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Transcript:
Q: What has the field
of genetics opened up for your research?
A: When it first became possible to manipulate genes -- to
take pieces of a chromosome and put it into a bacterium and grow it
there and study it -- people started studying the genes in things
that were very abundant. For example, the genes that make the red
pigment in blood that carries oxygen.
But the greater mystery, in a way, was to identify genes that are
the architects of the whole animal body, and these initially were not
accessible -- it was too hard to find them. But genetics made it
possible to find them, because the genetics essentially provided a
map of the chromosomes. You could find out where in the chromosome
was a gene that controlled the shape of a limb, or the size of the
body, or the growth of the wings. Those kinds of genes had been very
mysterious. No one knew how to think about them; nobody knew how to
isolate those kinds of genes. But the map you got from genetics said
there's a gene that does that right here. And if you go look at that
part of the chromosome, you can find it.
Q: What do you mean when you say genetics gives you a map?
A: Let me say it another way: One of the best ways to find
out how something works, if you're talking about biology, is to break
it and to find out what you've broken. Genetics is essentially a
science of breaking things and then finding out what you did. So,
imagine an engine. You do something to break it, then you go in and
try to fix it, you try to understand what's wrong in that engine.
Well, genetics does that. You look for something that is strange --
in flies it might be the structure of the wing or of the head or
something. Then you go try to find out what's broken and how it works
because you know that that thing must be necessary to make the normal
wing, head, heart, or whatever it might be. You're trying to find out
what genes are necessary to make that particular organ, appendage, or
structure.
More than a century ago, a guy named Bateson wrote a book and
described all sorts of varieties in nature. He described things like
polydactyly which is [a variation] in the number of fingers or toes
on a person. He described insects that had legs growing out of their
heads instead of antennae. He described all sorts of abnormalities in
development, which essentially constituted a whole encyclopedia of
mysteries that we have to try to understand.
Why should we bother understanding these things? Well, we want to
understand the normal process that works so beautifully to shape
these structures perfectly and functionally so they work extremely
well. To understand that process, we look at cases where there's a
change. Not always a detrimental change; sometimes just a difference.
We try to understand what happened when those changes happened, and
that tells us something about the normal process.
As people began to use standard laboratory organisms like the
fruit fly, they noticed all sorts of strange things going on.
Especially if they treated the flies with something that would change
their genes in some way, like a poison of some sort. When they did
that, they found flies with changed wing structures, changed legs,
and some very special flies that had one part of the body in the
wrong place, or a copy of a normal part of the body in another place.
For example, the antennae would be transformed into legs. Or the eyes
would start growing pieces of wing out of them. Very strange
things.
The exciting thing was that these variations were useful in two
ways. First of all, they might be evolution in process, a gradual
change into a structure that might be more useful to the organism.
The second idea is that the abnormalities might lead us to the
mechanisms that create the normal body. And this, in fact, has proven
to be the case. In laboratory organisms, it's possible to take a fly,
for example, that's perfectly normal, treat it with radiation or
chemical poisons that damage its genes, and then find a fly, amidst
thousands of flies, that has a change in the wing structure, or a
body part in the wrong place. Because we've damaged a particular
gene, it allows us to identify the genes that are normally involved
in building the structure properly.
What was incredible to realize was that mutations in a single
gene, in just one gene out of the thousands that we have, could cause
a dramatic transformation of a whole section of the body into another
part. It wasn't so hard to imagine that damaging a gene would lead to
a failure to build something, but that a single gene could cause a
transformation of a part of the body into a copy of another part was
amazing. It argued that there were some sort of central coordinating
genes that must coordinate the activities of many other genes to
accomplish this.
So out of thousands of genes scattered about the chromosomes in
the genome are a few that have special properties. And the strange
flies [Bateson wrote about] led us to those genes. Specifically, they
led [biologist Dr.] Ed Lewis to those genes. He realized that these
genes were affecting different parts of the body. Oddly enough, the
genes were in a little cluster in one place in one chromosome. As
Lewis looked at these genes, he said, "This one affects this part of
the body, this affects the next part of the body, and this effects
the next part of the body." That was an astonishing observation. And
it preceded by a long time any sort of DNA analysis or molecules.
Q: What was so astonishing about it?
