Isn’t that exactly what mRNA is?
No - mRNA is made up of different bases (nucleic acids instead of amino acids) and acts as the template for protein production. The mRNA vaccines are so innovative because they pass into the cells near the injection site, and then the cell makes the proteins that stimulate the immune system. Really clever. I think they’re now figuring out how to use the technology as a cancer treatment…
I just can’t figure out why they don’t cut out the middleman and just inject the protein, instead of having the cells make it.
Ahh - my point was that by injecting the mRNA you are making factories that produce the spike protein (and will keep doing so until wiped out), thus requiring the immune system to have a response.
Perhaps it’s a quantity thing?
Hmmm - you could be right there… I guess the protein wouldn’t be degraded either…
Thanks for all the responses and thank you to @KenKnight for the thorough explanation and providing citations. It’s going to take a while to go through them.
I know starting this thread, at all, was taking a chance it could go off the rails and I’m sure some of my questions have made that even more possible. My thanks to everyone for keeping this thread civil. I’ve learned a lot. Y’all are the best.
Probably because making proteins is a very tricky business, and you can’t beat having the cells make them themselves. If we need specific proteins otherwise, we usually trick bacteria (E. coli) to make them for us, but then you still need to “fish” for the right protein in the whole bacteria soup and do some painstaking, expensive and not always 100% efficient clean-up.
Much smarter to pass the cells some instructions and let them do what they are good at.
I guess …
Also… maybe it’s easier to retool for a different mRNA sequence than a different protein?
@joergkutter +1. Exactly. Lots of different ways to make vaccine (7 main categories or types) but you have to either get something to make the protein antigen (usually engineered bacteria, or recombinant synthetic using cultured cells - very cool, very complicated, very expensive), then “fish” out that protein (I like that metaphor), purify it, and bottle it up OR just grow the virus itself (usually in millions of fertilized chicken eggs) and then inactivate (kill) it or weaken (attenuate) it. Either way you have to grow and then purify. Growing is a mess, millions of eggs or huge vats of bacteria, or finicky expensive synthetic cell lines. Then purification is messy because you have tons of stuff you don’t want in the mix (like eggs and parts of bacteria).
mRNA is purely in the “test tube” - scientists identify the virus DNA or RNA section that has the instructions for the antigen like the spike protein (viruses can use either as their genetic backbone - COVID uses DNA). From there we use an enzyme and heat process to create trillions of copies and purify. But purification is easy because this isn’t messy bacteria or virus or eggs - its just small amounts of synthetic leftovers from the copying process).
mRNA is almost certainly the future of vaccines. We can make them quicker, cheaper, and cleaner and then rapidly modify if a virus mutates. I know that mRNA vaccines are under development for cytomegalovirus, chikungunya virus, influenza virus, rabies virus, and zika virus. Parasitic and bacterial mRNA vaccines are also being looked at, and three HIV vaccines are being developed too. In particular - parasitic mRNA vaccine for malaria is under development - and it’s hard to overstate how important it could be. In 2020 alone malaria made 241 million people sick and killed 627,000. The vast majority of the dead are children under 5. That happens every year. Every single year a half million kids die of malaria. That never ceases to stop me in my tracks. An effective vaccine could transform Africa.
(And I didn’t even mention mRNA cancer vaccines…)
This is one smart thread!
And very straightforward and clear.
Thanks for all the great info.
I’d like to sincerely thank all of the really smart people who contributed to this thread. I know i didn’t understand all of it, but it reinforces what i knew- that vaccines are safe, effective and the very best prophylactic response against things like the 'rona, measles, mumps, rubella, chicken pox and the good old flu-Because lest we forget, that crud ain’t gone, and it kills a great number of people yearly.
I wouldn’t ever want to try to change anyone’s mind about vaccines-and i don’t think i reasonably could-but if you do your research rather than getting medical advice from Facebook and Twitter and tiktok, you may be healthier and live longer. That doesn’t really sound so bad to me…
All I know is that over a year after COVID, I still have no sense of smell. No matter how good or bad something smells, I am oblivious. And the brain fog is still with me on most days.
So today is day +4 after the new hip. Walked just a hair over a mile yesterday, first Lap today was about .6 miles with another one planned for the evening.
