by Charles Baum
ously at hydrothermal vents, where the less acidic vent water contacts
the more acidic ocean water. These bubbles form primitive cell-like
structures that enclose metabolic chemicals. The bubbles also main-
tain a strong contrast of acidity between inside and outside—an ener-
getic difference that can promote metabolic reactions.
By contrast, Wächtershäuser advocates “flat life.” The first self-
replicating entity in his proposed Iron–Sulfur World was, as we saw in
Chapter 8, a thin layer of chemical reactants on a sulfide mineral sur-
face. The entity grew laterally, spreading from mineral grain to mineral
grain as an invisibly thin organic film. Bits of these layers could break
off and reattach to other rocks, like cloned colonies. Given time, differ-
ent minerals and environmental conditions might have induced varia-
tions in the film, fostering new “species” of flat life.
The bold, heretical concept of flat life—a self-replicating chemical
layer of molecules built on a solid mineral foundation—raises an in-
triguing geochemical possibility. A simple layered collection of mol-
ecules might be more tolerant of high temperatures and other
environmental extremes than life based on nucleic acids, which break
down close to 100°C. If so, then colonies of flat life might exist today in
deep zones of Earth’s crust. Such film-like molecular systems might
persist for eons, because they survive at extreme conditions beyond
the predation of more efficient cellular life.
If so, how would we know? Such a layer would be invisible under
an ordinary light microscope and would appear as a nondescript film
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GENESIS
using more powerful atomic microscopes. Flat life would also be unde-
tectable in standard biological assays, which rely on the presence of
DNA and proteins. Is it possible that layer life is abundant on Earth
today, yet remains overlooked?
There’s much to learn about the emergence of self-replicating
chemical systems. Whether they first formed as chainlike peptides or
films, self-replicating molecular systems appear to be a necessary ante-
cedent to life. Nevertheless, a self-replicating metabolism by itself is
not sufficient for life as we know it, and many scientists still argue that
genetics came first.
16
The RNA World
It is generally believed that there was a time in the early
history of life on Earth when RNA served as both the genetic
material and the agent of catalytic function.
Gerald Joyce, 1991
In spite of the elaborate detail of Wächtershäuser’s Iron–Sulfur
World, most origin experts dismiss the idea of a purely metabolic
life-form in favor of a genetics-first scenario. In order to repro-
duce, even the simplest known cell must pass volumes of information
from one generation to the next, and the only known way to store and
copy that much information is with a genetic molecule similar to DNA
or RNA.
No one has thought more deeply about genetics and the origins of
life than Leslie Orgel at the Salk Institute for Biological Studies in San
Diego. His classic 1968 paper, “Evolution of the genetic apparatus,” has
guided generations of researchers, and he continues to exert a tremen-
dous influence on origin theory and experiment. Orgel states that the
central dilemma in understanding a genetic origin of life is the identi-
fication of a stable, self-replicating genetic molecule—a polymer that
simultaneously carries the information to make copies of itself and
also catalyzes that replication. Accordingly, he catalogs four broad ap-
proaches to the problem of jump-starting such a genetic organism.
One possibility is the emergence of a self-replicating peptide of the
kind made by Reza Ghadiri’s group at Scripps, or perhaps a protenoid
as championed by Sidney Fox. The idea that proteins emerged first and
then “invented” DNA holds some appeal, because amino acids, the con-
stituents of proteins, are thought to have been available in the prebi-
otic environment. The problem is that the random prebiotic assembly
215
216
GENESIS
of amino acids would have been a messy business, as Fox’s critics were
quick to point out. Cells have learned how to form neat, chainlike poly-
mers—the proteins essential to life. But left to their own devices, amino
acids link together in irregular, undisciplined clusters—hardly the stuff
of genetics.
The second of Orgel’s possibilities, the simultaneous evolution of
proteins and DNA, seems even less likely, because it requires the emer-
gence of not one but two improbable macromolecules.
Graham Cairns-Smith’s Clay World scenario provides an intrigu-
ing third option, with genetic-like sequences of elements replicating
and acting as templates for organic assembly. So far, however, the Clay
World scenario is totally unsupported by experimental evidence.
The fourth and favored genetics-origin model of Orgel and many
followers is based on a nucleic-acid molecule such as RNA—a single-
stranded polymer that acts both as a carrier of information and as a
catalyst that promotes self-replication. Orgel proposed this model in
1968, long before any experimental evidence supported such a notion.
“I must confess to a strong, longstanding bias in favor of [this] expla-
nation,” he remarked recently. “It is, at the very least, the model that
can be studied most easily in the laboratory.”
