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  • This is how coronavirus invades your body.

  • Sinking its crown-like spikes into your cells,  

  • using molecular deception to pick  their locks, and hijacking your body.

  • But there IS one way to prevent this.

  • By using one of the virus's weapons on itself… 

  • Hey smart people, Joe here.

  • Right now, there's about 7 billion  people all waiting for the same thing:  

  • A vaccine that will protect us  from the virus causing COVID-19.

  • And if you're like me you want to know  what's in it…  what makes it work?   

  • Making a vaccine and getting it out to the  public is a long process with a lot of steps,  

  • so we can make sure the  vaccine is safe and effective

  • And it's pretty typical for  that to take ten years or more,

  • In an emergency, like this pandemicwellwe can't skip any of those steps,  

  • but we can speed this up by  doing some at the same time

  • But none of that can happen until  you figure out the first step:  

  • What do you put in your vaccine  that will make it protect people.

  • and it's what we're going to talk about today.

  • We're gonna visit a lab and meet some  scientists who study the coronavirus.  

  • We're also gonna meet a really big Awesome  Science Machine, and learn how they used  

  • it to design this: the key ingredient  inside the very first COVID-19 vaccines.

  • Here's my goal with this video: To show you  what exactly is in the new COVID vaccines  

  • that makes them workand how they got  made faster than any vaccine in history.  

  • My hope is that you'll be better  informed when you get your shot,  

  • and you'll have a new appreciation for  why science like this is so important.

  • This is how to make a COVID-19 vaccine.

  • It turns out that some of the most  important research for making the  

  • COVID-19 vaccine is happening  right down the road from me

  • at the University of Texaswhich is pretty  cool. Because I did my PhD right *here*,  

  • and in *here* is the lab of

  • Dr. Jason McLellan. He studies how pathogens  like the coronavirus cause disease

  • There are four human coronaviruses that occur seasonally and generally cause the common cold.  

  • And then there've been three coronaviruses that have caused pandemics.  

  • And that's the first SARS  coronavirus back in 2002,  

  • the MERS coronavirus in 2012. And now  SARS-CoV-2, which emerged earlier this year.

  • So at the end of December, 2019, it was on the  news that there's these pneumonia clusters in  

  • China. Uh, in the scientific community, we thought  maybe a new flu virus or possibly a coronavirus

  • I was actually snowboarding with my family and  my collaborator, Barney Graham at the vaccine  

  • research center at the NIH called. And he  said, he's been in contact with US CDC,  

  • Chinese CDC. Uh, it looks like it's a  betacoronavirus similar to SARS coronavirus, and  

  • they want it to move rapidly, try and makevaccine. And I said, we're definitely in

  • So you're just like scrolling  through your phone. in this ski  

  • lodge, and you're  like we gotta get to work!

  • So while the rest of us were  focused on royal family drama  

  • and just hearing the first mentions of  “coronavirusfor the very first time,  

  • scientists like Jason knew this was seriousand they were already getting to work.

  • As soon as researchers in China decoded  the virus' genome and published it online,  

  • Jason's lab could start designing a vaccine… I texted Daniel Wrapp my graduate student  

  • and let them know be on high alert  because as soon as we get the sequence,  

  • we're going to race on this thing  and move as quickly as we can.

  • Jason was on that winter vacation and texted  me that it was a CoronavirusAnd eventually  

  • in early January, the sequence  was released online publicly.

  • That's when the clock started ticking because we  

  • knew a bunch of people were  going to be working on this.

  • Uh, and then things started moving pretty quickly

  • Let's step back for a minuteWhat does a vaccine do?  

  • It trains your immune system to  know what a germ, like a virus,  

  • looks like. So it can recognize the germ, fight it  off, and keep you safe, without you getting sick.

  • This is the virus that causes COVID-19.  The outer shell is made of a few different  

  • kinds of proteins, butthese proteins  sticking off the side are the most  

  • important part. The spike.These spikes are  what give this family of viruses their name:  

  • The coronaviruses, because  they look kinda like a crown.

  • The coronavirus uses that spike to sneak  into our cells. The 3-dimensional shape of  

  • that spike is super important, because that  exact shape is what lets the virus latch on  

  • to receptors on the outside of our cellsalmost  like picking a lock. And then, it sneaks inside.

  • Those shapes sticking out on the outside of  a virus are also what your immune system is  

  • feeling for, to figure out if this isforeign invader, if it should attack or not.

  • The problem is, the first time your body seesvirus, your immune system responds so slowly that  

  • the virus has time to make gazillions of copies  of itself, and you can still get very, very sick.

  • That's what's great about a vaccine. It  trains your immune system what to look for,  

  • so when the real virus shows up,  

  • your body can respond super fastand destroy the  virus before it has a chance to hijack your cells.

  • So what's actually in a vaccine? Sometimes,  a vaccine has a weakened or dead virus.  

  • That's how polio and measles and  mumps and some other vaccines work

  • But these days, a vaccine usually just  contains a little piece of the virus.

  • The newest COVID-19 vaccinesThey're just the spike.

  • But for that spike to work as a vaccine, to train  your immune system to recognize the actual virus,  

  • it has to have the same 3-dimensional shape  as the spike on the whole, complete virus.

