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>>MARK FARMER: This evening we are joined by Dr. Claiborne Glover,
Professor of Biochemistry and Molecular Biology. And when I was thinking about the speakers
that I wanted to participate in this, Claiborne was first on my list.
Those of you who have known him for many years know that he is
a deeply-committed scientist, a deeply-committed educator,
And he actually teaches a rare course at the University of Georgia,
and that is one that is cross-disciplinary, specifically designed to talk about
the importance of science in society and in our lives.
And for that reason primarily, as well as his expertise in biochemistry,
I thought he would be an ideal speaker for this series.
I also want to thank him personally, for because those of you who know Claiborne,
know that he has a deep appreciate for music, and tonight apparently we are up against
the Boston Pops. Which I did not know when I scheduled this
this evening, and I apologize to all of you
who may have bought tickets and have had to give them to friends.
But I'm glad that you're here with us tonight, and I am especially glad that
Dr. Claiborne Glover is here to speak to us about the origin of biomolecules. Claiborne?
[applause]
>> CLAIBORNE GLOVER: Well, good evening and welcome to everyone,
and a particularly warm welcome to those of you
from the broader Athens community. You are particularly ones
that we wanted to reach with this series, and I have met some of you
already this evening, and I am delighted
that you could join us.
This slide which forms the basic image of the entire series here
looks like poetic license, all these molecules floating around in space,
but it turns out this may actually be important in the evolution of biomolecules.
I want to begin by focusing on the title of this course,
and I want to thank Mark Farmer for adding the "s" to origins.
I called it Origin of Biomolecules, but indeed there are multiple origins
for biomolecules presumably, or at least possibly.
And I want to start here and divide this into three questions.
I have already apologized to Mark for stepping on his territory.
The next talk is about the Origin of Life and I can't stay away from it completely,
so I'll try not to take too much of his territory,
but we need to know what the first living thing was
if we are going to figure out what molecules it was made of
so that we can ask when, where, and how those molecules were made abiotically,
i.e., in the absence of life. So I am going to give you the answer
to all three of these, what was the first living thing,
what molecules were they made of, and when, where, and how were they made.
We don't know [laughter]. And as Sherlock Holmes says
"It is a capital mistake to theorize in advance of the facts."
[laughter] So, I guess we could all go home now [laughter]
except that Sherlock Holmes also said,
"It is, I admit, mere imagination, but how often is imagination
the mother of truth." And it is not even true
of Sherlock Holmes that it was mere imagination.
He made use of that glorious mixture, alloy really, of reason and observation
that we call science to achieve the wonderful things that he did.
And so we will use that mixture. Unfortunately, in many instances
we've got the reason but we don't have
a whole lot of observations, so it's unconstrained by facts in some cases.
I will start here with this rather busy slide
from Steve Benner. It talks about four approaches
to elucidating the Origin of Life. These four Quadrants.
I will simplify this quite quickly. They come in two pairs,
the horizontal pair and the vertical pair. I'll dismiss this horizontal pair.
This is look around the cosmos and find another instance
of the origin of life, or build it yourself
in the lab from scratch. Neither one of these has been done,
and more to the point, even if they had been done,
they might not necessarily bear on our origin.
So we will simplify his diagram.
There is actually a temporal sequence here [in the remaining, vertical pair],
proceeding from prebiotic chemistry to the origin of life
and from there out to the glorious collection of organisms we see
on the planet about us now, including ourselves and E. coli.
So what I propose to do is to try to work backwards first.
My main job is to do this, to work forwards from chemistry.
But I want to start here to try to sketch a family portrait
if you will of what the first living thing is,
which would be right at the end of this little green stem here.
We can try to work our way back to that, either with the fossil record,
but we not only run out of bones pretty quickly,
but we even run out of rocks because this was a long time ago
and there aren't rocks as old presumably as the origin of life.
So there is another way to reconstruct this, and that's with phylogenetic comparison
of all the organisms here and use that to reconstruct
the last final common ancestor of all extant organisms.
It's called the LUCA. I don't know why I think of LUCA
as a female but I can't help it, and that's the way I'll refer to her,
the Last Universal Common Ancestor of all living things.
What did that organism look like? Basically you compare
all the living things here and ask what they have in common.
Here's a family portrait [laughter], including animals, plants, the fungi,
a lot of microorganisms, prokaryotic and eukaryotic, you can't see,
and here is our great-, great-, great-, great-, great-, great-grandmother, LUCA.
So I want to blow this up a little bit so that you can get a little more detail
about what LUCA might have looked like. First of all, the size of things.
So, you all know what a meter stick looks like.
The smallest division is a millimeter so that 1 to 1000 jump
I want you to imagine two such additional jumps,
divide the millimeter in a thousand parts to get micrometers,
the micrometer into a thousand parts to get nanometers.