How to choose? When evaluating various origin-of-life models,
scientists aren’t restricted to chemical experiments alone. The metabo-
lism-first models of Wächtershäuser, de Duve, and others are equally
influenced by top-down studies of molecular phylogeny, which point
to deeply embedded, primordial biochemical pathways. The principle
of continuity demands an unbroken path from ancient geochemisty to
modern biochemistry. Hence, the citric acid cycle that lies at the heart
of all modern metabolism becomes a prime target for studies of
protometabolism.
In like fashion, top-down studies of molecular genetics have ze-
roed in on RNA as the essential core molecule of ancient genetics.
THE RNA WORLD
Few events have electrified the origin-of-life community as much as
the early 1980s discovery of RNA ribozymes—strands of RNA that not
only carry genetic information, but also act as catalysts. Sidney Altman
of Yale and Thomas Cech of the University of Colorado independently
demonstrated that a particular segment of RNA can accelerate key bio-
THE RNA WORLD
217
chemical reactions. This startling finding, which won Altman and Cech
the Nobel Prize in 1989, inspired a new vision of life’s origin.
Modern life relies on two complexly interrelated molecules: DNA,
which carries information, and proteins, which perform chemical
functions. This interdependence leads to a kind of chicken-and-egg
dilemma: Proteins make and maintain DNA, but DNA carries the in-
stru
ctions to make proteins. Which came first? RNA, it turns out, has
the potential to do both jobs
The RNA World theory quickly emerged following the discovery
of ribozymes. It champions the central role of genetic material in the
dual tasks of catalyst and information transfer. Over the years, “RNA
World” has come to mean different things to different people, but three
precepts are common to all versions of the theory: (1) Once upon a
time, RNA rather than DNA stored genetic information; (2) ancient
RNA replication followed the same rules as modern DNA replication
by matching pairs of bases: A-U (the pyrimidine uracil, whose DNA
equivalent is thymine) and C-G; and (3) ancient RNA played the same
catalytic roles as modern protein enzymes. In this scenario, the first
life-form was simply a self-replicating strand of RNA, perhaps enclosed
in a protective lipid membrane. According to most versions of this hy-
pothesis, modern metabolism emerged later, as a means to make RNA
replication more efficient.
Two factors may have contributed to the speed with which the
RNA World idea caught on. For one thing, a generation after the
Miller–Urey experiment, there were still few solid clues about how to
make the transition from the prebiotic soup to cellular life. The origin-
of-life community was poised to try something new, and RNA pro-
vided a compelling original angle, rich in experimental possibilities. In
addition, evidence of the dual role of RNA, as both catalyst and carrier,
proved seductive to the new generation of biologists, who were born
and raised in the age of molecular genetics. To many researchers, life
and genetics are synonymous, so the RNA World idea resonates deeply.
The more that biologists learn about RNA, the more remarkably
versatile it seems. One big surprise came from the study of ribosomes,
lumpy cellular structures that help to assemble proteins. Ribosomes
consist of a complex intergrowth of proteins and several RNA strands.
Many biologists assumed that the proteins play their usual active role
as the enzymes that do the actual assembly work, while RNA merely
holds the ribosomes together. However, recent studies prove just the
218
GENESIS
opposite—that RNA mediates the critical step of linking up the
protein’s constituent amino acids. In essence, RNA does the heavy lift-
ing in protein assembly—a discovery that strongly reinforces RNA’s
presumed ancient role in biochemistry.
RNA’s probable antiquity is underscored by a growing list of other
biochemical studies. For example, RNA nucleotides play key structural
roles in a variety of essential biological catalysts called coenzymes.
These versatile catalysts promote vital reactions at the very heart of the
citric acid cycle (the difficult synthesis of citrate from oxaloacetate, for
instance). Coenzymes also mediate the manufacture of lipids and other
essential biomolecules. And recently, scientists at Yale discovered
“riboswitches”—remarkable segments of RNA that change shape when
they bind to specific molecules in the cell. These chemical sensors then
regulate the cell’s chemistry by turning genes on and off.
The inevitable conclusion: RNA is a very ancient molecule that
seems to “do it all.”
CAVEATS
Today, every origin-of-life meeting features sessions dedicated to RNA
World studies. A thousand articles amplify the idea, and hundreds of
researchers have pursued variations on the theme. There can be little
doubt that the emergence of RNA represents a crucial step in life’s ori-
gin. However, decades of frustrating chemical experiments have dem-
onstrated that the RNA World could not possibly have emerged fully
formed from the primordial soup. There must have been some critical
transition stage that bridged the prebiotic milieu and the RNA World.
