by Charles Baum
THE PRE-RNA WORLD
231
ecules, such as adenine and guanine (the A and G of the RNA alphabet
to the system and see if the PAHs bond to them. Finally—and we all
knew that this would be a long shot—add a molecule that might serve
as a backbone, such as formaldehyde, and see if the bases would link
together into a long sequence reminiscent of a genetic polymer.
The experimental protocols looked good on paper, but there were
problems from the start. Pure PAHs (as opposed to random sooty mix-
tures) turn out to be almost impossible to find commercially, and when
you do, they’re impossibly expensive. Nick located one European sup-
plier who would sell us tiny amounts of HBC for a thousand dollars—
the equivalent of more than a million dollars for ten grams! That clearly
wasn’t going to work.
Nick contacted other labs in Europe and Japan, hoping for a com-
plimentary supply, but tracking one down might take weeks or
months. Meanwhile, he manufactured some PAHs of his own by burn-
ing acetylene in air and catching the sooty residues in one of my more
expensive glass beakers. Gradually, the soot, which is a mixture of hun-
dreds of different PAHs ranging in size from a few rings to hundreds,
piled up.
I offered to try another angle: purifying PAHs from soot by TLC—
the thin-layer chromatography technique I had learned in Dave
Deamer’s lab (see Chapter 11). Nick agreed, and we ordered a supply
of trichlorobenzene, one of the solvents of choice when working with
PAHs.
Nick had other concerns besides experiments. He was still deter-
mined to publish his idea, so he prepared a new version of the short
paper and submitted it to Science on Thursday, July 15th.
Lots of people at Carnegie had been aware of the PAH World buzz
and wanted to hear from Nick first hand. He presented an informal
talk to the Carnegie campus on Friday afternoon July 2nd and again
for a NASA Astrobiology Institute video seminar on Monday, July 12th.
Each talk provided an opportunity to hone his arguments and to field
a new round of questions and comments from origins experts across
the spectrum.
His thesis defense also loomed large. Scrambling to write up an
expanded description of his hypothesis and assemble whatever sup-
port he could from the published literature, Nick cobbled together a
doctoral dissertation and headed back up to Troy for a July 20th de-
fense. We all wondered whether he could pull it off. As it turned out,
232
GENESIS
his thesis committee, chaired by chemistry professor Gerry
Korenowski, was more than a little impressed by Nick’s elegant vision.
In five years of graduate work he had demonstrated his depth of chemi-
cal understanding and intuition. The PAH World hypothesis estab-
lished beyond doubt that he had earned the right to be called “Doctor
Platts.” They granted Nick an extra week to polish up his prose, and on
July 27th he successfully defended what has to be one of the most un-
usual chemistry theses in RPI’s history.
MOVING ON
Having his doctorate in hand was a tremendous relief, but Nick’s prob-
lems weren’t over. His visa was about to run out unless he could find a
science job in the United States. Could I help?
Nick’s inspiration centered on the behavior of self-organizing
amphiphilic molecules. The logical person to call was Dave Deamer,
who received some support from our NASA Astrobiology Institute
grant to study molecular self-organization. Dave had also published
some intriguing speculations about the energetic role of functionalized
PAHs, which might have gathered light to power a sort of primitive
photosynthesis. I sent Dave a long e-mail describing Nick’s unusual
circumstances and his special gifts. Dave, always kind and gracious,
responded almost immediately. Yes, he thought he would have a re-
search slot opening up in the fall. When could Nick start?
Nick is in Santa Cruz now, attempting the experiments that may sup-
port or refute his ingenious model. It’s too soon to tell if the PAH World
hypothesis will pan out, but whatever the outcome of Nick Platts’ work,
we’ll know more than we did before. PAHs, or PNA, or some other
information-rich, self-replicating genetic system must have emerged
on the path to the RNA World. That first genetic molecule must have
been much more resilient than RNA, though it was undoubtedly sig-
nificantly less efficient as a replicator. At some point, as self-replicating
genetic molecules became more competitive, RNA took over. The era
of Darwinian evolution had begun.
18
The Emergence of Competition
It is evident that once a self-replicating, mutating molecular
aggregate arose, Darwinian natural selection became possible
and the origin of life can be dated from this event. Unfortu-
nately, it is this event about which we know the least.
Carl Sagan, 1961
Life’s most poignant hallmark is inescapable, inexorable change.
Each of us is born, grows old, and dies. Each species arises from
prior species, fills its own niche for a time, and eventually becomes
extinct. In such a sweeping, undirected evolutionary drama, the hu-
man species might be seen as but one small, insignificant player. Little
wonder that Darwin’s theory of evolution by natural selection has met
with so much hostility.
