Using Gene Editing To Repaint Butterfly Wings

Thanks to The Great Courses Plus for supporting PBS Digital Studios 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 do butterflies have such awesome looking wing patterns, and how
do they form? So I’m here at George Washington University. And I’m gonna go CRISPR some butterflies. Now, there’s been a lot of hype around CRISPR. CRISPR RRRRRRRRRRRRR But what is it actually? CRISPR is a DNA hacking system with two parts. 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. AM: You see this red stuff here? JH: Mhmm
AM: This is CRISPR (wink) JH: A tube full of CRISPR
JH: So, everytime you hear someone say CRISPR, now you know what it looks like. That’s Dr. Arnaud Martin. 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 butterfly
and moth – all with their own unique wing patterns. We know they use those patterns to attract
mates, hide from predators, and 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? I mean, genes–the letters of DNA–are just
codes. How do we go from those letters and codes
to the many beautiful shapes and colors we see in nature? This is a question CRISPR can help us answer. AM: Those fundamental basic questions of how
genes make shapes, this is relevant to us. I mean, what I want to understand is how DNA
makes, you know, people. 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. JH: That’s why I feel so tropical. OJ: Yeah, it’s maybe 72 fahrenheit in here. Maybe a little warmer. And about 85% humidity. We keep Gulf fritillary butterflies here. If the team is lucky, they can collect around
40 eggs a day from these butterflies to modify with CRISPR. JH: These are one of my favorite butterflies. They’re super pretty. They have these lovely silver patches on the
underside of their wings, which I just think are really, really beautiful. JH: So you wait for the butterflies to lay
enough of the eggs, and you collect them so you can do the work you’re going to do? Exactly! What we do 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 wanted to understand how
a car worked, so you open the hood and just started smashing pieces. And then found the way in which the car stopped
working. 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 you smashed has something to do with the
radiator. So that’s the version of this that we’re
doing. Very broad strokes, breaking bits and seeing
what breaks. 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. Alright, your turn! 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 can see the little red burst inside. CRISPRRR 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. Okay, let’s talk metamorphosis. You’ve maybe heard that when a caterpillar
morphs into its final form, inside the chrysalis, it completely liquifies into soup, and that
liquid rearranges to form a butterfly. This misconception has been repeated so often
it’s replaced the truth. And what actually happens is way cooler. Caterpillars mature from the inside out. The larvae move through stages of growth,
called instars. When an instar gets big enough, it crawls
out of its skin and the next stage of growth emerges from inside. And when the caterpillar is just about big
enough to form a chrysalis, it already has some pieces of the adult butterfly inside
it… What you’re about to see absolutely blew
my mind: So, you see this and you’re thinking
no way this thing has wings, it’s a larva, it’s not even flying! What the heck… I’m going to make an incision between the
two nostrils, between the diaphragms. Check that out. This is incredible. That… is…. That’s a larval wing. That’s a baby wing! Here we go! You can see the veins and everything,
it looks like a tiny, clear butterfly wing. Wow! That’s right. This is the stage where not only the shape
of the wings 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 need 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 patterns are determined
super early. It’s during metamorphosis in the pupa or
chrysalis that really the scales are emerging, and the colors happen. It’s like a paint by numbers. The genes they’ve identified draw in the
boundaries and say “paint here.” Later on, inside the chrysalis different genes
paint in the colors based on those early instructions. But the basic shapes, the organization,
the concentric rings, stripes – the position of all the system is established super early
in the larva. Which is mind blowing. So now you know caterpillars don’t turn
into total mush as they mature, and they have some adult body parts hidden inside them. BUT! There’s 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: What my lab tries to understand is how butterflies
form their wings and their scales, which occurs in the pupal stage. Now If you’ve ever stared a pupa for long
enough, you may have been a 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 do contain the precursors to
their adult wings: a small cluster of cells known as an imaginal disc. And these cells have all the information necessary
to transform into an adult wing when the time is right. A couple of scientists- Julian Kamura and Ryan Null–figured out on accident that if you remove this imaginal disc, 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. 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. …in the 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. Here is the butterflies 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. We literally just go in and smash it with a hammer so it’s not there anymore, and what we get is this. There are still silver spots, but the arrangement of those silver spots is completely different. 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 a master paintbrush. Messing with it can turn some butterflies
black, and 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. 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 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 and actually design
butterfly artwork of our own? Make butterflies look the way we want to? I think we will be able to, so yes, we
can… but should we? It’s a new power, a new tool to harness
nature, so we’re responsible, we need to do things that are relatively ethical, I would say.


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