So these three jumps of a thousand-fold define four scales,
the human scale - the length of a man's stride; the smallest things we can see, roughly speaking;
the smallest cells, again roughly speaking; and nanotechnology, the size of atoms.
LUCA is presumably going to be a small cell,
about a micrometer in diameter, so I'll blow up that photograph of her
that was hanging on the wall, and if there is a thousand atoms
across this distance, a thousand wide, a thousand deep, a thousand tall,
we ought to have a billion atoms in it, roughly speaking.
If you actually do a careful calculation, since atoms are smaller than a nanometer,
you get about 50 billion atoms. Already LUCA is looking like
a very complicated gal.
What does she contain? Well, she's got a container to begin with,
and I've drawn the plasma membrane that forms the boundary between her
and the outside world to scale here. Inside, we have a lot of stuff,
but certainly the central dogma of molecular biology,
DNA makes RNA makes protein, in the two processes
of transcription and translation, catalyzed by RNA polymerase
in the former case, ribosomes and transfer RNAs in the other.
LUCA has all those things because all extant living organisms
have those things. She also has an essentially modern genetic code.
This is maybe a better picture of what LUCA might look like.
This is actually a watercolor by David Goodsell from his wonderful book
The Machinery of Life. It is actually an existing, extant organism,
but it might be a good model for LUCA. It is a little bit small that a micrometer.
It has roughly a billion atoms now, for real. It's got a sequenced genome,
roughly a million base pairs encoding a thousand genes
which get expressed as a thousand proteins.
Now I want to blow up portions of this to show you at the atomic level
a little piece of the membrane, an RNA polymerase
catalyzing transcription of a messenger RNA,
and then a ribosome translating a messenger RNA
into one of the proteins. Those thousand proteins there
are shown in blue and green in the cytoplasm and in the membrane
of this organism. So here is a picture of the membrane.
It is made up of amphiphilic molecules. One end hates water
and the other loves it. The part that doesn't like it
gets together here in the middle of the bilayer.
Two such leaflets come together. The part that loves water is facing it.
In this molecular dynamics simulation here you can see the water
on the outside of the cell, the water on the inside.
Headgroups like the water and interact with it,
and the hydrophobic portions form this bilayer that is the boundary
between the inside and the outside of the cell.
This occurs by self-assembly; you don't have to have anybody
with hammers and nails to build it.
Here is a picture of the gene expression machinery
I boxed on the earlier slide. That's RNA polymerase,
at the same scale as the ribosome. There's DNA being transcribed
into a messenger RNA, messenger RNA would thread through here,
tRNAs read it, and the protein is exported through a pore.
In this particular case, in this wonderful structure,
there is actually a little piece of a lipid bilayer.
This is a protein that is going to be put into the membrane,
and it is being threaded into the membrane
as it is being synthesized. That's just one protein.
What do all these proteins do? There's a thousand of them in this cell.
A bunch of them in the membrane are involved in exporting and importing materials.
The rest of them run the metabolism of the organism and allow it to function
gather energy from the environment and reproduce itself.
LUCA is one complicated gal. This is not something
that is going to spring together from a simple set of atoms.
We need to go further back. And we don't have any way
to get further back really. We are sort of stuck here.
Phylogeny doesn't help; there's no real information
coming from the rocks, the history of the life on the planet.
So this is largely inference. We are with Sherlock Holmes now,
basically at the stage of mere imagination.
But some of us aren't daunted. So the Initial Darwinian Ancestor
is what this is called. You could call it
the First Universal Common Ancestor. I'm going to try to draw you
a quick family portrait of that, much shorter than the last
because we don't know much about it. It's called the Darwinian Ancestor
because a Darwinian process is one exhibiting reproduction, variation, and selection,
and hence is capable of evolution. And I'm going to invoke
the principle of continuity. Not everybody in this field does,
trying to get from LUCA to IDA. We call this also the principle of parsimony
or Ocham's razor or keep it simple, or as the statistician said,
"If the first one comes out that way (think IDA),
it's clearly a trend (think LUCA)." So IDA and LUCA are going to be
pretty similar to one another. And two intrepid researchers here,
David Deamer and Jack Szostak, actually are willing to speculate
about what IDA might look like. Here's a picture on the cover of their book.
This is a protocell, made up of a lipid bilayer, but with simpler lipids
than are in modern organisms. And the artist has come along with a knife,
and he sliced off the top of this spherical object
so that you can see what's inside, which is an RNA molecule
undergoing replication. So we have not only replication
of this primitive genome, but we also have as new lipids
are incorporated into this membrane it can pinch in two.
And people have NIH grants to study this sort of thing and build it.
