Artificial evolution is not merely confined to silicon, however.
Evolution will be imported wherever engineering balks. Synthetic
evolution technology is already employed in the frontier formerly called
Here's a real-world problem. You need a drug to combat a disease whose
mechanism has just been isolated. Think of the mechanism as a lock. All
you need is the right key molecule -- a drug -- that triggers the active
binding sites of the lock.
Organic molecules are immensely complex. They consist of thousands of
atoms that can be arranged in billions of ways. Simply knowing the
chemical ingredients of a protein does not tell us much about its
structure. Extremely long chains of amino acids are folded up into a
compact bundle so that the hot spots -- the active sites of the protein -- are
held on the outside at just the right position. Folding a protein is
similar to the task of pushing a mile-long stretch of string marked in
blue at six points, and trying to fold the string up into a bundle so
that the six points of blue all land on different outside faces of the
bundle. There are uncountable ways you could proceed, of which only a
very few would work. And usually you wouldn't know which sequence was
even close until you had completed most of it. There is not enough time
in the universe to try all of the variations.
Drug makers have had two traditional manners for dealing with this
complexity. In the past, pharmacists relied on hit or miss. They tried
all existing chemicals found in nature to see if any might work on a
given lock. Often, one or two natural compounds activated a couple of
sites -- a sort of partial key. But now in the era of engineering,
biochemists try to decipher the pathways between gene code and protein
folding to see if they can engineer the sequence of steps needed to
create a molecular shape. Although there has been some limited success,
protein folding and genetic pathways are still far too complex to
control. Thus this logical approach, called "rational drug design," has
bumped the ceiling of how much complexity we can engineer.
Beginning in the late 1980s, though, bioengineering labs around the
world began perfecting a new procedure that employs the only other tool
we have for creating complex entities: evolution.
In brief, the evolutionary system generates billions of random molecules
which are tested against the lock. Out of the billion humdrum
candidates, one molecule contains a single site that matches one of,
say, six sites on the lock. That partial "warm" key sticks to the lock
and is retained. The rest are washed down the drain. Then, a billion new
variations of that surviving warm key are made (retaining the trait that
works) and tested against the lock. Perhaps another warm key is found
that now has two sites correct. That key is kept as a survivor while the
rest die. A billion variations are made of it, and the most fit of that
generation will survive to the next. In less than ten generations of
repeating the wash/mutate/bind sequence, this molecular breeding program
will find a drug -- perhaps a lifesaving drug -- that keys all the sites of
Almost any kind of molecule might be evolved. An evolutionary
biotechnician could evolve an improved version of insulin, say, by
injecting insulin into a rabbit and harvesting the antibodies that the
rabbit's immune system produced in reaction to this "toxin." (Antibodies
are the complementary shape to a toxin.) The biotechnician then puts the
extracted insulin antibodies into an evolutionary system where the
antibodies serve as a lock against which new keys are tested. After
several generations of evolution, he would have a complementary shape to
the antibody, or in effect, an alternative working shape to the insulin
shape. In short, he'd have another version of insulin. Such an
alternative insulin would be extremely valuable. Alternative versions of
natural drugs can offer many advantages: they might be smaller; more
easily delivered in the body; produce fewer side effects; be easier to
manufacture; or be more specific in their targets.
Of course, the bioevolutionists could also harvest an antibody against,
say, a hepatitis virus and then evolve an imitation hepatitis virus to
match the antibody. Instead of a perfect match, the biochemist would
select for a surrogate molecule that lacked certain activation sites
that cause the disease's fatal symptoms. We call this imperfect,
impotent surrogate a vaccine. So vaccines could also be evolved rather
All the usual reasons for creating drugs lend themselves to the
evolutionary method. The resulting molecule is indistinguishable from
rationally designed drugs. The only difference is that while an evolved
drug works, we have no idea of how or why it does so. All we know is
that we gave it a thorough test and it passed. Cloaked from our
understanding, these invented drugs are "irrationally designed."
