Kyle: Okay. Well, Dr. Patrick, this next question's for you, and it's about spike protein. We know that the spike protein can be dangerous and cause a significant immune response, and there's this idea floating around that because spike protein is dangerous from the SARS-CoV-2 virus, therefore, the COVID-19 vaccines must be as dangerous as well. What are your thoughts on that?

Dr. Patrick: Well, I have a lot of thoughts on that, Kyle. I've thought long and hard about it. But sort of before I get into some of the details, I think, the spike protein has really become a common household name. At this point, most people around the world know what the spike protein is mostly because it's the entry point for the SARS-CoV-2 virus to get into our cells. There are about 26 different spike proteins. I shouldn't say different. There are about 26 spike proteins that line the surface of a SARS-CoV-2 viral particle, and these spike proteins will bind to a receptor on many different cell types we have in our body that have a receptor called ACE2. And when the spike protein then binds to the ACE2 receptor, it undergoes a conformational change that essentially refers to the structure of it changes. So it binds on to this receptor, and it then elongates, and sort of twists and turns around, and then it fuses with the cell membrane and is, you know, engulfed inside of the cell. Another way it happens is through endocytosis. But essentially, the point I want to make here is that conformational change happens because when the spike protein initially binds to the ACE2 receptor, it's in a conformation called the pre-fusion conformation. You can think of it more like a closed type of conformation. Once it binds, this triggers a conformational change for it to, again, like I said, elongate and sort of twist around. When it does that, that is referred to as the post-fusion conformation. And the reason that's really important is because all of the vaccines that are available in the United States under either emergency use authorization or under FDA authorization or up and coming vaccines, so that includes the Moderna and the Pfizer-BioNTech mRNA vaccines, the Johnson & Johnson adenoviral vaccine, as well as the Novavax vaccine, they all contain an insertion of two proline amino acids into the spike protein to lock it into the pre-fusion conformation. And this was brilliant work done by the structural biologist, Dr. Jason McLellan. He's at the University of Texas in Austin. And he thankfully had figured out this way to lock viral proteins into the pre-fusion conformation. First it was with the respiratory syncytial virus, RSV, and then later, he had figured out for the other beta coronavirus, the MERS coronavirus. And so he really had a running start there. And the reason that is so important is because, when you're comparing the spike protein from the SARS-CoV-2 virus, as I mentioned, there's 26 of them on every viral particle, to the spike protein that is in the vaccines, including the mRNA vaccines and the vaccines in the United States, it's a different spike protein. It's a spike protein that cannot undergo that structural change. It does not elongate and, you know, dig into the cell membrane and fuse with it. It's a different spike protein because of those two proline amino acids that were inserted to lock it into the pre-fusion conformation.

And one of the first things you learn as a scientist, as a budding young scientist is that you can't compare apples to oranges. You can't compare two different things. You have to compare apples to apples or oranges to oranges. And so when you're talking about a different spike protein, structurally, it's different, right? You can't take a study that's looking at the spike protein that is from the surface of SARS-CoV-2 and say everything that that spike protein is doing applies to the spike protein in the vaccines that are available in the United States because it's different. And so, I think, that's a really, really upfront important thing to understand. And the burden of proof is on, you know, people making the claim that the spike protein from the mRNA vaccines is dangerous because some studies have shown that the spike protein from the SARS-CoV-2 by itself can be dangerous. You have to show that, and it has not been shown. So, what these studies that have shown that the spike protein from SARS-CoV-2 virus, how it can be dangerous, there's been some in vitro studies, which means cells in culture in a dish. When you dump spike protein on them, it can cause the activation of cell signaling pathways that could lead to cell death. This is often referred to as cytotoxicity. There's also been some animal studies shown where either recombinant protein, which is just basically made in a lab, so they make the spike protein, or what's called pseudovirus expressing the spike protein, so this is not the SARS-CoV-2 virus, but it sort of acts like a virus to allow it to get into cells, if you directly inject the pseudovirus with a spike protein into the trachea of hamsters, it causes severe lung damage and also gets into the circulation and causes circulatory damage and vascular damage to the vascular system.

And so these studies, and there's been, you know, a few of those, have really spurred this idea that the spike protein from the vaccines must be dangerous because these studies showing the spike protein that's found on the surface of SARS-CoV-2 is. And again, you can't compare. You can't make that comparison, and that's really just one aspect of, you know, this story. The other aspect has to do with where the spike protein goes in the body. And, you know, I think, first and foremost, anyone that's concerned about these studies showing that the spike protein by itself is dangerous should be terrified about getting SARS-CoV-2 because, for one, you're getting, as I mentioned, 26 of those spike proteins on one viral particle. How many viral particles are replicating inside of your cells at any given moment? You know, thousands of them. And on top of that, there have been studies that have shown that SARS-CoV-2 virus is detected in multiple organs. You know, this isn't just in the nose and in the trachea and in the lungs, which in and of itself is bad. I mean, the damage to your lungs is, you know, one major concern. But the SARS-CoV-2 virus, again, with spike protein has been detected in the heart in humans. It's been detected in the brain. It's been detected in cerebrospinal fluid. It's been detected in kidneys. It's been detected in the GI tract. It's been detected in the testes. It's in many different tissues in humans. Oh, and it's been detected in plasma in the circulatory system. So, again, you know, the concern should be amplified for actually contracting the SARS-CoV-2 virus if you are concerned about the study showing spike protein itself is dangerous.