So this may be what IDA looked like. And if we have reproduction,
here we have differences in the progeny, the possibility for selection,
we've got the possibility for evolution. And this is possibly something
that could assemble on its own from simple precursors.
OK, so LUCA and IDA get us that far. We now need to talk
about working the other way. And again I'll invoke
this principle of continuity, that the sorts of molecules
one finds in modern day life we can predict are present in LUCA
and may be present in IDA, are the kind of molecules
that we have to make. And Steve Benner works
on this sort of stuff, and he has shown a whole bunch
of different organic molecules here up at the top,
some of which are found in the interstellar medium between the stars.
This is the Orion nebula here. I'll return to that toward the end.
So I'm going to begin simply. Before we can talk about biomolecules,
we need to talk about what they are made of,
which is the bioelements, and my predecessor in this series,
Dr. Freeman-Lynde, did a wonderful job of explaining where the atoms come from,
hydrogen from Big *** nucleosynthesis, basically all the rest from stellar nucleosynthesis.
We want to focus our attention primarily on four of these atoms,
hydrogen, carbon, nitrogen, and oxygen, which together make up 96.8% of your body.
It doesn't matter whether you are a human being or an E. coli,
it's pretty much the same number. Sulfur and phosphorus
present in proteins and nucleic acids and other molecules in cells,
and a bunch of ions, sodium chloride, salt and so forth,
make up the remaining 3.2%. The sum of these two is 100%
so these trace elements here really are pretty trace.
There's not a lot of them. And if this is your favorite part
of prebiotic synthesis, I'm going to disappoint you
because I'm going to restrict my talk to hydrogen, carbon, nitrogen, and oxygen,
and their covalent interactions. These are crucial transition metals
in modern [bio]chemistry and many people think they are crucial
in the origin of life as well. I'm only going to make one more statement
about these things I'm not going to talk about. And that's just to point out
that tungsten here was added to this list of essential trace elements
by our own Lars Ljungdahl who's sitting there in the audience.
An admirable contribution to the literature.
OK, so I assume not everyone's a chemist. I'm going to try to teach you chemistry
in five or six slides here. This is not so simple.
I'm going to start simple though, with the simplest possible chemical reaction
that there is, two hydrogen atoms coming together
to make a hydrogen molecule by sharing a pair of electrons.
That is a covalent bond, which we indicate as a straight line.
And the energy of this particular covalent bond
is 436 kJ/mol. Now the way we use words you tend to think,
oh that's the energy you gotta invest to MAKE the bond
I have to get out my tools and my ladder and my hammers;
I gotta build this bond. That's exactly backward.
The language is misleading. That's the energy you have to put in
to BREAK the bond, to get it back into two hydrogen atoms.
The bond forms spontaneously. It's at lower energy than the separated atoms.
Just to drive that point home, the man that discovered atomic hydrogen
invented the atomic hydrogen arc welding torch. He set up a method where he could spray
atomic hydrogen at a surface, and the heat generated as it turned
into hydrogen molecules is the third hottest flame known to science.
It is sufficiently hot to weld tungsten, which you almost can't do any other way.
This never became commercially available, but it certainly makes the point
that you get energy out as you make these bonds.
Now in my biochemistry 4010 class I tell my students about the HONC rules.
I'm not sure if anybody else in chemistry uses these,
but I think the HONC rules are going to be helpful.
So I'm going to tell you how you can draw basically
an infinite number of organic molecules, which if you could synthesize
would probably be stable, they wouldn't explode,
they would be good stable molecules. And so I've taken these four atoms,
hydrogen, oxygen, nitrogen, and carbon, and put them in that order spelling HONC,
because hydrogen has one bond, oxygen two, nitrogen three, carbon four.
If you draw any molecule on a piece of paper which doesn't violate the HONC rules,
it is probably going to be a good molecule. There are some other molecules
you can draw that do violate it that are still good molecules,
but this [is still] an infinite number of molecules I've just given you here.
These bonds are arranged in these different ways here,
so the hydrogen only has one possibility, but there's two possible ways for oxygen,
two single bonds or a double; [for nitrogen] three single bonds,
a single and a double, a triple; [for carbon] all these possibilities.
Again, there one, two, three, and four ways to arrange the one, two, three, and four bonds.
There is no such thing as a quadruple bond --
well, there is, but not for an element in the second row.
I tell my students in 4010 that I'm thinking of making a bumper sticker
["HONC If You Love Biochemistry" - laughter]. You can tell me you if think there's a market
for this or not [laughter]. I've been skeptical [laughter].
So here are a few of the things you can draw of the infinite number of compounds
that obey these HONC rules. So there are hydrogen, oxygen, and nitrogen
� one, two, and three bonds.
This is graphite, water, ammonia, methane. Some of these, these four here,
will figure in the Miller experiment in a moment.
