Life's Ratchet: How Molecular Machines Extract Order from Chaos

by Hoffmann, Peter M.

  For most scientists, philosophical debates over holism versus reductionism are a nonissue. Even most physicists understand that we need to put the parts back together again. Many physical properties, such as elasticity, conductivity, or transparency, arise “holistically” from the interactions of large numbers of atoms. Statistical mechanics, as we saw in Chapter 3, was born to explain the emergence of holistic laws from the reductionist picture of swirling atoms.

  Science works on many levels. For a living organism, we may start at quarks and electrons. Using these, we can, in principle, predict the properties of nuclei and atoms. Once we have atoms, we can, in principle and with difficulty, explain the properties of molecules. But even at this point, the connection between the level of quarks and that of molecules is weak at best. We can understand many things about molecules by determining their atomic structure, but the quark structure is already too far removed to yield much insight or even a useful explanation for the properties of a molecule. As we move further along, these links become ever more tenuous, until there is really no meaningful conceptual connection between a highly complex entity and the most fundamental levels of matter and energy.

  The difficulty in understanding biology is that it operates on many of these levels: from molecules to ecosystems. All of these levels contribute to the understanding of what life (or rather, living) is, and they are all important. As a physicist, I am most fascinated by the levels that connect life to physics, but I am aware that this is just a small part of the complexity of life.

  Cows and Quarks

  At this point, you might object to my assertion of no meaningful conceptual connection between a complex entity and the most fundamental levels of matter and energy. How did I arrive at this conclusion?

  I recently had a discussion on holism versus reductionism with my colleague and friend, Sean Gavin, a theoretical nuclear physicist at Wayne State University. Sean told me that he had listened to a talk by Steven Weinberg, a strong supporter of research in particle physics. As such, Weinberg made his usual argument that particle physics is fundamental to all other sciences, even chemistry and biology. As a physicist, I understand that there is nothing more fundamental than to find out what matter is made of and what forces determine the shape of our universe. This is important work. If we want to learn what our universe is all about—if we want science to progress in the long run—we need to join Weinberg and support the work of the particle physicists. With the recent start-up of the Large Hadron Collider in Geneva, Switzerland, the largest particle accelerator currently in existence, we can expect many new and surprising findings about the deep fundamental structure of our universe. Sean and I, and just about every physicist I know, would agree on this point. But then, Sean said something very funny and to the point: “But how do you predict a cow from particle physics?” A great question!

  Is it just too complicated to predict the existence of cows from particle physics, or is it fundamentally impossible to predict a cow from the properties of quarks and electrons? A cow is made of molecules (many of which we discussed in this book). These molecules are made of atoms. The properties of these molecules can, with some difficulty, be reduced to the properties of the atoms they are made of. Atoms are made of quarks, which are held together by gluons (quarks plus gluons form protons and neutrons in the atom’s nucleus), and electrons. The chemical properties of different atoms are due to the arrangement of electrons around the nucleus. Thus, we could say that a cow can be explained by particle physics, since quarks and electrons (and the forces acting between them) make atoms with different properties, which in turn make molecules, which in turn make cells, which in turn make cows.

  Somewhere along the line, however, we lost sight of why there is such a thing as a cow. To say a cow is explained by what it is made of is to say that bricks explain a house. A better answer is that a cow is the result of evolution—a process made possible by the underlying material reality of particles—but which is essentially unpredictable. If we were to rerun the tape of life, would a cow reemerge? Nobody knows—it is likely that something like a cow could emerge again, but the new being might have six legs and only two stomachs. Thus there is no formula for “cow” based on the laws of particle physics. Particle physics may be necessary to make a cow (because we need atoms and molecules), but it is clearly not sufficient.

  However, all material objects in this universe are based on the particle physics we know. But if a different universe were to exist, the laws of particles might be quite different from our laws. As long as these laws permit the creation of complicated structures, they may lead to the emergence of something we could justifiably call a cow. The concept “cow” is completely independent of the particular properties of quarks and electrons. A philosopher would say that a cow is not explained by particles, because particles cannot give a reason for the cow’s “cow-ness.”

  What about the reality of molecular machines? As was the case with quarks and electrons, we need to understand molecular machines to understand life on this planet. But we have seen that the molecular machinery of most organisms is not unique to a particular animal or plant. Thus, we cannot derive a cow or any other animal from molecular machines, either. Does this make our insight into molecular machines useless? Do molecular machines tell us nothing about whole organisms? No, molecular machines tell us more than just how cells work. By their similarity in all life on earth, they tell us of evolution and life’s unity; by their ability to tame chaos, they tell us a creative universe is only possible through chance and necessity; by their ability to be regulated and to regulate, they tell us that life is matter and program; and by their incessant activity, animated by the molecular storm, they tell us that life is a process, not a thing.

  I wager these things would not be so different in a different universe. But then again, who can prove me wrong?

