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I am the other half of
the teaching team for 7.01.

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You've already gotten to meet
my good colleague Bob Weinberg.

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My name is Eric Lander. And Bob
and I are both faculty here in the

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Biology Department. In fact,
we're both members over at

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the Whitehead Institute
for Biomedical Research.

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In fact, we just spent the whole
weekend together at the Whitehead

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Retreat. And so, Bob and
I have been doing this

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course together for a number
of years. And we very much

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love it. I am -- I'll
take a brief moment and

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introduce myself, since I
haven't had the opportunity

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to do so yet. I am by training,
well, actually, I'm really a

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geneticist. By training I'm
actually a pure mathematician.

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That was actually what my
undergraduate degree was in,

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and even my PhD was in, but
then wandered into biology.

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And for the last almost 20 years,
I have been doing genetics in some

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form or another. So I love
genetics and look forward

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to talking a lot about genetics.
And it's really lovely that my

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first lecture today is actually
going to be our first introduction

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to genetics. I am -- Just
for other backgrounds,

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I direct this new Broad Institute
that is here. And it's actually a

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joint institute between MIT and
Harvard. And you will know it now

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as a hole in the ground
next to Legal Seafood.

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If you see a bunch of cranes and
things opposite the biology building

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and opposite Legal Seafood
next to the Whitehead,

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that's the Broad Institute. And
we have ambition some day to be

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more than the hole in the ground but
to actually rise above the ground.

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And the Broad is about genomic
medicine and using genomes

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and things like that. And
the Broad Institute includes

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this center at MIT that was one
of the leading participants in the

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Human Genome project. So
that's a lot of what I do with

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my day job, in addition to teaching,
is work on things like the Human

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Genome project. And, now
that we actually have a

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sequence to the human genome,
figuring out what in the world it

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all means. And I hope I'll
get a chance to tell you,

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during the course of this class,
about the human genome and about

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what's in it and things like that.
Like I say, that's one of the things

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I tremendously love about
teaching biology as opposed,

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if I can get in trouble,
to any of the other required

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introductory courses, is that
our curriculum changes every

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year because the field is moving
so rapidly. I look back at what we

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taught ten years ago in this course,
because I've been teaching it that

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long, and all sorts of open
questions now we know the answers to

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and are part of the curriculum.
Some of the things we thought we

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knew we now know are false
and we know new things.

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And every year we get
to introduce new stuff.

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And I know, I mean with
all due respect to calculus,

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it's just not the case for calculus
that there's anything really new to

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introduce. Most of it sort of
settled down about three or four

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centuries ago.
And, you know,

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that's just not the case
with what we do. Anyway,

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so that's why I love it. All
right. So Bob has been talking

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to you about biochemistry largely.
And I'm going to now turn to

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genetics. But I want you to
understand that that is an

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overarching framework that explains
how all the materials you're going

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to see, at least in the first half
or more of this course fit together.

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And Bob may have mentioned it,
but I'm going to mention it again,

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I would use this following diagram
as kind of our roadmap or subway map

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of where we're going in this
course. What we really want to do is

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understand biological function.
That's what we most want. How is

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it that an organism is able to
breathe in air and distribute it to

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its cells? How is it that an
organism is able to move its muscles?

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How is it that an organism is able
to fight off invaders to its body,

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microbes, things like that? How is
it that an embryo develops into a

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full adult? Zillions of questions.
That's what I mean by biological

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function. The two complimentary
approaches to studying biological

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function, over the course of the
past century or so in biology,

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have been the following. There
have been the biochemists.

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Biochemistry seeks to break
down the organism into individual

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components and study them
on their own in a test tube.

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They will take an organisms, and
to a biochemist wishing to study

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the beauty of a butterfly flapping
in the wind and understanding all of

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the mechanics of how it could
possibly flap those wings and all,

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he or she would start by taking the
butterfly, putting it in the blender,

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pressing puree and making an extract,
and trying to purify individual

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components that would explain
muscles moving back and

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forth and all that.
This is, of course,

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a geneticist's point of view,
but it's all right. You have Bob

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who will represent biochemistry just
fine. And they want to purify out

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individual components. Individual
components away from the

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organism. And the most
important individual

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type of component that they study
are proteins because there are

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zillions of proteins and they do
all sorts of things in the body.

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And so you could say, in some
sense, that this whole theme of

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biochemistry, which got started
at the turn of the 20th century,

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really just a few years before
the turn of the 20th century,

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of grinding up an organism,
studying its components and being

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able to find, for example, I
want to understand how I can

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digest lunch. Well. Or how
yeast can digest the sugar.

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Grind up yeast, fractionate it and
find some protein that's able to

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digest the sugar all by itself
without the rest of the organism,

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an enzyme to do that. That's
the logic of biochemistry.

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Genetics is the complimentary point
of view. Genetics is the study of

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organisms minus one component.
Of course, what I mean by that are

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mutants. The
geneticist who wants to

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understand the butterflies and how
the butterfly can fly would isolate

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butterfly strains that have
lost the ability to fly.

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And ideally one is extremely
closely related to the normal

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butterfly, but for some reason,
ideally due to the mutation of a

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single component they're now unable
to fly. And the geneticist would

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then say, ah-ha, that
component must matter an awful

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lot for the ability to fly because
the butterfly that lacks that

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component cannot fly. It's
a totally complimentary point

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of view. And the
objects the geneticists

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study in order to do that are genes.
Now, what is of course hard for you

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guys to understand but will form a
structure for some of the lectures

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that I'm going to give over the
continuing part of this course,

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is that through most of the 20th
century the folks who studied

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biochemistry and tried to understand
proteins and the folks who studied

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genetics and tried to understand
mutants had nothing to say to each

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other. They didn't
speak the same language.

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They had nothing to relate to each
other by because there was no idea

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of how this gene stuff, which
started as a totally abstract

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business, could possibly relate to
this protein stuff which started as

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a very practical in the test-tube
thing. And they went for a very

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long time as if they were just ships
sailing in the dark unaware of each

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other. And I exaggerate,
but it's more true than not.

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The great intellectual event was
the unification of these two points

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of view through the discipline
of molecular biology.

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Molecular biology was the
discipline that realized,

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oh, my goodness, these are
two different sides of the

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same coin. That, in fact,
genes encode proteins,

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proteins are encoded by genes.
Ah-ha. This was a wonderful and

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important thunder clap
in the 20th century. Now,

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it was a theoretical piece
of information at first.

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The idea that genes and proteins
were related in this way was

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abstract, very important, but
you couldn't do anything really

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with it, because it turned out
you couldn't actually work with

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individual genes. The next
great revolution of the

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20th century was a technological
revolution that let you actually

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work with genes. And that
was the recombinant DNA

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revolution in which the tools to
be able to study genes on their own

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away from the organism, study
proteins, use genes to figure

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out what protein they encode,
given a protein and figure out what

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the gene is, given a gene and
actually go in and make a mutant in

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it, not wait for a random one to
rise in the lab but deliberately

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knock it out, all of that
operationalized this intellectual

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procedure, this intellectual
framework. So that is,

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in some sense, a roadmap to coming
lectures that I'm going to give.

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I'm going to talk about genetics,
I'm going to talk about molecular

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biology, and I'm going to
talk about recombinant DNA.

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That's the structure of the next
several weeks of this course.

