Dr. Bow Tie
I'm Probably Overdue to Talk About mRNA, Aren't I?
Updated: Feb 14, 2022
The vaccines against COVID-19 are true medical marvels. I wrote back in December of 2020 about the development of the vaccines (trying to bust myths that still persist today about the speed of development), and I have written several posts since then (but most of you knew that). Still, as COVID-19 vaccines near a year of availability to the general public, people are still hesitant about this "new technology" in Pfizer and Moderna's vaccines, made even more reticent by the tidal wave of disinformation about their creation, their ingredients, and their effects. So let's talk about what mRNA vaccines actually are, and how they are not as new as previously thought, and how good they actually can be.
SO...WHAT IS MRNA?
mRNA is a molecule composed of nucleotides, similar to DNA, with some key differences. RNA and DNA have some structural similarities, but where DNA is 2 strands of nucleotides (adenine, guanine, cytosine, and thymine), RNA is 1 strand of a combination of adenine, guanine, cytosine, and uracil. DNA is transcribed (copied, in a way) to create RNA. The RNA is spliced and edited (mRNA in this case, although there are other types) and then, in its mature form, is translated (read and interpreted) by a ribosome which then produces a chain of amino acids called a polypeptide. Polypeptides form proteins. The translated mRNA molecule then goes through decay or degradation and that’s the end of it (which also explains how mRNA vaccines leave your body as well after they give your immune system the instructions it needs to fight disease).
AND THEN IN 2020 THEY MADE IT INTO A VACCINE? WHAT HAPPENED IN BETWEEN?
The story of mRNA vaccines goes back decades. In 1969, scientists figured out how to induce mRNA translation in vitro. By 1978, labs were experimenting with lipid molecule delivery systems. More developments would occur, but the story kicks into gear in 1990, when Dr. Katalin Karikó noted the potential with synthetic mRNA injected into mice to create immunity (from experiments at the University of Wisconsin that year). She then saw in 1992 when vasopressin mRNA was injected into a rat's brain to correct disease. Others were able to induce T-cell production against the influenza virus in animal trials by subcutaneous injection in 1993. Unfortunately Karikó's research did not go past its initial stages at first, because the immune system attacked the foreign-appearing mRNA molecule so quickly that it couldn't deliver its message. She struggled with how to get around this barrier. In 1995, while other scientists were injecting mRNA to induce tumor inhibition in vitro, Karikó was actually demoted from her track because she had had so many rejections and had not been able to get any output. Meanwhile in 1999, mRNA injection was used to induce a T-cell response against tumors in vivo (after decades of experiments! This would be the precursor to the first mRNA immunotherapy against cancer cells in humans a decade later).
Eventually, after slogging through experiment after experiment, in 2005 Karikó and her research partner at the University of Pennsylvania Drew Weissman discovered that you could modify nucleosides (components of the mRNA described above) to synthesize an mRNA compound which did not trigger the immune system so quickly. Based on their experiments, Derrick Rossi (who would go on to form Moderna, originally designed to make synthetic stem cells in order to avoid the controversy surrounding them) began to craft ideas that would fuel his company's research. Somewhat concurrently, Ugur Sahin and Ozlem Tureci (in Germany) teamed up with investors the Strungmann brothers to form BioNTech. Moderna was meant to come out with new mRNA-based therapies for a variety of diseases, with little success. BioNTech would, at one point, try to work with Pfizer on an influenza vaccine (early experiments had shown disease correction with mRNA vaccines in 2011, and they initiated preclinical trials around 2012).
Then in December of 2019, there came reports of an unexplained pneumonia in Wuhan, China, and by January 2020 the genome of SARS-CoV-2 was sequenced (just yesterday I heard someone try to say they have never isolated the virus, which is preposterous - we had that early on). The rest, as they say, is history.
The challenge was combining the best qualities of live-virus vaccines and killed-/attenuated-virus vaccines: the antigen expression and T-cell induction of the former, with the defined composition and safety of the latter. They needed a vaccine that contained solely the elements for spike protein expression (or whichever protein meant to be recognized on a virus) that could get into cells to be read by the ribosomes without triggering the immune system to go after the vaccine itself. To this end, the synthetic modified mRNA was combined with a lipid nanomolecule, which prevented immediate immune degradation and delivered the mRNA to the ribosome to be read and translated to instructions for the immune system.
Incidentally, you know who's not mentioned in a lot of the articles about mRNA vaccine development? Robert Malone.
BUT ROBERT MALONE IS THE INVENTOR OF mRNA VACCINES...RIGHT?
