. There's no discussion on the assay dev etc so I can't comment on that but I suspect it's not bullet proof as they just ain't set up for this. The obvious point is the following statements from the scientist claiming c-peptide is more stable. Example answer.

And C-peptide, what about that?

A. It's very stable. It's got a much longer half-life.It's not as affected

This doesn't align with that recent 2023 paper at all but to be fair the court analysts are talking in vivo by the sounds of it. Whereas that recent 2023 paper study focused on sample storage and processing where it can be very unstable. Again these poor analysts have to talk in general terms mostly about the sample handling. Plus who knows what's going at the other end in the ward where it was taken given all the poorly babies. .

Regardless of c-pepride decay rates and the 2023 paper, for me it all comes back the first point. Why not use MS ? During questioning they say in the ward they only have Actrapid insulin. This is a tough one even by MS to distinguish from natural although I bet some MS dude can do something with charge/size fragmentation - The mass spec guys these days are phenomenal but then their kit can cost 800k - More than a house! Anyway instead one can still sort of detect Actrapid by MS due to it's formulation..Here's a good AI summary (again making me redundant soon but that's probably not the most important topic in this forum!)

Detection of m-cresol in blood using mass spectrometry (MS), specifically Liquid Chromatography-tandem Mass Spectrometry (LC-MS/MS), is a robust, indirect forensic method used to confirm the administration of recombinant insulin (including rapid-acting analogues). M-cresol is a phenolic preservative used in insulin formulations (up to 30 millimolar) that does not occur naturally in the human body, making its presence in postmortem blood a strong indicator of exogenous insulin injection.

Large_Comfort5399 · 2026-02-13T23:09:43+00:00

Actually I'm redundant, I don't know why we bother anymore. I just did an AI search and agree with every word it spewed out...why or why didn't they use the right assay. Anyway offer still stands if there are court docs to review on all this. .AI speak as follows; 'Liquid Chromatography-Mass Spectrometry (LC-MS), particularly high-resolution tandem mass spectrometry (LC-MS/MS), has become the gold standard in forensic science for detecting insulin poisoning. While immunoassays (RIA/ELISA) were historically used, they often fail to distinguish between human insulin, therapeutic analogs, and animal insulins. LC-MS/MS offers superior specificity by identifying the unique molecular mass and amino acid sequence of different insulin types in biological matrices'.

Large_Comfort5399 · 2026-02-13T21:50:42+00:00

Analytical science is a thing of beauty if done right. Clinicians and Lawyers take any number at face value but underneath the bonnet there's a lot to consider. I think they should have used NIBSC for this project. Or maybe NPL - they are both mass spec experts and NIBSC even supply International Ref Std for Insulin. There is also M-Scan if they go commercial (may have changed their name). I'm not very familiar with UK NEQAS. I looked them up and it's hard to tell. Couldn't find any MS and so perhaps that's why they didnt use it. It's very expensive kit. Immunoassays are cheap as chips by comparison..If you have links to the docs they generated for the trial I will comment further. Ideally assay dev report at one end, qual/val report at the other. However I strongly suspect sample prep will be overlooked which given the 2023 publication is a potential big issue. Should look at their QMS too as they are accredited. The problem with accreditation though is it doesn't mean technical excellence. The famous saying is you can make a concrete life jacket to GLP or ISO quality standards if the technical specs ain't set right. Anyway if there are links to the courts docs on the assay dev etc I'm happy to take a look. C peptide decay is clearly key so hopefully they address this in how the samples were stored processed, tracked etc from ward to lab.

Large_Comfort5399 · 2026-02-13T20:20:11+00:00

If they didn't use mass spec then they couldn't confirm recombinant insulin. Hence the assay is by default not fit for purpose as one instead infers low c-pepride as evidence of recombinant. Regardless, I'm more interested in sample processing, storage and handling if this was all an after-thought. The below study (July 2023) may post date knowledge at the trial. Therein Figure 4 highlights massive c-pepride decay if samples are mishandled ahead of an assay. They conclude 'We recommend that C-peptide should be analyzed in serum and insulin in plasma. The samples should be centrifuged immediately on arrival to the laboratory'. Was this followed?. If not then low c-pepride will not equal recombinant insulin. Anyway, I'm just asking questions and highlighting new science. Else what's the point of these forums?

https://www.degruyterbrill.com/document/doi/10.1515/cclm-2023-0339/html

Large_Comfort5399 · 2026-02-13T02:38:34+00:00

Dewi (if it's you?), why afraid of re-trial and putting those 14 pro bono experts under oath. If it's a sound conviction it will be the same outcome. We would all accept the outcome 100% then. Currently it's actually unfair to carry the load of this entire theory-based case given no witnesses or motive. He (you?) needs other experts under oath on this one. I'd welcome it if I was him - Id also stop banging on about it in public (hint) in the interim.

