Life's Ratchet: How Molecular Machines Extract Order from Chaos (40 page)

Evolution, like life, is also a game on the chessboard of time, space, and physics. The outcome of this game cannot be determined a priori. The game can create an enormous number of possible outcomes, and the role of evolution is to find some of these outcomes. By tweaking a protein here, or regulating a DNA sequence there, we see what effect this has; evolution has created a world inhabited by a limited set of all possible creatures that could theoretically exist. One of them happens to be us.

Creationists argue that humankind is the goal of Earth’s history. If you start with this assumption, it would certainly be difficult to see how a playful process such as evolution could have necessarily ended up with us. Once you abandon this idea, however, and realize that evolution would have come up with
some
viable organisms, but not necessarily the same we encounter on our planet, it all starts making sense. Am I arguing for chance here? Chance is important, but I believe that life is inevitable and that myriad forms of life would have evolved in any case. As we have seen before, pure chance creates chaos; pure necessity, rigidity. Chance and necessity together become creation. What is created may be unpredictable, but creation itself is unavoidable.

This discussion is reminiscent of the differences between the views espoused by D’Arcy Thompson and Jacques Monod (
Chapter 2
). Monod believed
that the existence of life is an incredible accident, the winnings of a cosmic lottery. It seems that Monod was too caught up in the DNA-centered view of life. Thompson, on the other hand, lived before we even knew about DNA. He emphasized necessity—he believed that all structures in living beings are the result of mathematical and physical laws. This is also clearly incorrect. Physical law by itself can make a rock, but without information, provided by evolution, we cannot make a living being. The views of Monod and Thompson can be combined to arrive at a fuller and more creationist-proof view of life: Information is important, but information comes from many sources—evolution, physics, chemistry, and the interaction of many complex entities in living cells.

The interaction of chance and necessity in evolution is mirrored by the interaction of chance (as molecular storm) and necessity (structure and physical laws) in the functioning of molecular machines. The second law of thermodynamics predicts that everything moves toward bland uniformity. Yet we have seen that the emergence of the bewildering complexity around us does not violate the second law, as long as we pay the free-energy cost. Still, to arrive at this complexity, we need some kind of free-energy-fueled mechanism. In our cells, directed motion, “purposeful” activity, is created by the action of molecular ratchets—molecular machines, enzymes, and motors, which by degrading free energy and due to their asymmetric structures, can rectify the random motions of the molecular storm to create order. Evolution is also a ratchet: It rectifies the random input from mutations into the creation of an ever larger number of possible creatures. This rectification is achieved by natural selection. Thus there is a pleasing analogy between evolution and its products, our molecular machines.

There is also a more direct connection between the molecular storm and evolution. As we saw from Delbrück’s green pamphlet, which inspired Schrödinger to write his book
What Is Life?,
thermal motion is the main contributor to mutations. Even more to the point, replication and DNA repair are performed by molecular machines, which are subject to the molecular storm and therefore sometimes, although rarely, make mistakes. These mistakes supply fodder for the ongoing evolution of life on the
planet. Interestingly, evolution strives to minimize mutations. The extremely high fidelity of replication (one base-pair mistake in ten billion base pairs) shows that there is, paradoxically, an evolutionary advantage to not evolve. Evolution is rarely radical. The low error rate ensures that it is a gradual process. Nevertheless, small differences can sometimes have a large impact on the final result, because DNA encodes a recipe, rather than a blueprint. The same is true in cooking. For example, consider leaving the baking powder out of your cake!

The observation that evolution acts like a ratchet also discredits the probability arguments of the creationists. Evolution builds improbability step by step, mutation by mutation, selection by selection. The question “What is the probability of creating a kinesin by randomly combining amino acids?” is irrelevant to how evolution works. Kinesin did not spring into existence fully formed; nor was it a goal of evolution. It is simply something evolution stumbled upon, as it ratcheted up more and more complexity, one small change at a time.

Looking at molecular machines has made me realize that evolution is the
only
way these machines could have come to exist. As we have seen, life exploits all aspects of the physical world to the fullest: time and space, random thermal motion, the chemistry of carbon, chemical bonding, the properties of water. Designed machines are different. They are often based on a limited set of physical properties and are designed to resist any extraneous influences. The tendency of molecular machines to
use
chaos, rather than resist it, provides a strong case for evolution. Why? If life started by itself, without a miracle, then life had to start at the molecular scale. The molecular scale has always been dominated by the molecular storm. The ability of life to somehow incorporate thermal randomness as an integral part of how it works—as opposed to giving in to the chaos— shows that life is a bottom-up process. It is not designed from the top down. A top-down design would have avoided the complications of thermal motion by making the fundamental entities of life larger, so they could resist the molecular storm more easily. This is what machines designed by humans do—until recently, as nanotechnologists have learned from life’s nanobots to create tiny machines of their own.