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And what I want you to do is to
recognize that although we're going

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to dive down into the
individual components of it,

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everything we're going to do over
the coming weeks fits into this very

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amazing intellectual framework.
And this is the intellectual

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framework that you inherit as the
new students coming into this field

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and going into the 21st century
is all this was worked out

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in the last century. You now
have an understanding of how

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all these pieces fit together, or
at least you will, how these can

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be used to study biological function
and, as I will also talk about,

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the recombinant DNA has grown into
a world of genomics that has given us

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the complete picture of all of the
components. It's actually not bad.

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You were very wise to have shown up
when you did because an awful lot of

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that groundwork has now been laid.
You know, if you would have come

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along 50 years earlier, you
know, all that would have been

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slogged through. Right
now you have this laid out

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for you very nicely. And
that's sort of what the theme

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will be. OK? I would ask
are there any questions,

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but there should be a
zillion questions about that.

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This is just intended
as a framework there.

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So let's now dive in.
Section 1. And I'll give a bit

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more background today than I will
in some of the other lectures,

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but we've got to get going. What
I really want to do first is talk

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about, in fact, most of
today will be about Mendel.

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I confess, Mendel is my hero. He
is one of my absolute heroes in

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science. I just love Mendel.
And so I'll dwell on him a little

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bit today. Now, here's
the problem with trying to

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tell you about Mendel. You
already know about Mendel,

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right? Who here hasn't met Mendel
and the peas and the stuff and all

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that in their high school textbooks?
So what am I doing talking about

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Mendel today? Well, I think
what you learn about Mendel

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in the textbooks in high school
does not really bring out what really

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went on with Mendel's thinking,
what's really important about those

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experiments, what's
really interesting.

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And so I want to ask you to put
aside what you think you know about

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Mendel and let's go back over
the setting of who Mendel was,

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what he was doing, how it all adds
up. Because I think in Mendel you

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can find just the seeds
of how to do great science.

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Now, for starters let me clear up,
I'll take five minutes to clear up,

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four minutes to clear up some
misconceptions about Mendel.

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It has generally been written that
Mendel was this monk working in this

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monastery often in the Chez
Republic, at that point in the

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Austro-Hungarian Empire, and
he was isolated, working by

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himself, and it was amazing
he discovered all this stuff.

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It's nonsense. Mendel working
on genetics was no accident.

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It was the result of extraordinary
historical and economic forces over

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the course of about three
centuries that culminated Mendel.

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Let me briefly explain why.
It starts with the Age of

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Exploration. Europe starts
sending out boats around the world,

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explorers to meet other parts
of the world in the 1500s.

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The boats come back. They
bring back stories of amazing

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lands. They also bring back
odd plants, odd animals.

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People begin to look at
these plants and animals.

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They begin to cross them, grow
them and cross them, and look

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at the weird odd combinations
of things that are going on.

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And they say, wow, there's
so much more variation out

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in the world than we thought about.
Some of it's kind of useful. We

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can make new kinds of varieties of
plants different than we had before,

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new kinds of varieties of apples.
Now, it turns out that's not just an

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intellectual curiosity that that
was the case because economics was

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changing in the face of Europe
in the 1600s and in the 1700s with

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better transportation networks.
So if you happen to be able to make

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a better apple, it was
good, not just for your

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family, but you would be able
to project that through lines of

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distribution to larger markets.
It became economically sensible to

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invest your efforts in producing a
better crop because you could sell

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it to more people because unified
markets and transportation systems

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were developing across Europe.
And, therefore, economic forces

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began to work toward getting a
hold on the understanding of how you

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could do better breeding.
Now, this turned out to be

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particularly important to the
folks in Central Europe in the

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Austro-Hungarian Empire, which
was the center of the textile

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industry. They were
particularly concerned,

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in the late 1700s, about the fact
that as the center of the textile

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industry they had to be concerned
about the raw materials like wool

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that they used. Wool you
could get from Central

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Europe, the Spanish had begun
producing by breeding better sheep

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with better wool. This
freaked out the guys in the

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Austro-Hungarian Empire because they
were risking now losing this stuff

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to the Spanish because
of their better sheep.

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And they began, around
1800, to say we better start

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understanding how to do breeding.
They put together societies to

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understand better the science
of inheritance and breeding.

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By 1820, a society which was
not about sheep but about plants,

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00:14:18,000 --> 00:14:22,000
in fact, apples and grapes, the
Pomological and Enological Society

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00:14:22,000 --> 00:14:26,000
of Braunau was organized.
Braunau being the capital of the

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Austro-Hungarian Empire. And
this society got all the town

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fathers of Braunau together. In
those days it was just fathers,

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you know. Together in Braunau and
started this society to encourage

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the scientific study of agricultural
inheritance. They had this big

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dinner and they were drinking and
things, and the speech is actually

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written down where the
president gets up and says,

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"Some day the world may be as
indebted as it is to Isaac Newton

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for physics. They may be as
indebted to the City of Braunau for

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its contributions to inheritance."
Which is just eerie to read that in

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1820 in setting up this society.
That was their high hopes for what

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they would do.
In particular,

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the president of this society,
one CF Nap was president of the

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society as a side job, his
main job was he was head of the

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Augustinian monastery in Braunau.
So he began keeping an eye out for

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bright young math and
physic students. Basically,

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00:15:23,000 --> 00:15:26,000
you know, MIT kids coming out of
high schools. And he identified a

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bunch of smart ones and attracted
them to the monastery and gave them

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problems to work on. He
particularly was impressed with

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00:15:33,000 --> 00:15:37,000
this relatively poor kid,
Gregor Mendel, who had been

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00:15:37,000 --> 00:15:40,000
floundering around with a couple
of things, didn't have bright family

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prospects, and attracted him to
the monastery to work on problems of

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inheritance. So this was no
accident. This was a biotech

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incubator that had been set up
in the Austro-Hungarian Empire.

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00:15:51,000 --> 00:15:54,000
Not of the sort we'd recognize
today, but it's just fascinating to

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realize Mendel was not in a
vacuum at all. He knew what

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he was doing here.
He really wanted,

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for the good of mankind,
to understand how to improve

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inheritance. But why do
we celebrate Mendel today?

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We celebrate Mendel today
because he went about it,

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lots of people were interested
in this problem, right?

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You could probably find hundreds of
people who tried to do something on

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this problem. Mendel was different
because he went about it as a

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scientist. He went about it with a
rigor and a persistence unlike all

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of his peers at the time. So
let's think about what it was

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00:16:32,000 --> 00:16:36,000
that Mendel did. So,
anyway, forgive me for the

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00:16:36,000 --> 00:16:40,000
historical digression, but
I think it's interesting.

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00:16:40,000 --> 00:16:44,000
What did Mendel do? Mendel
started by taking peas.

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Now, he went off to the market and
he got different varieties of peas.

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And he brought back all of these
varieties of peas and he tried

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growing them. Now, actually,
although I don't have the

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records, I'm sure he
did lots more than peas.

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He brought probably lots of
stuff and he tried growing it.