A whole bunch of different ones, and if you get creative,
you can sit [with] a piece of paper and draw a molecule yourself.
Maybe you come up with this. Probably many of you have ingested
this molecule within the last day or so. It's caffeine.
I tried to find out if this was prebiotic or not [laughter],
but I couldn't confirm it. One very much like it though that's prebiotic,
and this is adenine, one of the four bases in DNA and RNA.
So we can draw a lot of molecules.
The last bit of chemistry is even more stressful than those.
Thermodynamics and kinetics. So thermodynamics tells you
which way and how far a given chemical reaction
will proceed, A going to B. The lower the energy [of] B is
compared with A, the more the equilibrium
lies in favor of B when the reaction comes to thermodynamic equilibrium.
Almost all reactions, however, have an activation energy.
So even though A has a higher energy than B
and it wants to go down this hill just like rocks want to go downhill,
it can't do so without an activation energy being provided �
this is the little man doing that here � to get it over this activation energy.
The activation determines how fast something will come to equilibrium � kinetics.
So we need energy. We need energy to get over the activation
energy for even favorable reactions.
For unfavorable reactions, we will even need more energy
to push things uphill against the gradient. So sources of energy
available on the earth, the early earth, look very much like current earth:
solar radiation is the main one present, electrical discharges from storms and so forth,
chemical energies � those three will figure in some of the slides,
but there�s quite a few others as well.
OK, so let's make an inventory of what we need to make
assuming that IDA looks like LUCA, as LUCA looks like current life.
We need the most important macromolecules in cells: nucleic acids; proteins; lipids,
which include amphiphiles to build membranes; carbohydrates; and a whole collection
of other intermediary metabolism molecules. Here is a more extended list.
I won't go through it all, but four nucleotides, twenty amino acids,
a bunch of different amphiphiles; ribose and deoxyribose are the sugars
that are in DNA and RNA so they are important.
And this is how this is going to work. Basically, we are going to start with the
atoms, which as I've already indicated tend to turn
into simple molecules pretty much spontaneously.
These simple molecules then get more and more complex up to the point
where they generate biological monomers, like adenine and guanine to build nucleic
acids, glucose and sugars, [amino acids], and so
forth. And then these biological monomers
are assembled into these polymers, DNA, RNA, protein, complex carbohydrates,
etc.
So the last of the three questions that I asked at the beginning of the hour:
When, Where, and How were biomolecules made abiotically,
in the absence of any preceding biology. So When.
Here is a little timeline of the earth's existence from its formation 4.5 billion years ago
up to the present. The last 3.5 billion years have been telescoped
rather badly here, but this is the interesting bit,
as far as the origin of life goes. And it's constrained by two points,
the end of the late heavy bombardment of the planet �
these are asteroid impacts which are large enough
to vaporize the oceans and destroy any previously formed prebiotic chemistry,
which may have happened numerous times and been destroyed again and again.
So we don't have IDA � we can't put IDA on that side
because she'd die, so IDA has to be to the right of this line.
And we have pretty good evidence in the rocks for the existence of complex microbial life,
microbial mats � they're called stromatolites �
we can see them in the rock record at 3.5 billion years.
So IDA and LUCA are presumably in between those two dates.
You could move them around. I've put them sort of in the middle there,
but they are somewhere between 4 billion years ago
and 3.5 billion years ago.
Where do these biological molecules come from? Well, the earth would be the logical thought,
and for many years, decades in fact, it was thought to be the place
where all the biomolecules were synthesized. But as this slide indicates,
over the last fifty years or so there has been increasing interest
in the rest of the universe as being the origin of the biomolecules
present on this planet, delivered as asteroids or comets
or even dust raining in on the surface of this newly formed planet earth here.
And these things that are raining in themselves may have a very ancient history,
older than the solar system itself. They may have been formed
in the accretion disk that gave rise to our star,
and that came from a dense cloud which has its own chemistry,
undergoing gravitational collapse; and a diffuse cloud which has different chemistry,
and this diffuse interstellar material is produced by old stars,
which as was explained in the last lecture, they make the atoms to begin with,
and then they swell up, become red giants, and they blow off much of their mass
into the interstellar medium, and there's additional chemistry
associated with that sort of environment. And so it possible that organic molecules
which gave rise to life didn't originate on earth
but originated on meteorites, and even the organics in those meteorites
might have come from one of these earlier things.
It could be not only 4.5 billion years old, but maybe 10 billion years old.