Yeah, if you look at his website and his social media, that's how he touts himself. He did publish a paper in 1989 call "Cationic liposome-mediated RNA transfection", which probably contributed to others' research, but it's a far cry from "inventing" mRNA vaccines. Malone sometimes tries to backtrack and rephrase to say he came up with "the vaccine technology" (which is also an outlandish claim, and not one that a respectable scientist would try to take *solo* credit for). He even reached out to the folks who wrote the fact check I list below, showing off his patents (none of which prove "inventing mRNA vaccines"). He has made the rounds on the talk shows and podcasts of members of the Disinformation Dozen and other conspiracy theorists (I mean, I guess he was on Tucker Carlson, if that counts as legitimate media), spreading myths about antibody-dependent enhancement, vaccine effects on fertility, and other myths which I and many others (utilizing properly-conducted research) have disproven over and over again. Instead, he touts his own more recent work on famotidine and ivermectin (which, as I have discussed, used fake or insufficient data and have also been disproven). He tried to make a name for himself with mRNA vaccines (that he did not earn) and then tried to undermine them with his own alternative work. He is not the only medical doctor to try to do this, but he is one of the most egregious, so you can understand why he is a target of my ire. In trying to discredit a proven-safe and effective vaccine, he has left a stain on my profession.
PEOPLE ARE SAYING THESE ARE NOT REAL VACCINES, THOUGH
A few months back, this myth made the rounds and is still doing so. Sherry Tenpenny, Del Bigtree, and other Disinformation-mongerers love to try to say this. It unfortunately convinced a lot of people, including someone on my Twitter timeline that did not take kindly to me refuting the claim. He tried to gaslight me into admitting that I was changing my definition of vaccines, and cited the Department of Health & Human Services' definition of vaccine: "made from very small amounts of weak or dead germs that cause diseases - for example, viruses, bacteria, or toxins. It prepares your body to fight the disease faster and more effectively so you won't get sick."
The problem here is that this is a rather oversimplified definition. The definition of a vaccine is a compound or substance meant to induce our immune system to create antibodies (a complex word in and of itself) against a disease - most often a virus these days. We can do that in a number of ways, and the technology is advancing, improving! As I said earlier, mRNA vaccines are a huge scientific breakthrough, accomplishing the same goals as older types of vaccines.
WHY HAVEN'T WE USED mRNA VACCINES MORE WIDELY?
I'm glad you asked (you didn't, this is just a contrivance I use to write my essays, but I digress)! This goes back to my first post about vaccines that I mentioned, back in December 2020. Pharmaceutical and vaccine development have been incredibly challenging for years, not just because of the difficulty of scientific advancement, but because of the money and bureaucracy involved. Grant applications sometimes take years or decades to come to fruition (just ask Dr. Karikó). If the financial winds shift, or if a pandemic dies down, or there just does not seem to be enough earning potential in the eyes of corporate folks who don't see the actual disease, the money disappears. For example, after the SARS-CoV pandemic in 2002 and the MERS pandemic (both coronaviruses) in 2012, intense study was initiated on coronaviruses and the possibility of vaccines (the MERS vaccine was created, but did not go past Phase I due to waning financial interest).
The other problem? Storage. mRNA is an incredibly unstable molecule (that's why the claims that the vaccine stays in your blood or lies dormant within you are easily disproven). Comirnaty (Pfizer-BioNTech's vaccine) requires storage around -70 degrees Celsius. The soon-to-be-formally-named SpikeVax (from Moderna) is somewhat easier, requiring -20 degrees Celsius storage. Both vaccines are thawed before administration (so you don't feel the cold) but must be used within a certain time after thawing). Both companies are working to alleviate this burden, but it definitely adds to costs (that ever-present and often determining factor). That cost was alleviated during this pandemic because emergency measures were taken - the government and private donors poured money into development and distribution and, yes, storage costs. Now that we have the money to address these problems, we can finally make progress in making them easier to use. It's funny what happens when medical research (or any sound science) gets the resources it needs.
SO, IS THIS GENE THERAPY?
Go back to the definition paragraph. Gene therapy is removing or changing a gene to treat a disease, but that requires genes which are made up of DNA. mRNA, as I illustrated above, is formed FROM DNA, but does not form DNA, so it cannot alter genes. There ARE specific gene therapy treatments we have for certain conditions, and that will have to be a different post some day. The most important thing is (for this post), the mRNA vaccines are NOT gene therapy, and cannot alter your genes.
So there you have it. A very brief summary on mRNA and how mRNA vaccines came to be. As you can see, this is not new technology, but rather built on decades of research. It got a jumpstart last year due to an influx of money and resources to combat this hellish pandemic, that is for sure, but it was not rushed nor is it haphazard. Scientists are already discussing making combination mRNA vaccines to vaccinate against COVID-19, influenza, and maybe RSV. Vaccines can be made to train our immune systems to fight against all sorts of diseases, with just a change in which protein is recognized. This could be a new era in immunology and in disease prevention. And as I have discussed so many times in the last year, they are safe and effective. They protect not only you, but - despite what some myths say - your community as well by preventing spread. Please get vaccinated!
Katalin Karikó and the players leading to Moderna and BioNTech: https://www.statnews.com/2020/11/10/the-story-of-mrna-how-a-once-dismissed-idea-became-a-leading-technology-in-the-covid-vaccine-race
RNA Biology article: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3597572/
Robert Malone Fact Check: https://www.logically.ai/factchecks/library/3aa2eefd