Molecular machines’ exquisite adaptation to their molecular environment is also a strong argument for evolution. Evolution is tinkering—the gradual improvement and better adaptation of biological structures. The history of life has been long, and evolution had ample time to create these amazing physics-exploiting machines that run our bodies. To achieve such near perfection, you need a process that designs dynamically. A onetime design is not enough. Conditions change over time, and our molecular machines need to remain adaptable. An external designer would do best if the designer used evolution to do the work. Adaptation is assisted by the fact that physical laws provide the missing ingredient. For example, many structures in our cells are made through self-assembly processes, which are the result of physical forces (vesicles, collagen, etc.). Evolution does not overdesign: It designs just enough to take advantage of physical laws. If physics does the work for you, then why bother designing what is already designed?

We also ought to consider the commonality of the molecular apparatus in the cells of every living being. Many molecules and cellular processes in an
E. coli
bacterium, a yeast, a bluebird, a begonia, or a human are almost identical. This strongly suggests common ancestry. At the same time, looking at the differences between organisms, we see how various molecular machines have been adapted to fulfill specialized functions peculiar to each species.

Yet, the best argument in favor of evolution and against a static-design view may be that any designer would have to work hard to keep organisms from evolving. This is what I alluded to in the beginning of the chapter. Paley’s reproducing watch would evolve. As we have seen, mutations happen. Some of these may impart an advantage to its bearer. Such an advantage would tend to spread through a population. How could you stop it? And why should anybody want to? If I were the all-powerful being in charge of the world, I wouldn’t bother. Why not sit back, relax, and enjoy what wonderful things evolution can create for you?

Neither DNA, nor any other kind of molecule can, by itself, explain life.

—L
YNN
M
ARGULIS
,
W
HAT
I
S
L
IFE
?

T
HE EMINENT HARVARD BIOLOGIST AND WRITER ERNST Mayr (1904–2005) wrote in
This Is Biology
that when scientists and philosophers have talked about life, they often considered life as opposed to the lifelessness of “an inanimate object.” The problem with this definition of life, according to Mayr, is that life seems to refer to some “thing”— an idea that has misled philosophers and biologists for centuries. If life is a thing, then it must be clearly distinguished from other things, and therefore the existence of a “life substance” or “vital force” must be invoked. However, Mayr explained, once we realize that life is not a thing, but a
process
, we can begin to scientifically study the process of living. We can make a distinction between living and nonliving. We could even attempt to explain how life’s processes can be the result of molecules.

Nobody can explain what life is. This has always been the problem with the question “What is life?”—a question that has led philosophers and scientists to look for a life force not only for centuries, but for millennia. While we cannot define life, we
can
explain how life works. We can explain the process. The molecular biophysics and nanoscience revolution has succeeded in explaining, as Mayr puts it, “how living, as a process, can be the product of molecules who themselves are not living.” This is an important step. To delineate life from the “lifelessness of an inanimate object,” we need to first understand how molecules can generate directed motion and activity, that is, how chaos becomes order. The new science of molecular machines has been successful in doing just that. But is that enough? Is “living” the sum total activity of all the molecular machines in our bodies?

Unfortunately, understanding kinesin or ATP synthase does not explain human life or even that of a single cell. I can throw all the molecules of a living cell into a test tube and shake them up—some of the motor proteins may wiggle for a while—but they will not assemble themselves into a living cell. Are we then back to square one? Do we require some invisible force, after all, to coordinate the molecular activity in our cells? No, we should have learned enough to see that this is not necessary. What distinguishes living organisms is not that they exist outside physics, but is that they are based on a self-organized, dynamic structure that perpetuates the organization of the organism from one point in time to the next. Life sustains itself. Life comes from life.

Every person’s atoms are replaced within seven years, yet we remain the same person. We are not the atoms that constitute us; nor are we our proteins, DNA, or molecular machines. We are, instead, a complex process, a program, as it were, running on chemomechanical hardware. The analogy of life with a computer program fits our modern times, where computers have taken over the iconic status once reserved for clocks or steam engines. However, we should be careful not to overuse the computing analogy of life. The “program” that constitutes the process of living is massively parallel, decentralized, self-adaptive, “squishy,” and controlled almost entirely by exchanges of matter (with the exception of nerve impulses, but even there, some matter exchanges are involved). It is also a program that has evolved over billions of years.