The process of evolution by natural selection rests on two incon-
trovertible facts. First, every population is genetically diverse, possess-
ing a range of traits. Second, many more individuals are born than can
hope to survive. Consequently, over time those individuals with more
advantageous traits are more likely to survive and pass on their genetic
characteristics to the next generation. This selection process drives
evolution.
Even today, almost a century and a half after the publication of
The Origin of Species, a vocal minority of Americans views the theory
of evolution as a dangerous and subversive doctrine that substitutes
materialism for faith. Efforts to expunge Darwin from textbooks and
to augment curricula with thinly veiled religious beliefs in the guise of
“scientific creationism” or “intelligent design” continue unabated in
many states.
But natural selection is not a sinister development in life’s emer-
233
234
GENESIS
gence. On the contrary, evolution is the natural and necessary sorting-
out process that led to the origin of life.
MOLECULAR SELECTION AND EVOLUTION
Imagine yourself back to the primitive Earth more than 4 billion years
ago, to a time before life had emerged. Oceans and shorelines must
have held a bewildering, chaotic diversity of organic molecules from
many sources. Somehow that confused chemical mess had to be sorted
out. Two connected processes—molecular selection and molecular
evolution—winnowed and modified the prebiotic mélange.
Molecular selection, by
which a few molecules earned starring roles
in life’s origin, proceeded on many fronts. Some molecules were inher-
ently unstable or unusually reactive and so they quickly disappeared
from the scene. Other molecules proved to be soluble in the oceans
and so were removed from contention. Still other molecular species
sequestered themselves by bonding strongly to surfaces of chemically
unhelpful minerals or clumped together into gooey masses of little use
for the emergence of life.
Earth’s many cycles amplified these emergent selection processes.
Tidal pool cycles of wetting and evaporation concentrated molecules,
while the Sun’s ultraviolet radiation fragmented the least stable mo-
lecular species. Pulses of hydrothermal seawater delivered new sup-
plies of chemicals to deep-ocean vents, where differential adsorption
and detachment of molecules on reactive mineral surfaces concen-
trated a select subset of molecular species. Day and night, hot and cold,
sun and rain, high tide and low—these and other periodic phenomena
refined the chemical mix.
In every geochemical environment, each kind of organic molecule
had its reliable sources and its inevitable sinks. For a time, perhaps for
hundreds of millions of years, a kind of molecular equilibrium per-
sisted, as the new supply of each molecular species was balanced by its
loss. Such an equilibrium assemblage features nonstop reactions
among molecules, to be sure, but the system does not necessarily
evolve.
At some point, by processes as yet poorly understood, a self-
replicating cycle of molecules emerged, thereby changing the charac-
ter of molecular selection. Even a relatively unstable collection of mol-
ecules could persist in significant concentrations if it made copies of
THE EMERGENCE OF COMPETITION
235
itself. Molecules within that first self-replicating collection would have
thrived at the expenses of other molecular species.
Theorists imagine a more interesting possibility—an ancient envi-
ronment in which two or more self-replicating cycles of molecules
competed for atoms and energy. Such competition inevitably arose as
new molecular species offered alternative chemical pathways, or per-
haps as changes in environment triggered slight variations in a cycle.
Dueling molecular networks would have vied for resources, mimick-
ing life’s unceasing struggle for survival. In such a competitive envi-
ronment, increasingly efficient cycles emerged and flourished at the
expense of less efficient variants, slowly shifting the molecular balance.
Molecular evolution had begun on Earth.
The dynamic, competitive tussle of molecular evolution differs
fundamentally from the more passive process of molecular selection.
Competition among self-replicating cycles drives evolutionary change,
fostering efficiency and introducing novelty. That’s why many origin
experts draw the arbitrary line that separates living from nonliving
systems at the emergence of a self-replicating chemical cycle that be-
gan to evolve by this powerful process of natural selection.
Replication of a cycle, in and of itself, is not enough to claim life.
The cycle must also possess a sufficient degree of variability so that
when it competes for resources, more efficient variants win out. Over
time the system changes, becoming more adept at gathering atoms and
energy. Under these conditions, the emergence of increasing molecu-
lar complexity is inevitable, as new chemical pathways overlay the old.
So it is that life has continued to evolve over the past 4 billion years of
Earth history.
EVOLUTION IN THE LAB
A theory, no matter how plausible, requires experimental testing, but
how can one test molecular evolution in a laboratory? That challenge
seems almost beyond imagining, yet that is exactly what a few teams of
biochemists have done.