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And the first order of question
he wanted to ask is if I study

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inheritance, I've got to start
with something that has constant

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properties. This seems obvious
to you guys, but it was not at all

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obvious at the time that the
most important thing you could do,

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if you wanted to understand the
transmission of traits and crosses

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and inheritance and all that,
is not to set up any crosses. It

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was first to set up your
experimental system and make sure it

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00:17:31,000 --> 00:17:35,000
was rock solid. He probably
devoted years to getting

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00:17:35,000 --> 00:17:39,000
varieties of different plants,
and in particular settling on peas,

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with a property that when he
had peas with different traits,

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like whether or not the pea
seed was round or wrinkled,

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which will be some of our favorite
traits here, that when you simply

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00:17:53,000 --> 00:17:57,000
selfed this plant, crossed
it to itself and looked at

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the next generation, it bred true.
Hard to emphasize how important that

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00:18:02,000 --> 00:18:08,000
was, but this was careful
experimental design.

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00:18:08,000 --> 00:18:14,000
So many biological
projects fail

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because people don't take the
trouble to set up a system that's

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00:18:17,000 --> 00:18:20,000
rock solid. They set up a system
that's noisy and you're not really

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00:18:20,000 --> 00:18:23,000
sure you're going to be
able to interpret the data,

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00:18:23,000 --> 00:18:27,000
etc. So Mendel did
that. Very good.

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00:18:27,000 --> 00:18:31,000
Always, no matter how long you
continued to breed these things,

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00:18:31,000 --> 00:18:36,000
you continued to get round or
you continued to get wrinkled.

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00:18:36,000 --> 00:18:41,000
Now Mendel was ready. He
was ready to set up his first

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00:18:41,000 --> 00:18:52,000
controlled cross.

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00:18:52,000 --> 00:18:57,000
So what he did was he took a
round pea and a wrinkled pea and he

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00:18:57,000 --> 00:19:01,000
crossed them together. Now,
that's again some serious work.

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00:19:01,000 --> 00:19:04,000
You first have to go along to one
of the peas, cut off its little

296
00:19:04,000 --> 00:19:07,000
pollen producing organs so it
doesn't self-fertilize because peas

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00:19:07,000 --> 00:19:11,000
will self-fertilize. You've
got to cut them off early,

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00:19:11,000 --> 00:19:14,000
make sure it doesn't get its own
pollen on it. Then you go over to

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00:19:14,000 --> 00:19:17,000
the other one with a paint brush,
you get some pollen and you paint

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00:19:17,000 --> 00:19:20,000
the pollen on the first plant.
That's how you set up the cross.

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00:19:20,000 --> 00:19:23,000
If you screw it up you could have
self-fertilization or the wind could

302
00:19:23,000 --> 00:19:26,000
carry some pollen from
something from somewhere else.

303
00:19:26,000 --> 00:19:30,000
So it had to be done very
carefully. He set it up.

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00:19:30,000 --> 00:19:35,000
And his first big-time
observation was? Now, again,

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00:19:35,000 --> 00:19:40,000
I know you know all this, so
feel free to chime in. In the

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00:19:40,000 --> 00:19:45,000
next generation all the peas were
round. We denote generations with

307
00:19:45,000 --> 00:19:51,000
an F. F stands for filial meaning
children. We sometimes denote them

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00:19:51,000 --> 00:19:56,000
with a G for generation.
Anyway, I tend to use F,

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00:19:56,000 --> 00:20:01,000
and most geneticists tend to use
F. The parental generation here is

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00:20:01,000 --> 00:20:05,000
called F0, the first generation is
called F1, the second generation F2,

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00:20:05,000 --> 00:20:10,000
etc. So why was this a big
deal? This was a huge big deal.

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00:20:10,000 --> 00:20:15,000
If you took a poll, a CNN Gallup
poll of Braunau at that time and you

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00:20:15,000 --> 00:20:19,000
ask voters what do you think would
happen if I cross a round pea to a

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00:20:19,000 --> 00:20:24,000
wrinkled pea, what do you think
the majority of voters would say?

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00:20:24,000 --> 00:20:29,000
Well, maybe half and half or
maybe all a little wrinkled,

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00:20:29,000 --> 00:20:34,000
you know, a little puckered
or something like that.

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00:20:34,000 --> 00:20:37,000
The notion that one trait would
be totally dominant over the other

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00:20:37,000 --> 00:20:40,000
trait was by no means the general
thinking. And you know what?

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00:20:40,000 --> 00:20:43,000
It wasn't even the general case.
If you took plants, you guys must

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00:20:43,000 --> 00:20:46,000
know. If you take plants and you
cross them, the F1 usually looks

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00:20:46,000 --> 00:20:49,000
like some kind of a mix. It's
some kind of a blend between

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00:20:49,000 --> 00:20:53,000
the two. And, of course,
that's because you're

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00:20:53,000 --> 00:20:56,000
really looking at situations where
you're crossing things in which

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00:20:56,000 --> 00:20:59,000
zillions of different traits
are being inherited and

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00:20:59,000 --> 00:21:03,000
it's a hodgepodge. But
Mendel had a situation here

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00:21:03,000 --> 00:21:09,000
where he got an absolutely crisp
dominance of one trait over the

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00:21:09,000 --> 00:21:15,000
other. And so wrinkled completely
disappears, round dominates,

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00:21:15,000 --> 00:21:24,000
wrinkled disappears completely.

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00:21:24,000 --> 00:21:30,000
Now, next he does
another generation.

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00:21:30,000 --> 00:21:35,000
He goes to the second generation.
And here he does this by selfing

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00:21:35,000 --> 00:21:41,000
this plant. That is he simply kind
of puts a bag over it and lets its

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00:21:41,000 --> 00:21:47,000
own pollen fertilize itself or he
takes a little brush and he brushes

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00:21:47,000 --> 00:21:53,000
its own pollen onto it. And
in the next generation his

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00:21:53,000 --> 00:21:59,000
remarkable thing was he saw
some rounds and some wrinkles.

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00:21:59,000 --> 00:22:12,000
What was remarkable
about that?

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00:22:12,000 --> 00:22:16,000
Wrinkled came back. I
thought wrinkled was gone.

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00:22:16,000 --> 00:22:19,000
And it didn't come back in some
half-hearted way like a little

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00:22:19,000 --> 00:22:23,000
puckered. It came back fully,
totally, every bit as wrinkled as

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00:22:23,000 --> 00:22:27,000
the parental wrinkled. And
the rounds were every bit as

340
00:22:27,000 --> 00:22:31,000
round. These were
discrete traits.

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00:22:31,000 --> 00:22:35,000
Wrinkled reappeared, and
it reappeared with no loss.

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00:22:35,000 --> 00:22:40,000
No change in the phenotype, no
change in the appearance. And

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00:22:40,000 --> 00:22:45,000
that was very important because
at the time some of the predominant

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00:22:45,000 --> 00:22:49,000
models were blending of traits.
And you would never imagine, if I

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00:22:49,000 --> 00:22:54,000
were to take grape juice and water
and blend them together to get some

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00:22:54,000 --> 00:22:59,000
kind of pinkish thing that I would
be able to separate that back out

347
00:22:59,000 --> 00:23:04,000
into clear water and
deep dark grape juice.

