by Charles Baum
sides had been coated with the target molecule. After sitting for a few
minutes, the vast majority of RNA chains had done nothing, but a few
RNA strands, by chance, were able to grab onto the target molecule
and thus remained firmly attached to the beaker. When they flushed
the RNA solution out of the beaker, those relatively few RNA sequences
that bonded to the target molecule remained behind.
At first, only the tiniest fraction of the random RNA sequences
attached to the target, but Szostak’s team collected those precocious
strands and made trillions of approximate copies—similar sequences
but with lots of random mutations thrown in. Then they repeated the
experiment and picked out a second generation of RNA sequences that
did the job better than those from the first. Again and again, they cycled
the RNA, each time copying the best sequences and thus improving
the speed and accuracy with which the RNA latched onto the glass-
bound target molecules. After several dozen cycles, the surviving RNA
strands had evolved to the point where they were perfectly adapted to
the assigned task. This elegant evolutionary process has now been ex-
tended to the design of numerous new RNA sequences with a wide
range of specialized functions, from locking onto viruses to splicing
DNA.
With their new procedures, Jack Szostak and his colleagues have
turned their attention to self-replicating RNA. In 2001, David Bartel, a
former Szostak graduate student now at MIT and the Whitehead Insti-
tute, managed to produce an impressive RNA sequence that can grab
onto a shorter piece of RNA up to 14 letters long and copy it. Optimis-
tic researchers are convinced that it’s only a matter of time before self-
replicating RNA strands more than a hundred letters long will be
commonplace. If so, then synthetic life may not be far behind.
SYNTHETIC LIFE
Self-replicating RNA is not alive, but it’s getting closer. It’s a big mol-
ecule that carries genetic information, catalyzes its own reproduction,
and mutates and evolves to boot. But no plausible geochemical envi-
ronment could feed such an unbound molecule, nor would it have
survived long under most natural chemical conditions.
One key to survival is protection, and that’s where a lipid mem-
THE EMERGENCE OF COMPETITION
239
brane comes in. Building on David Deamer’s discoveries, Szostak
protégés Martin Hanczyc and Shelley Fujikawa have experimented with
ways that membranes might have encapsulated RNA strands. Among
their findings: Lipid vesicles that are squeezed through tiny pores
stretch out, divide, and start to grow larger—a process that mimics cell
division. What’s more, the process is greatly accelerated by the addi-
tion of fine-grained clay minerals, some of which end up inside the
vesicles. Recall that Jim Ferris at RPI demonstrated that clays can at-
tract and help to assemble RNA strands. So, in the spirit of Pier Luigi
Luisi’s Lipid World, it might be possible to make cell-like structures
that spontaneously incorporate RNA-bound clay particles.
This behavior of lipids and RNA has led Szostak and his students
to propose a remarkable scenario for the first life-form to evolve by
natural selection. Imagine a lipid vesicle that contains self-replicating
RNA. Previous authorities have suggested that RNA must have played
many roles in such a protocell (roles that DNA and proteins play to-
day)—manufacturing new membrane molecules, controlling cell
shape and size, copying itself, and more.
Szostak’s team realized that RNA could drive cell growth by the
much simpler process of internal pressure. RNA pushes out on the
membrane, which in turn presses on neighboring protocells. They
speculated that this contact would promote the transfer of lipids from
cells with less internal pressure (hence, less RNA) to those with more.
Thus the competition for space would lead to a natural-selection pro-
cess. Protocells with more RNA would be more successful.
To test their ideas, they first prepared one set of vesicles filled with
a solution of the sugar sucrose and another set filled with pure water.
When mixed together and confined, the sucrose-ladened vesicles grew
larger by drawing lipids from their sugarless neighbors. Repeating the
experiment with RNA strands yielded the same results. Vesicles swol-
len with RNA grew, as the adjacent empty vesicles shrank.
Previous workers had assumed that RNA would have to learn how
to accomplish several tasks—lipid synthesis, self-replication, metabolic
functions, and more—before a protocell could evolve by natural se-
lection. Szostak’s latest results suggest a much simpler scenario, in
which the only essential task for protocell competition is RNA self-
replication. “If we can get self-replicating RNAs,” Szostak suggests,
“then we can put them into these simple membrane compartments
and hope to actually see this competitive process of growth.” The more
240
GENESIS
RNA a vesicle captures and copies, the more successfully it will com-
pete with its neighbors—a sort of molecular the-rich-get-richer
scheme. In such a world, the most efficient RNA replicators would
enjoy a tremendous advantage. With the emergence of competition,
Darwinian evolution could take center stage.
