UKH

https://www.bbc.co.uk/news/business-61578956

Outstanding decision by Pfizer. I guess the salient point is whether any other drug companies will now stand up and be counted.

Not sure why this is getting dislikes, it seems like a good thing 

Sounds great....there may be a lot of small print but a definite step in the right direction...

looks like you have dislike stalkers, or... they have pfizer shares, and some greed

: )

Maybe just not appreciating my viagra based punning.

Joking aside it sounds like a good thing to me.

Very good....I missed that initially!

GSK started this c. 10 years ago

There is a person who has had (at least) a couple of dozen accounts on UKC since the start of the pandemic, and who consistently and dementedly advocated against AZ and for Pfizer regardless of any contextualised facts.

It's hard to tell if this was due to their fervent anti-British mindset or if they were invested in Pfizer; they certainly seemed interested in investments and so on over the years.  They were particularly noisy over the science-driven and since highly vindicated decision by the UK to extend the gap to the second dose from 3-weeks  to 12-weeks.

They're back right now I think.  Usual spread of topics, almost every post edited within 0-3 minutes of posting.  I won't name them but if anyone wants to test their suspicion against mine, the sum of all the digits in their profile number is 23.

and if you add those up, you might get the last bit of their User Name? 

Good observation. I hadn't spotted that.  

FactorXXX’s observation I think confirms that I guessed who you had in mind correctly, but where do you find profile numbers?

Click on a profile, and look at the URL.  For example, mine is "https://www.ukclimbing.com/user/profile.php?id=68300"

Often this person will have accounts called SockPuppet1, SockPuppet2, SockPuppet3 and so on with sequentially enumerated profile numbers.  They seem to have missed out the 4 previous burner accounts on this occasion.

(I thought mine was a pretty low profile number, but there's a few 3-digit posters regularly active I think.  Hopefully we're not in the kind of f**ked up place Slashdot became where 5-digit sums of money would be exchanged for two-digit profile numbers...)

Bingo, yep found your Sum=23 on the first guess. 

One trick if you're so inclined is to change the last digit of the URL to one higher/lower and see if there's any obvious pattern for the User Names.
 

I hadn't stumbled across this person but a quick browse of likely threads and it was easy to pick out. Now I feel worse for having read some of those comments 

If you see the same person coming out with the same old shite, do please take a moment to hit the 'report' button and let the mods know.  If it causes him even a moment's inconvenience having to re-register under yet another new username it's worth it.

wow, every day's a school day : )

thanks for that

It's probably one to watch closely.

"US drugs giant Pfizer has said it will no longer make a profit from selling its patented medicines to 45 of the world's low-income countries."

Is there a risk that when stocks of drugs are low, profitable markets will be prioritised? Obviously the PR backlash from this would be worse than making massive profits from Covid vaccines, but worse things have happened.

I'm in the 500s.

Don't know about that, but if anyone wants to make me a 5 digit offer - as long as it's 5 digits in pounds not pence - I'll consider it!

I'm 156.

Who's got the lowest valid uid

Alan, I think.

I'm 294, but predate registration and accounts. I think I decided I should probably register. Oddly enough, my registration date in July 01; yours is October 01... Toby is 527, but registered October 00.

Al Evans was/is 14 26/06/01
Alan James is 15 18/06/21
However, there is something strange going on as all of the really low numbers have a User Name beginning with A.
Also, for example, Adam Lincoln is 20, but has an earlier registration date (17/10/00) than either of the above two and Alison 21 has a registration date of 16/03/01.

All of the above is academic and pointless as Rom had already registered multiple accounts and had done so before Rocktalk/UKC had even been thought about...


 

Wonder what Mick Ryan's was?

https://www.ukclimbing.com/user/profile.php?id=454

Awesome picture!

I'd prefer it if Pfizer came clean about the integrity of the RNA in Cominarty and address Specific Obligations SO1 (a)-(c) raised by the EMA in the "Assessment report  on the annual renewal of the conditional marketing authorisation" published 14 October 2021.

Replacing all the U's with N-1-m-psuedo-U and the extreme codon optimisation to increase GC content are all known to produce transcription errors during manufacture and translation errors in vivo both of which are known to cause ribosomal pausing and frameshifts. All of this leads to truncated protein, mis-folded protein and even extended protein which is why you get streaky Western blots. Inconsistences between batches 1 and 2 were identified and highlighted by the EMA as the primary specific obligations for Pfizer to answer and as yet they've said nothing. There are tens of thousands of full SARS2 genomic sequences uploaded to GenBank and none, zero, diddly squat sequences for any batches of the mRNA vaccines. anyone would think they have something to hide and it completely beggars belief! 

Well you learn something every day, thanks. There seems to be a few accounts out there waiting to be used...

Thankfully we've got you to draw our attention to this between your various posts complaining about what a woke, left-wing echo chamber UKC is.  I guess you hang out for the experts in transcriptomics (they're here, and they're not me).