So it might be useful to go through that as a logical sequence
from stellar synthesis of the atoms down to the earth in the end,
but I'm going to do it a different way. I'm going to organize
the rest of my talk here on an historical timeline,
a different timeline, much shorter, decades, a couple of centuries at most,
not billions of years. I'm going to start �
we could start in lots of places, probably all the way back to Lucretius in
fact � but I'm going to start
with Darwin's �warm little pond� comment which is from 1871,
and then we�ll then proceed up through Oparin and Haldane,
1924 and 1929, respectively. These two people are largely responsible
for our intellectual thinking about the origin of life.
They started the discipline from the point of view of speculation,
not from the point of view of experiments. Oparin wrote a short paper in 1924;
it was published in Russian. Haldane, a British biochemist,
an important genetics contributor, also interested in the origin of life,
wrote a similar pamphlet. They both had the same title:
The Origin of Life. Neither one of them knew about the other
so even though Haldane was five years after Oparin,
he did it independently. They have some subtle differences,
but there is a great deal of similarity in their thinking about this,
and they get sort of dual credit for the notion of the prebiotic soup.
Both of them thought that there was an atmosphere which chemistry could take place in,
organic molecules were synthesized there, rained down into the ocean,
and the oceans became a �hot dilute soup�, Haldane's characterization of it,
and that's led to this notion of a prebiotic soup.
It was not until 12 years later that Oparin wrote a book-length description
of The Origin of Life � same title � published again in Russian, and that was 1936,
and two years later someone translated that, and it was only at that point that
Oparin and Haldane realized one another's existence,
and they are given joint credit for a similar set of hypotheses.
This notion of the origin of life only became an experimental science though in 1953.
Basically, he [Stanley Miller] tested Oparin's theory at that point
(World War II intervened in there, and so that prevented people
from maybe testing it earlier). This was a galvanizing experiment.
It led to many more, including the synthesis of adenine by Oro.
And then the Murchison meteorite, I�ll mention that, fell in 1969
and gave us the first real indication of what might be coming into the planet
from outer space. And then I'll end with the Herschel space
telescope because our efforts to understand this continue.
So here is this quote from Charles Darwin: �It is mere rubbish, thinking at presen�
� that is an important qualifier for Darwin I sense as I read this �
�of the origin of life; one might as well think
of the origin of matter.� Ironically, we understand the origin of matter
now much better than we understand the origin
of life. Obviously, he thought it was the other way
around. That was in 1863 in a letter to Joseph ***.
In 1871, according to his son Francis, he wrote, �But if (and oh! what a big if!)
we could conceive in some warm little pond, with all sorts of ammonia and phosphoric salts,
light, heat, electricity, &c., present, that a protein compound was chemically formed
ready to undergo still more complex changes . . .�
It is almost a prescription of the Miller-Urey experiment.
Very prescient, Charles Darwin.
So here is just a beautiful painting here by Don Dixon of the early environment of the
earth. It�s always impressive to me
how an artist can do better than all the molecular [computer] graphics
that we manage to use to draw things with these days in science. An artist really captures
it. The young moon, look at all this lighting
storm here, volcanic action, there's the ocean �
it's almost a picture of the Miller experiment I'll show you in a moment.
If you want to look at some more photographs [of paintings] like this go to Cosmographica.
So here is Stanley Miller's experiment, A Production of Amino Acids
under Possible Primitive Earth Conditions. He worked with Harold Urey, published in 1953,
started the real first experimental description of origins of life research.
The first paragraph is important: �The idea that the organic compounds
that serve as the basis of life were formed when the earth had an atmosphere
of methane, ammonia, water, and hydrogen, instead of carbon dioxide, nitrogen, oxygen,
and water� � which is the current composition �
�was suggested by Oparin� � this is the 1924 paper he references there
� �and has been given emphasis recently by
Urey� � who was his postdoctoral mentor
at the University of Chicago. He put these four gases into this apparatus
here, which he was basically using
to try to mimic this. This is a little bit better picture of it.
This is the ocean. Water is down here. You heat the water so that it boils off,
evaporates off the ocean, goes into the gas phase here,
into the atmosphere; the atmosphere is composed
of methane, ammonia, hydrogen, and water, which Oparin had suggested,
and the lightning is provided by tungsten electrodes here
which spark it periodically. So basically you have this hydrological cycle
here where the water circulates around,
and you have got sparking of this atmospheric gas mixture.
He ran this for a week. After a day he could tell
that this clear water that he had put in there
was starting to turn a little orange. A week later it was a dark ruddy color,
and the inside of this bulb had black goo on the walls,
and he analyzed the water-soluble stuff which came out of the bottom of the flask.
And he ran paper chromatography on the water-soluble material he got out of
there. I put exclamation points
after aspartic acid, glycine, and alpha-alanine, which are three of the 20 amino acids
that are in all of the proteins in our bodies. It's a spectacular result.
A simple experiment, and in one week's time � you might think it would take a billion
years to make something organic like that �
but, no, you get it in a week. And you get it in very good yield.