Every year, Jack Szostak moves closer to his goal of creating a self-repli-
cating, encapsulated, evolving chemical system in the lab. If and when
he or his successors accomplish this, it will be a historic achievement.
Synthetic life will also trigger a new flood of ethical questions about
the potential dangers of scientific research, as well as philosophical
questions about the meaning of life. But will synthetic life tell us how
life emerged on Earth?
A synthetic RNA organism will certainly give credibility to the
RNA World hypothesis that a strand of RNA (or some precursor ge-
netic molecule) formed the basis of the first evolving, self-replicating
chemical system. But laboratory-created life will not have emerged
spontaneously from chemical reactions among the simple molecular
building blocks of the prebiotic Earth. Researchers still stack the deck
by supplying a steady source of RNA nucleotides and vesicle-forming
lipids. And so, for the time being, deep mysteries remain.
19
Three Scenarios for the Origin of Life
Anyone who tells you that he or she knows how life started on
the sere Earth some 3.45 billion years ago is a fool or a knave.
Stuart Kauffman, At Home in the Universe, 1995
What do we know for certain? Scientists have learned that abun-
dant organic molecules must have been synthesized, and must
have accumulated, in a host of prebiotic environments. They have also
demonstrated many processes by which biomolecular systems—in-
cluding lipid membranes and genetic polymers—might have formed
on mineral surfaces. As molecular complexity increased, it seems plau-
sible that simple metabolic cycles of self-replic
ating molecules
emerged, as did self-replicating genetic molecules.
So we’ve learned a lot, but what we know about the origin of life is
dwarfed by what we don’t know. It’s as if we were trying to assemble a
giant jigsaw puzzle. A few pieces clump together here and there, but
most of the pieces are missing and we don’t even have the box to see
what the complete picture is supposed to look like.
The greatest mystery of life’s origin lies in the unknown transition
from a more-or-less static geochemical world with lots of interesting
organic molecules to an evolving biochemical world in which collec-
tions of molecules self-replicate, compete, and thereby evolve. How
that transition occurred seems to boil down to a choice among three
possible scenarios.
1. Life began with metabolism, and genetic molecules were incor-
porated later: Following Günter Wächtershäuser’s hypothesis, life be-
gan autotrophically. Life’s first building blocks were the simplest of
molecules, while minerals provided chemical energy. In this scenario, a
241
242
GENESIS
self-replicating chemical cycle akin to the reverse citric acid cycle be-
came established on a mineral surface (perhaps coated with a protec-
tive lipid layer). All subsequent chemical complexities, including
genetic mechanisms and encapsulation into a cell-like structure,
emerged through natural selection, as variants of the cycle competed
for resources and the system became more efficient and more com-
plex. In this version, life first emerged as an evolving chemical coating
on rocks.
The true test of this origin scenario rests on chemical synthesis
experiments. Starting with simple molecules and common minerals
subjected to plausible prebiotic conditions, researchers must discover
a way to jump-start a self-replicating cycle of molecules that mimics
the core citric acid metabolism of modern life-forms. We’re close, and
several of the essential steps have been accomplished. A key missing
experiment is the synthesis of 4-carbon oxaloacetate from 3-carbon
pyruvate, perhaps using sulfur analogs in an environment rich in hy-
drogen sulfide. If that step can be demonstrated, and a self-sustaining
cycle of reactions maintained, then metabolism-first will be the model
to beat.
2.
Life began with self-replicating genetic molecules, and metabo-
lism was incorporated later: According to the RNA World hypothesis, life began heterotrophically and relied on an abundance of molecules
already present in the environment. Organic molecules in the prebi-
otic soup, perhaps aided by clays or PAHs or some other template, self-
organized into information-rich polymers. Eventually, one of these
polymers (possibly surrounded by a lipid membrane) acquired the
ability to self-replicate. All subsequent chemical complexities, includ-
ing metabolic cycles, arose through natural selection, as variants of the
genetic polymer became more efficient at self-replication. In this ver-
sion, life first emerged as an evolving polymer with a functional ge-
netic sequence.
This scenario, with its appealing reliance on the multiple ancient
roles of RNA, lacks only the crucial support of an experiment that dem-
onstrates the plausible prebiotic synthesis of a genetic polymer—RNA
or its precursor. If an experiment successfully demonstrates the facile
synthesis of such a polymer from prebiotic building blocks, then the
biggest gap in our understanding of life’s origin will have been filled.
In that case, many experts will conclude that the problem of life’s
chemical origin has been solved.
