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>> TEACHER: Thank you very much!
>> DR. PINCUS: So, as Dr. Milks told you, I work on worms, but the sort of worms that
I study are very different from the earthworms that you see crawling around on the sidewalk
after a rain. They're much, much simpler, much smaller and more humble organisms. The
worms that I study have only about 1000 cells total, a very simple animal, and I'll show
you a couple pictures of these worms.
Here’s a baby worm. It's just hatched out of its egg. You can see it's crawled away
just a few minutes before this photo was taken. A few days later, the animal develops into
an adult worm. Again, a thousand cells. So this image was taken through a microscope.
The actual side of the animal, from head to tail, is only about a millimeter long. That
means that, if you took a millimeter-long chunk of your hair, this worm would fit comfortably
inside it. It's very simple, but nevertheless, it has a lot of characteristics that are very
similar to characteristics of higher animals, even ourselves. It has a digestive tract,
it eats food, has a very simple brain in its head made out of the same sort of neurons
that make our much more complicated brains.
The reason that a scientist such as myself and thousands of other scientists around the
world spend all of their days studying a simple organism like this is to turn it into what's
know as a model organism: a creature that's exhaustively studied, very carefully studied,
by scientists all over so that we understand not only how this sort of creature is built,
but how all other creatures are built. Because all life is related to one another, we've
all evolved from the same starting place, so that means that we're all made out of the
same parts. This simple worm, with its thousand cells, and us, with millions and billions
of cells of very different types, are all made out of the same pieces. And so if we
study this worm, we can also understand things about all sorts of life. It's the same way
as a doghouse is made out of pieces of wood and nails, much as an apartment building or
skyscraper is made. If we study a doghouse and we understand how a piece of wood is held
together by nails, we'll understand a little more about how a skyscraper might be constructed,
even though the doghouse (in this case, a simple animal) is easier to take apart, easier
to study, easier to manipulate.
Now, in particular, what I'm going to be talking about today is the process of development:
how we go from a single cell, a ball of goo essentially, with no top, no bottom, no left
or right, to something that's completely orderly, that has a head and arms in the right place,
legs in the right place... How do we get that introduction of order to a completely disordered
ball of goo? That’s the central question about development.
Now how a biologist typically works to try to understand a process like development
- How does the plan from head to tail get established? - is to find something, a case
in which that’s completely broken and then to understand, from how something’s broken,
how it might work normally. To make this more clear, imagine a biologist
is trying to figure out what happens in a car when you press the brake pedal, why that
causes the car to stop moving. A biologist's approach to this might be to find two very
similar cars, one of which the brakes work, and one of which the brakes don't work.
…and then, if I were doing that, I would take apart the working car and take apart
the car that doesn’t work and try to understand what’s different between the two cars, and
I would find, ah, maybe it's the brake cable or the brake pads or something to do with
the brake pedal. I would start to understand how something works by taking a broken thing
apart. In particular, we use model organisms, because it's much easier to take apart a Power
Wheels little car than a Lamborghini...much easier to understand how the basic concepts
work in a simple creature, and then use that understanding to teach us how more complicated
animals, such as ourselves, work in very similar ways.
So, for the rest of this time, I'm going to tell you about a different model organism,
one that we’ve all seen before. This is a fruit fly. It's one of the first creatures
that scientists decided to study and study and study, day in and day out, to understand
everything they could understand in it. We've seen these guys hovering around rotting bananas
and oranges. You swat them away, but if you look very closely, they're a fully functioning
animal. They're a fantastic little creature. We're looking at this fly in side view. It's
got big eyes, little antennae coming out of its forehead, jaw parts for sucking up rotting
fruit juice, two wings to help it fly around, the normal number of legs a little fly ought
to have...
Because scientists have been, for years and years, looking for different kinds of fruit
flies where things go wrong, studying these little animals over and over again, finally
one day a scientist found a fruit fly that looked a little bit different. So this is
the same kind of animal, but it's a mutant, and instead of having two wings it has four
wings. Everything else is normal. It grows and reproduces all right. It can fly around
with its four wings. Nevertheless, something is very wrong with this animal. Something
went wrong in the process of going from an unordered ball of goo into an animal that
has all the parts in the right place. Something happened that caused a part to get repeated.
So that's interesting - that tells us something about how parts might get put in the right
place during the process of development. Alone, it doesn’t tell us enough, but it turns
out that this is just one of many different kinds of fruit flies that scientists found
that have the right parts but in the wrong places.
So here's another picture. This is a side view of the fly. Here we're looking at the
fruit fly head-on from an electron microscope, which is a very powerful microscope, and you
can see again it's got its two eyes. Here are the antennae, coming out of its forehead,
and then its jaws for sucking up the fruit juice. This is a completely normal fly...but
scientists found a different fly where, instead of antennae, it’s got legs coming out of
its forehead.
Can you imagine that? Legs coming out of its forehead? Everything else is normal. These
legs work. They look like legs ought to look. They're just not where legs ought to be. And
that's not the only place that you can get legs where they ought not to be. So here we've
got them coming out the forehead. In this animal, this fly not only has legs coming
out of the forehead, but it's got legs coming out of its jaws, too.
So this is kind of crazy, kind of gross, but it also tells us something about how organismal
development happens. What it tells us is that there is some process by which the developing
organism says, "All right, it's time to make a leg." If that process happens at the right
time in the right place, the leg comes out of the right place and grows properly. But
that process can also be messed up in some way so that you get a completely normal leg
in the complete wrong place. It's almost as if there was some sort of series of dominos,
where if you push the domino over at the right time and the right place, all of the little
steps necessary to build a leg happen and you get the right leg. If you push it over
at the wrong time or build all your dominos up in the wrong place, you'll still get the
right cascade of everything falling down to make a leg, but just a little bit wrong and
in the wrong place.
Over many years, scientists began to understand exactly what these dominos are. In particular,
as you've studied, you know that proteins are the molecules in cells that cause things
to happen, and there's a class of proteins, each that show up at different places at different
times during the development of the animal from this ball of goo into something that
has structure from head to tail, called Hox proteins, H-O-X in case you want to look it
up on Wikipedia afterwards. In particular, different kinds of these Hox proteins show
up at the right time and the right place to turn on more proteins that turn on other proteins
that bring all of the machinery necessary together to make a wing at the right place.
However, if one of these Hox proteins shows up at the wrong time or in the wrong place,
you get another wing, an extra set of wings where it doesn’t belong.
So this is really interesting, because it tells us something about how development happens.
Now, let's imagine that you’re trying to design a building. You're an architect, and
you're designing a house, and you might have a basic high-level blueprint that says, "All
right, I'm going to put a kitchen here, a dining room here, a living room here," and
you might not specify, you might not put all the details about the kitchen on that first
blueprint. It might be, "for details about where the stove goes, see page 17." You can
imagine that a tiny typo on that first part of the blueprint might lead you to having
two kitchens. "See page 17 over here and see page 17 over here." A tiny typo...leading
to a complete mess as the builders come in and are just following the broken blueprints.
The same thing happens here. This protein usually says, "All right, to build a wing,
see page 17, and follow the procedure thereon." Sometimes there's a little typo, and you get
that second set of wings...but the wings get built correctly.