Tried to play a little bit yesterday, did some octave drop exercises and some spider walks. Wasn’t really able to keep it going very long-if i tried for 10 minutes it would have been a lot-but the bass sitting on my thigh pretty much right on the incision wasn’t very becoming to extended practice. Maybe i should get a stand and play it like a lap steel? Or i could maybe tie a bunch of helium balloons on it and make it really light? Or attach it to my walker? I guess what in saying is i miss playing, but it’s short term. I’ll be ruining songs again faster than anyone who can hear me would wish😂
MUCH easier! Choose a new sequence of mRNA that codes for the new antigen you want - instantly put it into production with no other changes to your production workflow. The change is literally just a different ordering of the 4 RNA amino acids (cytosine, guanine, adenine and uracil). So you might have been producing vaccine who’s mRNA was “CGCGAUA”, but now you want “AUAGCGC”. Just stop old production and clean your equipment - plug the new “AU…” template into the same workflow you were using before and you’re making the new mRNA. All other aspects remain exactly the same.
(This is a simplification of course, and ignores a boatload of QA/QC steps, but the point is that it’s much easier to alter mRNA vaccine production than any other vaccine production process.)
For those who are messaging with specific questions. Here’s your source on mRNA vaccines. If you can understand 80% of what’s in this journal article you’re way smarter than me. But this is the state-of-the-art knowledge in mRNA vaccine as of winter 2022. I’m sure there have been advances in the last 6 months that are either unpublished, pre-published or are stewing around in some post-doc’s brain waiting until she has time to write them up.
Fang, E., Liu, X., Li, M. et al. Advances in COVID-19 mRNA vaccine development. Sig Transduct Target Ther 7 , 94 (2022). Advances in COVID-19 mRNA vaccine development | Signal Transduction and Targeted Therapy
And here are the technical details of how mRNA vaccines work including the details like evading endosomal activity, and most of the various immune cells and enzymes involved:
mRNA delivered in an mRNA vaccine enters cells by endocytosis and, after release from the endosome, is translated into protein by ribosomes. Translated proteins can then activate the immune system primarily in two ways: i) proteins are degraded by the proteasome into peptides subsequently presented as antigens on the cell surface by major histocompatibility complex (MHC) class I molecules which bind to the T cell receptor (TCR) to activate CD8+ T cells to kill infected cells thorugh the secretion of perforin and granzyme; ii) proteins secreted extracellularly are engulfed by antigen-presenting cells (APCs) and degraded into peptides subsequently presented on the cell surface by MHC class II molecules for recognition by CD4+ T cells, which can activate both the cellular immune responses by secreting cytokines and the humoral immune responses by co-activating B cells. In addition, single-stranded RNA and double-stranded RNA delivered in mRNA vaccines bind to Toll-like receptor (TLR) in the endosome to activate the antiviral innate immune responses via the production of type-I interferon (IFN-I) which results in the induction of several IFN-1-stimulated genes involved in antiviral innate immunity, in a mechanism known as the self-adjuvant effect of a sequence-engineered mRNA. This figure is created with BioRender.com
That’s some really good stuff and information you have put together here in this thread, @KenKnight - thanks! You have a knack for explaining things and showing how different aspects are connected - are you writing about science in more popular formats (beyond publishing in peer-reviewed journals)? If not, you might want to consider it
(PS: are we still in a bass forum here??
)
Yes, this is bass-ic scientific learning-osity going on right here.
Yes. And proving that bass players are the smartest in the band after all!
I lost my sense of smell after my brain sloshed in an accident and basically ripped the receptors ( probably the wrong term) that send the signals from the nose to the brain so I genuinely feel your pain. It’s pretty crap not being able to take a step back and smell the roses
Thanks for the high praise. Ironically, back in the 90’s, my original intent in college was to be a science journalist - but then the science grabbed me and I went down a different path. In 2020 I retired from lab & emergency work with the military and made the single worst career move in the history of career moves: It’s fall 2019, and I applied for a nice, sleepy, sedate, calm job as Emergency Director for a large public health department. By the time I made it through the process and was offered the position it was Spring 2020. The world was locked down, and I realized my sleepy, nothing-dramatic-ever-happens-in-public-health job was about to explode. So now the past 2.5 years have somehow seemed like both 25 years and 2.5 months. Our Dept. calls that “covid time” - things moving too fast and too slow at the same time.
BUT… my bass timeline coincides exactly. Bought first bass in Spring 2020 and started B2B - and it’s been my outlet. When I’m practicing or playing (at least for me) I can’t think about anything else. It’s a complete escape from the rest of the world. I have to set a timer to make sure I end at a reasonable time and spend time with the family. That combined with lockdowns that reduced other potential activities meant I probably played more, and got better, much faster than I would have otherwise.
Oh, man, that’s rough - basically, you were looking for an Einstein-at-the-patent-office type of job and ended up having to manage pandemonium
That’s how I feel as well when I practice or play music - such an important “escape route” for the brain!