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TECHNOLOGY REVIEW MAY/JUNE
doing traditional biophysical studies on membranes, but now
some of my research is funded by NASA's astrobiology pro-
gram, and many of our experiments could be described as
synthetic biology: the application of engineering techniques
to design or redesign biological functions and systems.
The field of synthetic biology is hot just now, because its
methods are potentially very powerful. Synthetic biologists
know enough about living systems to alter genetic programs
in useful ways, the way expert computer programmers alter
software. But what does such high-tech science have to do with
volcanoes and the origin of life? Louis Pasteur once commented
that chance favors the prepared mind; very often, even the most
basic research produces an undreamed-of application. For
example, one of the most powerful tools of molecular biology is
the polymerase chain reaction (PCR), which is used to amplify
DNA---that is, to make multiple copies of a given sequence. In
PCR, cycles of heating and cooling combine with DNA syn-
thesis by a polymerase, an enzyme that catalyzes the building
of large molecules (polymers) from small molecules (mono-
mers). Kary Mullis came up with the idea in 1983, first using
a polymerase from ordinary E. coli bacteria, but a polymerase
was needed that could survive near-boiling temperatures. In
1965---in completely unrelated research---Thomas Brock discov-
ered a primitive bacterium, which he named Thermus aquaticus,
living in the volcanic hot springs of Yellowstone National Park.
This organism is the original source of the heat-resistant Ta q
polymerase now used in all commercial PCR devices.
If we follow Pasteur's advice, we can increase the chances for
more such serendipitous discoveries. In particular, we can pre-
pare our minds by broadening the scope of synthetic biology to
encompass studies of the origin of life. I will begin by describing
nature's version of synthetic biology; then I will show how our
growing understanding of life's molecular mechanisms sug-
gests a way to reproduce the origin of life in the laboratory.
FIRST LIFE: SYNTHETIC BIOLOGY IN THE WILD
To take on the question of life's origin, we need to have some
idea of what Earth was like four billion years ago. There is good
evidence that oceans were already present, predating life by
several hundred million years. The oceans were salty, probably
somewhat acidic, with volcanic land masses rising above sea
level. Precipitation onto those islands produced freshwater
ponds, so a marine environment is not the only one in which
life could have begun. The atmosphere was a mixture of car-
bon dioxide and nitrogen, with little or no oxygen, and the
average global temperature was 60 to 70 °C, much higher than
today's 15 °C. Thus the first forms of life probably resembled
the thermophilic bacteria that inhabit hot springs today.
How could life begin in such an unpromising environment?
Charles Darwin occasionally wondered about that, though he
was too conservative to speculate in public about the origin of
life. In a private letter to his friend Joseph Hooker, he wrote:
"But if (and Oh! what a big if!) we could conceive in some warm
little pond, with all sorts of ammonia and phosphoric salts,
light, heat, electricity, etc., present, that a protein compound
was chemically formed ready to undergo still more complex
changes, at the present day such matter would be instantly
devoured or absorbed, which would not have been the case
before living creatures were formed." And his great book
On the Origin of Species touches on the question in a single
sentence: "Looking to the first dawn of life, when all organic
beings, as we may believe, presented the simplest structure,
how, it has been asked, could the first steps in the advance-
ment or di erentiation of parts have arisen?"
Less eloquently, what would be required for the evolution of
life to begin? First of all, evolution works on populations, not
single organisms, so we need to find a way to generate large
numbers of molecular systems in the prebiotic environment.
Furthermore, there must be great variation in their properties.
The requirement of variation within a population means that
the first life forms capable of evolution could not be random
mixtures of replicating molecules unable to assemble into dis-
crete entities; instead, they would be systems of interacting
molecules encapsulated in something like a cell.
The systems would have to exhibit the two primary func-
tions of life: growth and reproduction. Cells grow by taking in
nutrients---simple molecules from the environment. They use
energy to link those molecules into the polymers that we call
proteins and nucleic acids. Reproduction requires a mecha-
nism by which genetic information can be stored and then
replicated, so that the information, in the form of genes, can
be passed on. But the transfer of information is necessarily
imperfect. A certain number of errors---mutations---must occur
to produce variations in the population such as those that
enabled primitive life to explore di erent niches and begin
evolving toward the magnificent biosphere of today's Earth.
A LABORATORY, OF SORTS The author sampling boiling
fumaroles in the crater of Mt. Mutnowski, in Kamchatka, Russia.
COURTESY OF DAVID DEAMER
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