348
00:23:04,000 --> 00:23:09,000
But somehow this trait had appeared.
Thus, the trait was discrete. Big

349
00:23:09,000 --> 00:23:14,000
difference. Big news. This
trait could be found still

350
00:23:14,000 --> 00:23:19,000
lurking there. It was
merely hidden in the first

351
00:23:19,000 --> 00:23:24,000
generation. Mendel did one other
thing, dear to my heart as someone

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00:23:24,000 --> 00:23:29,000
trained as a mathematician, he
counted. When he counted up the

353
00:23:29,000 --> 00:23:35,000
rounds and the
wrinkles he found what?

354
00:23:35,000 --> 00:23:44,000
Sorry? Three to one
round to wrinkled? No,

355
00:23:44,000 --> 00:23:53,000
it's not. He found 5, 74 to
1,850. That's what he found.

356
00:23:53,000 --> 00:24:03,000
Now, what do you
recognize about that?

357
00:24:03,000 --> 00:24:09,000
Three to one? No, it's
not. It's 2.96 to one.

358
00:24:09,000 --> 00:24:16,000
It's not three to one. What's
this three to one business?

359
00:24:16,000 --> 00:24:23,000
[LAUGHTER] Why isn't there
a famous 2.96 to one rule?

360
00:24:23,000 --> 00:24:30,000
No, no, I'm serious. Mendel
did one more thing. He counted.

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00:24:30,000 --> 00:24:34,000
And then he did something
a little bit outrageous.

362
00:24:34,000 --> 00:24:38,000
He intuited. He said although
the data do not say three to one,

363
00:24:38,000 --> 00:24:42,000
notwithstanding your textbook, I
think the data are trying to tell

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00:24:42,000 --> 00:24:46,000
me it's three to one. [LAUGHTER]
This is part of science.

365
00:24:46,000 --> 00:24:50,000
I'm sorry? Two sig figs, right.
You know, this is actually a

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00:24:50,000 --> 00:24:54,000
big deal because so many people are
unwilling to kind of look at their

367
00:24:54,000 --> 00:24:59,000
data to say what's the
data trying to tell me?

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00:24:59,000 --> 00:25:02,000
And, of course, there are
so many people who are too

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00:25:02,000 --> 00:25:06,000
willing to look at their data and
say what's the data trying to tell

370
00:25:06,000 --> 00:25:10,000
me? Because you can go off
the tracks in both directions.

371
00:25:10,000 --> 00:25:14,000
So Mendel tried some experiments,
3.04 to one, 2.91 to one, etc. And

372
00:25:14,000 --> 00:25:18,000
occasionally, yes?
No. How could he?

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00:25:18,000 --> 00:25:22,000
Nobody had done this. He
had no textbooks he could

374
00:25:22,000 --> 00:25:26,000
consult. So do you think it's
possible he experimented with other

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00:25:26,000 --> 00:25:30,000
things that didn't show these
properties and said maybe these are

376
00:25:30,000 --> 00:25:33,000
lousy traits to work on. I'm
getting such good results on

377
00:25:33,000 --> 00:25:36,000
wrinkled, let's stay with wrinkled
for a while. That is an incredible

378
00:25:36,000 --> 00:25:39,000
act of experimental judgment to
know that some problems are too

379
00:25:39,000 --> 00:25:42,000
complicated, we'll come back to
them later. It's not cheating.

380
00:25:42,000 --> 00:25:45,000
You get to say this is
an interesting problem,

381
00:25:45,000 --> 00:25:49,000
I'm going to work on it.
Not only that. I'll tell you,

382
00:25:49,000 --> 00:25:52,000
occasionally Mendel did these
experiments and he got completely

383
00:25:52,000 --> 00:25:55,000
abhorrent results. They
didn't match three to one at

384
00:25:55,000 --> 00:25:58,000
all. You know what he did? He
threw out the data. Do you know

385
00:25:58,000 --> 00:26:01,000
why? No, not
small sample.

386
00:26:01,000 --> 00:26:04,000
Large numbers. He's sitting
there in this garden.

387
00:26:04,000 --> 00:26:07,000
You know, I've actually
been to Mendel's monastery.

388
00:26:07,000 --> 00:26:10,000
He's in the garden in Braunau.
Remember, he's got to go cut off

389
00:26:10,000 --> 00:26:13,000
the little pollen producing organs,
he's got to paint the stuff. What

390
00:26:13,000 --> 00:26:16,000
if he screws up? What if
the wind blows and stuff

391
00:26:16,000 --> 00:26:19,000
like that? If an experiment was
way off, he had to consider the

392
00:26:19,000 --> 00:26:22,000
possibility that he just screwed up
because he hadn't gotten to it soon

393
00:26:22,000 --> 00:26:25,000
enough and pollen had blown in
and had fertilized his plants.

394
00:26:25,000 --> 00:26:28,000
Now, boy, that's a dangerous
thing to do, discarding data.

395
00:26:28,000 --> 00:26:31,000
But let's be honest.
Sometimes experiments screw up.

396
00:26:31,000 --> 00:26:34,000
And if an experimentalist hasn't
got enough judgment to know that

397
00:26:34,000 --> 00:26:37,000
sometimes you cannot believe
the data you also can go wrong.

398
00:26:37,000 --> 00:26:40,000
So Mendel, who sometimes is
accused for cheating for that,

399
00:26:40,000 --> 00:26:43,000
it's not at all cheating.
What you have to do is say,

400
00:26:43,000 --> 00:26:45,000
OK, I've got a problem here. I'm
going to redo this experiment a

401
00:26:45,000 --> 00:26:48,000
bunch more times. I'm always
getting about this three

402
00:26:48,000 --> 00:26:51,000
to one thing, but occasionally I get
something that's way off there and I

403
00:26:51,000 --> 00:26:54,000
feel comfortable saying that's an
error. You can go wrong with that,

404
00:26:54,000 --> 00:26:57,000
but Mendel exercised very good
judgment in excluding that rather

405
00:26:57,000 --> 00:27:00,000
than trying to muck this all
up by saying occasionally I

406
00:27:00,000 --> 00:27:04,000
get something weird. So I
know the textbook summarizes

407
00:27:04,000 --> 00:27:08,000
this beautiful 3:1 ratio,
but so much creativity. First

408
00:27:08,000 --> 00:27:12,000
discipline of counting and
creativity of interpretation went

409
00:27:12,000 --> 00:27:17,000
into all of this. So in
the modern world what would

410
00:27:17,000 --> 00:27:21,000
Mendel do? In the modern world,
upon seeing this three to one result

411
00:27:21,000 --> 00:27:25,000
which he, I will note, he saw
for a couple of other traits.

412
00:27:25,000 --> 00:27:30,000
Actually, what he did next
was he wanted to explain --

413
00:27:30,000 --> 00:27:36,000
This was also part of his
brilliance. He made a model,

414
00:27:36,000 --> 00:27:42,000
the model of what was going on.
Mendel said how can I possibly

415
00:27:42,000 --> 00:27:48,000
explain this beautiful observation
that for round and wrinkled,

416
00:27:48,000 --> 00:27:54,000
and for other traits, I observe an
approximately 3:1 ratio in the F0,

417
00:27:54,000 --> 00:28:00,000
F1 and F2 generations? Mendel,
my heart beats for Mendel. Oh.

418
00:28:00,000 --> 00:28:03,000
A mathematician he is. He
says let's make a very simple

419
00:28:03,000 --> 00:28:07,000
model. Let's assume that there
are two factors of the control

420
00:28:07,000 --> 00:28:11,000
inheritance of this trait. I'll
call them big R and little R.