  • But making the spike all by itself,  

  • not attached to the rest of the  virus, turns out to be really hard.

  • Because the spike is actually pretty  floppy just floating around on its own.

  • It doesn't look much like the  spike on the actual virus.

  • And this is the key thing Jason's lab figured  out how to makeFor years they'd studied SARS  

  • and MERS viruses, which are really closely  related to the virus that causes COVID

  • So they already knew what tiny tweaks  to make to freeze coronavirus spikes  

  • in the perfect shape. Um, so we got to work  designing our stabilizing mutations into the  

  • new spike sequence. There was just two amino acids  that we knew would, uh, if we mutated them that  

  • would stabilize the spike protein and make it a lot easier to work with in the laboratory.

  • A protein, like the coronavirus spike… 

  • ...is a long, folded string of  individual units called amino acids.

  • And these strings of amino acids are built  using code written in RNA, and stored in DNA*.

  • By changing, ormutuatingthe letters of  DNA code, we can change the amino acids in  

  • our protein string. So that's cool. You're like  building scaffolding into the protein, to be like  

  • freeze in this shape.”   

  • Yeah, that's a good way to put it

  • How do you get from there to  making the actual spike protein?

  • I can show you… 

  • Scientists are able to grow special immortal  human cells outside the body which they use as  

  • factories. They put a modified gene for something  like their spike protein, into those cells

  • and then they'll start spitting out this protein

  • So they're just pumping it  out into the liquid, right?

  • Yeah, that's right.

  • They take that liquid, run it through  special purification machines,  

  • and are able to isolate a pure  sample of their spike protein.

  • But how do they know for sure  that this special spike protein  

  • looks like the real thing, 3-D shape  and all? They take pictures of it

  • using a big Awesome Science Machine.

  • (VO) This is a cryo-electron microscope

  • This machine took a 3D picture  of the coronavirus spike,  

  • and helped design the first COVID-19 vaccines

  • Check out the big science machine!

  • It looks like a giant microwave

  • Am I ok to walk up here?

  • Yeah, it's ok. I mean the room is a million  dollars, and the microscope is another million

  • So you're saying don't touch  this screen right here.

  • You can see the floor is separate  from the instrument, it's on its  

  • own, free-floating. So vibrations are bad. These are wall panels that contain water  

  • running behind them to keep the  temperature constant in the room.

  • Oh wow, that's…

  • Then it also has to be  electromagnetically shielded too

  • That is nuts.

  • Look at this beefy cable over here.

  • That's the high-tension, that's the  200,000 volts comin in over here

  • Oh ok, so don't lick that one!

  • Oh this is

  • Sciencey!

  • Look at all that science happening in there

  • It's kind of a marvel of physics and engineering.

  • Joe N (OS): Can you play Doom on this thing

  • Um, some of our computers you  can play Far Cry at max settings.

  • So maybe this sounds like a super stupid question,  

  • but why can't you just use a regular light  microscope to take a picture of a protein?

  • Well, the wavelength of visible light is  on the order of hundreds of nanometers.

  • And that means the smallest things  you can see with visible light are  

  • also on the scale of hundreds of nanometers.

  • But what we want to seethe atoms inprotein moleculethey're angstroms apart,  

  • tenths of a nanometer, so  we can't use visible light

  • We have to use a special electron microscope. So super high energy electrons make very  

  • tiny wavelengths, which lets you see  very, very small resolution things.

  • Okay. I want a camera like that. That's  better than 4k. We can go angstrom-K. 

  • So, to take a 3D picture of a protein  with a cryo-electron microscope,  

  • first you put a drop of protein  onto a special metal grid

  • Then you freeze it in place with liquid ethaneWhen we shoot a beam of electrons at it,those  

  • proteins will be in all kinds of random  orientations, some like this, some like that.

  • Each orientation leaves a particularshadow”.

  • Powerful computers look at all those 2D  images, and combine them into a final 3D shape.

  • It's kind of like using a bunch of 2D  photos of someone's head to make a 3D model.

  • And when Jason and Daniel and their team  looked at the spike they made, with their  

  • tiny little tweaks and mutations, their spike has  the same 3D shape as the spike on the whole virus.

  • Now we can put that spike into people, and see if  it trains their immune system, and protects them  

  • from the real virus. And? It works. This protects  people from COVID-19. The research you just saw,  

  • from those scientists, is literally what's  being used in the very first COVID-19 vaccines.

  • And some of those vaccines work inreally cool way. Instead of having to  

  • make the actual spike protein, in big factorieswith huge tanks of cells like the ones we saw…  

  • some of these new vaccines, the genetic  instructions for making the spike is  

  • all that's in the shot, on a molecule called mRNA.

  • Your body uses those instructions to  make the spike. YOU are the factory

  • That's awesome. This is a really incredible piece  of science. A year ago, no one had ever seen this  

  • virus before, and thanks to these scientists  and thousands of others around the world,  

  • now we have vaccines that work.

  • It's gonna take months, maybe years to get these  vaccines, and the dozens of others still being  

  • worked on, to the billions of people that need  them, and that is a huge challenge on its own.

  • But this is a