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 pandemic,  well… we 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 work—and 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 Texas—which 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 make a  vaccine. 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  “coronavirus” for the very first time,  

scientists like Jason knew this was serious,  and 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 minute.  What 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 cells … almost  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 is a  foreign invader, if it should attack or not.

The problem is, the first time your body sees a  virus, 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 fast—and 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 vaccines?  They'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 make.  For 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, or “mutuating” the 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 see—the atoms in a  protein molecule—they'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 ethane.  When 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 particular “shadow”.

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 in a  really cool way. Instead of having to  

make the actual spike protein, in big factories,  with 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 really hopeful story. No  vaccine in history has ever been invented  

this fast, and we were able to do it safely. 

And we were able to do this so quickly  because scientists like Jason and his lab  

and others, they were ready. Because they  were studying basic scientific questions about  

other coronaviruses, SARS and MERS, they've  spent years trying to figure out their secrets,  

so when this one showed up, they were  already ten steps ahead. And to me,  

that's why work like this—supporting basic  research—is so important, and why we need it.

Stay curious…