421
00:28:11,000 --> 00:28:15,000
The round plants have big R and
big R. They have two copies of this

422
00:28:15,000 --> 00:28:18,000
factor that controls shape. The
wrinkled plant has two copies

423
00:28:18,000 --> 00:28:22,000
of the factor that control shape,
and the copy of the factor they get

424
00:28:22,000 --> 00:28:26,000
is different. So the flavor here is
big R, the flavor here is little R.

425
00:28:26,000 --> 00:28:30,000
This has two copies,
this has two copies.

426
00:28:30,000 --> 00:28:34,000
And let's assume that this plant
transmits one at random of its two

427
00:28:34,000 --> 00:28:39,000
factors onto the next generation.
It will transmit a big R. Let's

428
00:28:39,000 --> 00:28:43,000
assume that this transmits
one of the two at random.

429
00:28:43,000 --> 00:28:48,000
It will transmit a little R. And
that plant there in the middle

430
00:28:48,000 --> 00:28:53,000
will be big R over little R.
And what will big R over little R

431
00:28:53,000 --> 00:28:57,000
be as an appearance? How
does he know that that's going

432
00:28:57,000 --> 00:29:02,000
to be round? Sorry?
From the result.

433
00:29:02,000 --> 00:29:06,000
He knows because that's what
happened. It's not an overwhelming

434
00:29:06,000 --> 00:29:10,000
reason. But to make the
data work he's got to say,

435
00:29:10,000 --> 00:29:14,000
well, then this must be round.
OK? So no points for that. He's

436
00:29:14,000 --> 00:29:19,000
just fitting the data. Then
here, when you self this,

437
00:29:19,000 --> 00:29:23,000
the two parental gametes
transmit either a big R,

438
00:29:23,000 --> 00:29:27,000
so we'll put it over here, big
R, big R, little R, little R,

439
00:29:27,000 --> 00:29:34,000
they transmit. And the
offspring are of that type.

440
00:29:34,000 --> 00:29:42,000
You can either get
that. Question there?

441
00:29:42,000 --> 00:29:58,000
Could be. So he
had some knowledge.

442
00:29:58,000 --> 00:30:01,000
But, of course,
this is his model.

443
00:30:01,000 --> 00:30:04,000
He's entitled to make his model.
And you're saying he had good

444
00:30:04,000 --> 00:30:07,000
reasons to think in these. So
everybody knows Mendel's model,

445
00:30:07,000 --> 00:30:10,000
right? So, now, in the modern world,
the minute you've got data like this

446
00:30:10,000 --> 00:30:13,000
and you've got a model to
explain it, what do you do?

447
00:30:13,000 --> 00:30:16,000
Publish. So Mendel, let's
put Mendel as a young

448
00:30:16,000 --> 00:30:19,000
assistant professor who is all
fired up about these results,

449
00:30:19,000 --> 00:30:22,000
writes this up for publication in
Nature. It's a short thousand word

450
00:30:22,000 --> 00:30:25,000
letter to Nature, let's
say. And he races it off,

451
00:30:25,000 --> 00:30:29,000
he emails it to the
offices of Nature in London.

452
00:30:29,000 --> 00:30:31,000
Because he's in Europe,
he'll use the London office of

453
00:30:31,000 --> 00:30:34,000
Nature saying I have this amazing
result, I did these crosses.

454
00:30:34,000 --> 00:30:37,000
Here are the results here. And I
have a model that explains the data

455
00:30:37,000 --> 00:30:40,000
perfectly. What does Nature do?
Sorry? Why does it reject it?

456
00:30:40,000 --> 00:30:43,000
Well, the first thing he does
is sends it out to referees,

457
00:30:43,000 --> 00:30:46,000
right? The way that scientific
publication works is it chooses two

458
00:30:46,000 --> 00:30:49,000
or three anonymous referees. It
sends the paper out anonymously

459
00:30:49,000 --> 00:30:52,000
to those two or three referees for
comment saying we've received this

460
00:30:52,000 --> 00:30:55,000
interesting paper from
this young monk in Austria.

461
00:30:55,000 --> 00:30:58,000
What do you think about it?
Give us your opinions? Please

462
00:30:58,000 --> 00:31:01,000
write back in two weeks,
etc. So you're the referees.

463
00:31:01,000 --> 00:31:04,000
You get Mendel's paper.
What do you advise Nature?

464
00:31:04,000 --> 00:31:08,000
Publish or not? No. Why
not? It's outrageous.

465
00:31:08,000 --> 00:31:11,000
Why? It's never been heard
of. Yeah, that's great.

466
00:31:11,000 --> 00:31:14,000
But, I mean, you sound like
a very conservative, you know,

467
00:31:14,000 --> 00:31:18,000
you cannot write that. You cannot
say it's wrong because it's never

468
00:31:18,000 --> 00:31:21,000
been heard of.
Yeah? Regenerate.

469
00:31:21,000 --> 00:31:24,000
It would be wonderful if referees
could regenerate the result

470
00:31:24,000 --> 00:31:28,000
themselves, but it's not practical.
For one thing, it takes a long time

471
00:31:28,000 --> 00:31:32,000
to grow peas. They might
not have those strains of

472
00:31:32,000 --> 00:31:36,000
peas. The best test really would
be independent replication of this,

473
00:31:36,000 --> 00:31:40,000
but unfortunately you cannot get
the referee to reproduce each result

474
00:31:40,000 --> 00:31:44,000
before accepting the paper.
So you have to go on the own

475
00:31:44,000 --> 00:31:48,000
internal results of the paper.
Has Mendel proved his case for this

476
00:31:48,000 --> 00:31:52,000
model? How many people vote Mendel
has proved his case for the model?

477
00:31:52,000 --> 00:31:56,000
He's my hero. How many people vote
that he hasn't proved the case?

478
00:31:56,000 --> 00:32:01,000
How many people are conscience
abstainers? [LAUGHTER]

479
00:32:01,000 --> 00:32:06,000
OK. Who says he hasn't
proved the case? Why? Exactly.

480
00:32:06,000 --> 00:32:11,000
I mean, great, the model fits the
data. He had the data first and he

481
00:32:11,000 --> 00:32:16,000
made a model to fit it.
Big deal. So you would say?

482
00:32:16,000 --> 00:32:21,000
Yes, he should be able to
make a variety of predictions.

483
00:32:21,000 --> 00:32:26,000
That would be a confirmation of a
model, at least the beginning of a

484
00:32:26,000 --> 00:32:31,000
confirmation of a model is
he could make some predictions

485
00:32:31,000 --> 00:32:35,000
based on a model. But
an ex post facto model to

486
00:32:35,000 --> 00:32:39,000
explain the data you already have,
of course you're going to have one.

487
00:32:39,000 --> 00:32:42,000
It might be a little whacky, but
you always make a model to explain

488
00:32:42,000 --> 00:32:46,000
your data. That's not the hard
thing. Now give me some predictions.

489
00:32:46,000 --> 00:32:49,000
So, guys, give me some predictions.
We write back to Mendel saying we

490
00:32:49,000 --> 00:32:53,000
find the author's work to be of
interest, it's a provocative and

491
00:32:53,000 --> 00:32:56,000
unheard of finding, and
it's a fascinating model,

492
00:32:56,000 --> 00:33:00,000
but it is just a model. We'd like
to see some predictions verified.