Two percent of all the carbon that went into the instrument, the simulation, as methane
came out as glycine, and another couple of percent is alanine,
other amino acids present in protein in smaller amounts but still substantial,
a number of other organic molecules 4%. Ten to 15 % of all the carbon that went in
there came out as soluble organic molecules
in the space of one week.
Subsequent to that 1953 publication, Miller and other people have worked out
somewhat of the chemistry. I won't belabor it, but here are the four
gases. They react initially to make
hydrogen cyanide and formaldehyde. Those don't accumulate,
but they are used to react with some of the ammonia and these others
� we've got six things coming together here basically.
It's called a Strecker synthesis. The formaldehyde and hydrogen cyanide
enter in these positions, and out comes glycine. One of the nice things about it is
you stick in a different aldehyde � acetaldehyde �
and out comes alanine, another amino acid which was made in such
bulk. A Strecker synthesis can generate
any one of the 20 amino acids if you start with the right aldehyde.
And you can see here the time course of the experiment:
the hydrogen cyanide and the aldehyde don't accumulate,
but they give rise to the amino acids, and it's very important that the amino acids
don't go on to react and become something else.
Some of them do, but a lot of it stays as the amino acids
so you accumulate a significant amount of this stuff.
In fact, it works too well. It's almost too easy to make biomolecules,
and this will be a common theme here for the rest of the hour � and in two senses.
So this molecule is beta-alanine, which looks much like alpha-alanine
except that the carboxyl group is on the wrong carbon.
This is trouble, because it is chemically very much like the alanine that's in proteins,
and it can get into proteins, and it is going to make a protein
that is probably not going to be functional. Even the alanine.
Nineteen of the 20 amino acids have a mirror image,
only one of which is utilized in extant proteins. This is the biologically relevant form
of alanine; it's L-alanine. This is it's mirror image, D-alanine.
We don't have D-alanine in our bodies, just the L-alanine.
And this has almost exactly the same chemistry as L,
and it can be polymerized with the L-form to make mixed polymers
which presumably would not be a useful path forward for IDA and LUCA.
So this is a problem, the fact that this synthesis gives both,
and I'll return to that later.
There is one nice addendum to this experiment by Miller.
He died in 2007, and Jeffery Bada and his colleagues
have gone through his -80 degree [Centigrade] freezer,
found all these vials, beautifully catalogued, all the notes that go with those vials
� they know exactly what was done. They contained dried residues
from a variety of different experiments, including the ones he published
� they could redo it with modern methods and see what additional things
they might be able to find in those samples. That was done here.
This is actually a different design, designed to spray steam into this vessel
mimicking a volcanic discharge � lots of lightening storms occur over volcanoes.
So a different sort of environment, and they confirm many of the things that Miller
saw, but also some additional ones as well,
and so it's nice to have his experiments back from the 50's and 60's resurrected here,
and there are several publications from that that are quite interesting.
Well, as I said, this one particular experiment in 1953
precipitated a host of experimental investigations into the origin of life
and the synthesis of prebiotic compounds; and one of the more spectacular ones
was by John Oro, who synthesized adenine in 1961
just from hydrogen cyanide and a little bit of light
of the appropriate wavelengths. So, one, two, three, four, five
of these [hydrogen cyanide] come together, each bringing one carbon and one nitrogen,
to give a 5-carbon, 5-nitrogen molecule, adenine, one of the crucial bases in DNA and RNA.
And again in extraordinarily high yields, a very efficient synthesis of adenine.
This is a busy slide, but one of the problems in prebiotic synthesis
is synthesizing the carbohydrates. Unlike the amino acids
and the nucleobases like adenine, you can make them alright,
but they don't stop they become intermediates
in some other continuing chemistry that destroys the carbohydrates.
I just wanted to point out this one recent discovery of Steve Benner.
The problem is that these carbohydrates as they are made turn into brown tar
and you can see this test tube on the right. That's a problem.
You can't make a sugar, and we need sugars, you need ribose for the backbone of RNA
and deoxyribose for the backbone of DNA. [But] if you do this in the presence of borate
this is a mineral here, colemanite,
which contains boron in it that sort of brown tar doesn't form.
You go through and you make these sugars that we need in order to be able to build
DNA and RNA chains and lots of other things. I've called this the Benner Synthesis.
I don't know whether that's gonna catch on as the name for it,
but I think it's a really important development.
OK, so this is the experimental approach to synthesizing biomolecules in the laboratory.
I want to point out three problems that have been encountered.
I have mentioned them to some extent. One of them is called prebiotic clutter.
I think that word was coined by Joyce, but it's an apt description.
Here is a picture of an RNA chain. It's actually quite long presumably.
It is made up of four different colored parts; it's color-coded.
