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The Big Picture

Page 46

by Carroll, Sean M.


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  into existence from non- life. For compartmentalization, we need to under-

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  stand how we got to bilayers made of phospholipids, and the answer might

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  be found in fatty acids. For metabolism, we need to know how we got to

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  cells driven by the proton- motive force, and the answer might be porous

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  chambers in alkaline vents. For replication, we need to know how we got to

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  DNA, and the answer might be RNA.

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  The relationship of RNA to DNA is like the relationship of an oral tra-

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  dition of poetry to words written down in books. The same information

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  can be conveyed, but DNA is much more reliable and stable. Yet it is suffi-

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  ciently sophisticated that it’s hard to see how it could have come into exis-

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  tence by itself. When DNA gets copied, an important part of the work is

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  done by proteins. But the proteins are supposed to be constructed using

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  information encoded in the DNA. How could either one arise without the

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  other already being present?

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  The favorite answer among abiogenesis researchers is a scenario called

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  RNA world. The basic idea was proposed by a number of people in the

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  1960s, including Alexander Rich, Francis Crick, Leslie Orgel, and Carl

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  Woese. DNA is good at storing information, and proteins are good at per-

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  forming biochemical functions; RNA is able to do both, although it’s not

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  as good at either one. RNA could have come along before either DNA or

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  proteins, and served as the basis for a primitive and less robust form of early

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  life, before evolution gradually distributed responsibilities to the more ef-

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  fective DNA and proteins.

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  The role of RNA in extracting information from DNA was recognized

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  fairly early on, but it wasn’t until later that biologists verified that RNA

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  could also act as a catalyst, expediting and governing the rate of biochemi-

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  cal reactions. In particular, ribozymes, discovered in the 1980s, are a par-

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  ticular kind of RNA that can catalyze their own synthesis, as well as that

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  of proteins. The word “ribozyme” is annoyingly similar to “ribosome.” It

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  turns out that the crucial part of the ribosome complex consists of ribo-

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  zyme RNA. That is, the ribosome is mostly ribozyme. (It’s jargon like this

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  that turns young scientists toward physics and astronomy.)

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  Further investigations have shown that there are a number of different

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  types of RNA, responsible for a variety of functions inside the cell. In ad-

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  dition to messenger RNA and ribosomal RNA, we also have transfer RNA

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  that brings amino acids to the right place to be made into proteins, regula-

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  tory RNA that helps guide the expression of genes, and more. These discov-

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  eries have helped popularize the RNA-world hypothesis. If you want to get

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  life started from a replication- first perspective, you need a molecule that can

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  carry genetic information without relying on other complex mechanisms

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  to reproduce itself. RNA seems to hit the sweet spot.

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  The idea that RNA may have been the first carrier of genetic information,

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  and was able both to self- reproduce and to assemble other biochemically

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  useful structures, is compelling and beautiful. Like any good paradigm, one

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  of the great features of the RNA world scenario is that it has spurred a

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  tremendous amount of exciting research.

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  Consider the fact that RNA can be an enzyme: it can catalyze chemical

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  reactions, both for self- assembly and for protein synthesis. Where did that

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  ability come from? It’s pretty clear how a string of nucleotides can store

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  information, but acting as an enzyme seems like a completely different kind

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  of talent.

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  This question was addressed in an interesting experiment by David Bar-

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  tel and Jack Szostak in 1993. (Szostak shared the Nobel Prize in 2009 for

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  his work on how chromosomes are protected when DNA divides.) Their

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  technique was basically a human- aided version of Darwinian evolution.

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  They started with a large amount of random RNA: trillions of molecules

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  with no particular sequence to their nucleotides. They then picked out a

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  fraction of those molecules, the ones that seemed to be associated with

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  somewhat higher rates of catalysis, and made many copies of those. This

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  procedure was repeated several times: look for RNA that seemed to be

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  catalyzing certain reactions, and make copies of it. At each copying stage,

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  random mutations occurred, which occasionally led to the copied RNA

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  being a better catalyst than its precursor. After just ten iterations of this

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  procedure, the results were clear: the last pool of molecules was approxi-

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  mately 3 million times better at catalyzing reactions than the original sam-

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  ple. It’s a vivid demonstration of how undirected, random mutation can

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  lead to enormous improvements in the ability of chemicals to perform bio-

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  logically useful functions.

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  Another exciting development came from biologists Tracey Lincoln and

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  Gerald Joyce in 2009. They were able to create a system of two RNA en-

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  zyme molecules— ribozymes— that together underwent self- sustained rep-

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  lication. Without any help from surrounding proteins or other biological

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  structures, these molecules are able to completely duplicate each other in

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  about an hour. Even better, the molecules occasionally mutate, and there-

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  fore undergo Darwinian evolution, with the more fit structures preferen-

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  tially surviving. It’s not a cell by any means, but you don’t need to strain to

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  see how it could be one of the steps along the road from chemistry to life.<
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  Even if RNA played a central role at the origin of life, we don’t yet have

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  a complete picture. Compartmentalization, metabolism, and replication all

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  have to be brought together. RNA and bilayers made from fatty acids may

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  be symbiotic— they could help each other flourish in the rough- and- tumble

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  environment of the early Earth. A membrane can shield the fragile RNA

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  from external commotion, helping it survive long enough to reproduce. An

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  RNA molecule, meanwhile, can attract other biological molecules into the

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  membrane, helping it grow to the point where it will naturally split in

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  two— a primitive form of cellular division.

