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So, we have another kind of very
interesting piece of the course

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right now.  We're going to continue
to talk about genetics,

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except now we're going to talk about
the genetics of diploid organisms,

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which apart from bacteria, most of
the organisms including us are

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diploid.  They have more than one
copy of each chromosome,

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and so we'll go through a segment on
this, and also talk about mitosis

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and meiosis, the central processes
of cell division and the segregation

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of genetic material that underlie
life as we know it.

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And then, were going to charge into
a session of recombinant DNA,

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and some of these technologies,
PCR and various things that you see

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in the newspapers all the time.
And then, I'll finish up with the

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session on the immune system,
which a few of you thought was

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surprising that bacteria recombines.
I'll tell you in that system it

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will feel like science fiction
relative to what I've told

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you up to now.
It's an absolutely amazing system.

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So, we are going to start today
with genetics of diploid organisms.

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So I'm going to go back to how this
was first understood.

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And most of you have probably heard
of Gregor Mendel,

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who discovered this,
and surely some fraction of you have

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run into an exposure to this topic
before.  But in keeping with what

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I'm trying to do in this course,
could you guys watch out there?

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I think I'm just going to unplug,
yeah, it's OK.  I think I'm just

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going to unplug it for just a minute
here.  You've probably heard of

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Mendel.  Some of you have seen these
different squares.

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You might have memorized it from a
textbook or something like that.

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I'm going to try and see if we can
go through this material up another

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level of sophistication because,
again, and I'm saying, science

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didn't just come down from on high
and end up with facts

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in a textbook.
What's in a textbook is somebody's

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effort to take a current state of
understanding which is based on

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experimentation and come up with
models.  And what you're seeing in

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the textbooks are the models such as
they were as of the time the

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textbook was submitted for
publication.  Sometimes they change

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even before the textbooks get out.
But anyway, it's a process.

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Mendel was one of the starting
people who started this process,

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really a key figure, and a guy with
an amazing intellect.

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But before we start in,
I just want to show you a couple of

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pictures because these kind of
knocked me over when I saw them.

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I don't know what kind of image you
have of Mendel.

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You probably know he was a monk,
and he did something with peas, and

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he figured out this stuff about
genetics.  And most people probably

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carry around an image probably
somewhat like this sort of

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romanticized drawing.
He was a monk all right,

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but it was at an Augustine monastery
in Bruno in Austria that was a very

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major intellectual center.
They even published a scientific

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journal.  They sent Mendel off to
Vienna to go to university.

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While he was there, he studied
physics, math,

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as well as botany.
So he had, in many ways,

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a background that is very similar to
you guys, very heavy on the

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quantitative physical science,
mathematical sort of background.

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And then he went on to do some
experiments in biology.

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And I think you maybe can get a
sense of this.

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You can see a picture of what
Mendel actually looked like.

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Here's one picture of him.  But the
one that really blew me away,

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I have a picture of the monks.
Just think of what ever image you

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had of the monks that
Mendel was at.

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Well there's a picture of them.
To me, they look nothing so much

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like a group of university
presidents or something sitting

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around for a portrait.
And he traveled very widely.

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Here he was on his way to London
here.  Here is a picture of him with

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a group of people on his way to,
I think he was in Paris on his way

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to London.  So this wasn't a little
isolated monk in a garden who

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stumbled across stuff.
He was a rather sophisticated guy

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going after some interesting
problems.

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And this was the garden in which he
did his experiments.

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Here's a picture of it.
So this was a straightforward

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experimental setup for these really
amazing things he did.

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So, with that kind of background,
Mendel was interested in a problem

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of inheritance.
And people have been aware that

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traits were inherited.
That was the whole principle of

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domesticating animals and
domesticating crops,

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that if you took parents with
certain characteristics and crossed

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them together,
the offspring then had the traits

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that were associated with the
parents.  And so people have able to

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get better domesticated animals or
better domesticated crops.

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But up until then, this mixing was
thought of sort of like blending

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liquids, stir together some green
and red, and a little

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this and that.
And it all stirred together.