493
00:33:00,000 --> 00:33:04,000
So what would they
be? Sorry? Color.

494
00:33:04,000 --> 00:33:08,000
Oh, show me more traits.
OK. Fine. We want to see more

495
00:33:08,000 --> 00:33:12,000
traits. In addition to seeing some
more traits, and Mendel actually did

496
00:33:12,000 --> 00:33:16,000
have more traits in the paper.
I'm just simplifying here. Prove

497
00:33:16,000 --> 00:33:20,000
this model. What predictions would
you make if this model is correct?

498
00:33:20,000 --> 00:33:24,000
Yes? Keep crossing them. So
tell me what you would do.

499
00:33:24,000 --> 00:33:32,000
Please send him
instructions here.

500
00:33:32,000 --> 00:33:34,000
OK, so you would like me
to cross one of the rounds,

501
00:33:34,000 --> 00:33:37,000
an F2 round by a wrinkled.
What will happen in the next

502
00:33:37,000 --> 00:33:45,000
generation?

503
00:33:45,000 --> 00:33:48,000
How do I do that? I
don't have DNA sequencing

504
00:33:48,000 --> 00:33:51,000
available or anything, so.
[LAUGHTER] See what happens.

505
00:33:51,000 --> 00:33:54,000
So what might happen? What
is this round plant here?

506
00:33:54,000 --> 00:33:58,000
What might it be? And what
are the probabilities of

507
00:33:58,000 --> 00:34:05,000
that?

508
00:34:05,000 --> 00:34:10,000
One-third of the time it will big
R, big R. Two-thirds of the time it

509
00:34:10,000 --> 00:34:15,000
will be big R, little
R. If it is big R,

510
00:34:15,000 --> 00:34:20,000
big R then the offspring
will all be what? Round. If,

511
00:34:20,000 --> 00:34:25,000
on the other hand, it is
the case that that's big R,

512
00:34:25,000 --> 00:34:30,000
little R then the
offspring will all be?

513
00:34:30,000 --> 00:34:34,000
They won't be all anything.
They'll be half round, a 1:1 ratio

514
00:34:34,000 --> 00:34:38,000
of round to wrinkled. OK?
That's an odd prediction that

515
00:34:38,000 --> 00:34:42,000
a third of the time the offspring
from such crosses will all be round

516
00:34:42,000 --> 00:34:46,000
and two-thirds of the time the
offspring will be 50/50 round and

517
00:34:46,000 --> 00:34:50,000
wrinkled. You wouldn't
normally think of that,

518
00:34:50,000 --> 00:34:54,000
right? That's the kind of
thing that has to be done.

519
00:34:54,000 --> 00:34:58,000
And Mendel, of course, did
crosses like that. I simplified

520
00:34:58,000 --> 00:35:03,000
here. This is really
what Mendel did was

521
00:35:03,000 --> 00:35:08,000
demonstrated that all sorts of
predictions would be satisfied.

522
00:35:08,000 --> 00:35:14,000
Another prediction that
Mendel could make, oops.

523
00:35:14,000 --> 00:35:19,000
Stop, stop, stop, stop.
Which should be wrinkled?

524
00:35:19,000 --> 00:35:24,000
Oh, my goodness. Oh,
wrinkle that pea. OK. Onward.

525
00:35:24,000 --> 00:35:30,000
Thank you very much,
Claudette. That's good.

526
00:35:30,000 --> 00:35:36,000
So he made more and more predictions
like this. His predictions,

527
00:35:36,000 --> 00:35:42,000
for example, let's just take that
F1 pea, round over wrinkled here.

528
00:35:42,000 --> 00:35:49,000
If you cross this back with
wrinkled then it's pretty simply

529
00:35:49,000 --> 00:35:55,000
because then always, if this
is an F1 as opposed to an F2,

530
00:35:55,000 --> 00:36:02,000
you're going to get a 50:50
ratio of round to wrinkled.

531
00:36:02,000 --> 00:36:06,000
Moreover, these rounds, if
you cross them back, will still

532
00:36:06,000 --> 00:36:10,000
give you a 50:50,
etc. That's science.

533
00:36:10,000 --> 00:36:14,000
That's the heart of science,
is being able to look at data,

534
00:36:14,000 --> 00:36:18,000
intuit what the data is trying to
tell you, build a model and test a

535
00:36:18,000 --> 00:36:22,000
model. All of that is in Mendel.
OK? So I know you all know Mendel,

536
00:36:22,000 --> 00:36:26,000
but this Mendel really.
OK? Now, some definitions.

537
00:36:26,000 --> 00:36:30,000
I need to give you, so
Section 2, some definitions.

538
00:36:30,000 --> 00:36:36,000
Because I've been skirting
around using some words here.

539
00:36:36,000 --> 00:36:42,000
OK? Number one, the word gene.
Gene is one of these factors of

540
00:36:42,000 --> 00:36:59,000
inheritance
controlling a trait.

541
00:36:59,000 --> 00:37:03,000
Mendel didn't use the word gene.
The word gene came along much later.

542
00:37:03,000 --> 00:37:07,000
The variant flavors of a gene,
big R and little R, are known as

543
00:37:07,000 --> 00:37:11,000
alleles from the Greek word meaning
other. These are the alternative

544
00:37:11,000 --> 00:37:19,000
forms of
a gene.

545
00:37:19,000 --> 00:37:22,000
It can come in the form big R,
little R. I might write big A,

546
00:37:22,000 --> 00:37:26,000
little A. I might write plus
for normal and M for mutant.

547
00:37:26,000 --> 00:37:30,000
There are a lot of different
notations geneticists use for that.

548
00:37:30,000 --> 00:37:38,000
The word phenotype means appearance.
The plant was round. The peas were

549
00:37:38,000 --> 00:37:47,000
round. That's a phenotype.
The individual was 7" 7' tall.

550
00:37:47,000 --> 00:37:55,000
That's a phenotype. OK? Those are
phenotypes. Genotype means the pair

551
00:37:55,000 --> 00:38:04,000
of alleles carried
by the individual.

552
00:38:04,000 --> 00:38:11,000
Big R, little
R is a genotype.

553
00:38:11,000 --> 00:38:16,000
Big R, big R is a genotype. Little
R, little R. Those are genotypes.

554
00:38:16,000 --> 00:38:20,000
An important difference
between genotype and phenotype.

555
00:38:20,000 --> 00:38:25,000
Other important words so that we
can actually talk to each other.

556
00:38:25,000 --> 00:38:31,000
Homozygous or homozygote. A
homozygote is an individual who

557
00:38:31,000 --> 00:38:38,000
has a genotype that has two of
the same alleles. Two copies of the

558
00:38:38,000 --> 00:38:45,000
same allele, the individual
is said to be homozygous.

559
00:38:45,000 --> 00:38:52,000
And, alternatively, an
individual is said to be

560
00:38:52,000 --> 00:39:00,000
heterozygous, heterozygote
if they have two alternatives.

561
00:39:00,000 --> 00:39:03,000
A couple of other
important definitions.

562
00:39:03,000 --> 00:39:11,000
Dominant.

