MAN: How to paint a butterfly wing.

Hey, smart people, Joe here.

CRISPR-- it's a DNA-editing technology that you've probably heard about in terms of disease, medicine, maybe making genetically- modified organisms.

But scientists are using it for some really interesting questions, like why butterflies have awesome-looking wing patterns, and how they form.

So I'm here at George Washington University.

And I'm going to go CRISPR some butterflies.

[MUSIC PLAYING] Now there's been a lot of hype around CRISPR-- CRISPR-- but what is it actually?

CRISPR is a DNA hacking system with two parts.

And one part is a piece of RNA that carries a set of coordinates matching a specific spot in the genome's DNA.

The other part is a protein that chews through DNA, which creates a small mutation.

And we can program CRISPR with a specific set of coordinates so it cuts exactly what we want.

See this red stuff here?

Mm-hmm.

This is CRISPR.

Tube full of CRISPR.

CRISPR.

JOE: Every time you hear somebody say CRISPR, now you know it looks like.

That's Dr. Arnaud Martin.

And Dr. Martin and his team are using CRISPR to understand how butterfly genes make so many crazy patterns and colors.

There's more than 200,000 species of butterflies and moths, all with their own unique wing patterns.

We know they use those patterns to attract mates, to hide from predators, to send warning signals.

But how and why these colors get painted is still a mystery.

But this is about more than just studying butterfly patterns.

These scientists are trying to answer an important question about our own biology and even life itself.

How do the instructions in DNA build bodies?

Genes-- the letters of DNA-- are just codes.

How do we go from those letters and codes to the many beautiful shapes and colors that we see in nature?

This is a question CRISPR can help us answer.

Those are the fundamental, basic questions.

Our genes make shapes.

And this is relevant to us.

I mean, what I want to understand is how DNA makes people.

JOE: The first step to figuring out the mystery is easy-- collect some butterfly eggs.

This is Joe.

This is also Joe.

He's a researcher in the lab.

So we're on the roof of a building in downtown Washington, DC, in a greenhouse.

That's why I feel so tropical.

Yeah.

It's about, I think, 72 Fahrenheit or something like that in here, maybe a little bit warmer than that, and about 85% humidity.

But the reason that we do that is because we keep go Gulf Fritillary butterflies here.

JOE HANSON: If the team is lucky, they can collect around 40 eggs a day from these butterflies to modify with CRISPR.

JOE: These are one of my favorite butterflies.

I think they have-- they're super pretty.

JOE HANLY: Yeah, we have these lovely silver patches on the underside of their wings, which I just think are really, really beautiful.

JOE HANSON: So you wait for these butterflies to lay enough of the eggs, and then you collect them to do the work you're going to do.

Exactly.

What we're doing with CRISPR, rather than being super precise, we're sort of going in with a hammer, and smashing the gene, and then seeing what happens.

It's like if you kind of wanted to understand how a car worked, so you opened up the hood, and just started smashing pieces, and then found the way in which the car stopped working.

So if the car just completely stops, then maybe that doesn't tell you anything.

But if the car still works except the radiator is now broken, then you understand that the bit that you smashed has something to do with the radiator.

And so that's the version of this that we're doing, kind of very broad strokes, of just kind of breaking bits and seeing what breaks.

JOE HANSON: The next step is we take those eggs down to the lab to inject them with CRISPR.

And by we, I mean me.

I'm going to do it.

All right, your turn, Joe.

OK.

If I can do it, you can do it.

OK, great.

ARNAUD: Here we have a Gulf Fritillary egg from the top.

You move the needle back, you approach gently, you get in, and you press the pedal.

There it is.

I did it.

Oh you see a little-- you can see a little red burst inside.

CRISPR.

JOE: The eggs will develop and hatch like usual, only the DNA inside has been altered by the CRISPR that we injected.

The caterpillars look, well, like normal caterpillars.

You'd never know the difference unless you look inside their bodies.

OK, let's talk metamorphosis.

You've maybe heard that when a caterpillar morphs into its final form inside the chrysalis, it completely liquefies into soup, and that the liquid rearranges to form a butterfly.

This misconception has been repeated so often that it's replaced the truth.

And what actually happens is way cooler.

Caterpillars mature from the inside out.

The larva move through stages of growth called instars.

And when an instar gets big enough, it crawls out of its skin, and the next stage of growth emerges from the inside.

And when the caterpillar is just about big enough to form a chrysalis, it already has some pieces of the adult butterfly inside of it.

What you're about to see absolutely blew my mind.

ARNAUD: You see this, and you're thinking, no way-- no way this thing has wings.

It's a larva.

It's not flying.

What the heck?

So I'm going to make an incision between the two nostrils, the two diaphragms.

Check that out, man.

This is incredible.