THREE SCENARIOS FOR THE ORIGIN OF LIFE
243
3. Life began as a cooperative chemical phenomenon arising be-
tween metabolism and genetics: A third scenario rests on the possibility
that neither protometabolic cycles (which lack the means of faithful
self-replication) nor protogenetic molecules (which are not very stable
and lack a reliable source of chemical energy) could have progressed
far by themselves. If, however, a crudely self-replicating genetic mol-
ecule became attached to a crudely functioning surface-bound meta-
bolic coating, then a kind of cooperative chemistry might have kicked
in. The genetic molecule might have used chemical energy produced
by metabolites to make copies of itself, while protecting itself by bind-
ing to the surface. Any subsequent variations of the genetic molecules
that fortuitously offered protection for themselves or for the metabo-
lites, or improved the chemical efficiency of the system, would have
been preserved preferentially. Gradually, both the genetic and meta-
bolic components would have become more efficient and more inter-
dependent.
Such a “dual origins” model might at first seem to introduce a
needless complication (not to mention sounding like a wishy-washy
compromise). Nevertheless, exactly this kind of symbiotic coupling of
metabolism and genetics is now thought to have occurred early in the
history of cellular life. Crucial features of our own cells suggest an an-
cient cooperative merging of early, more primitive cells. If experiments
establish easy synthetic pathways to both a simple metabolic cycle and
to an RNA-like genetic polymer, then such a symbiosis may provide
the most attractive origin scenario of all.
We don’t yet know the answer, but we’re poised to find out. Each day,
new experiments expose more of the truth and winnow the possibili-
ties. Each day, we get closer to understanding. And whatever the cor-
rect scenario, of one thing we can be sure: Ultimately, competition
began to drive the emergence of ever more elaborate chemical cycles
by the process of natural selection. Inexorably, life emerged, never to
relinquish its foothold on Earth.
Epilogue
The Journey Ahead
Once to every man and nation comes the moment to decide,
In the strife of truth with falsehood, for the good or evil side;
Some great cause, some new decision, offering each the bloom or blight,
And the choice goes by forever ’twixt that darkness and that light.
James Russell Lowell, 1845
The theory of emergence points to a gradual, inexorable evolution
of the cosmos, from atoms to galaxies to planets to life. Each emer-
gent step arises from the interactions of numerous agents and yields an
outcome much greater than the sum of its parts. Each emergent step
increases the degree of order and complexity, and each step follows
logically, sequentially from its predecessor.
We recognize this majestic progression only in hindsight. Emer-
gent phenomena remain elusive—exceedingly difficult to predict from
observations of earlier stages. Given hydrogen atoms, a tremendous
conceptual leap is required to predict the brilliance of stars or the
variety of planets. Given planets, no theoretician alive could predict
the emergence of cellular life in all its diversity—nor, given cellular
life, could anyone forese
e the emergence of consciousness and self-
awareness. The inherent novelty and layered complexity of emergent
phenomena all but preclude prediction.
We are left, then, to ponder the possible existence of higher orders
of emergence—stages of complexity that our brains can no more com-
prehend than a single neuron can comprehend the collective state of
consciousness. Does the universe hold levels of emergence beyond in-
dividual consciousness, beyond the collective accomplishments of hu-
man societies? Might the cooperative awareness of billions of humans
ultimately give rise to new collective phenomena as yet unimagined? If
245
246
GENESIS
higher stages of emergence await our discovery, then science and the-
ology may someday converge into a more unified vision of the cosmos
and our place in it.
As we search beyond the cookbook “how” of life to questions of
meaning and value, the concept of emergence holds a powerful mes-
sage. Each of our lives is shaped by the same two competing powers of
creation and destruction that have held sway throughout the history of
the cosmos: emergence and entropy. The second law of thermodynam-
ics states that entropy—the disorder of the universe—must increase.
Yet in discrete, precious pockets of matter—on planets, in oceans,
within our own conscious brains—astonishing levels of emergent com-
plexity arise spontaneously.
This dramatic contrast provides a metaphor for our own lives.
Some people choose the paths of hate, war, intolerance, destruction,
and chaos to hasten the triumph of entropy—the dark side of the uni-
verse. By contrast, most people use their energies to foster emergence—
to build cities, feed the hungry, create art, heal the sick, promote peace,
and add to human joy and well-being in countless other ways, both
large and small.
What awesome power each of us holds to do good or ill; a single
cutting insult, a single winning smile. Perhaps therein lies life’s mean-
ing and value.
Notes
PREFACE
p. xiii
It is possible: A significant literature explores the contrasting
views of life as a chance event (Monod 1971) versus a cosmic imperative (de Duve 1995a, Morowitz 2002).