563
00:39:11,000 --> 00:39:18,000
A phenotype round
is said to be

564
00:39:18,000 --> 00:39:23,000
dominant over a phenotype wrinkled
if what? If the heterozygote shows

565
00:39:23,000 --> 00:39:29,000
that phenotype, the
heterozygote between pure

566
00:39:29,000 --> 00:39:39,000
breeding strains.
So phenotype one,

567
00:39:39,000 --> 00:39:53,000
pheno one is dominant over phenotype
two if the F1 of pure breeding

568
00:39:53,000 --> 00:40:02,000
strains shows phenotype one.
Similarly, we have the word

569
00:40:02,000 --> 00:40:06,000
recessive. Now, I'll
mention, and you will then

570
00:40:06,000 --> 00:40:10,000
proceed to promptly forget,
because all of my colleagues forget,

571
00:40:10,000 --> 00:40:14,000
dominant and recessive do not refer
to alleles. Big R is not dominant.

572
00:40:14,000 --> 00:40:18,000
Round is dominant. Big R is an
allele. Now, you say who cares?

573
00:40:18,000 --> 00:40:22,000
The textbooks get this wrong
all the time, it's true.

574
00:40:22,000 --> 00:40:26,000
You won't even find the
textbooks use this correctly.

575
00:40:26,000 --> 00:40:30,000
They will tell you
big R is dominant.

576
00:40:30,000 --> 00:40:34,000
What if it turned out that big R
controlled three different traits?

577
00:40:34,000 --> 00:40:38,000
Maybe roundness. An ability to
grow with low salt in the soil.

578
00:40:38,000 --> 00:40:42,000
An ability to bloom in May. Some
of those traits might be recessive.

579
00:40:42,000 --> 00:40:47,000
Some of them might be dominant.
We know examples of that,

580
00:40:47,000 --> 00:40:51,000
where the same allele can
control multiple traits,

581
00:40:51,000 --> 00:40:55,000
some of which show dominance,
some of which show recessiveness.

582
00:40:55,000 --> 00:40:59,000
So real card-carrying geneticists
try hard to use the word dominant

583
00:40:59,000 --> 00:41:04,000
and recessive to refer to phenotypes,
not to alleles or genotypes.

584
00:41:04,000 --> 00:41:07,000
Now, since 80% of the facility in
the Biology Department don't use the

585
00:41:07,000 --> 00:41:10,000
word with that degree of precision,
I don't have high hope that you will

586
00:41:10,000 --> 00:41:13,000
either. But I'm going to try to
say the words dominant and recessive

587
00:41:13,000 --> 00:41:16,000
refer to phenotypes. OK?
This is a geneticists' kind of

588
00:41:16,000 --> 00:41:19,000
hang-up. We all have our shtick,
but this one of mine, is that these

589
00:41:19,000 --> 00:41:22,000
really do refer to phenotypes.
And it's quite important because

590
00:41:22,000 --> 00:41:25,000
otherwise you could get quite
bollixed up. And I'll come to a

591
00:41:25,000 --> 00:41:28,000
case with sickle cell anemia where
you won't be able to describe the

592
00:41:28,000 --> 00:41:32,000
sickle cell anemia allele as
recessive, dominant or co-dominant.

593
00:41:32,000 --> 00:41:36,000
OK? Good. Those are some
definitions. They're worth knowing.

594
00:41:36,000 --> 00:41:41,000
If we get those definitions
right the rest of it is pretty

595
00:41:41,000 --> 00:41:53,000
easy.
All right.

596
00:41:53,000 --> 00:41:56,000
So Mendel publishes this
paper in 1865. It's accepted.

597
00:41:56,000 --> 00:41:59,000
It appears not in Nature but in
the proceeding the Royal Academy of

598
00:41:59,000 --> 00:42:02,000
Braunau and it's
published. And what happens?

599
00:42:02,000 --> 00:42:05,000
Nothing. It sinks like a stone.
Mendel's paper is totally ignored.

600
00:42:05,000 --> 00:42:09,000
Nobody really pays any attention
to it. This paper was sent to many

601
00:42:09,000 --> 00:42:12,000
people. Charles Darwin has a copy
of Mendel's papers in his files.

602
00:42:12,000 --> 00:42:15,000
But, in those days,
the way printing worked,

603
00:42:15,000 --> 00:42:19,000
in order to read a book you
had to slit the pages open.

604
00:42:19,000 --> 00:42:22,000
Darwin never slit the
pages of Mendel's paper,

605
00:42:22,000 --> 00:42:25,000
so it's pretty clear he never read
the paper, even though it had the

606
00:42:25,000 --> 00:42:29,000
answer to much of what he
wanted to know about evolution.

607
00:42:29,000 --> 00:42:32,000
No one really read Mendel's paper
because it was so far ahead of its

608
00:42:32,000 --> 00:42:35,000
time, it just was pretty strange.
It had all these concepts. And,

609
00:42:35,000 --> 00:42:39,000
anyway, you could always dismiss it
with that kiss of death of biology

610
00:42:39,000 --> 00:42:42,000
"it's just the model". Right?
You can kill things with

611
00:42:42,000 --> 00:42:46,000
"it's just the model". People
were just not prepared to

612
00:42:46,000 --> 00:42:49,000
deal with Mendel.
So Mendel, in fact,

613
00:42:49,000 --> 00:42:52,000
poor Mendel, maybe he had
a good time, I don't think,

614
00:42:52,000 --> 00:42:56,000
instead didn't really do much more
on this topic of genetics per se.

615
00:42:56,000 --> 00:43:00,000
He became an administrator.
Became abbot of the monastery and

616
00:43:00,000 --> 00:43:05,000
did other things.
Worked on meteorology,

617
00:43:05,000 --> 00:43:11,000
etc. And we don't really hear from
Mendel again. So what really begins

618
00:43:11,000 --> 00:43:16,000
to reignite interest in this is the
understanding in the late 1800s of

619
00:43:16,000 --> 00:43:21,000
chromosomes. Very briefly,
cytologists, people studying cells

620
00:43:21,000 --> 00:43:27,000
in the microscope.
Cytologists are folks who study

621
00:43:27,000 --> 00:43:34,000
cells. They noticed
these very funny little

622
00:43:34,000 --> 00:43:42,000
structures in cells. They
noticed these structures that

623
00:43:42,000 --> 00:43:50,000
when you stain then with a
dye would stain very funny.

624
00:43:50,000 --> 00:43:58,000
They picked up dye in a certain way.
And they noticed that they had this

625
00:43:58,000 --> 00:44:06,000
very interesting choreography that
when a cell underwent mitosis these

626
00:44:06,000 --> 00:44:14,000
funny things would divide down the
midline and these little x-shaped

627
00:44:14,000 --> 00:44:22,000
structures would go to the
two daughter cells like this.

628
00:44:22,000 --> 00:44:28,000
That is these Xs
would become single

629
00:44:28,000 --> 00:44:32,000
individual pieces. Again,
you know about these things.