And the parts we need are this particular version of phosphate,
that particular version of the sugar, these two purine nucleotides,
and those two pyrimidine ones. In all these biosynthetic experiments,
we get those, but we get a lot of other things, we get clutter.
All these things can get into the same sort of molecule,
and then the backbone's not right. The furanose has also got a mirror image
so you can get the L form in there, and again the molecule will not be built right.
And you can put in all these other substituted bases
that can't hydrogen bond properly as you expect to get out of a nucleotide
double helix for example. This problem has not been solved,
how to keep the clutter out of the way so that you make a polymer
only of the things that you need in order to build a coherent molecule
that will have a function.
The second problem is [that] all biological polymers
are thermodynamically uphill in water. They want to come apart into their pieces,
so all these colored pieces were put together by taking a water molecule out
at each junction between one color and another. That's uphill, like A in that thermodynamic
picture; downhill would be to hydrolyze
all those linkages back to the parts. And to synthesize a large molecule like this
in the absence of a living thing, to keep it repaired and so forth,
is a very difficult conceptual problem, and it is a difficult experimental one.
There are ways to address this by keeping the water activity low,
let it dry, and so forth but it's still a serious problem.
And the third one is: Was Oparin right? Was the early earth atmosphere reducing?
And a decade or two after his work was published,
the conclusion of the general scientific community, I would say, was
No, actually that's wrong, it's oxidizing. And when you do similar sorts
of in vitro experiments trying to synthesize biological molecules,
you get very few and in very poor yield. So if the early earth was oxidizing,
we are in trouble. All this chemistry we've got in the laboratory
is not going to help. There are ways around that,
and in fact the debate continues. I just read a recent review that said,
No, it was pretty reducing actually a little oxygen around but mostly reducing.
And even if the atmosphere looks like it currently does
or oxidizing in some fashion, you can find a microenvironment on the planet
that is reducing, so maybe this chemistry is still useful
and that's where life evolved, maybe in a deep thermal vent or something
under the ocean.
But still this problem concern about whether the planet
is capable of making biomolecules leads one to look to space
as a possible origin for biomolecules. And this really took off in 1969.
The Murchison meteorite is probably the most famous meteorite to hit the planet,
with the possible exception of the one that landed last week [laughter],
very apropos for my discussion here today. This one was particularly interesting for
several reasons. First of all, it was a carbonaceous chondrite,
which is a typical kind of asteroid, but one rich in organic molecules.
It was an observed fall, people saw it, just like in Russia,
and it fell in a very deserted part of Australia, out here in the West.
And most of it, or a large chunk of it, was recovered, 100 kilograms total.
Probably the most important thing that has made Murchison
the most studied meteorite on the planet is that it fell in September of 1969.
What else happened in 1969? The first moon landing, the Apollo landing.
The astronauts came back with moon rocks in July of that year,
and those moon rocks were fed into this machinery which had been set up ahead of time
to study the moon rocks, to quarantine them, and all this analysis and instrumental capability,
and the Murchison meteorite went right in behind the moon rocks
and got subjected all of that sort of analysis. And all sorts of compounds
have been found in there, amino acids, purines and pyrimidines,
hydrocarbons, sugar alcohols; and any one of these if you pick it up and
look this is one amino acid shown here
as an example, alanine but here's just a few of the 70 amino acids
from that one particular category that have been found in the Murchison meteorite.
None of these shown here happen to be ones that are in proteins so this is more prebiotic
clutter.
On the good news side of things, several of those amino acids
actually have a slight predominance of the correct mirror image form of the amino
acid, so it gives us some feel that maybe
something in space has biased it in the direction which it needs to go
in order to become the L amino acids that we currently see here on the planet
in biological things. Nucleobases have been found there.
Some of those are present in DNA and RNA, others are prebiotic clutter.
Probably my favorite is the amphiphiles. This is an experiment from David Deamer in
1985. Almost everyone had been extracting these
meteorites with water to see what was water-soluble.
He extracted them with chloroform and methanol to see what was hydrophobic in there.
And I like this quote: I evaporated a drop of the extract
on a microscope slide. As it dried a strange aroma wafted up,
and I realize that I was smelling something that was over 4.5 billion years old.�
That's how old the meteorite is, and that history of whatever organics are
in it could go back into interstellar material
so it could have been 10 billion years old for all he knew.
The interesting part of this experiment though is after that material dried out,
he then dissolved it, not in chloroform/methanol, but in water,
and he looked at it under the microscope. And it must contain amphiphiles
because they spontaneously formed these protocellular-like structures in the
microscope. Perhaps this is the beginning of IDA.
It's half of IDA. All we need now is nucleic acid in there perhaps
to have a genome inside that cell.
I want to show you how serious this biotic clutter problem is.