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And as you'll see, what one of
Mendel's great insights was,

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was that it wasn't like mixing
liquids.  And to study this problem,

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then, he picked a system.  It wasn't
that he was just fiddling around

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with peas.  He was a pretty
sophisticated guy,

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and he picked peas as an
experimental organisms

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for three reasons.
And so, why peas?

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Well one, they were easy to grow,
and that's still a major

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consideration of any model system
that you want to use and science

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today.  It's really tricky to grow,
it's very hard to work with.  It was

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easy to pollinate in
a controlled way.

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Just the structure of the pea flower
makes it very easy to make sure to

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either put the pollen right on the
pistol of that same flower,

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which is a kind of self
fertilization,

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or to make sure that the pollen goes
from one flower to another,

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which is basically cross-pollination.
And the third thing,

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and this was a really important
thing, was the system had worked on

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before.  And there were a number of
what were called pure

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breeding lines.
If he had just grabbed peas out of

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the wild it would be sort of like me
starting to do genetics by crossing

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a couple of you guys.
We'd get offspring, all right,

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and we'd cross those offspring, we'd
keep getting things,

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people that look different and
different, maybe something like the

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parents, but what had happened with
peas is people had taken a pea,

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and then they continually inbred it
until it finally sort of settled

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down.  It always had
white flowers.

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It always had wrinkled seeds.
It always had whatever the

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particular trait was.
And so, I think I showed you the

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slide earlier.
This shows two things.

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You can see there are smooth seeds
and then wrinkled seeds.

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And it may be a little hard to tell
in this light,

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but there is sort of two colors here.
One's kind of greenish and one's

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sort of yellowish.
So there, you see two of the traits

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right there.  There were also flower
colors, and height,

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and other things that had the
characteristic.

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They were pure breeding.
Every time you took that line and

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if you self crossed it and put out
its progeny, you'd see the same

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characteristic each time.
So, this was the system that Mendel

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started to study this problem of
inheritance.  And how does blending

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come together when two organisms
brought pollen?

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Or, if it was other animals like us,
it would be sperm and egg.

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But somehow, you did something that
ended up giving you an egg that got

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fertilized.  And out of that came
the progeny.  So,

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what Mendel did, the term that's
used, they say he carried out a

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cross.  This is genetic-speak here
now.  So he took pollen

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from one plant.

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And used it to fertilize another
plant, collected the seeds that came

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out of this, and he examined the
progeny.  And I think an interesting

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way of thinking about this
is a UROP project.

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You'd come into Mendel's lab and
wanted to do a UROP project,

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it was pretty easy.  I could
probably show you all the techniques

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you needed to know,
and this is it.  You'd show how you

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pollinate, collect seeds,
and then we'd look at the

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characteristics.
So, it's just some fairly simple

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manipulations and some observational
stuff.  So, let's suppose you're

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doing Mendel's thing as a UROP
project, and let's just see where

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that will take us.
So, what Mendel did to begin with,

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he took one of these pure breeding
lines that was smooth or all

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abbreviated as a capital S.
And he pollinated it with something

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that was wrinkled.
I'll do that as little S.

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And then he collected the seeds
from what's known as the first

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generation, starting with
something like this.

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And geneticists use the term F1 for
this first generation in a cross

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like this, and what he found was
everything, all the seeds,

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were smooth.  So, the wrinkled trait
had, if you will, disappeared.

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That's your first UROP experiment.

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[Time doesn't?] submit to nature,
or science, or something,

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and read a little paper like Watson
and Craig that turns the world on

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its end.  What would you do next?
No gels, no Whitehead Sequencing

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Facility.  Anybody got any ideas?
I've showed you all the techniques

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that he knew about.
Pardon?  Cross it again?

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What's your thinking?  Do you think
the traits disappear,

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or do you think it's hiding?
It might be hiding, right?

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I don't know what he thought,
but I think that's a reasonable to

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think about it is he's probably
trying to figure out,

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did this wrinkled trait just
disappear from the face of the Earth,

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or is it hiding in those
first-generation seeds?

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So, let's put that up here.
So, that's exactly what he did.