JOE: That's a larval wing.

ARNAUD: That's a baby wing.

Here we go.

JOE: You can see the veins and everything.

It looks like a tiny, clear butterfly wing.

Wow.

ARNAUD: That's right.

This is the stage where not only the shape of the wing is defined, but also the position of patterns.

That's right.

Caterpillars have baby butterfly wings inside them.

And even at this early stage, the butterfly's wing pattern is being painted.

The team can label which genetic instructions are turned on in that baby wing.

And what's crazy is where we see certain genes turned on lines up perfectly with where the patterns will be on the adult butterfly.

And when CRISPR messes up that DNA instruction, we can also see how the pattern is disrupted.

So the different genes that you study here in the lab lay down different parts of this pattern?

Exactly, so during larval development, you have a canvas of cells that are communicating.

And the wings needs to decide where to make, maybe, reflective scales or dark scales.

And it's really a little bit, if I can make an analogy of sketching process, where the outlines of each pattern are determined super early.

It's during metamorphoses in the pupa or chrysalis that really the scales are emerging, and really the colors happened.

It's like a paint-by-numbers.

The genes they've identified draw in the boundaries, and sort of say, paint here.

Later on, inside the chrysalis, different genes paint in the colors based on those early instructions.

The basic shapes-- the organization, the concentric rings, the stripes, the position of all the systems is established super early in the larva, which is mind-blowing.

So now you know the caterpillars don't turn into total mush as they mature.

And they have some adult body parts hidden inside them.

But there is still a ton we don't know about how wings form inside the chrysalis.

If only we could see inside.

Well, some scientists have figured out a way to do that, like our old friend Aaron Pomerantz, a PhD candidate at UC Berkeley.

AARON: What my lab tries to understand is the process of how butterflies form their wings and their scales, which occurs in the pupal stage.

If you've ever stared at a pupa for long enough, you may have been a little bit underwhelmed.

It doesn't look like they're doing a whole lot.

They don't really move, they don't often look that flashy.

But just below the surface, there's an incredible amount of change happening.

Caterpillars actually do contain the precursors to their adult wings, a small cluster of cells known as an imaginal disk.

And these cells have all the information necessary to transform into an adult wing when the time is right.

A couple of scientists, Julian Kimura and Ryan Null, figured out on accident that if you removed this imaginal disk, then now you would have a window into the pupa.

So now we can set up a time lapse under a microscope to watch this entire process happen.

JOE: And what we see is incredible.

The cells in the immature wing start to specialize, or differentiate, into elaborate shapes and colors.

Those gene instructions laid down in the baby butterfly wing tucked inside the caterpillar tell the wing where to paint in these colors.

It's both fascinating to me and important to science that we can watch the wings as they develop, and see how colors are filled in.

The adult butterfly wing is covered in thousands and thousands of scales.

And this is where the color comes from.

Because each one of those scales produces a specific color, either through the architecture of the scale that creates a certain wavelength-- known as structural color-- or from pigments that become deposited inside those scales.

JOE: In these CRISPR mutants, some of those cells are broken, like the car's radiator.

So we can see how that changes the wing pattern.

When metamorphosis is complete, the butterfly that emerges is called a mosaic mutant.

It has a change in some part of its body.

JOE HANLY: So here is the butterflies that we had in the cage over there, Agraulis, where you have these lovely, precisely placed silver spots all over the wing surfaces.

And then we knock out one gene, a gene called WntA.

I literally just go in and smash it with a hammer so it's not there anymore.

And what we get is this.

So there are still silver spots, but the arrangement of those silver spots is completely different.

JOE HANSON: In other butterfly species, switching off that gene had totally different results.

It can make patterns fade or even disappear.

WntA seems to be the master sketching pencil for butterfly wing patterns.

And they've identified another gene, called optix, that's more of the master paintbrush.

Messing with it can turn some butterflies black, and even make others iridescent blue.

These genes are part of the master set of instructions to build a body.

And we have similar genes in our bodies.

And we can't go in and break those genes in humans to understand how they work.

But we can learn something about them by decoding how these beautiful insect patterns are painted.

When people talk about CRISPR, they like to think of creating mutant creatures or superhumans.

But here in real life, CRISPR has given scientists more power than ever to study how genetic instructions give us all of life's diversity of shapes and forms.

CRISPR has made this kind of gene tweaking cheaper, faster, and more accurate than ever.

This really makes me wonder, if you have this ability to tweak how butterfly patterns end up coming out, can we get more control one day, and actually design butterfly artwork of our own, make butterflies look the way that we want them to?

I think we would be able to.

So yes we can, but should we?

It's a new power.

It's a new tool that we have to also harness nature.

So we are responsible to do things that are relatively ethical, I would say.

[MUSIC PLAYING]