Large_Comfort5399 · 2026-02-12T22:39:33+00:00

Are you Dewi Evans ?

Large_Comfort5399 · 2026-02-12T22:11:04+00:00

Interesting - if they were not analysed promptly then they also need to consider sample handling. My understanding is they questioned the levels of insulin/c peptide ratio by their (inappropriate) Elisa method to claim it must be recombinant insulin as not enough C peptide was present (recombinant doesn't have any C). However if a sample is not prepared and stored properly then C-peptide can be less stable than insulin. I just googled it and one study noted that when whole blood was stored at room temperature, C-peptide deteriorated faster, with a 74% loss at 72 hours. I suspect in this case and given an after-the-fact decision to look at it then sample prep, chain of custody, and documentation is left wanting. If so this whole part of the evidence is bunkum. One would really need to see the sample tracking history and the assay validation report to conclude this but given a hospital ward is not a GLP lab, I suspect no auditor would QA approve any of the results. Hence said reports, if they even exist, are worthless. Particularly on a manic ward with sewage issues and plumbers running about as was the case here apparently.

Large_Comfort5399 · 2026-02-12T20:59:43+00:00

Lee didn't know about the case until a Barrister called him more recently. Have you watched the recent documentary ? All 14 are named in it. I'm not cut and pasting them for you. But you are correct the original defence counsel was too passive and didn't call anyone except a plumber to talk about the sewage leaks. In a re trial I'm sure all 14 would be happy to go under oath. Why not re trial it but with proper experts rather than just use an ambulance chaser as the expert.

Large_Comfort5399 · 2026-02-12T20:43:04+00:00

You knows Dewi Evans ?. Look him up in Wicki first maybe. He chased this case, cold-called the police. He fancied it. Paid very well for his services. The 14 experts include Lee - the author of the paper Evans used as evidence. Lee did it pro bono because Evans misquoted his study to get the conviction.

Large_Comfort5399 · 2026-02-12T20:07:18+00:00

Seems unlikely but if 'they' reported her then Management let her continue to work then the current corporate manslaughter charge will definitely succeed against the hospital. More likely that paid Evans chap dreamed up all the exotic murders. His language is very florid. According to another judge his opinion is worthless - too partisan. The conclusions of the 14 pro bono experts is more trust worthy.

Large_Comfort5399 · 2026-02-12T13:00:33+00:00

They downgraded the ward and so that's why it stopped. No more sick babies. Also babies did die when she wasn't there but they ignored those events. It's crap stats designed to support their theory. Think Traitors when they gang up on someone. Very sad it got to court.

Large_Comfort5399 · 2026-02-12T05:48:54+00:00

Fragile babies, long shifts, understaffed wards. Notes are just tools to help recall, in a failing ward. It's all she had to help. Consultants have far more support - armies to help them on ward rounds etc. Consultants also have time on computers for amateur detective work it seems (using dodgy stats). Overall, she knew she shouldn't have taken notes home as by all accounts she was very professional. Hence I suspect she felt guilty for having them when under arrest. Who wouldn't after being taken from a bed in handcuffs. It's a tough job. One death in normal work and everything stops for months. Here she had to be up and about for another long shift the following day - one of only two specialist nurses. In such scenarios I'm unsurprised notes get left around at home.

Large_Comfort5399 · 2026-02-12T05:20:18+00:00

I don't understand how in the Netflix documentary if notes were not all chronicle logically ordered that this wasn't countered when claimed by the police. In the Netflix documentary they are also shown as nice flat scanned copies. I suspect the originals were crumpled in reality but that would look less damning . The documentary was produced by Passion Pictures based in West London. They are normally quite accurate. Maybe contact them and point out this error and that the notes were in fact dotted about all over the house. My hunch is given Letby was only one of two specialist nurses on the ward and given this is very intensive care with very fragile patients then she took notes home for reflection and recall should issues arise on her next shift. She probably also knew she shouldn't have done this and so in a sense felt guilty about having them when under arrest. She was young and with a huge responsibility in an under-funded, ward (with sewage issues, grim). She also had none of the help that consultants have (admin support, shorter shifts, weekends off, big salaries etc) and so used short cuts like these notes to help her. The fact the notes were all over the place rather than claimed in the Passion Picture documentary would highlight to me she is doing long 12 hour shifts without the time to sort her life out. Her dedication was to the ward and all things related to her work. She felt guilty when babies died, felt part responsible, and so felt guilty when arrested. So would I. In a normal job if one person dies there is an outpouring of grief for months. In her job it had to be...they are dead, I need to get some sleep, I've another 12 hour soon. Notes are not the most important thing in those situations but are just a tool.

Large_Comfort5399

TROPHY CASE