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So, he took these seeds, now, that
were the smooth F1.

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These are not the same smooth as
the parental up here.

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Just to make clear, you guys
understand these are pure breeding.

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These are the ones that people have
been breeding for a long time,

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this one and this one.
In this case, even though I'm trying

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it in circles,
this is a smooth F1,

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smooth F1.  And, this time when he
did the experiment he looked at the

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second generation,
or the F2 generation as a geneticist

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would call it.
What he found,

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he got some smooth and he got some
wrinkled.

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So, the wrinkled trait reemerged in
the F2.  So it wasn't really gone.

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It was hiding.
OK, time to submit to nature's

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science cell.  Got it?
He didn't try and publish it at

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that point.  He did something else.
He had the same kind of background

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you guys have.
Can he think what he might've done?

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He could cross again.  There's
something else he did with this

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experiment, though.
Well, you're thinking of new

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experiments.
He's got a little data processing he

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can do here.  What did you say?
I'm not able to hear, sorry.

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Statistics, OK.
I'll simplify it even slightly

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before that.  I've got some of each.
Count them, right, exactly.  So

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that's what he did,
and I think the numbers were,

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if I remember, five, four, seven,
four in 1850.

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So, what should I do now?
Ratio: absolutely.  We could count

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another million of them,
but that probably would not be

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terribly productive.
And what he found out is that when

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he did that, he found that he got a
ratio that was pretty

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close to 3:1.
And, so that was sort of what he

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found out from this by doing this
sort of thing over again was a

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pattern.  A trait disappeared in the
F1.  The trait reemerged in the F2,

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and the two traits had this.
The ratio of the two traits would be

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about 3:1.  If you don't think this
is sort of like a UROP project or

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something, that's a page out of some
of Mendel's actual notes while he

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was doing his crosses.
And what he did next, then,

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was to take some other traits.
Yeah?  Sorry?  Excuse me?

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Reemerged in F2.  So, he took some
other traits, white and purple

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flowers, tall,
short, I found that there were at

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least certain other traits.
It didn't work for everything he

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studied, but some of them he could
see the same pattern.

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One of the traits disappeared.
It reemerged in the F2, and when he

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counted them, he'd find that the
trait that reemerged was at one,

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and the other one there were three
times as many.

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So, he'd seen a pattern.
And all he's done at this point is

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to cross flowers and count the
progeny.  So, at that point Mendel

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tried to explain his data.
So, he had to, now, take the next

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part of the scientific process.
And what's kind of nice about

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thinking about Mendel,
in this sense, is we are not

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overwhelmed by complicated
techniques.

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You can see, I think,
the scientific process.

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And it's a very bare bones thing
marching along.

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So now he's got some data.
He's quantitated his stuff.

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He's founded reproducible.  It's
not only for seeds.

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It seems to be some general feature.
And the thing about this,

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I guess, I don't know what he
thought but it seems to be likely

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that he could see that this didn't
fit very well with the blending idea.

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Like, you'd pour together two
liquids, and you'd

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stir them all up.
Instead, he really made this

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monumental leap in thinking that
genetic information must come in

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some sort of particular form,
come in particles, or units, or

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quanta if you want to think about if
it if you're a physicist.

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We know those units as genes right
now.  We grow up with it right now,

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but to go from the idea that genetic
information was kind of like two

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00:18:22,000 --> 00:18:27,000
liquids blending to the idea it was
a little particle,

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00:18:27,000 --> 00:18:31,000
so it was just about the same kind
of leap as thinking that energy

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00:18:31,000 --> 00:18:36,000
comes in particles instead of a
continuous sort of thing.

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00:18:36,000 --> 00:18:48,000
So, that was the kind of insight
that Mendel had.

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00:18:48,000 --> 00:19:00,000
And so genetic info comes in
particles, units.

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00:19:00,000 --> 00:19:05,000
I was going to say,
we now call these genes,

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00:19:05,000 --> 00:19:11,000
and if that was what it was then he
started to think about these traits

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00:19:11,000 --> 00:19:16,000
as particles that had a different
character associated with each of

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00:19:16,000 --> 00:19:22,000
them.  That would mean there would
be one particle that was a big S,

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00:19:22,000 --> 00:19:28,000
and that was smooth.  There was some
other particle that was specified.

