This is how coronavirus invades your body. Sinking its crown-like spikes into your cells,  using molecular deception to pickÂ
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 billionÂ
people all waiting for the same thing:Â Â A vaccine that will protect usÂ
from the virus causing COVID-19. And if you’re like me you want to knowÂ
what’s in it… what makes it work?   Making a vaccine and getting it out to theÂ
public is a long process with a lot of steps,  so we can make sure theÂ
vaccine is safe and effective. And it’s pretty typical forÂ
that to take ten years or more, In an emergency, like this pandemic,Â
well… we can’t skip any of those steps,  but we can speed this up byÂ
doing some at the same time But none of that can happen untilÂ
you figure out the first step:Â Â What do you put in your vaccineÂ
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 someÂ
scientists who study the coronavirus.  We’re also gonna meet a really big AwesomeÂ
Science Machine, and learn how they used  it to design this: the key ingredientÂ
inside the very first COVID-19 vaccines. Here’s my goal with this video: To show youÂ
what exactly is in the new COVID vaccines  that makes them work—and how they gotÂ
made faster than any vaccine in history.  My hope is that you’ll be betterÂ
informed when you get your shot,  and you’ll have a new appreciation forÂ
why science like this is so important. This is how to make a COVID-19 vaccine. It turns out that some of the mostÂ
important research for making the  COVID-19 vaccine is happeningÂ
right down the road from me… …at the University of Texas—which is prettyÂ
cool. Because I did my PhD right *here*,  and in *here* is the lab of… Dr. Jason McLellan. He studies how pathogensÂ
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 SARSÂ
coronavirus back in 2002,  the MERS coronavirus in 2012. And nowÂ
SARS-CoV-2, which emerged earlier this year. So at the end of December, 2019, it was on theÂ
news that there’s these pneumonia clusters in  China. Uh, in the scientific community, we thoughtÂ
maybe a new flu virus or possibly a coronavirus. I was actually snowboarding with my family andÂ
my collaborator, Barney Graham at the vaccine  research center at the NIH called. And heÂ
said, he's been in contact with US CDC,  Chinese CDC. Uh, it looks like it's aÂ
betacoronavirus similar to SARS coronavirus, and  they want it to move rapidly, try and make aÂ
vaccine. And I said, we're definitely in… So you're just like scrollingÂ
through your phone. in this ski  lodge, and you'reÂ
like we gotta get to work! So while the rest of us wereÂ
focused on royal family drama  and just hearing the first mentions ofÂ
“coronavirus” for the very first time,  scientists like Jason knew this was serious,Â
and they were already getting to work. As soon as researchers in China decodedÂ
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 alertÂ
because as soon as we get the sequence,  we're going to race on this thingÂ
and move as quickly as we can. Jason was on that winter vacation and textedÂ
me that it was a CoronavirusAnd eventually  in early January, the sequenceÂ
was released online publicly. That's when the clock started ticking because we  knew a bunch of people wereÂ
going to be working on this. Uh, and then things started moving pretty quickly… Let’s step back for a minute.Â
What does a vaccine do?  It trains your immune system toÂ
know what a germ, like a virus,  looks like. So it can recognize the germ, fight itÂ
off, and keep you safe, without you getting sick. This is the virus that causes COVID-19.Â
The outer shell is made of a few different  kinds of proteins, butthese proteinsÂ
sticking off the side are the most  important part. The spike.These spikes areÂ
what give this family of viruses their name:Â Â The coronaviruses, becauseÂ
they look kinda like a crown. The coronavirus uses that spike to sneakÂ
into our cells. The 3-dimensional shape of  that spike is super important, because thatÂ
exact shape is what lets the virus latch on  to receptors on the outside of our cells … almostÂ
like picking a lock. And then, it sneaks inside. Those shapes sticking out on the outside ofÂ
a virus are also what your immune system is  feeling for, to figure out if this is aÂ
foreign invader, if it should attack or not. The problem is, the first time your body sees aÂ
virus, your immune system responds so slowly that  the virus has time to make gazillions of copiesÂ
of itself, and you can still get very, very sick. That’s what’s great about a vaccine. ItÂ
trains your immune system what to look for,  so when the real virus shows up,  your body can respond super fast—and destroy theÂ
virus before it has a chance to hijack your cells. So what’s actually in a vaccine? Sometimes,Â
a vaccine has a weakened or dead virus.  That’s how polio and measles andÂ
mumps and some other vaccines work. But these days, a vaccine usually justÂ
contains a little piece of the virus. The newest COVID-19 vaccines?Â
They’re just the spike. But for that spike to work as a vaccine, to trainÂ
your immune system to recognize the actual virus,  it has to have the same 3-dimensional shapeÂ
