Seeking to Restart Evolution With Life's Simplest Ingredients
By William Booth
Washington Post Staff Writer
BOSTONJack Szostak is no Dr. Frankenstein, but if he succeeds in his
work, the soft-spoken biologist may be the first to create life in
Szostak and his colleagues at Massachusetts General Hospital here
plan to manufacture not a hulking monster with electrodes in his neck,
but nature's most elemental unit of life: a cell.
Their cell, to be built almost from scratch in the next year or so,
will not be very sophisticated. Little more than a fat bubble containing
bits of genetic material, Szostak's creations will be so simple and
primitive that some rival researchers say it would be almost hyperbolic
to call them life.
"I think it's a perfectly neat thing to do, but really, calling them
cells?" said Norman Pace of Indiana University. "It's probably more
tongue-in-cheek than anything else."
But Szostak is not kidding, and he is not alone. There are at least
three major scientific groups around the country trying to create life
in the laboratory. Szostak himself is convinced that his cells will be
technically alive, at least by his definition. They will replicate. And
as important, they will be playthings for the forces of natural
selection. As such, Szostak believes his little cells could evolve into
more complex beings.
The work of Szostak and his colleagues is designed to address some of
the looming questions of how life originated: How simple can life be?
And what might the first forms have looked like as they began their long
journey toward complexity and variety?
Most people think life as we know it today is quite complicated. But
Szostak and his colleagues are attempting to reduce biology to its
simplest ingredients. In essence, Szostak's recipe is as follows:
Spermidine (a ubiquitous but somewhat mysterious compound of carbon,
hydrogen and nitrogen first detected in human sperm)
A special segment of RNA from a protozoan called Tetrahymena
Modify the RNA slightly. Set aside. In a separate bowl, mix the other
ingredients. Slowly add RNA to broth of fat, water and spermidine.
Allow soup to sit while fats self-assemble into membranes that curl
up into cell-like bubbles, encapsulating bits of RNA, water and
spermidine. These are the cells.
Replenish periodically with small bits of RNA, which serve as food
for the new cells. Shake vigorously to make cells divide.
Repeat feeding and shaking indefinitely. Check occasionally for
The central ingredient in Szostak's cells is the RNA, for ribonucleic
acid, which many scientists believe was the first master molecule of
life, contained in the original cells that arose from the primordial
soup about 4 billion years ago. Today, the master molecule is the
similar but more complex deoxyribonucleic acid, DNA. But in the
beginning, DNA's more primitive and unstable ancestor may have reigned
supreme, in a realm molecular biologists call the "RNA World."
Why wasn't DNA the first molecule of life? All cells living today
rely on DNA to act as their genes, carrying the instructions for making
various specific kinds of proteins, the workhorses of life. But there is�a hitch. To replicate itself - an essential step in the reproduction of
life - DNA needs proteins. Specifically, it needs certain kinds of
proteins to act as enzymes that carry out the DNA replication. So
scientists who study the origin of life are faced with a paradox: Which
came first, the chicken or the egg? DNA or proteins?
RNA offers an answer. A few year ago, Tom Cech of the University of
Colorado discovered that RNA was capable of doing more than its
well-known job of carrying a set of instructions from the DNA in the
cell's nucleus to its factory floor. Cech (pronounced check) found that
a particular bit of RNA from a certain protozoan, or one-celled
organism, could also act like an enzyme, cutting up pieces of RNA and
then splicing the ends together again. For this, Cech won a Nobel Prize
last year. The RNA enzymes are called ribozymes.
Szostak is working with the same segment of RNA that Cech discovered.
However, he and his group modified the RNA so that instead of cutting
and splicing, the ribozyme would only splice. Using itself as a pattern,
Szochak believes his modified RNA could take subunits of RNA, which
Szostak would feed his cells as a kind of food, and splice them into
copies of itself.
RNA, like DNA, is made of four different kinds of subunits than can
be chained in any sequence to any length. Szostak's ribozyme would use
its own special sequence as a template to dictate the sequence in which
to splice new subunits.
All this activity would be happening inside bubbles of a special kind
of fat - the same kind of fat that forms the membranes around all living
cells. Scientists who study special fatty acids called phospholipids
have learned they can do a trick. When simply dumped into water, the
lipids spontaneously aggregate to form thin, impermeable sheets and
bubbles, called vesicles.
"Take a breakfast egg and extract phospholipid out of it and place
the lipids in water and you'll get little vesicles," said David Deamer
of the University of California at Davis. "You'll get a primitive cell
Deamer, who is also working to create life in the lab, has found that
meteorites contain all the ingredients needed to make membranes, adding
credence to the popular idea that the basic building blocks of life were
ferried to Earth from space.Mimicking the Primordial Environment
Once Szostak gets his RNA inside a membrane, and once he gets his RNA
to make copies of itself, he is close to his definition of life. But he
must still figure out a way to get the cells to fuse and spill their
contents into one another. He must also devise a way of encouraging his
cells to divide.
In the primitive world, he speculates, the first cells probably could
not divide on their own. They needed help from nature: from crashing
waves, lightning bolts, hot geysers. Deamer believes that cells in the
lab can be made to fuse and separate by drying and wetting them,
mimicking the cycles of a tidal pool, a likely habitat for early life
Szostak is considering shaking his cells to mimic wave action or
pushing them through a sieve, which would break them into smaller
"If we could create a system that would begin to run autonomously and
replicate itself, then a lot of people, myself included, would say it's
alive," said Gerald Joyce of the Research Institute of the
Scripps Clinic in La Jolla, Calif., another leading contender in
the race to create life in the lab.
Once their systems are running, Szostak, Joyce, Deamer and others
maintain that their primitive cells would evolve over time, producing
new cellular machinery.
This would happen because as the RNA copied itself, it would make
mistakes. Some of these mistakes would be improvements. The cells with
new and improved RNA would reproduce more prolifically and eventually
replace the losers. Given a few million years, and enough funding,
Szostak and his colleagues say that in theory they could rerun evolution
"I really think we'll learn to make life in the laboratory long
before we find it someplace else in the universe," Joyce said. "The most
likely source of discovery is here on Earth."
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