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00:19:28,000 --> 00:19:34,000
The wrinkled character, that would
be called a small s.

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00:19:34,000 --> 00:19:38,000
So, what was happening in these
crosses, then,

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00:19:38,000 --> 00:19:42,000
he was now mixing particles instead
of liquids.  Again,

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00:19:42,000 --> 00:19:46,000
I don't know how he got to,
how many particles there had to be

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00:19:46,000 --> 00:19:50,000
of each per organism.
It could have been anywhere from

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00:19:50,000 --> 00:19:54,000
two upwards.  He had to have two in
order to explain the sort of stuff

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00:19:54,000 --> 00:19:58,000
he was working with.
There's no reason he couldn't have

235
00:19:58,000 --> 00:20:03,000
thought of 12 or something.
But I assume you start with the very

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00:20:03,000 --> 00:20:11,000
simplest thing,
number that you can think of,

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00:20:11,000 --> 00:20:18,000
and see if you can make this work.
So, what he hypothesized, then, was

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00:20:18,000 --> 00:20:26,000
that each organism had two copies of
each of these particles.

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00:20:26,000 --> 00:20:34,000
So, two copies of each particle,
so this would mean that there were

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00:20:34,000 --> 00:20:41,000
two types of particles.
So, there would be the S and the

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00:20:41,000 --> 00:20:48,000
smooth.  So, he can get three types
of things.  He could get one that

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00:20:48,000 --> 00:20:55,000
was both big S or smooth.
Or you could have the ones that

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00:20:55,000 --> 00:21:03,000
were the two little S's.
And these would be wrinkled.

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00:21:03,000 --> 00:21:09,000
Or, if you had the other combination,
what he figured out,

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00:21:09,000 --> 00:21:15,000
what fit with this model is these
would have to be smooth.

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00:21:15,000 --> 00:21:21,000
That would have to mean that one of
them is dominant over the other when

247
00:21:21,000 --> 00:21:27,000
you put them in combination.
So, in this thing, the big S would

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00:21:27,000 --> 00:21:32,000
be said to be dominant.
And the little s Would be said to be

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00:21:32,000 --> 00:21:38,000
recessive.  There's another little
term here that I'm going to

250
00:21:38,000 --> 00:21:43,000
introduce because it'll help us talk
about this stuff over the next few

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00:21:43,000 --> 00:21:49,000
days, terms geneticists use all the
time.  Because these both have two

252
00:21:49,000 --> 00:21:54,000
of the same, they're said to be
homozygous, do the same.

253
00:21:54,000 --> 00:22:00,000
And this one, with one of each,
is said to be heterozygous.

254
00:22:00,000 --> 00:22:04,000
OK, so there is,
I think, sort of the setup for

255
00:22:04,000 --> 00:22:09,000
Mendel's model.
He had to contend with one other

256
00:22:09,000 --> 00:22:14,000
issue, though,
and that was if every organism has

257
00:22:14,000 --> 00:22:19,000
two, and two parents get together
and each donate something,

258
00:22:19,000 --> 00:22:24,000
unless you did something, the
offspring would have four.

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00:22:24,000 --> 00:22:29,000
When those offspring got together,
the next one would have twice as

260
00:22:29,000 --> 00:22:34,000
many, and so on.
So, from probably,

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00:22:34,000 --> 00:22:39,000
I don't know whether it was just
from first principle,

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00:22:39,000 --> 00:22:43,000
but I would imagine he figured out
that if organisms had sex with

263
00:22:43,000 --> 00:22:48,000
pollen and whatever,
or egg and sperm, that something had

264
00:22:48,000 --> 00:22:53,000
to be done to get around this
problem of an ever increasing number

265
00:22:53,000 --> 00:22:57,000
of particles.  So,
he envisioned that when there were

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00:22:57,000 --> 00:23:02,000
specialized cells for sex,
and that they have the number so

267
00:23:02,000 --> 00:23:07,000
that the sex cells would have half
the number of particles so that when

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00:23:07,000 --> 00:23:12,000
each parent donated one, you'd
be back up to two.

