by Charles Baum
tungsten
electrode
stopcock for
admitting H2,
CH2, NH3
condenser
stopcock for
withdrawing
samples
water
(“ocean”)
heat
The Miller–Urey experiment used a tabletop glass apparatus to mimic the early
Earth’s ocean and atmosphere, while electric sparks simulated lightning. This device rapidly transformed simple gases into essential biomolecules (after Trefil and Hazen, 1992).
STANLEY MILLER’S SPARK OF GENIUS
89
pumping out the system to remove any traces of atmospheric oxygen.
Then he filled his apparatus with water and a 2:2:1 gas mixture of
methane, ammonia, and hydrogen. He heated the water, set off tiny
electric sparks in the gases to simulate lightning, and waited.
When the experiment began, the water was pure and clear, but
within a couple of days the solution had turned yellowish and a black
residue had begun to accumulate near the electrodes. It’s easy to imag-
ine Stanley Miller’s excitement as he cut his first experiment short to
analyze the tantalizing products. Had he produced amino acids?
Organic chemical analysis was no easy chore in the early 1950s.
Miller resorted to paper chromatography, a classic and relatively quick
technique that separates different molecules into discrete colored spots
on absorbent paper. Miller opened the valve and removed the yellow
solution. Concerned that microbes might begin to grow in the liquid
and confuse his results, he added a lethal dose of mercury chloride to
preclude any bacterial contamination. Then, after the tedious routine
of drying down and concentrating his sample, he placed a small drop
of concentrated run product near one corner of the chromatography
paper. It dried as a small yellow dot.
Miller suspended the paper above a narrow trough filled with a
freshly made alcohol–water solution. He carefully lowered the paper so
that one edge close to the yellow spot just barely dipped into the clear
solution, which gradually soaked into the paper and rose up the sheet
by capillary action. As the alcohol solution moved, it carried the un-
known molecules along with it. Within a few minutes the chemical
spot had been smeared out into a narrow, 3-inch-long streak of un-
known, mostly invisible chemicals.
Miller let his paper dry, rotated it 90 degrees, and repeated the
process with a second solvent, this time a phenol solution. Molecules
move differently through paper under the influence of different sol-
vents, so this second step spread the 3-inch streak of chemicals into a
diagnostic two-dimensional pattern of spots. After a second drying,
Miller’s final step was to treat the paper with ninhydrin, a chemical
that stains otherwise invisible amino acids into distinctive colors.
Almost immediately a discrete purple spot appeared exactly at the
expected position for glycine (C H NO ), the simplest of life’s amino
2
5
2
acids. Starting with nothing more than water and a few simple gases,
Miller had made one of life’s essential biomolecules. The graduate stu-
90
GENESIS
dent and his advisor were elated, for the tabletop experiment had
worked much faster than they expected.
Miller repeated the entire experiment for a week’s duration, crank-
ing up the heat to a slow boil. The results were amazing. The water
quickly yellowed, then gradually turned intriguing shades of pink and
eventually to a deep red, while black gunk oozed down the sides of the
larger flask. This time when Miller analyzed the contents of the flask,
he found a complex mixture of organic molecules including at least a
half-dozen different amino acids. Reactions of water and air had pro-
duced organic molecules in abundance.
Harold Urey encouraged the young investigator to write up his
results immediately. Miller obliged and submitted a short manuscript
to the high-profile journal Science in mid-February 1953, a scant five
months since the project’s inception. Urey also generously withdrew
his name from the paper so that the graduate student, not the Nobelist,
would receive the lion’s share of credit.
Stanley Miller’s first publication was a bombshell. His two-page
article in the May 15, 1953, issue of Science announced “A Production
of Amino Acids Under Possible Primitive Earth Conditions.” The press
had a field day. The New York Times printed a feature story, LIFE AND
A GLASS EARTH, while tabloids speculated about synthetic life crawl-
ing out of test tubes.
THE COTTAGE INDUSTRY OF PREBIOTIC CHEMISTRY
The Miller–Urey experiment transformed the science of life’s chemical
origins. For the first time, an experimental protocol mimicked plau-
sible life-forming processes. For decades to come, Miller and his stu-
dents would dominate the origin-of-life community.
Given such an exciting result, other groups jumped at the chance
to duplicate the amino acid feat. Independent confirmation of Miller’s
claims came within a few years from chemists at the University of
Bristol in England and at the Carnegie Institution in Washington, D.C.
