by Charles Baum
playing a key role in the integrated network.
Kauffman sees an important payoff in the behavior of such elabo-
rate catalytic networks. Unlike a single self-replicating molecule, such
vast networks of reactive molecules have the potential to increase in
complexity and efficiency through numerous different interactions
among molecules. The large number and variety of molecular interac-
tions foster the emergence of new metabolic pathways and nested cycles
of synthesis. Like a living metabolic cycle, Kauffman’s networks incor-
porate a certain degree of sloppiness. Through such variations, the sys-
tem can change by shifting to new, more efficient reaction pathways
and in the process display a defining trait of life—the ability to evolve.
THE GAME OF METABOLISM
Kauffman’s theory provides an intuitively appealing model for the
emergence of primordial metabolic life. For one thing, if molecules in
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GENESIS
a complex autocatalytic system efficiently catalyze each other, then
there’s no need, at least at first, for a genetic mechanism. Accurate rep-
lication of the entire system is, in effect, intrinsic to the network. At the
same time, the system has the potential to vary and gradually evolve.
Growth, reproduction, evolution—the autocatalytic network would
appear to meet the minimum criteria for life.
Kauffman’s model sounds good on paper, but there’s a dramatic
gap between plausible theory and actual experiment. For example,
what exactly is the chemical “A”? What is “B”? When asked, Kauffman
shrugs and says, “That’s for the chemists to figure out.” And that’s what
chemists have done.
If you want to make protolife in the lab, it’s best to start by design-
ing a simple metabolic cycle. Metabolism is a special kind of cyclical
chemical process with two essential inputs. First you need a source of
energy—preferably chemical energy, since that’s what all known simple
living cells use. (Photosynthetic cells use sunlight, to be sure, but these
advanced organisms possess layers of chemical complexity far beyond
those of more ancient, simple cells.) Second, you need reliable supplies
of simple molecules, such as carbon dioxide and water, to provide the
raw materials.
Living cells undergo chemical reactions not unlike burning, in
which two chemicals (oxygen and some carbon-rich fuel) react and
release energy. However, the objective in metabolism, unlike in an open
fire, is to capture part of that released energy to make new useful mol-
ecules that reinforce the cycle. So metabolism requires a sequence of
chemical reactions that work in concert.
Three basic rules govern this game of metabolism:
Rule 1—The Cycle: Describe a cycle consisting of a sequence of
progressively larger molecules. The largest of these molecules should
then be able to split into two smaller molecules, both of which are also
in the cycle. In this way you end up with two sets of molecules, where
before there was only one set and the cycle keeps on reproducing itself.
Rule 2—The Environment: Identify a plausible prebiotic environ-
ment that provides a reliable supply of raw materials (i.e., small mol-
ecules made up of carbon, nitrogen, sulfur, and other essential
elements) and energy (preferably the chemical energy of unstable min-
erals). Furthermore, all of the different types of molecules in the cycle
have to be able to survive in that environment long enough to keep the
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cycle going. Extremes in temperature, pressure, or acidity, for example,
may stabilize some kinds of molecules, while destroying others.
Rule 3—Continuity: An unbroken chemical history must link
Earth’s earliest metabolic cycle with the metabolism of today’s cells.
Deep within the metabolism of all of us, there are likely to be “fossil”
biochemical pathways that point to life’s simpler beginnings. So any
plausible model must conform to this “principle of continuity” and
use molecules and energy sources that lie close to the basic metabolism
of modern organisms.
Experimental evidence provides the ultimate test of any chemical
theory. Each chemical step in a hypothetical metabolic cycle is a poten-
tial experiment, so you get bonus points if these crucial experiments
work.
Three influential models exemplify the metabolism game at its
best: the “Protenoid World” of Sidney Fox, the “Thioester World” of
Christian de Duve, and a group of related hypotheses based on the
reverse citric acid cycle, including the elaborate “Iron–Sulfur World”
hypothesis of Günter Wächtershäuser.
THE PROTENOID WORLD
The granddaddy of all metabolism-first models emerged as the brain-
child of protein chemist Sidney Fox, who began thinking about origin-
of-life chemistry shortly after the publication of Stanley Miller’s 1953
paper. Fox’s career was strongly influenced by Thomas Hunt Morgan,
a famed geneticist and a member of Fox’s Caltech thesis committee.
“Fox,” Morgan would often remark, “all the important problems of life
are problems of proteins.” Fox took this lesson to heart and began
studying proteins’ role in life’s origin as a faculty member at Florida
State University in the mid-1950s.