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00:23:12,000 --> 00:23:18,000
It's pretty simple,
straightforward thinking once you've

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00:23:18,000 --> 00:23:24,000
gotten the idea that these things
are coming in a particular form.

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00:23:24,000 --> 00:23:30,000
So, with this, could he now explain
his results?

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00:23:30,000 --> 00:23:37,000
Let's do it over here.
So, what happened in the first

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00:23:37,000 --> 00:23:45,000
cross?  He had a smooth,
pure breeding line crossed with,

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00:23:45,000 --> 00:23:52,000
so the sex cells from this, each one
would have been a big S,

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00:23:52,000 --> 00:24:00,000
and the sex cells from each one of
this would have been a little s.

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00:24:00,000 --> 00:24:08,000
And as you recall, what he got was
all smooth, right?  Remember?

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00:24:08,000 --> 00:24:13,000
So, if we try and figure out what's
happening here,

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00:24:13,000 --> 00:24:19,000
a way of representing this would be
to think what happens if all of the

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00:24:19,000 --> 00:24:25,000
combinations that you could get,
so if we paired them in all possible

280
00:24:25,000 --> 00:24:31,000
ways, then every combination would
be identical from that first cross,

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00:24:31,000 --> 00:24:37,000
one from one parent, one from the
other.

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00:24:37,000 --> 00:24:41,000
And, if one was dominant over the
other, it's going to look like this.

283
00:24:41,000 --> 00:24:46,000
This is really the word I
introduced you to.

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00:24:46,000 --> 00:24:50,000
That's the genotype.
That's what's going on down at the

285
00:24:50,000 --> 00:24:55,000
genetic level.
What you're seeing up here is the

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00:24:55,000 --> 00:25:00,000
observable characteristics
of the organism.

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00:25:00,000 --> 00:25:06,000
That would be the phenotype.
So, then what would happen then

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00:25:06,000 --> 00:25:13,000
with this if he crossed the F1's?
Well, as you recall, they were

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00:25:13,000 --> 00:25:20,000
smooth, but he was now seeing them
as being like this.

290
00:25:20,000 --> 00:25:27,000
So that means that the sex cells
that are generated from this,

291
00:25:27,000 --> 00:25:34,000
each one will generate one big S,
and one little s.

292
00:25:34,000 --> 00:25:42,000
And then, if you put them together
to see how this would work out,

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00:25:42,000 --> 00:25:51,000
well, this one's two big S's.  This
is a big S and a little s,

294
00:25:51,000 --> 00:26:00,000
a big S and a little s, and two
little s's.  So,

295
00:26:00,000 --> 00:26:09,000
what he's got over here is SS,
SS, and a ratio of 1:2:1.

296
00:26:09,000 --> 00:26:14,000
But when you look at the phenotype,
what would we expect?  Well, this

297
00:26:14,000 --> 00:26:19,000
would be smooth,
big S and little s.

298
00:26:19,000 --> 00:26:24,000
That's smooth.  Big S,
little s, smooth again, and two

299
00:26:24,000 --> 00:26:31,000
little s's, that's wrinkled.
There's his ratio of 3:1.

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00:26:31,000 --> 00:26:41,000
Has he proved anything?  It works.
Beautiful.  The model must be right?

301
00:26:41,000 --> 00:26:50,000
What do you think?
Are you ready to publish?

302
00:26:50,000 --> 00:27:00,000
Why is that?  Why did the model
work?

303
00:27:00,000 --> 00:27:04,000
Has the model predicted anything yet?
No, it works because it describes

304
00:27:04,000 --> 00:27:08,000
the data.  To some extent,
it's kind of like hitting a curve.

305
00:27:08,000 --> 00:27:12,000
You said it, but you don't really
know yet.  Of course it's going to

306
00:27:12,000 --> 00:27:16,000
work, because if you got different
data it would've had a different

307
00:27:16,000 --> 00:27:20,000
model.  So, you're putting your
finger on a really important point,

308
00:27:20,000 --> 00:27:24,000
and that is that you can do an
experiment.  You can get data.