(A careful search of the scientific literature also turned up a remark-
ably similar series of experiments that had been conducted decades
earlier by the German chemist Walter Löb.) Thousands of subsequent
experiments during the past half century have outlined the promise, as
well as the limitations, of this idea that life arose as a chemical process
at the surface of the Earth. Time and time again, variations of the
STANLEY MILLER’S SPARK OF GENIUS
91
Miller–Urey process, including experiments using ultraviolet radiation,
different gas mixtures, powdered minerals, and more, have demon-
strated the synthesis of life’s most basic building blocks. Relatively easy
to run, and now a relative cinch to analyze, these experiments continue
to be a sort of cottage industry in origin-of-life research circles.
This genre of experiments yields amazing results. Dozens of amino
acids have been synthesized from scratch, along with membrane-
forming hydrocarbons, energy-rich sugars and other carbohydrates,
and metabolic acids. The early inventories even included some of the
building blocks of the genetic molecules DNA and RNA, though at
first the 5-carbon sugar ribose (the “R” of RNA) and the two purines
essential to both, adenine (C H N ) and guanine (C H ON ), were
5
5
5
5
5
5
notably absent.
Much of this molecular diversity occurs because electric sparks
and ultraviolet radiation trigger the formation of highly reactive
chemical species, such as hydrogen cyanide (HCN) and formaldehyde
(CH O), which readily link to other molecules. Miller suspected, for
2
example, that most of the amino acids produced in his experiments
arose by a chemical process known as Strecker synthesis
, in which hy-
drogen cyanide reacts with formaldehyde and ammonia.
Enthusiasm grew as other scientists discovered promising
new chemical pathways. In 1960, John Oró of the University of Hous-
ton turned scientific heads when he discovered that a concentrated
hydrogen–cyanide solution, when heated, produced lots of adenine,
one of the missing purines and a crucial biomolecule that also plays a
role in metabolism. Other chemists conducted similar experiments,
starting with relatively concentrated solutions of formaldehyde
(CH O), a molecule thought to be common in some prebiotic envi-
2
ronments. These experiments produced a rich, though random, vari-
ety of sugars, including a modest yield of ribose. Gradually, through
such specialized experiments, gaps in the prebiotic inventory of life’s
molecules were filled in.
The experiments of Oró and others, relying as they did on rela-
tively concentrated solutions of reactive organic molecules, raised some
eyebrows. The Miller-type spark experiments by themselves had never
yielded hydrogen cyanide in sufficient concentrations to produce much
adenine, or enough formaldehyde to make much ribose. But discover-
ies in the mid-1960s in the lab of Salk Institute pioneer Leslie Orgel
pointed to a plausible fix. The early Earth was not uniformly hot; it
92
GENESIS
probably had ice caps and may have periodically experienced more
extensive “ice ages,” as well. Orgel realized that such conditions might
promote intriguing organic reactions. When an organic-rich water so-
lution freezes, pure water ice crystals grow, while the dwindling reser-
voir of residual liquid becomes an increasingly concentrated organic
brine (and recall that a higher concentration of “agents” may facilitate
emergence).
Orgel and co-workers exploited this idea by slowly freezing flasks
of dilute HCN solutions to –20°C. The procedure produced tiny vol-
umes of extremely concentrated hydrogen cyanide, which reacted over
weeks to months to produce small linkages of up to four HCN mol-
ecules. This curious phenomenon became the inspiration for one of
the longest experiments in the history of origins research. Sometime in
the mid-1970s, Miller, now a professor at the University of California,
San Diego, and his co-workers repeated the Orgel protocol and stored
their frozen flasks in the back of a freezer. In the late 1990s, more than
two decades later, they removed the frozen solutions, which had devel-
oped curious dark concentrated clumps that were rich in organics.
Analysis revealed an abundant production of adenine. It takes a lot of
time for reactions to proceed at ultracold temperatures, but the primi-
tive Earth had time to spare.
These remarkable results seem to defy convention: Heat, not cold,
normally drives chemical reactions. You don’t make a cake by freezing
batter. Nevertheless, additional freezing experiments have produced
amino acids and other interesting biomolecules by this counterintui-
tive process of concentration. In this curious way, prebiotic cycles of
freezing and thawing may have enhanced the emergence of biomol-
ecules and thus provided a pathway to life.
DOUBTS
As exciting and important as the Miller–Urey results may be, seem-
ingly intractable problems remain. Within a decade of Miller’s tri-
umph, serious doubts began to arise about the true composition of
Earth’s earliest atmosphere. Miller and Urey had exploited a highly re-
active atmosphere of methane, ammonia, and hydrogen, which seemed
a plausible early atmosphere to them. But by the 1960s, new geochemi-
cal calculations along with data from ancient rocks pointed to a much
STANLEY MILLER’S SPARK OF GENIUS
93
less reactive early atmosphere of nitrogen and carbon dioxide, two
gases that do almost nothing of interest in a Miller–Urey apparatus.