as the spike on the whole, complete virus. But making the spike all by itself,  not attached to the rest of theÂ
virus, turns out to be really hard. Because the spike is actually prettyÂ
floppy just floating around on its own. It doesn’t look much like theÂ
spike on the actual virus. And this is the key thing Jason’s lab figuredÂ
out how to make. For years they’d studied SARS  and MERS viruses, which are really closelyÂ
related to the virus that causes COVID. So they already knew what tiny tweaksÂ
to make to freeze coronavirus spikes  in the perfect shape. Um, so we got to workÂ
designing our stabilizing mutations into the  new spike sequence. There was just two amino acidsÂ
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 ofÂ
individual units called amino acids. And these strings of amino acids are builtÂ
using code written in RNA, and stored in DNA*. By changing, or “mutuating” the letters ofÂ
DNA code, we can change the amino acids in  our protein string. So that's cool. You're likeÂ
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 toÂ
making the actual spike protein? I can show you… Scientists are able to grow special immortalÂ
human cells outside the body which they use as  factories. They put a modified gene for somethingÂ
like their spike protein, into those cells… …and then they'll start spitting out this protein So they're just pumping itÂ
out into the liquid, right? Yeah, that's right. They take that liquid, run it throughÂ
special purification machines,  and are able to isolate a pureÂ
sample of their spike protein. But how do they know for sureÂ
that this special spike protein  looks like the real thing, 3-D shapeÂ
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 pictureÂ
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 millionÂ
dollars, and the microscope is another million. So you’re saying don’t touchÂ
this screen right here. You can see the floor is separateÂ
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 theÂ
temperature constant in the room. Oh wow, that’s… Then it also has to beÂ
electromagnetically shielded too. That is nuts. Look at this beefy cable over here. That’s the high-tension, that’s theÂ
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 youÂ
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 lightÂ
microscope to take a picture of a protein? Well, the wavelength of visible light isÂ
on the order of hundreds of nanometers. And that means the smallest thingsÂ
you can see with visible light are  also on the scale of hundreds of nanometers. But what we want to see—the atoms in aÂ
protein molecule—they’re angstroms apart,  tenths of a nanometer, soÂ
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 seeÂ
very, very small resolution things. Okay. I want a camera like that. That'sÂ
better than 4k. We can go angstrom-K. So, to take a 3D picture of a proteinÂ
with a cryo-electron microscope,  first you put a drop of proteinÂ
onto a special metal grid. Then you freeze it in place with liquid ethane.Â
When we shoot a beam of electrons at it,those  proteins will be in all kinds of randomÂ
orientations, some like this, some like that. Each orientation leaves a particular “shadow”. Powerful computers look at all those 2DÂ
images, and combine them into a final 3D shape. It’s kind of like using a bunch of 2DÂ
photos of someone’s head to make a 3D model. And when Jason and Daniel and their teamÂ
looked at the spike they made, with their  tiny little tweaks and mutations, their spike hasÂ
the same 3D shape as the spike on the whole virus. Now we can put that spike into people, and see ifÂ
it trains their immune system, and protects them  from the real virus. And? It works. This protectsÂ
people from COVID-19. The research you just saw,  from those scientists, is literally what’sÂ
being used in the very first COVID-19 vaccines. And some of those vaccines work in aÂ
really cool way. Instead of having to  make the actual spike protein, in big factories,Â
with huge tanks of cells like the ones we saw…  some of these new vaccines, the geneticÂ
instructions for making the spike is  all that’s in the shot, on a molecule called mRNA. Your body uses those instructions toÂ
make the spike. YOU are the factory. That’s awesome. This is a really incredible pieceÂ
of science. A year ago, no one had ever seen this  virus before, and thanks to these scientistsÂ
and thousands of others around the world,  now we have vaccines that work. It’s gonna take months, maybe years to get theseÂ
vaccines, and the dozens of others still being  worked on, to the billions of people that needÂ
them, and that is a huge challenge on its own. But this is a really hopeful story. NoÂ
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 quicklyÂ
because scientists like Jason and his lab  and others, they were ready. Because theyÂ
were studying basic scientific questions about  other coronaviruses, SARS and MERS, they’veÂ
spent years trying to figure out their secrets,  so when this one showed up, they wereÂ
already ten steps ahead. And to me,  that’s why work like this—supporting basicÂ
research—is so important, and why we need it. Stay curious…
Great informative piece. Thanks