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00:27:24,000 --> 00:27:28,000
It doesn't have to involve DNA
sequencing or fancy technique.

310
00:27:28,000 --> 00:27:33,000
You're getting data out of a
biological system.

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00:27:33,000 --> 00:27:37,000
You've come up with a hypothesis
that explains it.

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00:27:37,000 --> 00:27:41,000
But of course it's going to explain
it because you wouldn't publish a

313
00:27:41,000 --> 00:27:46,000
model that didn't explain your own
data.  But what he hasn't done is

314
00:27:46,000 --> 00:27:50,000
tested it.  Will his model predict
the outcome of something that he

315
00:27:50,000 --> 00:27:55,000
hasn't already done?
So, the suggestion was that he

316
00:27:55,000 --> 00:27:59,000
should carry out another cross.
And that's what Mendel then did

317
00:27:59,000 --> 00:28:05,000
again.
This is what he had to work with.

318
00:28:05,000 --> 00:28:11,000
He could cross, and he could count,
and he could do some calculating and

319
00:28:11,000 --> 00:28:18,000
some thinking.
But, those were the techniques.

320
00:28:18,000 --> 00:28:24,000
I really like thinking about this,
because you can sort of put yourself

321
00:28:24,000 --> 00:28:31,000
in his shoes.  So,
what would you guys like to cross?

322
00:28:31,000 --> 00:28:37,000
We haven't got much, right?  One,
he did.  One cross he did,

323
00:28:37,000 --> 00:28:44,000
the F1 with the homozygous dominant
parent, the pure breeding lines.

324
00:28:44,000 --> 00:28:51,000
So, he's got this smooth,
that's a big S and a little s,

325
00:28:51,000 --> 00:28:58,000
and he's crossing it with something,
two big S's.  So, the sex cells that

326
00:28:58,000 --> 00:29:05,000
you'll get out of this,
so if you set this one up and see

327
00:29:05,000 --> 00:29:11,000
what happens, there's the two.
You will get to big S's,

328
00:29:11,000 --> 00:29:16,000
big S, little S, the big S,
little S.  This is sort of

329
00:29:16,000 --> 00:29:22,000
uninformative.
If you want to look at your notes

330
00:29:22,000 --> 00:29:27,000
afterwards, and have this be
consistent, let me just

331
00:29:27,000 --> 00:29:32,000
flip this slightly.
I put the two big S's up here,

332
00:29:32,000 --> 00:29:37,000
and this is our F1 down here.  That
way I'll be following the same

333
00:29:37,000 --> 00:29:42,000
pattern as I did before.
OK, so there we are.  In any case,

334
00:29:42,000 --> 00:29:47,000
they're all smooth, but that's not
particularly helpful.

335
00:29:47,000 --> 00:29:52,000
He's seen that result before.
It hasn't really proven out.  Given

336
00:29:52,000 --> 00:29:57,000
the sort of unexpected result that's
predicted by his model.

337
00:29:57,000 --> 00:30:03,000
But he tried another one that's
very, very similar.

338
00:30:03,000 --> 00:30:15,000
And in this case,
he crossed the F1 with the

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00:30:15,000 --> 00:30:27,000
homozygous recessive parent.
This is a really important process

340
00:30:27,000 --> 00:30:35,000
in genetics.
And the reason,

341
00:30:35,000 --> 00:30:41,000
because it's so important,
it's given a special term that's

342
00:30:41,000 --> 00:30:47,000
called a test cross.
Let's see what happens with this

343
00:30:47,000 --> 00:30:53,000
one, because this one's more
interesting.  So,

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00:30:53,000 --> 00:30:59,000
we take the F1.  So,
this is the F1.  He's now crossing

345
00:30:59,000 --> 00:31:05,000
it with this homozygous recessive,
so a parent that's got two particles

346
00:31:05,000 --> 00:31:11,000
that are little s.
And so, will the sex cells look like

347
00:31:11,000 --> 00:31:17,000
this, a big S little s as before,
to little S's here?  So, if we set

348
00:31:17,000 --> 00:31:23,000
up this, as we've done,
there are the sex cells from this F1.

