Map of life expectancy at birth from Global Education Project.

Friday, December 18, 2020

A word about mRNA vaccines

I note that many people are concerned that mRNA vaccine technology has never before been approved for use in humans. They worry about unknown risks and nasty surprises, and are reluctant to accept the Pfizer and Moderna vaccines.

I am actually not worried about it, and I'll try to explain why. First I'll just note that this technology has been under development for decades, and has been tested extensively in animal models and experimentally in humans before the large-scale clinical trials that have led to Emergency Use Authorization. So there is a lot of evidence for safety, although it is true that the follow-up time for the clinical trials is so far less than is usually required for full approval. The trial subjects are still being followed so we will get a signal if anything untoward might happen -- but there is very good reason to be confident that it won't.


This is pretty technical, and it's hard for people who haven't studied a lot of biology to get this stuff sometimes, but I'll do my best. Many readers will already know this, others may not. In animal cells (also plant cells, actually) the DNA in the nucleus, that kind that's in our chromosomes, contains instructions for making proteins. In simple terms, one gene consists of the instructions to make one protein. Proteins are long chains of smaller molecules called amino acids.  The instructions consist of three unit combinations of four different "letters," which are also specific small molecules, and you probably know these are abbreviated A, T, C, and G.* So AAT might mean one amino acid and GTC another. But these instructions need to be translated by a mechanism for assembling proteins.

The instructions are carried out by molecular machines in the cell called ribosomes. Messenger RNA, mRNA, is the molecule that carries the instructions from the nuclear DNA to the ribosomes. There are regulatory regions in DNA that mark where a gene begins and ends  (some genes consist of separated regions whose instructions need to be spliced together, not important) and for turning on and off reading of a gene by mRNA. Fortunately we don't have to worry about any of this because the mRNA vaccines skip all that.

Here's what they do instead.  Cells are wrapped in a membrane that  has little portals that selectively let molecules in and out, called receptors. Viruses consist of genetic material inside a protein capsule, with little keys that unlock one of the receptors so the virus can get its genetic material into the cell. The immune system learns to recognize one or more of the proteins in the viral capsule and make antibodies that attack that protein. In the case of these particular mRNA vaccines, that protein happens to be the key that gets the virus into the cell, which is often the case.


Note that the protein by itself is completely harmless. It's only dangerous when it's part of the virus; it can't reproduce on its own, and it doesn't hurt anything if it binds to a receptor if it's not associated with any viral genes to inject. So the vaccine manufacturer makes a whole lot of mRNA that consists of the instruction to make the viral protein. They make it a little bit different in some ways from natural mRNA, so it won't provoke an immune response itself, is more stable, and can sneak into cells. That part is very technical but don't worry about it. You can read all about it here if you're interested.

So you get injected with this and some of your cells take it up and start making the viral protein. They display it on their surfaces, your immune system recognizes it and starts making antibodies. Then the cell destroys the mRNA as it does all mRNA in the normal course of events -- it's job is done. So there is really no evident way that you could suffer any long-term ill effects from this.

Now, because the vaccine provokes such a strong immune response you may briefly experience typical symptoms of a viral infection. That's because those symptoms are actually caused by the immune response, not the virus itself. You don't have a viral infection, so the symptoms will go away quickly. I'm talking a fever, or feeling fatigue, or a headache. From what we've seen of the clinical trial data, something like 20% of people might have this experience, but it sure beats suffocating alone. 

So when you have the chance, that's the information you should consider. By then, we'll have at least a couple more months of follow up anyway. So I'm not worried. This technology has all sorts of incredible potential, not only against viruses but also against cancer and maybe some other applications. Once you have the basic platform, you can plug in any protein you want, very easily. These are the days of miracles and wonder.

*Not that it matters but these stand for adenine, thymine, cytosine and guanine.


mojrim said...

Nice, non-technical briefing. Embarrassingly, I've never heard of mRNA vax until now.

Alexander Dumbass said...

Scientists told us in early spring when President Trump said there would be vaccines available by years end, they told us it was a pipe dream, that it would take "a miracle".

Media now tells us that because this platform has been in the works for years, Operation "Warp Speed" gets little to no credit for the speed at which the vaccines were produced and distributed.

So, which is it?

Cervantes said...

Actually the consensus prediction early on was that a vaccine might be available by around year's end. Pfizer did not participate in Operation Warp Speed, nor did the Oxford collaborative. So it's neither.

Alexander Dumbass said...

The timetable for a coronavirus vaccine is 18 months.

WASHINGTON — As nations around the world race to lock up coronavirus vaccines even before they are ready, the Trump administration on Wednesday made one of the largest investments yet, announcing a nearly $2 billion contract with Pfizer and a German biotechnology company for 100 million doses by December.

Cervantes said...

So what? The administration contracted to buy Pfizer's vaccine, but Pfizer developed it on its own. The long-end estimate for development time was originally 18 months, it ended up taking a few months less. What the fuck is your point?

Alexander Dumbass said...

Credit given where credit is due...that's the "fucking point".

Sebelius said she gives "a lot of credit to the Trump administration for understanding that the muscle of the federal government, the financing from the federal government, the urgency from the federal government, makes a huge difference, while also praising the speed with which Moderna and Pfizer have made on a potential vaccine.

While Moderna did take research and development funding from the Trump administration and worked under National Institutes of Health oversight, Pfizer developed its vaccine independently, although it took an upfront payment of $1.95 billion for future delivery of vaccines under Operation Warp Speed.

Sen. Dick Durbin, D-Ill., a top critic of President Trump, gave the administration praise as a second COVID-19 vaccine tied to Operation Warp Speed is expected to receive emergency use authorization from the FDA.

"The Warp Speed project appears to be a dramatic success," Durbin said on the Senate floor on Thursday. "I pray that it will be. Although I’ve been a frequent critic of this administration, I want to give them credit for organizing this effectively, and delivering a vaccine in a timely way, almost amazing timely way in this pandemic that we face."

Cervantes said...

Right. Your beloved, Donald J. Trump, personally developed the Pfizer vaccine, using his very stable genius.

Cervantes said...

By the way, I thought you were a libertarian conservative. All of a sudden you want the federal government to spend hundreds of millions of dollars to buy a product and give it away free to millions of people. Sounds like socialism to me.

Alexander Dumbass said...

And I thought you were a progressive that viewed the market as unable to meet the needs of people without the guiding hand of the government.

Just kidding...

This kind of characterization is the reductio ad absurdum of the others side's political beliefs that commonly pervades politics today where everyone thinks if you're a Democrat, you must be a commie and if you're a conservative, you must be a White supremacist or something.

My comment had less to do with politics and more to do with mischaracterization of the government's role and your unwillingness to assign any credit to those in power who helped. As demonstrated, many Democrats recognized Trump's role both in leadership and in deeds.

BTW, libertarians do understand that there are things that only collectivism can solve such as police, armed forces, etc., and a pandemic just might be one of them, too.

mojrim said...

Really, Alexander? Because the libertarians I know would eliminate both those entities and rely on private security, arbitration agreements, and volunteer militias.

Alexander Dumbass said...

There is a wide spectrum of positions of those who consider themselves "libertarians", most wanting a smaller, more transparent government with more individual responsibility and freedom.

The few contacts you've made are on the fringe if they don't want an ordered society.
I'd say those you've described would be closer to anarchists.