I've seen a detailed study on mis-expression in the J&J and AZ vaccines, although that was more focused on the consequences of weird codon compatibility stuff between the DNA and RNA systems.

You clearly disagree with my stance regarding UKC and that's fine by me. We live in a supposed democracy with free speech although over the last two years that fundamental right appears to be rapidly eroding.

There is no codon optimisation in either the J&J or AZ vaccines as they are dsDNA. Apart from the standard 2P substitutions at the AA level to maintain the pre-fusion state of S-protein they're identical to the original Wuhan strain. How do I know this? because an FOIA request was made to the MHRA to disclose the base sequences for all vaccines deployed in the UK. The Pfizer sequence was already in the public domain and the Moderna sequence had been determined by retro-engineering it from dregs left in vials by Andrew Fire's group at Stanford but the first time this sequence was publicly disclosed to the World by Moderna themselves was in reply to the UK FOIA. Similarly the AZ sequence in full was also disclosed for the first time in the same request. J&J were the only ones holding out and the request was refused on grounds of commercial confidentiality!!

I just find it amusing the number of new sign ups that complain in great length about the woke leftiness.  It's bizarre.

This is a non-sequitur.  

• It is fully possible to optimise the codon sequences in dsDNA.

Here is an EMA document referring to the codon optimisation in the AZ vaccine

• https://www.ema.europa.eu/en/documents/assessment-report/vaxzevria-previous...
• "Brief but sufficient information has been presented to understand the steps followed to generate the AZD1222 recombinant adenovirus vector. [...] The nucleotide sequence encoding the recombinant S protein was codon optimised to improve expression in human cells"

Here is a paper looking at differences in the codon optimised sequences for AZ and J&J, and how these contribute to the number of unintended splicing markers. 

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8846585/
• "Codon optimization performed to enhance expression levels further augmented the abundance of splicing and was most prominently observed for the ChAdOx1-S vector."

So, it seems that you have some fundamental misunderstandings about the level to which some of the sequences have been studied by third parties, and about the process of codon optimisation.

It seems unlikely that you have sufficient understanding and/or clarity of mind to understand the implications for the picture you're trying to paint around Pfizer.

Edit: Just to paint another incongruity in your understanding

You say:

• "J&J were the only ones holding out and the request was refused on grounds of commercial confidentiality!!"

The paper I linked above says:

• "[...], the Spike sequence of Ad26.COV2.S was obtained directly from Janssen (kindly provided by Roland Zahn)".

So, the sequence would appear to be directly available to credible scientists, and I also note those scientists had no problem recovering the AZ sequence from a sample.

I'm not sure where you're getting your long life science words from as they're not a simple google away, but I'd be surprised if you were capable of originating all this content yourself as then you would have had the ability and the professional drive to perform a simple literature review before turning to UKC for answers. If you are getting these concerns from a channel such as Telegram, I respectfully suggest the possibility that they're not being put across in good faith.

Edit 2: Forgot to comment before

No-one likes a streaky western blot.  

I think the subject around mis-expression of these vaccines is fascinating, and the study of the various expression based Covid vaccines is going to mark the start of improvements to good practice for future expression based therapeutics.  Really interesting area, but I'm not sure there's much grounds for this sort of conspiracy level claim against Pfizer...  If there are specific EMA actions that have not been fulfilled that is noteworthy and a credible evidencing of that would hold more water tan technical language soup.

I have got under your skin but hey ho.

First of all thanks for the Rolf Marschalek paper I have not seen that and its very interesting. 

Maybe I was being a little bit flippant and a bit generalist regarding codon optimisation, which I now regret, but here are the facts plain and simple (1) the DNA vector vaccines do not swap out all U's for N-1-m-psuedo-U they leave U intact and (2) any other codon optimisation of the S-transgene itself is minimal compared to the RNA equivalents. For example the RNA vaccines went all in with GC content. Wild SARS2 has 36% GC whereas Pfizer have codon optimised to boost this to 53% and Moderna optimised to the max with 61%. Does this matter - yes very much so.

There is a lot of genetic manipulation in the DNA vaccines too but this is at either end of the S-protein gene which is pretty much the same as the native virus.

I have no reason to either justify my knowledge, experience or qualifications so I'll leave your somewhat belittling assertions on this matter alone.

What I would say is there is a lot of recent scientific literature out there and I have spent the best part of two years reading and researching. I am not saying I am right or wrong and I certainly don't know or have read everything out there, the Marschalek paper being a case in point.

"[...], the Spike sequence of Ad26.COV2.S was obtained directly from Janssen (kindly provided by Roland Zahn)"

This is interesting but irrespective of your views regarding my scientific credibility or otherwise it is the only sequence of the main four vaccines that currently isn't in the public domain and the only one refused to be disclosed by the MHRA.