A: It was amazing that there would be genes that controlled
a specific part of the body, when after all the substance in that
part of the body looks just like the substance in the next part of
the body over. Take, for example, an arm and a leg. If you look at
the molecules in them, they have exactly the same stuff in them. And
yet they're shaped differently. So these are the genes that are
shaping things, that are giving differences in pattern and
organization rather than changing the substance of the material.
You can take it even further. You can look at two arms. They are
composed of exactly the same substances, but the pattern is a mirror
image. How is that controlled? That's the kind of mystery that
developmental biologists try to understand in figuring out how these
genes work.
Ed Lewis had figured out that there was a cluster of genes close
to each other. Each gene worked in a particular part of the body.
They were lined up. So his idea was that these genes originally had
been one gene acting on one part of the body. And that in evolution
there had been a duplication and then triplication and so on of the
genes. So now there were multiple copies of the original gene, each
dedicated to a particular part of the body. So he predicted from his
work that these genes would be related to each other in some way.
If you look at how our bodies are organized, we have these
vertebrae that repeat down our backbones, with slight differences in
the vertebrae. Sometimes large differences in the vertebrae. So it's
a repeating unit with variations. In insects, their body segments --
everybody's familiar with the yellowjacket that has a striped abdomen
-- are repeating units with little differences. Some of them not so
little, because all the segments in the thorax have legs. All the
segments in the abdomen do not have legs. Of the three segments in
the thorax in a fly, only one has full-fledged wings. The other
segments do not have full-fledged wings. So there are differences
between the segments. We now know that there is a whole system of
genes that controls the subdivision of the body into repeating units,
whether it be vertebrae or the segments in an insect body.
These genes that Ed Lewis had discovered, that give different
character to those segments, are the ones that act on one segment but
not another to make them different from each other. The same genes
that do that in a fly -- to put the wings in the right place and the
legs in the right place and so on -- those same kind of genes give us
the vertebrae their difference shapes and characteristics.
Q: How does this relate to evolution? What did people think
before this discovery?
A: As recently as 20 years ago, people thought that every
animal would have its own program, a genetic program that would
control how that animal grows and what shape it ends up. Everybody
knew there had to be a program like that because that's why we look
like our parents, or like a blend of our parents. There are genes
that we inherit from them that control the shape of our faces and the
shape of our bodies. So we knew genes had to be able to do that. But
everyone thought that genes would be completely different for frogs,
and insects, and people, and so on, that the diversity of animals out
there and the diversity even among people might be due to tremendous
differences between genes. So it was an absolutely astonishing thing
to discover that there are many genes in common between animals that
look very different. All of our thinking was focused on the
differences. And yet underlying those surface differences in shape of
the body is this genetic program where most of the components are in
common between insects and mammals.
People had known for a long time that the structure of the genes,
the DNA, was the same in pretty near all organisms. People knew that
the so-called genetic code was the same, that many of the proteins
that do the sort of energy handling in our bodies were the same, even
in very simple organisms like bacteria. And yet, when it came to
shaping the body, everyone thought that at that point, all the
similarities would stop. That every diverse kind of animal --
jellyfish, people, sea urchins, frogs, insects, and so on -- would
all be different, that the genetic program would be unrecognizably
different. And that therefore you couldn't study a simple animal in
order to learn about humans.
That turned out to be completely wrong. In fact, now there's a
common language among researchers in biology because it's realized
that a discovery you may make studying flies, or frogs, or worms, or
even yeast, will be applicable in many cases to study in human
biology and human medicine.
Q: So what does it all mean?
A: What this means is that we, humans and all the other
animals, descended from a common ancestor who had these gene systems
already working, building that body plan. And what we see now, among
all the animals, are just variations on a body plan that existed half
a billion years ago.
We have much more in common with other animals than we ever
dreamed, which is amazing and exciting because it offers a window
into our past. We can now, in a much better way, try to understand
where we came from. There's no question that our brains are something
very special, and yet the mechanisms that built them exist in other
animals. So what happened? We can now start to think about problems
like that.
Another exciting aspect of this is that the similarity between
other types of animals and us means that we can translate an
understanding of animals we can study in the laboratory and in the
field into medical discoveries and other discoveries that are very
practical for application to human benefit.
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