349
00:31:23,000 --> 00:31:29,000
Here are the sex cells from the
homozygous, recessive parent.

350
00:31:29,000 --> 00:31:35,000
Up here, we get a big S and a
little s for each of those.

351
00:31:35,000 --> 00:31:40,000
But here, we get two little s's.
So, if we look at the phenotype,

352
00:31:40,000 --> 00:31:46,000
if you're out on the field or out in
the garden sitting in the kitchen,

353
00:31:46,000 --> 00:31:52,000
after you brought your seeds in or
wherever he was working,

354
00:31:52,000 --> 00:31:58,000
what would you predict you'd see in
a cross like this?

355
00:31:58,000 --> 00:32:04,000
These would be both smooth,
but these would both be wrinkled.

356
00:32:04,000 --> 00:32:09,000
So, here at the genotypic level,
we've got a ratio, now, of 1:1.  And

357
00:32:09,000 --> 00:32:15,000
here as well, there's now a ratio of
1:1.  So, there you have a result

358
00:32:15,000 --> 00:32:21,000
that you haven't seen before.
And, if you do that cross and get

359
00:32:21,000 --> 00:32:27,000
that result, again,
it doesn't prove your model.

360
00:32:27,000 --> 00:32:33,000
Scientific proof is never a QED.

361
00:32:33,000 --> 00:32:37,000
Somebody can always come up with an
experiment tomorrow that disproves

362
00:32:37,000 --> 00:32:42,000
it.  It tends to work more.
You just keep shoveling on evidence,

363
00:32:42,000 --> 00:32:47,000
and finally someone says,
enough, enough, I believe you.

364
00:32:47,000 --> 00:32:52,000
So, this was at least a test of the
model, and the model survived this

365
00:32:52,000 --> 00:32:56,000
task.  Now, he did one other
experiment.  Of the things that

366
00:32:56,000 --> 00:33:01,000
we've got on our plate right now,
is there anything else we might do

367
00:33:01,000 --> 00:33:08,000
you can think of?
He did another cross.

368
00:33:08,000 --> 00:33:16,000
Pardon?  Two of the heterogeneous
ones, we did the F1's against each

369
00:33:16,000 --> 00:33:24,000
other.  That's where we got the 3:1.
We've already crossed the F1's, but

370
00:33:24,000 --> 00:33:33,000
I like your idea.  What
if we took the F2's?

371
00:33:33,000 --> 00:33:37,000
In this case, it's going to be
pretty complicated because they've

372
00:33:37,000 --> 00:33:42,000
got this 2:1:1,
but one of the things you can do

373
00:33:42,000 --> 00:33:46,000
with peas is you can self fertilize
them as well as cross them with

374
00:33:46,000 --> 00:33:51,000
their neighbors because they've got
the ability to make the eggs.

375
00:33:51,000 --> 00:33:55,000
It'll become the seeds, and they
have the pollen,

376
00:33:55,000 --> 00:34:00,000
which would be equivalent to the
sperm.  So it got both.

377
00:34:00,000 --> 00:34:06,000
So, as long as there's some plants
that you can self fertilize and some

378
00:34:06,000 --> 00:34:12,000
you can't, one of the really nice
things about peas,

379
00:34:12,000 --> 00:34:19,000
they have the property that you can
self fertilize them.

380
00:34:19,000 --> 00:34:25,000
So, another kind of experiment that
Mendel did, then,

381
00:34:25,000 --> 00:34:32,000
was to self fertilize another test
of the model, self fertilize the

382
00:34:32,000 --> 00:34:38,000
F2's.  Well, the model predicts,
if we look back over there, that

383
00:34:38,000 --> 00:34:45,000
what you'll have there is a mix of
things in a ratio of 1:2:1.