Evolving drugs allows a researcher to be stupid, while evolution slowly
accumulates the smartness. Andrew Ellington, an evolutionary biochemist
at Indiana University, told Science that in evolving systems "you let
the molecule tell you about itself, because it knows more about itself
than you do."
Breeding drugs would be a medical boon. But if we can breed software and
then later turn the system upon itself so that software breeds itself,
leading to who knows what, can we set molecules too upon the path of
Yes, but it's a difficult job. Tom Ray's electric-powered evolution
machine is heavy on the heritable information but light on bodies.
Molecular evolution programs are heavy on bodies but skimpy on heritable
information. Naked information is hard to kill, and without death there
is no evolution. Flesh and blood greatly assist the cause of evolution
because a body provides a handy way for information to die. Any system
that can incorporate the two threads of heritable information and mortal
bodies has the ingredients for an evolutionary system.
Gerald Joyce, a biochemist at San
Diego whose background is the chemistry of very early life, devised a
simple way to incorporate the dual nature of information and bodies into
one robust artificial evolutionary system. He accomplished this by
recreating a probable earlier stage of life on Earth -- "RNA world" -- in a
RNA is a very sophisticated molecular system. It was not the very first
living system, but life on Earth at some stage almost certainly became
RNA life. Says Joyce, "Everything in biology points to the fact that 3.9
billion years ago, RNA was running the show."
RNA has a unique advantage that no other system we know about can boast.
It acts at once as both body and info, phenotype and genotype, messenger
and message. An RNA molecule is at once the flesh that must interact in
the world and the information that must inherit the world, or at least
be transmitted to the next generation. Though limited by this
uniqueness, RNA is a wonderfully compact system in which to begin
open-ended artificial evolution.
Gerald Joyce runs a modest group of graduates and postdocs at Scripps
Institute, a sleek modern lab along the California coast near San Diego.
His experimental RNA worlds are tiny drops that pool in the bottom of
plastic micro-test tubes hardly the volume of thimbles. At any one time
dozens of these pastel-colored tubes, packed in ice in styrofoam
buckets, await being warmed up to body temperature to start evolving.
Once warmed, RNA will produce a billion copies in one hour.
"What we have here," Joyce says pointing to one of the tiny tubes, "is a
huge parallel processor. One of the reasons I went into biology instead
of doing computer simulations of evolution is that no computer on the
face of the Earth, at least for the near future, can give me 1015
microprocessors in parallel." The drops in the bottom of the tubes are
about the size of the smart part of computer chips. Joyce polishes the
image: "Actually, our artificial system is even better than playing with
natural evolution because there aren't too many natural systems that
come close to letting us turn over 1015 individuals in a hour, either."
In addition to the intellectual revolution a self-sustaining life system
would launch, Joyce sees evolution as a commercially profitable way to
create useful chemicals and drugs. He imagines molecular evolution
systems that run 24 hours, 365 days a year: "You give it a task, and say
don't come out of your closet until you've figured out how to convert
molecule A to molecule B."
Joyce rattles off a list of biotech companies that are today dedicated
solely to research in directed molecular evolution (Gilead, Ixsys,
Nexagen, Osiris, Selectide, and Darwin Molecule). His list does not
include established biotech companies, such as Genentech, which are
doing advanced research into directed evolutionary techniques, but which
also practice rational drug design. Darwin Molecule, whose principal
patent holder is complexity researcher Stuart Kauffman, raised several
million dollars to exploit evolution's power to design drugs. Manfred
Eigen, Nobel Prize-winning biochemist, calls directed evolution "the
future of biotechnology."
But is this really evolution? Is this the same vital spirit that brought
us insulin, eyelashes, and raccoons in the first place? It is. "We
approach evolution with a capital D for Darwin," Joyce told me. "But
since the selection pressure is determined by us, rather than nature, we
call this directed evolution."
Directed evolution is another name for supervised learning, another name
for the Method of traversing the Library, another name for breeding.
Instead of letting the selection emerge, the breeder directs the choice
of varieties of dogs, pigeons, pharmaceuticals, or graphic images.