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  Fitting in metabolism may be trickier, though Szostak doesn’t think it’s

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  a big problem. He envisions a proto- cell, RNA encapsulated in a simple

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  membrane, floating in a pond that is warm on one end and cold on the

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  other. Convection currents push the proto- cell back and forth between the

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  two sides. In the cold end, the RNA grows by gathering nucleotides from

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  its surroundings, and two RNA strands huddle together as if seeking

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  warmth. When it drifts to the warmer side of the pond, the increased tem-

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  perature gradually peels the two strands apart; the membrane accretes a few

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  more fatty- acid molecules until it divides in two, and (hopefully, some-

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  times) we now have two proto- cells with a single strand of RNA each. They

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  both drift back to the cold side of the pond, and the cycle of proto- life be-

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  gins again.

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  Russell and the metabolism- firsters don’t think it will be nearly that

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  easy. They believe that the hard part is assembling a complex system of

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  chemical reactions that can take advantage of the ambient free energy, set-

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  ting up proton- motive forces in chambers of porous underwater vents.

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  From there, they suggest, these reactions will naturally feed on any sur-

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  rounding free- energy fuel they can find. That might mean that they break

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  free of the rocks by entering fatty- acid membranes, and they keep going by

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  regulating their reactions through enzymes, which eventually be-

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  come RNA.

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  Or maybe both scenarios are right, or maybe neither is.

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  There is no reason to think that we won’t be able to figure out how life

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  started. No serious scientist working on the origin of life, even those who

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  are personally religious, points to some particular process and says, “Here

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  is the step where we need to invoke the presence of a nonphysical life- force,

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  or some element of supernatural intervention.” There is a strong conviction

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  that understanding abiogenesis is a matter of solving puzzles within the

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  known laws of nature, not calling for help from outside of them.

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  This conviction comes from the incredible historical track record sci-

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  ence has established. While there are many questions about life’s origin that

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  science hasn’t answered, there are a large number that it has, any one of

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  which could have been a problem that science all by itself was unable to

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  address. (Recall Immanuel Kant’s confident proclamation that there will

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  never be a Newton for a blade of grass.) How do species evolve from earlier

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  species? How do organic molecules become synthesized? How do cellular

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  membranes assemble themselves? How can complex reaction networks

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  overcome free- energy barriers? How can RNA molecules develop the abil-

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  ity to act as catalysts for biochemical reactions? These are questions we have

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  answered. Our Bayesian credence that this string of successes will keep go-

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  ing should be very high indeed.

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  This perspective meets resistance in certain quarters, and not only

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  among religious fundamentalists. The idea that life could just start out of

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  no life at all isn’t obvious. We don’t see it taking place before our eyes, no

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  matter what Jan Baptist van Helmont might have imagined. Modern- day

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  organisms are mind- bogglingly complex, and made of individual parts that

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  work together amazingly well. The idea that it “just happened” is a chal-

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  lenging one.

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  Fred Hoyle, an esteemed British astrophysicist known for his staunch

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  opposition to the Big Bang model, attempted to quantify this unease. He

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  considered the configuration of atoms in a biological structure such as a

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  cell. Then, in a move taken from Ludwig Boltzmann’s playbook, he com-

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  pared the total number of ways such atoms could be arranged to the much

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  smaller number that would qualify as a cell. Multiplying together a bunch

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  of tiny numbers, he concluded that the chance of life assembling all by itself

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  is something like 1 in 1040,000.

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  Hoyle was a master of vivid imagery, and he illustrated his point with a

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  famous analogy:

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  The chance that higher life forms might have emerged in this

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  way is comparable to the chance that a tornado sweeping

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  through a junkyard might assemble a Boeing 747 from the ma-

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  terials therein.

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  The problem is that Hoyle’s version of “this way” is nothing at all like

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  how actual abiogenesis researchers believe that life came about. Nobody

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  thinks that the first cell occurred when a fixed collection of atoms was re-

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  arranged over and over in all possible ways until it just happened to take on

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  a cell- like configuration. What Hoyle is describing is essentially the

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  Boltzmann Brain scenario—
truly random fluctuations coming together to

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  create something complex and ordered.

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  The real world is different. The “unlikeliness” associated with low-

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  entropy configurations is built into the universe from the start, by the in-

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  credibly low entropy near the Big Bang. The fact that the development of

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  the cosmos proceeds from this very special initial condition, rather than

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  wandering through a more typical equilibrium ensemble of states, imposes

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  a strong nonrandom aspect on the evolution of the universe. The appear-

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  ance of cells and metabolism is a reflection of the universe’s progression

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  toward higher entropy, not an unlikely happenstance in an equilibrium

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  background. Like the swirls of cream mixing into coffee, the marvelous

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  complexity of biological organisms is a natural consequence of the arrow

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  of time.

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  We’ve made amazing progress in understanding what life is and how it

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  came to be, and there’s every reason to think that progress will continue

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  until we have figured it out. The work ahead will involve chemistry, physics,

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  mathematics, and biology, not magic.

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  Evolution’s Bootstraps

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  n 1988, Richard Lenski had a brilliant idea: he was going to turn evo-

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  lutionary biology into an experimental science.

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  Evolution is the idea that provides the bridge from abiogenesis to

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  the grand pageant of life on Earth today. There’s no question that it’s a sci-

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  ence; evolutionary biologists formulate hypotheses, define likelihoods of

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  different outcomes under competing hypotheses, and collect data to update

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  our credences in those hypotheses. But chemists and physicists have an ad-

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  vantage over evolutionary biologists or, for that matter, astronomers: they

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  can perform repeated experiments in their labs. It would be very hard to set

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  up a laboratory experiment to see Darwinian evolution in action, just as it

 

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