Miller and his supporters continue to counter with a pointed ar-
gument, difficult to dismiss. Life’s biomolecules match those of the
original Miller–Urey experiment with great fidelity, they say. Doesn’t
that fact alone argue for an atmosphere rich in reactive methane?
Harold Urey is said to have often quipped, “If God did not do it this
way, then He missed a good bet.” Nevertheless, most geochemists now
discount the possibility of more than a trace of atmospheric methane
or ammonia at the time of life’s emergence.
Added to this atmospheric concern is the fact that the molecular
building blocks of life created by Miller and his colleagues represent
only tiny steps on the long road to life. Living cells require that such
small molecules be carefully selected and then linked together into
vastly more complex structures—cell membranes, protein catalysts,
DNA, RNA, and other so-called macromolecules. The prebiotic ocean
was an extremely dilute solution of many thousands of different
organic molecules, most of which play no known role in life. By
what emergent processes were just the right molecules selected and
organized?
The Miller–Urey scenario suffers from yet another nagging prob-
lem. Macromolecules tend to fragment, rather than form, when sub-
jected to the energetic insults of lightning and the Sun’s ultraviolet
light. These so-called ionizing forms of energy are great for making
reactive molecular fragments that combine into modest-sized mol-
ecules like amino acids. Combining many amino acids into an orderly
chainlike protein, however, is best accomplished in a less destructive
energy domain. Emergent complexity relies on a flow of energy, to be
sure, but not too much energy. Could life have emerged in the harsh
glare of daylight, or was there perhaps a different, more benign origin
environment?
Faced with such an impasse, a few maverick scientists began to
look at other plausible venues for the cradle of life.
7
Heaven or Hell?
It is we who live in the extreme environments.
Thomas Gold, The Deep Hot Biosphere, 1999
For centuries the primary source of life’s energy has been as well
established as any precept in biology. Every high-school textbook
proclaims what we all have accepted as intuitively obvious: All life de-
pends ultimately on the Sun’s radiant energy. Nor has there been rea-
son to doubt that claim until recently. But new discoveries of deep
life—life-forms at the darkest ocean depths and microbes buried miles
beneath Earth’s surface in solid rock, forever beyond the Sun’s influ-
ence—have toppled this comfortable certainty.
If science has taught us anything, it’s that cherished notions about
our place in the natural world often turn out to be dead wrong. We
observe that the Sun rises in the morning and sets at night. An obvious
conclusion, reached by almost all observers until relatively recently in
human history, is that the Sun circles the Earth. Yet we now know that
sunrise and sunset are consequences of Earth’s rotation; Earth orbits
the Sun, and we are not at the physical center of the universe. We ob-
serve mountains and oceans as grand unchanging attributes of the
globe—on the scale of a human life, these features are for all intents
and purposes permanent. Yet we have learned that through the inexo-
rable processes of plate tectonics, every topographic feature on Earth is
transient over geological time and that our war-contested political
boundaries are destined eventually to disappear.
The great power of science as a way of knowing is that it leads us to
conclusions about the physical universe that are not self-evident. Re-
peatedly, the history of science has been punctuated by the overthrow
95
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GENESIS
of the obvious. Could our intuitive view of life’s original energy source
be in error as well?
ENERGY
All living cells require a continuous source of energy. Without energy,
organisms cannot seek out and consume food, manufacture their cel-
lular structures, or send nerve impulses from one place to another.
Lacking energy, they cannot grow, move, or reproduce. Reliable energy
input is also essential to maintain the genetic infrastructure of cells,
which are constantly subjected to damage by nuclear radiation, toxic
chemicals, and other environmental hazards.
Metabolism, the means by which organisms obtain and use en-
ergy, is an ancient chemical process that takes place in every living cell,
including all of the tens of trillions of cells in our bodies. Until re-
cently, scientists claimed that the metabolic pathways of virtually all
life-forms rely directly or indirectly on photosynthesis. At the base of
the food web, we find plants and a host of one-celled organisms that
use the Sun’s light energy to convert water and carbon dioxide into the
chemical energy of sugar molecules (carbohydrates) plus oxygen.
Plants manufacture carbohydrates, such as the starch of potatoes and
the cellulose of celery, to build leaves, stems, roots, and other physical
structures. They also process sugar molecules to provide a source of
chemical energy that powers the plant cell’s molecular machinery.
While plants synthesize their own carbohydrates, animals and
other nonphotosynthetic life higher up the food chain must find an-
other source of sugar. That’s why we eat plants, or eat animals that eat
plants. Plants synthesize sugar molecules and oxygen from water plus