H00102--00A, Front mat Genesis
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pleteness in the integration of the solid, liquid, and gaseous parts of
our planet to make life. Nevertheless, I find the reliance on clays a bit
unsettling. It seems that all a chemist needs to do is sprinkle in a little
clay powder and voilà: polymerization, self-assembly, synthesis, stabili-
zation! Clays seem to do it all. The phenomenology is fascinating, but
what’s actually going on at the atomic scale? Clays are inherently vari-
able in their composition, ill-defined in their surface properties, and so
fine-grained that it’s virtually impossible to be sure what molecule is
binding to what surface. The “magic powder” aspects of clays leave me
frustrated.
Given the choice between a poorly characterized fine-grained pow-
der and an elegant faceted single crystal, I’ll take the crystal any day.
And, as it turns out, that’s the only way you can tell left from right.
13
Left and Right
Assemblage on corresponding crystal faces of enantiomorphic
pairs of crystals, such as right-hand and left-hand quartz
crystals, would provide us with a most simple and direct
possibility of localized separate assemblage of right- and
left-hand asymmetric molecules.
Victor M. Goldschmidt, 1952
Prebiotic processes produced a bewildering diversity of molecules.
Some of those organic molecules were poised to serve as the essen-
tial starting materials of life—amino acids, sugars, lipids, and more.
But most of that molecular jumble played no role whatsoever in the
dawn of life. The emergence of concentrated suites of just the right
mix remains a central puzzle in origin-of-life research.
One of the stages of life’s emergence—an early and confounding
one at that—must have been the incorporation of handedness. Many
of the most important biomolecules, amino acids and sugars included,
come in mirror-image pairs: something like your two hands, which
have the exact same structure, but can’t be exactly superimposed. In
the same way, pairs of these so-called chiral molecules have the exact
same composition and structure, and many of the same physical prop-
erties, but they are mirror images of each other.
Virtually all known prebiotic synthesis pathways produce chiral
molecules in 50:50 mixtures. No obvious inherent reason exists why
left or right should be preferred. And yet living cells display the most
exquisite selectivity, choosing right-handed sugars over left and left-
handed amino acids over right. In spite of a century and a half of study,
the origin of this biochemical “homochirality” remains a central mys-
tery of life’s emergence.
167
168
GENESIS
THE HANDEDNESS OF LIFE
Molecular chirality arises from a common circumstance of organic
molecules. In many molecules, one carbon atom forms four bonds to
four different groups of atoms. The amino acid alanine, for example,
has a central carbon atom linked to one NH molecule (an amino
2
group), one COOH molecule (a carboxyl group), one CH molecule (a
3
methyl group), and one lone hydrogen atom. If you orient the hydro-
gen atom up and look down on the molecule, there are two ways to
arrange the remaining three components . So-called “right-handed” or
D-alanine has a clockwise arrangement of carboxyl–amine–methyl
groups. Chemists employ the letter “D” after the Greek “dextro” for
“right” (though the designation of molecular “right” vs. “left” is a com-
pletely arbitrary convention.) Alternatively, “left-handed” or L-alanine
features a clockwise arrangement of amine–carboxyl–methyl groups.
In this case the “L” comes from the Greek “levo,” for “left.”
For reasons that are still not well understood, life selects L-amino
acids and D-sugars almost exclusively over D-amino acids and L-sugars.
One critical consequence of this selection is that our cells often re-
spond very differently to other kinds of chiral molecules. The familiar
flavoring limonene, for example, tastes like lemons in its right-handed
form, but like oranges in the left-handed variant. More sinister is the
behavior of the infamous drug thalidomide: The left-handed form
cures morning sickness, while the right-handed form induces birth
defects. Consequently, the Food and Drug Administration demands
1
1
C
4
4
C
2
2
3
3
Many biomolecules occur in both left-handed and right-handed variants, which are
mirror images of each other. This situation arises when a central carbon atom is
linked to four different groups of atoms—groups that can be arranged clockwise or
counterclockwise.
LEFT AND RIGHT
169
chiral purity in many pharmaceuticals—a difficult processing step that
adds more than $100 billion annually to our drug costs.
Chirality is an essential, diagnostic characteristic of cellular life.
But how did this selectivity emerge in the seemingly random prebiotic
world? A dozen theories, from the mundane to the exotic, have been
proposed, but all ideas fall into one of two general categories.