This experiment, analysis of Murchison, continues. This is 2010.
Really high sensitivity instrumentation has been brought to bear on this.
Ever spot on here is a different molecular composition
so many carbon, so many hydrogen, so many nitrogen;
they don't know what the molecule is, but they know what it's composition is.
There are tens of thousands of spots. Almost any spot you pick
almost certainly has hundreds of different isomers of that composition,
so they speculate there are probably millions of structures in the Murchison meteorite.
This is prebiotic clutter with a vengeance. How the things that we need
to build biological molecules are sorted out of there, I don't know.
I am just going to finish up here in the last few minutes
going a little bit further back. We've considered prebiotic chemistry
on planet earth, on meteorites, which means in this solar system here,
but many of those organics that rain into the earth
from meteors and comets and so forth may have been synthesized in the accretion
disk that gave rise to our stellar system.
Or they may even have been inherited from the dense cloud from which our sun
and its planets condensed, or even from interstellar space,
possibly even from the circumstellar envelope of evolved stars
that contributed to the interstellar medium. Our ability to analyze that sort of thing
is clearly confined to remote sensing. We can't actually go and sample it.
Here is a picture in the plane of the galaxy, aimed in the general direction
of the constellation of Orion, which you can see in the sky.
There is Orion's belt; the sword's hanging down here.
This region right here, part of the sword, is actually a nebulosity,
a very active star-forming region. This whole thing is called the Orion Cloud
Complex; this is the Orion nebula, known since historical
times, it's Messier object 42.
Here's a beautiful Hubble Space Telescope image of that.
Stars are being born here; there are both dark [dense] molecular clouds and diffuse
ones all sorts of chemistry.
And our ability to analyze this to date has yielded already at least 120 compounds,
just from the interstellar medium alone, not including those other sorts of environments.
Most of these are detected by microwave spectroscopy, which sees bending motion in these molecules,
and you can infer what they are by looking at the spectrum.
We've been analyzing photons coming to planet earth
from the cosmos for a number of years now. We have telescopes in orbit
that cover basically the entire electromagnetic spectrum
from gamma rays through the visible out even into the radio
though most radio astronomy is done from the ground
because the telescopes have to be enormous since the wavelengths are long.
There's the Hubble space telescope that took that picture I just showed you;
it brackets the visible region. But the Herschel was sent up
by the European Space Agency specifically to look in the infrared
and microwave region of the spectrum to look at organic molecules in space
in all those environments that I just described. Here is a picture of it.
It actually lives out at Lagrange Point 2. There is the sun, the earth, the moon.
It's 1.5 million miles away from it [the earth]; it goes around the sun with the earth,
keeping up with it, cycling around that point in space;
it's a gravitational saddle. It's got three instruments on it,
and it's cooled by liquid helium -- colder than space is the way they advertise
it. It's about to run out;
it's lifetime ends at the end of March; they've got one more month of observing.
When it was first made operational in 2010, this spectrum was obtained, across here,
and superimposed on the place it was gotten from,
which is the Orion nebula. It's a spectacular spectrum with really sharp
lines. There's a lot of information here.
We can see some of our old friends: there's hydrogen cyanide, there's formaldehyde,
compounds which are important in the synthesis of the sort of biomolecules
we have been discussing. In 2012 was the first data release
from the HiFi instrument; that's the particular one of the three
that's designed to look for these organic molecules
in all of these stellar environments. And as I said, this is due to run out of its
helium and go blind sometime at the end of next month,
at which point they will have collected all of the data they are going to collect.
I am happy to report that everything has worked perfectly.
They have gotten all of the data and achieved all of the missions of the telescope.
And they have got to process the data now, and there are going to be many, many publications
-- this is a whole issue, 120-something publications, and we will see many more coming.
So I shall end with that, and with this quote from Alexander Oparin
-- his nice smile there. It's from the 1924 version of his book
The Origin of Life, translated from the Russian by Ann Synge,
in this book by J. D. Bernal, also called The Origin of Life.
This is the last four sentences of Oparin's 1924 essay.
"What we do not know today we shall know tomorrow.
A whole army of biologists is studying the structure and organization of living matter"
-- that's top down -- "while a no less number of physicists and
chemists are daily revealing to us new properties of
dead things" -- that's bottom up.
"Like two parties of workers boring from the two opposite ends of a tunnel,
they are working towards the same goal. The work has already gone a long way
and very, very soon the last barriers between the living and the dead
will crumble under the attack of patient work and powerful scientific thought."
Perhaps he was a little bit optimistic about the "very, very soon";
it's been 90 years [laughter], but then 90 years is just a blink in geologic
time.
"What we do not know today we shall know tomorrow."
On that optimistic note I end. I thank you very much for your attention,
and I would be happy to answer any questions that I can.