You may believe I am some complete quack who gathers information they don't really understand from Telegram and then regurgitates it using copy and paste. So don't believe anything I've written but please continue with your own research and reading.

Finally have a look at this short video from Kevin McKernan who is way more qualified than me and possibly a bit more qualified than you. Through debate we all become better, have a good weekend dude!

youtube.com/watch?v=2-tMP_YM8Ds&

PS edited to add this comment. The OP was applauding Pfizer's position to not sell drugs for profit in poor nations, this is obviously positive and already happens across the board with all Big Pharma for HIV drugs.

My post was to say that personally I'd prefer it if Pfizer came clean about the RNA integrity in their vaccine. Considering that a large proportion of the human population has received this it seems perfectly reasonable to ask the manufacture to disclose that every batch of their medicine is of high fidelity/purity as you would expect for any drug or medical product/device. As I am sure you're aware the vaccine is a pro-drug for the S-protein antigen which is the active pharmaceutical ingredient (API) so it is equally valid to ask the manufacturer to demonstrate the API is also of high fidelity. The Pfizer vaccine along with the others have been deployed under an emergency use authorisation, Regulation 174, so having this data is of extreme importance. At the very least please give us the basic FastQ files for each batch tested, if indeed they have been tested. The only data we have is from the first two batches that demonstrated differences and streaky WB's and this is a huge concern which is why the EMA addressed it as their primary specific obligations. The fact this hasn't been answered and various FOI requests around the World about this subject have been refused is utterly wrong. The millions and millions who have taken this medicine have a god given right to know.

No, afraid not.

Well, you said "There is no codon optimisation in either the J&J or AZ vaccines as they are dsDNA".  Using "no" instead of "lots" is not flippant or generalist, it's just plain wrong.  Likewise "as they are dsDNA" is not flippant or generalist, it's a non-sequitur.

Indeed you don't.  On the other hand, you appear to want credibility for your views, and if you were professionally qualified I would expect you to take the time to present them with credibility not factually wrong statements that can be checked with a minimum amount of literature review.

I'm not really making a critique of your comments for you, but for others.  They can listen to what I have to say or write me off as a raving mad person.

I don't actually know what your theory is - you've only hinted around it in a rather conspirational way so I've no idea if you're right or wrong with where you're going.

You see, pointing to the refusal from the MHRA comes across as conspirational; they have confidentiality clauses with the people submitting material to them and will not be legally able to release that material.  If the manufacturer has already put it in public, that changes the MHRAs position.  I imagine if I bothered to chase down the FOIA request, I'd find legal verbiage to that effect.  As it stands, J&J have released the sequence to scientists studying potential adverse effects of their codon optimisation so they hardly seem to be trying to stop such research, and the sequence is readily discernible to anyone suitably equipped and who has a vial of the stuff. 

Well, telegram was my first guest...

I retract my telegram suggestion.

 FYI in my 22 year career as a scientist, do you know how many times someone has said to me "Have a look at this short video?"

• ZERO.   I have had a scientist try and communicate science with me zero times by a short video.  

Do you know how many citations I have on talking heads videos from other scientists?  

• ZERO.  I have made zero talking heads videos

Do you know how many citations I have on written papers from other scientists?

• Around 1,600.   (It would be more but I've been doing other stuff lately).

Once again thanks for the link to the Rolf Marschalek paper 

Have a nice evening

How the **** did this happen.

A sensible post about ethics and profit gets derailed by yet another cluster of COVID vaccine spike protein posts, surely the world has had more than enough of those. If this was 2020 I'd have expected it, in 2021 I'd have tolerated it, but in 2022 I've lost my patience.

David Cannon shame on you for this, Wintertree don't you know well enough by now to ignore? Consider yourselves on the naughty step, 1 minute for every year of your age to think about what you've done, face the wall too! 

Thanks for your original post DaveHK, wish you luck steering it back onto the original interesting topic again.

Sorry my bad, this was a kind of daftness I’d not seen before and I was morbidly curious about where it had come from - now answered with the YouTube link...  I’ve mostly been out of the top 20 for months now and should work harder on staying out…

I’m on the fence with regards the OP’s article.  Clearly a beneficial move, but I wonder how much it’s done to defuse regulatory internet and so to ringfence the company’s ongoing ability to generate staggering profits from wealthier nations, which themselves contain many impoverished people without access to fully state funded healthcare.

After a couple of posts you're into pig wrestling/pigeon chess territory, but I'm always happy to see at least one rebuttal before ignoring subsequent posts.  (At least I am when I actually understand what they're on about.)  So fwiw I don't think Wintertree deserves to be on the naughty step for that.

I was just making hard-on puns.  

Yes, a noble thread, upstanding 

Typo.

"And the quarterback is toast!".

Thank goodness.

I was in a hard-on pun competition once - didn't win anything, but I did get through to the semis.

Loving your work.