Chemical transformations - The chemistry of almost everything (26/31)

Uploaded by OUlearn on 03.09.2009

Back in 1956 whilst studying for his PhD,
Stanley Miller carried out an historic experiment
in organic chemistry.
He wanted to simulate the production of the basic building blocks,
organic compounds used in the creation of all life.
This consists of a 500cc flask
which represents the ocean
and a three-litre flask which represents the atmosphere
with the reduced gases in it.
This spark represents the corona discharges of lightning.
The water is boiled, comes into the flask,
gets hit with the electric discharge along with the methane and ammonia,
and the organic product is synthesised in the atmosphere.
That's the only way you can make organic compounds
in an efficient manner.
It had been a chemist who first managed to produce
nine out of the 20 or so amino acids,
carbon-based molecules which make up all of life.
It's these molecules which string together to form proteins,
the powerhouse of every organism on Earth.
Unfortunately, Miller's amino acids aren't enough on their own.
To create life we're going to need much more complex molecules than that
like DNA.
And once we've got those, then the ball's really rolling.
Hang on a minute.
Just to make one of these simple sub-units of DNA
is difficult enough.
It takes lots of different chemical transformations,
all taking place in a particular sequence to make something like this.
In fact, now hold on to your seat,
it's been estimated that the odds of the right chemical transformations
taking place in the right sequence are something in the order
of 10 billion billion billion billion billion billion billion billion
billion billion billion billion to one.
Now I'm not a gambling man but they don't seem very good odds to me.
Chemists and biologists are still looking for life's origin
but back in the 17th century the physiologist William Harvey
had a more practical approach.
His seminal book contained a picture of God holding an egg
with a key phrase,
'ex ovo omnia'.
Meaning, out of the egg, everything.
A phrase not lost on modern day biologists and chemists.
There is this question about how life begins
and what's the beginning of life.
Life has to be passed from generation to generation.
The egg is alive and the sperm is alive
and a dead egg and a dead sperm will go nowhere.
So life is continuous from one generation to the other.
And it's as if the chemistry of life is so complicated
that is just has to be kept alive, it can't be allowed to die.
An element like calcium might trigger the first stages of fertilisation
but could other chemicals then control subsequent development?
What we're trying to understand are the mechanisms
by which a single cell, the fertilised egg
divides, makes an embryo
and how is it a hand forms on the end of your arm,
not a foot, and how come the retina has a lens overlying it
rather than the lens forming somewhere else completely?
So we're trying to understand, for example,
the cell interactions which are involved
in making the right cell type form in the right place.
And what we're finding and beginning to identify
are the chemicals that are involved in this process.
Jim Smith's been studying frog eggs and their detailed internal chemistry
but his findings may be general to all vertebrates.
The early vertebrate embryo, not only frogs,
mice and humans as well, for example, has three layers of cells.
The cells on the outside are the cells of the ectoderm.
They make the skin and they make the nervous system.
The cells on the inside, the blue cells,
they're the cells of the endoderm and they make liver,
and they make intestine, for example.
Here, the cells I'm interested in the mesodermal cells,
they make notochord,
a rod of cells running along the centre of the embryo,
somite cells which make the muscle which allow the frog to swim.
These lateral cells here form lymph buds
and the ventral cells here make blood.
So I want to know, how do cells know they should make mesoderm
and how does the right sort of mesoderm form in the right place?
We know that cell interactions
play a very important role in early development.
One set of cells makes a chemical signal
which another set of cells sees
and what we've been able to do now is really identify
what some of those chemicals are and show that what's important
is the level of the chemical, the concentration of the chemical
that make cells do what they do.
The ions of one element, calcium, kick off fertilisation
and now it seems an organic molecule, a complex protein called activin.
might play a role in the subsequent process of embryo development.
One of the most exciting things that we've found
is that what's important is the activin concentration
and that it's the concentration of activin
that specifies what type of cell eventually forms.
For example, one particular concentration of activin
makes cells form muscle.
If you increase the concentration of activin by only a factor of two,
you can switch cells from forming muscle into forming a rod of cells
which runs along the length of the embryo
which is the primitive backbone.
Simply changing the factor concentration by a factor of two
gives you this qualitative change in cell type.
And the implications of Jim Smith's work are not just academic
or theoretical.
15% of women have problems conceiving their first child.
23% of those are lost in the first five months
and 2% of newborn children have a serious genetic defect.
If we want to find out what is going wrong in those cases,
we first have to find out what's going right in normal development.