Laboratory studies of molecular evolution began in the 1960s at
the University of Illinois, where Professor Sol Spiegelman and his col-
leagues investigated a tiny virus called Qβ (pronounced “que-beta”)
that attacks the common bacterium E. coli. Qβ is nothing more than a
protein shell surrounding a small loop of RNA. Its entire existence is
236
GENESIS
devoted to infecting E. coli cells and inducing those cells to make more
copies of the Qβ virus. To do that, one of Qβ’s proteins, Qβ replicase,
has to make copies of Qβ RNA.
This close relationship between Qβ replicase and Qβ RNA sug-
gests a promising experiment. If you put some Qβ replicase and a Qβ
RNA strand into a test tube along with lots of small RNA building
blocks, you’ll wind up with countless new Qβ RNA strands. One ca-
veat: Qβ replicase makes lots of mistakes, so each new RNA strand is
likely to vary slightly from the original.
Here’s what Spiegelman and co-workers did to make their mol-
ecules evolve. They allowed the chemical mix to make copies for just
20 minutes. During that short period, some RNA sequences bound
strongly to Qβ replicase and duplicated rapidly, while others interacted
poorly with Qβ replicase and were inefficiently copied. After 20 min-
utes, when the solution had become enriched in RNA strands that eas-
ily replicate, they transferred a small amount of that liquid into a new
beaker with fresh Qβ replicase and RNA building blocks. Then they
ran the experiment for another 20 minutes and transferred a small
amount of the second batch of RNA copies into a third beaker with
fresh Qβ replicase.
Seventy-four times they repeated the process, gradually reducing
the time allowed for the reaction to proceed. Each step preferentially
selected those RNA strands that were copied most efficiently. By the
end of the experiment, the length of the most efficient RNA strands
had been shortened to a sixth of the original size, and these evolved
RNA sequences were being copied 15 times faster than before. Similar
experiments generated strands of RNA that were unusually resistant to
high temperature or to the effects of damaging chemicals. Under such
severe selection pressure (time, temperature, or some other stress), the
Qβ RNA evolved.
SELF-REPLICATING RNA
“Spiegelman monsters,” as these systems came to be known, are not
alive. Only by the most overt manipulation (cycling through a succes-
sion of beakers, for example) does the Qβ RNA evolve. But the repeti-
tive selection process developed by Spiegelman’s group proved that
molecular systems under competitive pressure can be induced to
evolve—a result that suggested to many researchers a brave new world
THE EMERGENCE OF COMPETITION
237
of artificially evolved molecules designed to accomplish specific chemi-
cal tasks.
Harvard Medical School biologist Jack Szostak has set his sights
even higher. Indeed, Szostak’s overriding ambition is nothing less than
to design an evolving life-form in his lab. “Our ultimate goal is to cre-
ate life,” he admits.
Jack impresses you as someone who is supremely happy in his pro-
fession. Unassuming and quiet by nature, he often wears a half-smile,
as if he were amused by a private joke. Despite his 50-odd years, his
slender build and the bright eyes behind round-framed glasses make
him look like a scientific Harry Potter—and he is in fact a bit of a
wizard.
For Jack, RNA is the key. He began his scientific career studying
yeast chromosomes—an important mainstream task in molecular bi-
ology that sheds light on how DNA operates in humans. Chromosomes
are elongated structures that divide and separate during cell division;
they carry all of yeast’s DNA. Szostak and his student, Andrew Murray,
synthesized one from scratch. “Even then,” he recalls, “my guiding prin-
ciple was that the best way to show that you really understand how
something works is to try to build it from pieces and then see if it
works as expected.” [Plate 8]
The study of yeast DNA was a crowded field, and Szostak itched to
try his hand at something different. The discovery in the early 1980s of
ribozymes—RNA that behaves as a catalyst—was too seductive to pass
up, and he soon changed research directions.
In their first series of ribozyme experiments, Szostak and a group
of his students focused on engineering chains of RNA that can copy
other RNA molecules. Such an “RNA replicase” represents a first key
step in designing a self-replicating chemical system. Success came in
1989, when he and Jennifer Doudna (now a professor at Berkeley)
made an RNA molecule that copies short RNA sequences, albeit rather
sloppily. Other high-profile papers soon followed, as their ability to
manipulate RNA improved. These were spectacular advances, but still
a long, long way from a reliable self-replicating RNA strand. They’d
have to do better, but how? Jack decided to let molecular evolution
work for him.
Szostak’s objective was to evolve an RNA molecule that would at-
tach strongly and selectively to a “target molecule” of distinctive shape.
His team tackled RNA evolution by first generating a solution with
238
GENESIS
more than 10 trillion random RNA sequences, each about 120 “letters”
long. They poured this RNA-rich solution into a beaker whose glass