384
00:34:45,000 --> 00:34:49,000
So, if you were to take seeds from
that F2, and then cross them with

385
00:34:49,000 --> 00:34:53,000
themselves, you could figure out all
the different outcomes,

386
00:34:53,000 --> 00:34:57,000
and then sum them up.  You'd have a
prediction for what this

387
00:34:57,000 --> 00:35:02,000
model would suggest.
All right, so let me just take you

388
00:35:02,000 --> 00:35:08,000
through the pieces.
Let's think about a quarter of them,

389
00:35:08,000 --> 00:35:14,000
according to the model,
a quarter are that.  So,

390
00:35:14,000 --> 00:35:19,000
if we self cross those, what we
should get is all wrinkled because

391
00:35:19,000 --> 00:35:25,000
the only thing we're dealing with is
the wrinkled trait.

392
00:35:25,000 --> 00:35:31,000
So, that would be a quarter of the
F2 seeds would be expected

393
00:35:31,000 --> 00:35:39,000
to give that outcome.
So, three quarters of them are

394
00:35:39,000 --> 00:35:51,000
smooth, but it's tricky because
there's two types of them in there,

395
00:35:51,000 --> 00:36:03,000
right?  So, of these, one third are
this, and two thirds have that.

396
00:36:03,000 --> 00:36:09,000
So, what would happen if we thought
about each of those individually,

397
00:36:09,000 --> 00:36:15,000
and thought about the outcome?  Well,
if we take the SS type,

398
00:36:15,000 --> 00:36:21,000
and we've self crossed them,
what we're going to get is all

399
00:36:21,000 --> 00:36:27,000
smooth because all we've got in the
cross are the traits for the smooth

400
00:36:27,000 --> 00:36:33,000
characteristic.
And, if we take these guys and

401
00:36:33,000 --> 00:36:39,000
we've self-crossed them, we've
already done that.

402
00:36:39,000 --> 00:36:46,000
We know what we will get is we will
get smooth to wrinkled in a ratio of

403
00:36:46,000 --> 00:36:54,000
3:1.  So, again,
you could now sit down with that and

404
00:36:54,000 --> 00:37:01,000
figure out in total what you would
predict in terms of smooth and

405
00:37:01,000 --> 00:37:09,000
wrinkled if you self crossed the F2,
and if the model is correct.

406
00:37:09,000 --> 00:37:14,000
So, that was basically [your?
first UROP project, or the end of

407
00:37:14,000 --> 00:37:20,000
the first term,
or the first year,

408
00:37:20,000 --> 00:37:25,000
or something like that.
And he did publish those results

409
00:37:25,000 --> 00:37:31,000
that were published in 1866,
which was the same year as those,

410
00:37:31,000 --> 00:37:37,000
about the same time as those results
that Pasteur was publishing that I

411
00:37:37,000 --> 00:37:43,000
told you about earlier on.
So, it was a very impressive in

412
00:37:43,000 --> 00:37:49,000
retrospect, a truly major
intellectual leap.

413
00:37:49,000 --> 00:37:56,000
But, it had almost no impact at all
on the world.  And there's a theme

414
00:37:56,000 --> 00:38:03,000
here that it sort of tried to hit up
several times.

415
00:38:03,000 --> 00:38:06,000
And we saw it,
to some extent,

416
00:38:06,000 --> 00:38:10,000
with the early work on DNA,
that someone can get evidence for an

417
00:38:10,000 --> 00:38:14,000
idea.  But if the scientific
community is ready to accept it,

418
00:38:14,000 --> 00:38:18,000
it can take quite awhile before that
idea becomes credible even if it's

419
00:38:18,000 --> 00:38:22,000
correct.  The data was there.
The DNA was genetic material quite

420
00:38:22,000 --> 00:38:26,000
a bit before the general scientists
thought it was,

421
00:38:26,000 --> 00:38:30,000
and it just seemed like it was too
simple a molecule,

422
00:38:30,000 --> 00:38:34,000
too boring a molecule to be possibly
able to encode anything.

423
00:38:34,000 --> 00:38:38,000
And the same sort of thing happened
here.  It was some geneticists

424
00:38:38,000 --> 00:38:41,000
picked up on this but not
until about 1900.