He imagined a hot primordial Earth where amino acids from the
soup dried and baked on cooling volcanic rocks. He mimicked these
conditions in his lab, drying amino acids on a hot surface at 170°C,
and found that his chemicals quickly polymerized into a lumpy sub-
stance he called “protenoid.” This discovery, announced in 1958, would
shape his checkered three-decade career in origins research.
Fox’s protenoids displayed fascinating behavior. They acted as cata-
lysts, though to a rather modest degree compared to the modern pro-
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GENESIS
tein catalysts that promote chemical reactions in every cell. When
placed in hot water, they spontaneously turned into microbe-sized
spheres, and sometimes these divided. He claimed that these spheres,
though not as orderly as biological proteins, possessed a nonrandom
structure with a permeable bilayer membrane. Increasingly, Fox sug-
gested that the protenoids were “lifelike” and represented the key to
life’s origins.
Fox and a small army of students carried out experiments to bol-
ster his origin model. Solutions of protenoids were heated and cooled
in a cycle that produced structures he called “microspheres”—cell-like
entities that could absorb more protenoids, grow, and divide, thus
forming a second generation of microspheres. These self-replicating
objects, growing from nutrients in solution and lacking any genetic
mechanism, formed the basis of a true metabolism-first model.
At first blush, the Protenoid World might seem to score well in the
game of metabolism. Rule 1: The cycle is formed from widely available
amino acids, which readily form protenoids that grow and divide. Rule
; 2: The environment, a volcanic setting near a tidal zone, is realistic for
the early Earth. Rule 3: Protenoids seemed to conform to the principle
of biological continuity, because closely related proteins are fundamen-
tal to modern life. What’s more, experiments seemed to support each
step of the hypothesis.
For a time, Fox’s career thrived. Starting in 1960, he received gen-
erous grants from NASA’s Exobiology program, which supported a va-
riety of research projects on the origin and evolution of life. Fox’s funds
soon exceeded $1.5 million and allowed him to establish his own Insti-
tute of Molecular Evolution at the University of Miami in 1964. A
steady stream of graduate students investigated protenoid properties.
As Sidney Fox increasingly fell in love with his Protenoid World
model, his claims became more and more extreme. The origin-of-life
problem had been solved, he said, and protenoids are “alive in some
primitive way.” In his 1988 book, The Emergence of Life, he even made
the bizarre and unsubstantiated claim that his protenoid microspheres
possessed a kind of “rudimentary consciousness.”
As early as 1959, the mainstream origin-of-life community, led
principally by Stanley Miller and Harold Urey, had begun distancing
themselves from Fox’s claims. They resented what they regarded as the
sensationalistic use of terms such as “protenoid” and “lifelike.” They
scoffed at the idea that amino acids might have baked into anything
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201
useful on a bed of lava. They questioned whether the protenoid struc-
tures were truly nonrandom in structure. The purported lifelike be-
haviors of microspheres were also challenged, especially the idea that
they “replicated” in the biological sense. Equally strong was their ob-
jection that the Protenoid World scenario ignored the knotty problem
of genetics. How would DNA and RNA have arisen in such a world?
Despite myriad objections to the theory, and the increasing scien-
tific isolation of Fox, the Protenoid World was influential for at least
two reasons. Not only did Fox develop the first comprehensive
metabolism-first model, but he also championed the important philo-
sophical position that origin processes might be nonrandom and
deterministic—a view later embraced by numerous other origins
workers. Nevertheless, by the late 1970s, Sidney Fox’s efforts had been
marginalized, and they remained the target of jokes and derision until
his death in 1998.
THE THIOESTER WORLD
The Belgian chemist Christian de Duve made his scientific name study-
ing the structural and functional organization of cells—work that won
him the Nobel Prize in physiology or medicine in 1974. In an oft-
repeated pattern, he then turned his attention to the origin of life, tack-
ling the classic question from his perspective as a cell biologist. Not
surprisingly, that background influences his origins theory.
De Duve takes a rather ambiguous stand in the metabolism- ver-
sus genetics-first controversy. For him, the simplest imaginable living
thing is a cell-like entity that has a full complement of genetic material
to control cellular functions. But he also recognizes the futility of jump-
starting genetics without a well-established, elaborate arsenal of chemi-
cal reactions—what he calls “protometabolism” (as opposed to the
more complex metabolism of modern cells). It’s really a question of
where you place the boundary between nonliving and living systems.
I’ve argued that the complex sequence of emergent events leading from
geochemistry to life requires a rich taxonomy of intermediate states.
De Duve appears to agree: His “Age of Chemistry” (protometabolism)
precedes the “Age of Information” (genetics), which in turn precedes
the “Age of the Protocell” (genetics and metabolism combined). Only
then, with the merger of metabolism and genetics, does modern life
truly emerge.