630
00:44:32,000 --> 00:44:36,000
They had no clue what these were.
What is the appropriate scientific

631
00:44:36,000 --> 00:44:41,000
procedure when you have no clue what
something is? You need to give it a

632
00:44:41,000 --> 00:44:46,000
name that somewhat covers up the
fact that you have no clue what

633
00:44:46,000 --> 00:44:50,000
you're talking about because it
sounds much better than just saying

634
00:44:50,000 --> 00:44:55,000
they are "these funny things".
And so they were referred to as

635
00:44:55,000 --> 00:45:00,000
chromosomes, meaning literally
colored things. [LAUGHTER]

636
00:45:00,000 --> 00:45:08,000
You need to
understand these sorts

637
00:45:08,000 --> 00:45:12,000
of things. OK? So
these chromosomes here,

638
00:45:12,000 --> 00:45:16,000
these colored things, for lack
of any other knowledge of them,

639
00:45:16,000 --> 00:45:19,000
that was the property they
could be given. Chromosomes.

640
00:45:19,000 --> 00:45:23,000
Look it up. They executed this
very interesting choreography during

641
00:45:23,000 --> 00:45:27,000
mitosis. That is cell division.
Oh, boy, is that going to be noisy.

642
00:45:27,000 --> 00:45:37,000
Someone should
shoot it and put it

643
00:45:37,000 --> 00:45:41,000
out of its misery.
[LAUGHTER] All right.

644
00:45:41,000 --> 00:45:45,000
But what they then noticed was the
following. And we're going to run

645
00:45:45,000 --> 00:45:50,000
just a couple of minutes over.
I'm going to keep it short. But

646
00:45:50,000 --> 00:45:54,000
they noticed that when organisms
made sperm and eggs rather than

647
00:45:54,000 --> 00:45:58,000
normal cell division, they
noticed that these chromosomes,

648
00:45:58,000 --> 00:46:03,000
instead of all of them lining up
on the midline, lined up in pairs.

649
00:46:03,000 --> 00:46:09,000
And the pairs underwent
a series of two divisions.

650
00:46:09,000 --> 00:46:16,000
There was a first division which
we call meiosis one in which --

651
00:46:16,000 --> 00:46:26,000
-- one copy of each
of these Xs went

652
00:46:26,000 --> 00:46:32,000
to each daughter cell. Very
different than mitosis where

653
00:46:32,000 --> 00:46:39,000
the Xs would be split down the
middle. Then a second division

654
00:46:39,000 --> 00:46:47,000
occurred, meiosis two. And
in that each of the daughter

655
00:46:47,000 --> 00:46:57,000
cells now the
X is divided.

656
00:46:57,000 --> 00:47:01,000
And they got that.
This one looked,

657
00:47:01,000 --> 00:47:05,000
for all the world, like
mitosis. But instead,

658
00:47:05,000 --> 00:47:10,000
at the end of the day instead of
ending up with four chromosomes,

659
00:47:10,000 --> 00:47:15,000
here we end up with only two
chromosomes in each gamete,

660
00:47:15,000 --> 00:47:19,000
sperm or eggs. And what
happened was from this pair,

661
00:47:19,000 --> 00:47:24,000
one member of the pair was selected.
Now, this is either producing sperm

662
00:47:24,000 --> 00:47:29,000
or eggs. When a sperm
like that came together

663
00:47:29,000 --> 00:47:35,000
with an egg like that and
fertilization occurred,

664
00:47:35,000 --> 00:47:41,000
you get back to four chromosomes.
You all know this. You learned

665
00:47:41,000 --> 00:47:47,000
this in high school. But the
important point about this

666
00:47:47,000 --> 00:47:53,000
was that people said, ha,
things lining up in pairs,

667
00:47:53,000 --> 00:47:59,000
one copy of each going to the
offspring, then a copy from mom and

668
00:47:59,000 --> 00:48:03,000
a copy from dad restoring the pair.
Sounds just like what that dead monk

669
00:48:03,000 --> 00:48:07,000
was talking about. [LAUGHTER]
It was just the reason

670
00:48:07,000 --> 00:48:11,000
people really didn't think much of
Mendel's paper was because it was so

671
00:48:11,000 --> 00:48:15,000
abstract. What were these genes?
He didn't point to anything. There

672
00:48:15,000 --> 00:48:18,000
was nothing concrete. And
folks hate that. By contrast

673
00:48:18,000 --> 00:48:22,000
they now began to see things and
vaguely remembered that this was

674
00:48:22,000 --> 00:48:26,000
just like what Mendel's story was
about. And three different groups

675
00:48:26,000 --> 00:48:30,000
around the world began to redo
this work on crosses and all that.

676
00:48:30,000 --> 00:48:35,000
And wonderfully in 1900 three groups
simultaneously published papers

677
00:48:35,000 --> 00:48:40,000
about this. Now, Mendel's
Law is rediscovered.

678
00:48:40,000 --> 00:48:46,000
Now, the explanation here. How
does the cytological observations

679
00:48:46,000 --> 00:48:51,000
about meiosis explain Mendel's
laws of inheritance of traits?

680
00:48:51,000 --> 00:48:57,000
Very simply. All you have to
imagine is that big R is being

681
00:48:57,000 --> 00:49:03,000
carried on one of these chromosomes.
Little R on the other one.

682
00:49:03,000 --> 00:49:09,000
And then half the offspring had big
R, half the offspring had little R.

683
00:49:09,000 --> 00:49:15,000
All of Mendel's laws can be
implemented by simply assuming that

684
00:49:15,000 --> 00:49:21,000
genes and the alleles of those
genes live on these chromosomes.

685
00:49:21,000 --> 00:49:27,000
So it's beautiful, except for one
problem. You may remember from your

686
00:49:27,000 --> 00:49:33,000
high schools that Mendel also had
another law about more than one

687
00:49:33,000 --> 00:49:38,000
trait, pairs of traits.
Not just that we have this

688
00:49:38,000 --> 00:49:42,000
segregations of alleles away for
one trait. What was his law about two

689
00:49:42,000 --> 00:49:46,000
traits? We'll go over this next
time. What was his law about two

690
00:49:46,000 --> 00:49:50,000
traits, like round and
wrinkled and green and yellow?

691
00:49:50,000 --> 00:49:54,000
That they would be inherited
independently of each other.

692
00:49:54,000 --> 00:49:58,000
How would that fit into this model?
Different chromosomes. They'd be

693
00:49:58,000 --> 00:50:02,000
on different chromosomes. But
what if I had three traits?

694
00:50:02,000 --> 00:50:06,000
Eventually, if I had, now, peas
actually have seven pairs of

695
00:50:06,000 --> 00:50:10,000
chromosomes. So if I
study eight traits in peas,

696
00:50:10,000 --> 00:50:14,000
two would have to lie on the same
chromosomes. So then the chromosome

697
00:50:14,000 --> 00:50:19,000
model would contradict independent
inheritance. So either Mendel

698
00:50:19,000 --> 00:50:23,000
cannot be right with this other law
of independent inheritance that you

699
00:50:23,000 --> 00:50:27,000
learned about or the Chromosome
Theory cannot be right of these

700
00:50:27,000 --> 00:50:32,000
living on these physical molecules
and getting distributed that way.

701
00:50:32,000 --> 00:50:36,000
Right? So we have a deep
problem because either Mendel,

702
00:50:36,000 --> 00:50:41,000
my hero, is wrong or this
chromosome model is wrong.

703
00:50:41,000 --> 00:50:45,000
And the problem is we don't have
enough time to resolve this today,

704
00:50:45,000 --> 00:50:50,000
so we're going to have to come
back on Wednesday and figure

705
00:50:50,000 --> 00:50:55,000
out what happens.