What are mRNA vaccines, and what do they have in common with America's sweetheart Bruce Willis?
There is no shortage of mRNA vaccine explanations around on the internet today, many if not most of which have been made by people more qualified than myself, which is why I’ve been a little hesitant to throw my own hat into the ring. The reason I am doing so now is that I still see misnomers and misunderstandings persisting about the possible ramifications of an mRNA vaccine, and if my explanation makes it to a single person who reads it, finally understands it, and makes the choice to receive an mRNA vaccine, it’d be worth it. I also feel a little guilty running a science communications blog and writing about anything other than COVID-19 these days, which just makes me all the more keen for everyone to be vaccinated so that we can hopefully return to some sense of normalcy and we can all start talking about something else.
Vaccines have historically worked in a myriad of different ways – live, weakened versions of viruses, dead or inactivated viruses, and components of viruses such as proteins or polysaccharides. The mRNA vaccine is a new type of vaccine, though research into designing mRNA vaccines goes back to at least the 1990s. Rather than explain all other types of vaccine, I’ll use a (hopefully) fun analogy so you can first understand this one, as that’s why you’re here.
mRNA vaccines and John McClane – my analogy
In my analogy there will be a few characters, and I’ll first introduce them. It helps to have seen the movie Die Hard, but I trust you’ll understand this analogy even if you haven’t. Your immune system is composed of many different types of cells which I’m going to combine and grossly oversimplify into a single character – John McClane, the all-American action hero of Die Hard. Your body, which your immune system is trying to protect, is the Nakatomi Plaza – a large tower. COVID-19 is to be played by Hans Gruber, the ‘toothy, perfectly manicured, sphinxlike villain’ of Die Hard (credit to Ian Crouch, writing for the New Yorker, for this wonderful description). In my analogy, Hans Gruber’s mission is to destroy the Nakatomi Plaza, even though in the movie he’s just trying to steal a bunch of money.* Of course, it’s a little misleading to think of viruses as actively trying to kill or harm you. Whether a virus is alive or not, let alone has a semblance of its actions or not, is a hotly debated topic, and even if an individual virus were sentient, it would be no more aware of what it was doing to a macroscopic multicellular organism than an Andalusian termite is aware of its effects on the Spanish economy. But this is a fun analogy, so don’t worry about that. Hans Gruber is evil and wants to blow up the Nakatomi Plaza, just to watch it burn.
Can John McClane stop him? Most of the time, yes! The frequency with which John McClane stops Hans Gruber is quite high, but varies depending on the age, location, and access to health care- I mean building care- of the tower. We also don’t know how long the residual damage done by Hans Gruber will last, and whether it will be repaired with time. Basically, we want a vaccine – something that will stop Hans Gruber at the door before he can do any damage at all. An mRNA vaccine is access to the coded plans of Hans Gruber. The coded plan we use in the vaccine is simple – the coded plan for the entry of Hans Gruber and his associates. The entry plan in Die Hard is simple – Karl and Theo, two of Gruber’s cronies, walk into the bottom of the building, engaged in what appears to be a pretty one-sided conversation about basketball. Karl then shoots the security guard at the reception desk in the head, who probably didn’t think the two were a threat anyway. In humans, COVID-19 gets into our cells by way of a spike protein – a spike shaped protrusion on the outside of the protein, which binds to receptors on our cells called ACE2 receptors – our unfortunately blindsided security guards, and is then let into the cell in its entirety.
Now we have the coded plans for this part of the plan, we can execute and re-execute this small subunit of the plan so John McClane can see it and knows how it works – and is ready for it. Your cells are able to read mRNA and turn it into proteins, and so when they receive the mRNA they produce spike protein, allowing your body to start to recognise it and become able to generate an immune response upon recognition. mRNA degrades in the cell very quickly, so it doesn’t overstay its welcome and won’t be in there permanently making new spike proteins. Now, if the real Hans Gruber came around and tried to get into the building, as soon as two people talking about basketball entered the building, they’d be shut down quicker than you could say “YIPPEE KI-YAY, M-"Studies so far have shown that these vaccines are incredibly effective at preventing Hans Gruber from doing any damage at all to the Nakatomi Plaza, and pretty much completely effective at preventing Hans Gruber from doing critical damage to the Nakatomi Plaza. Armed with the mRNA vaccine, John McClane seems to clinch victory every time.
Wait - what if it becomes part of my DNA?
Another important thing you should know that I can tell you for free is that there’s no reason to think the mRNA will suddenly become part of your DNA. This would go against the central dogma of molecular biology – DNA transcribes RNA translates into protein, and not the other way around. It’s a key point that the central dogma is sometimes reversed – RNA does sometimes become DNA, but only in extremely specific situations and with the help of a protein called reverse transcriptase. Pieces of RNA that become DNA are generally either retroviruses, such as HIV, which carry their own reverse transcriptase, or pieces of RNA transcribed from regions of the genome known as retrotransposons, which have evolved to plonk themselves around various locations on the genome, and usually also carry their own reverse transcriptase.
Of course, this means it’s possible in theory that the mRNA will stumble accidentally upon a retrotransposon with reverse transcriptase and by sheer serendipity be reverse transcribed and then inserted into the genome. But we shouldn’t move forward on what is merely possible in theory when we have a significant amount of gathered evidence, none of which suggests it will happen in practice. If we restrained from doing things because they were possible in theory, we would never leave the house, for fear we may be trampled by a rogue rhinoceros on the run from the zoo. I can’t guarantee that will never happen to me. But the possibility of it happening will never stop me going to the shops.
The end
I hope, if you came in unsure about the rationale about mRNA vaccines and their function, or were uncertain about them becoming part of your DNA, this article has helped. I’ve deliberately eschewed a more molecular description in this article, partially because I don’t think most people are really looking for a dry description of molecular mechanisms, but mainly because if that’s the detail you want, it’s not hard to find plenty of more detailed articles by people with much more experience in the field than me, including people who design vaccines for a living. It’s such a hot topic right now that you can find any amount of detail you want on the subject, including in visual and video formats. To my knowledge, however, I am the first to include a Die Hard analogy, for which I take full credit.
I hope you learned something new!
*SPOILER ALERT: In the movie, he arguably comes far closer to destroying the tower than he does to stealing the money. Perhaps he’d have been more successful if this was his goal all along.
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