I am persuaded by those who argue that a self-replicating meta-
bolic system must have emerged first, followed by some form of ge-
netic molecule that was both structurally simpler and chemically more
stable than RNA. Only much later did the mechanisms of RNA genet-
ics and ribozymes come into play. Here are some reasons:
1. Metabolism, which in its earliest stages uses rather simple
molecules in the C–O–H (and maybe S) chemical system, seems vastly
easier to jump-start than genetics. By contrast, the RNA World sce-
nario relies on exact sequences of chemically complex nucleotides in
the C–O–H–N–P system. Accordingly, modern cells synthesize nucleic
acids through metabolism, but RNA synthesis is several steps removed
THE RNA WORLD
219
from the core metabolic cycle, the citric acid cycle. This layering of a
simple core metabolism surrounded by successively more complex lay-
ers of synthesis suggests that metabolism came first and other chemi-
cal pathways were added later.
2. Many of the presumed protometabolic molecules are synthe-
sized with relative ease in experiments that mimic prebiotic environ-
ments, à la Miller–Urey. RNA nucleotides, by contrast, have never been
synthesized from scratch, in spite of decades of focused effort.
3. Even if a prebiotic synthetic pathway to nucleotides could be
found, a plausible mechanism to link those individual nucleotides end-
to-end into an RNA strand has not been demonstrated. So it’s not ob-
vious how catalytic RNA sequences would have formed spontaneously
in any prebiotic environment.
Sometimes you have to place your bets and put your cards on the
table. I view the RNA World as a critical, but relatively late, transitional
stage that occurred when life was well established on Earth—well after
the emergence of a stable, evolving metabolic world, and before the
modern DNA-protein world. Biologists seem reasonably confident that
the last stages of this evolution—the transition from the RNA World
to a DNA-protein genetic system—can be understood. Top-down stud-
ies of modern life-forms and the genetic code provide abundant clues
about that process.
The greater mystery lies in the seemingly intractable gap between
primitive metabolism and RNA. Before we can contemplate the RNA
World, therefore, we have to address the pre-RNA World. By what
chemical process did the first information-bearing system emerge?
17
The Pre-RNA World
I’ve been waiting all my life for an idea like this.
Simon Nicholas Platts, 2004
What preceded the RNA World? We understand a lot about the
possible earliest stages of life’s emergence—how to make the
prebiotic soup with all sorts of interesting molecules and how to as-
semble those molecules into a variety of larger useful structures. At the
other end of the story, we have a good handle on how strands of RNA
might function as evolving, self-replicating systems (as we’ll see in the
next chapter). But there’s that maddening gap between the primordial
soup and the RNA World. Stanley Miller sums up the problem: “Iden-
tifying the first gene
tic material will provide the key to understanding
the origin of life. RNA is an unlikely candidate.”
To be sure, there have been numerous creative attempts to close
this gap. Several researchers have approached the problem by propos-
ing simpler types of precursor genetic polymers that might have arisen
before RNA. In a tour de force research program, the Swiss chemist
Albert Eschenmoser explored the stabilities of more than a dozen vari-
ants of RNA with modified sugar-phosphate backbones. He systemati-
cally replaced the 5-carbon sugar ribose with various other 4-, 5- and
6-carbon sugars and discovered seven new kinds of stable nucleic-acid-
like structures. Most significant was the discovery by Eschenmoser and
colleagues of a nucleic acid with the 4-carbon sugar threose (the mol-
ecule was dubbed TNA). Unlike ribose, which must be synthesized
through a rather cumbersome sequence of chemical steps, threose can
be assembled directly from a pair of 2-carbon molecules. This differ-
ence makes TNA a much more likely molecule than RNA to arise spon-
taneously from the prebiotic soup.
221
222
GENESIS
Other scientists took a different chemical tack. In 1991, the Danish
chemist Peter Nielsen and colleagues synthesized a novel genetic mol-
ecule—a “peptide nucleic acid” (PNA), which features RNA-like bases
bound to a backbone of amino acid molecules. The reliance on readily
available amino acids, rather than problematic sugar phosphates for
the polymer backbone, appealed to many members of the origins com-
munity. The discovery of PNA also underscored the chemical richness
of plausible genetic molecules.
These immensely creative efforts expand the repertoire of prebi-
otic possibilities. They also hold the promise of providing new kinds of
synthetic genetic molecules that can interact with modern cells yet not
interfere with cellular function—a potential boon to medical research.
Nevertheless, no one has managed to achieve a plausible prebiotic syn-
thesis of these alternative nucleotides, much less a viable genetic poly-
mer. The door is wide open for new ideas.
THE PAH WORLD
***WARNING: The following section presents an intriguing hy-
pothesis, but one that is highly speculative and as yet untested. Such