Some experts suspect that prebiotic synthesis was an inherently
asymmetrical process, leading to an inevitable global excess of L- over
D-amino acids on the prebiotic Earth. More than a century and a half
ago, Louis Pasteur demonstrated that left- and right-handed crystals
cause polarized light to be rotated in opposite directions. Conversely,
the orientation of polarized light shining on a chemical-rich environ-
ment might influence the relative proportions of left- versus right-
handed molecules, either by selective synthesis of L-amino acids, or by
selective breakdown of D-amino acids. Though the effect is generally
small, this kind of chiral-selective process might conceivably have oc-
curred in deep space near a rapidly rotating neutron star, or perhaps
on Earth’s surface as the result of polarized sunlight reflected off the
ocean surface. No one knows for sure what hundreds of millions of
years of such processing might yield.
Other physicists echo this theme, but posit that asymmetric syn-
thesis resulted from so-called parity violations that occur during ra-
dioactive beta decay. In physics, the parity principle states that physical
processes appear exactly the same when viewed in a mirror. Beta decay,
which occurs when an unstable radioactive atom loses an electron (or
a positron) in the process of becoming a stable atom, is the only known
physical event that violates this parity principle. Beta-decay events pro-
duce polarized radiation of only one handedness, and this chiral radia-
tion, in turn, could have enhanced the synthesis of L- versus D-amino
acids. One problem with these asymmetric processes is that they seem
to yield only the slightest excess of one handedness over the other—
generally less than a minuscule fraction of 1 percent. Such minute ef-
fects hardly seem sufficient to tip the global balance toward L-amino
acids or D-sugars.
LOCAL SYMMETRY BREAKING
Many origin-of-life researchers (myself included) argue that chiral se-
lectivity more likely occurred as the result of an asymmetric local, as
170
GENESIS
opposed to global, physical environment on Earth. After all, the emer-
gence of life consisted of a series of chemical events, each of which
occurred at a specific place and a specific time. It is very possible that
those emergent steps were repeated countless millions of times across
the globe, but each individual emergent event was local: It occurred at
specific location with specific molecules. Consequently, if the local en-
vironment where a reaction occurred was strongly chiral, then chiral
molecules might have emerged.
The chemical process of life’s origin is in some respects like the
formation of a crystal. In life, as in crystals, two essential and largely
independent steps are necessary. The first step in crystal formation,
nucleation, requires the precise organization of a relatively small num-
ber of atoms or molecules into a “seed.” This seed might by chance
have either a D or L character. Then comes growth, as the original seed
provides a template for the ordered assembly of more atoms and mol-
ecules. Each step in the chemical origin of life must also have required
nucleation, followed by growth.
In life, as in crystal formation, these two stages usually proceed at
very different rates. Nucleation may take place with ease, while growth
is slow. Such a situation leads to the myriad microscopic crystallites
that give colorful agates and frosted glass their distinctive translucent
optical properties. If, on the other hand, nucleation is rare while growth
is rapid, then a single large crystal may form.
Since life is vastly more complex than any crystal, it is reasonable
to think that nucleation—the self-organization of molecules into a rep-
licating entity—is relatively rare, perhaps even a singular event in
Earth’s history (though that is by no means a certainty). But, once
formed, this protolife must have grown rapidly, in the process con-
suming every available molecular feedstock and frustrating further ori-
gin events. If that life-form was by chance homochiral, D or L, then that
handedness would be passed on to subsequent generations. All it takes
is an initial local chiral environment.
We now realize that such local environments abounded on the pre-
biotic Earth. Indeed, every chiral molecule is itself a tiny local chiral
environment that might select other molecules of similar handedness.
The pioneering chirality studies of Louis Pasteur relied on this charac-
teristic: When he evaporated a 50:50 solution of D- and L-tartaric acid,
the mixture spontaneously divided into pure D and pure L crystals. Such
LEFT AND RIGHT
171
a circumstance arises because D-D or L-L pairs of tartaric acid mol-
ecules happen to fit together more easily than D-L pairs.
Might prebiotic organic molecules have displayed the same behav-
ior? Evidence is still spotty, but a few experiments do reveal a strong
tendency for chiral self-selection in certain polymers. The Swiss chem-
ist Albert Eschenmoser, who explored the stabilities of more than a
dozen variants of RNA with modified sugar-phosphate backbones, has
found that some (but not all) of these molecular chains grow sponta-
neously with greater than 90 percent chiral purity. Perhaps prebiotic
polymers became homochiral by a similar self-selection process.