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GENESIS
Let’s assume, de Duve says, that some early Earth environment
(rather vaguely specified as a “volcanic setting” in his writings) was
rich in hydrogen sulfide gas and iron sulfide minerals, along with the
usual cast of carbon-based molecules. One chemical consequence of
this sketchy scenario might be the production of sulfur-containing
molecules called thioesters, which incorporate a strong bond between
one sulfur atom and one carbon atom—a bond that can release a lot of
energy if broken. De Duve’s hypothesis rests on the assumption that a
steady supply of these energy-rich thioester molecules was available on
the ancient Earth—hence the Thioester World.
Why focus on thioesters? For one thing, they are essential in the
metabolism of modern cells. By breaking the strong carbon–sulfur
bond, they can transfer energy to promote metabolic reactions, thus
building larger molecules from smaller ones. In the Thioester World, a
steady supply of thioesters provides the chemical energy required to
drive protometabolism.
Of particular import, thioesters have a propensity to bond with
amino acids, which would have been readily available in the prebiotic
soup. Remarkably, when placed in solution, these amino acid–thioester
groups spontaneously assemble into peptidelike chains (de Duve calls
them “multimers,” because they differ in some chemical details from
true peptides). At first, the multimers thus formed would have had
little effect on the chemical mix. But, he speculates, eventually some of
these big molecules by chance acquired catalytic properties (reminis-
cent of Fox’s protenoids). Gradually, as the environment became en-
riched in chemically active multimers, an autocatalytic cycle might
have emerged, producing, he says, “protoenzymes required for
protometabolism.”
The Thioester World hypothesis fits nicely with the primordial-
soup paradigm favored by Miller and his allies. De Duve’s scenario
relies on the environment to provide a steady input of various molecu-
lar building blocks, including amino acids, carbohydrates, and of
course the essential energy-rich thioesters themselves. Such a model
metabolism, in which the first cells eat and assemble components from
their surroundings, is said to be heterotrophic (from the Greek, “other
nourishment”). Heterotrophs must scavenge their molecules from the
environment.
So how does de Duve’s Thioester World score in the game of me-
tabolism? He certainly gets high marks for identifying a viable prebi-
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203
otic environment rich in plausible simple molecules. Using thioesters
as a reliable, renewable energy source is especially attractive, because it
echoes the action of thioesters in modern biology. But he never speci-
fies the molecules that comprise his metabolic cycle; the chemistry is
vague. For de Duve, protometabolism is an awkward, transient, ill-
defined phase that is necessary to set the stage for genetics. Thioesters
> promote the synthesis of catalytic multimers, which in turn promote
the manufacture of a genetic molecule such as RNA. Only then does a
well-defined biochemistry take root.
The bottom line: de Duve’s scenario is appealing in its broad out-
lines, but lacking in specific chemical details. And so, if you like details,
there’s no better place to turn than Günter Wächtershäuser’s Iron–
Sulfur World.
15
The Iron–Sulfur World
You don’t mind if I brag a little, but something like this has
never been done in the entire field.
Günter Wächtershäuser, 1998
In bold concept, epic sweep, and sheer mass of detailed predictions,
Günter Wächtershäuser’s Iron–Sulfur World hypothesis for the ori-
gin of life stands alone. Since its first presentation in 1988, this theory
has changed the landscape of origins research by calling into question
many of the most deeply rooted assumptions about life’s beginnings.
Wächtershäuser (whom we first met in Chapter 8 because of his
pleasing reliance on minerals) argues for a strikingly original metabo-
lism-first model, based on an autotrophic (self-nourishment) model.
Autotrophic metabolism begins with chemical simplicity. All of life’s
essential biomolecules are manufactured in place, as needed, from the
smallest of building blocks: carbon dioxide (CO ), water (H O), am-
2
2
monia (NH ), hydrogen sulfide (H S), and so forth. All chemical syn-
3
2
thesis is accomplished stepwise, just a few atoms at a time. [Plate 8]
The contrast between heterotrophic and autotrophic existence is
profound and represents a fundamental point of disagreement among
origin-of-life researchers. Supporters of a heterotrophic origin argue
that it’s much easier for a primitive cell to use the diverse molecular
products available in the prebiotic soup rather than to make them from
scratch. Why go to the trouble of synthesizing lots of amino acids if
they’re already available in the environment? Modern heterotrophic
cells are much simpler than autotrophic cells, because they don’t need
all the complex chemical machinery to manufacture amino acids, car-
bohydrates, lipids, and so forth. It makes sense to assume that the sim-
pler mechanism—heterotrophy—came first.