One caveat: In a dilute, complex primordial broth, the chances of
linking together any two types of molecule, much less two useful
monomers of the same handedness, would have been exceedingly
small. That’s why James Ferris, Leslie Orgel, Graham Cairns-Smith, and
others have resorted to mineral surfaces, which induce polymerization
by concentrating and aligning desirable molecules. But some mineral
surfaces have an added advantage. Every rock, every grain of sand or
particle of silt also has the potential to offer chiral environments, in the
form of asymmetric mineral surfaces. Left- and right-handed mineral
surfaces might provide the perfect solution for concentrating and sepa-
rating a 50:50 mixture of L and D molecules.
Minerals often display beautiful crystal faces, which might have
provided ideal templates for the assembly of life’s molecules. A few
minerals, most notably quartz (the commonest grains of beach sand),
occur in both right-handed and left-handed structural variants. The
quartz structure features helices of atoms that in some crystals spiral
to the left and in other crystals to the right. Every grain of beach sand
thus provides a chiral environment.
But even though the vast majority of minerals are “centrosymmet-
ric,” and thus not inherently handed, their crystals commonly feature
pairs of faces whose surface structures are mirror images of each other.
Like quartz, these chiral surfaces have arrangements of atoms that are
ideally suited to select and concentrate L versus D molecules, such as
amino acids or sugars.
Natural left- and right-handed surfaces occur in roughly equal
numbers, so there’s not much chance of chiral selection occurring on a
global scale. But, once again, here’s the key: The chemical origin of life
was not a global event. The first common ancestor—the precursor to
172
GENESIS
Left
Right
The common mineral quartz forms both left-handed and right-handed crystals.
all of the varied life-forms we see on Earth today—arose as a bundle of
self-replicating chemicals at a specific place and time. Once that chiral
system began making copies of itself, the handedness of life was fixed.
To many experts in the field, the choice of L- versus D-amino acids
seems to have been a one-time, chance event, and that scenario points
to a simple mineralogical mechanism for chiral selection.
CHIRAL MINERAL SURFACES
As a mineralogist for more than a quarter of a century, I love the idea
that crystals may have played a central role in life’s beginnings. For a
time, the question of origins took me away from minerals, but they
have called me back to some of the most delightful experiments of my
career.
The chirality problem represents a particularly puzzling aspect of
the more general question of molecular selection, but it’s also an as-
LEFT AND RIGHT
173
pect that can be studied with well-controlled experiments. We know
that prebiotic synthesis processes yield huge numbers of different mol-
ecules, of which life uses relatively few. It would be impossible to study
that full range of prebiotic products in one experiment. But using pairs
of chiral molecules makes things a lot easier: Because all known prebi-
otic syntheses result in equal amounts of left- and right-handed mol-
ecules, it’s relatively easy to design an exp
eriment that starts with a
50:50 mix and looks for environments that separate left from right. If
we can discover the processes by which handed molecules were se-
lected and concentrated, then there’s hope that we can solve the more
general selection problem as well.
For most of the twentieth century, scientists have recognized the
power of minerals to select molecules—processes in which one kind of
molecule sticks more strongly to a surface than another. If two mol-
ecules differ significantly in size and shape, then such selection is easy
to comprehend; it’s just a matter of which molecule fits best. But selec-
tion between two mirror-image molecules is more difficult. Such pairs
of molecules are chemically identical, so each type of molecule forms
exactly the same kinds of bonds with the mineral surface. The only
way for chiral selection to occur is for the molecule to form three sepa-
rate points of attachment, and those three bonds can’t be in a straight
line. You’ve experienced this kind of selection process if you’ve ever
gone bowling. The ball has three holes, for your thumb and second
and third fingers. A left-handed bowler can’t use a right-handed ball
and vice versa, because the three holes aren’t in a line.
By the 1930s, scientists in Greece and in Japan had applied these
ideas and tried separating left- and right-handed molecules by pour-
ing D- and L-solutions over left- or right-handed quartz. During the
next half-century, a dozen similar experiments were attempted. The
basic idea was sound: Different-handed molecules do have the poten-
tial to stick selectively to different-handed surfaces. Nevertheless, these
early experiments were flawed. In an effort to maximize the surface
area of interaction, and thus the magnitude of the desired effect, the
scientists ground their beautiful quartz crystals into fine powder. Pow-
dering increases the surface area of a peanut-sized crystal a thousand
times or more, but it destroys the flat crystal surfaces that might pro-
mote selection. A powder displays every possible crystal surface si-
multaneously. Some of these surfaces may very well select L-amino
acids with great efficiency, but surfaces with a different exposed atomic
174
GENESIS
structure might just as likely select D-amino acids. Even if an experi-