  Quotation from Lynn Margulis and Dorion Sagan, What Is Life? © 2000 by the Regents of the University of California. Published by the University of California Press.

  Epilogue

  Life, the Universe, and Everything

  WE HAVE COME A LONG WAY—FROM THE VITAL FORCES of the ancients to the molecules of molecular biologists and biophysicists. If we were seeking the “life force,” the force that animates life, then our search has been successful. This animating force is the random force of atoms, the jittering afterglow of the creation of the universe. The molecular machines, which take this undirected force and give it direction, embody the tight embrace of chance and necessity and are themselves the product of this embrace. Sculpted by evolution, the molecular machines of our bodies tame the molecular storm and turn it into the dance of life.

  The universe is the child of chance and necessity. Every star and galaxy, planet and mountain, microbe and elephant is a testament to the interaction between these two basic tendencies of nature. Should this view of the universe, as informed by modern science, influence how we think about ourselves? On one hand, maybe not. Life happens on many levels, from colliding atoms to the mind of a genius. The molecular machines are part of who we are, but they do not determine who we are. We are intelligent, creative beings, a natural extension of the creativity of the universe, but we are not determined by nature. While based on machines, we are not machines ourselves.

  On the other hand, science has allowed us to learn something very profound about ourselves. Life is a wonderful molecular mechanism. This should make us admire life even at its most “primitive.” Even a virus is a miracle of nature. Humans are part of that same nature—and moreover, we are the most miraculous part of it. We are all the same, and at the same time, we are very different. By necessity, we are all bound to the unity of life, but by chance, we are all unique. We are supposed to be here—in one shape or another.

  If there is life elsewhere in the universe, it will be based on molecular machines. As far as we can determine, the laws of physics are the same everywhere. Everywhere, the nanoscale is the special scale where energi
es can be easily transformed, providing the potential for autonomous nanoscale machines. Even the humblest living organism is incredibly complex. To attain such complexity, the organism must consist of many interacting parts. These parts must be small, active, varied and complex—only molecules can fit the bill.

  To understand the world as a whole, we need to abandon our linear, deterministic thinking. The complexity of life, of our minds, of human society, is the result of adding a dash of randomness to the rules of the game—a game that is played on a network of complex relationships, a game full of emergent properties. I believe (but I cannot prove) that life was inevitable in our large and ancient universe. Consider that life on Earth contains only a tiny fraction of all the matter in the universe. Even if there were millions of inhabited worlds in every galaxy in the universe, the total amount of matter contained in all living beings would still only be a miniscule fraction of all the matter in the universe.

  The universe is not a victim of the second law of thermodynamics. If this were so, the universe would just contain diffuse nebulae of hydrogen and helium. But this is not the case. Before life appeared, gravity acted to concentrate atoms. Stars cooked up heavier elements. Planets provided a surface where atoms could be concentrated further, which enabled the creation of complex molecules. The universe is 13.75 billion years old. It had plenty of time and plenty of matter to come up with life somewhere. Considering the inherent drive of matter to form ever more complex structures, life seems inevitable.

  Of course, there are many who refuse these findings of modern science. They would like to maintain a view of themselves that puts them apart from nature and apart from the universe. In a memorable passage from his 1925 essay “What I Believe,” the philosopher Bertrand Russell contrasted such a view with the vision that science has provided: “Even if the open windows of science at first make us shiver after the cozy indoor warmth of traditional humanizing myths, in the end the fresh air brings vigor, and the great spaces have a splendor all their own.” To which I would add that once we learn more about science, we find that this shiver is the shiver of excitement—excitement over the grandeur of our universe and our astounding ability to understand a small, but growing corner of it.

  Many people express incredulity that something like a human could be the result of the “blind forces” of chance and necessity. They want to believe that the creation of complex structures requires the planning mind of a designer. But how does a mind invent? How do new ideas arise? Are new ideas not chance events, popping into our heads like uninvited houseguests? Could not the same molecular storm that animates our cells sometimes shake our thoughts and create sudden insights? Such random thoughts may cause us to create new connections between seemingly unconnected experiences, leading us to think outside the box. This model of human thought makes sense to me. How could new ideas come about any other way? Where would they come from? From the outside? No, we know that ideas are generated by brains, which are complex networks of biological cells, communicating via chemical and electrical signals. The only way to generate new ideas is by involving some degree of randomness. Even if we invoke an all-powerful mind to explain the origin of the universe or of life, we are thrown back to the same basic forces of chance and necessity. Even this all-powerful mind would have to depend on them.

  Are we getting closer to understanding all there is to understand? One hundred and fifty years ago, Charles Darwin threw up his hands and exclaimed, “I feel most deeply that this whole question of Creation is too profound for human intellect. A dog might as well speculate on the mind of Newton! Let each man hope and believe what he can.” I understand the sentiment. We are still far away from penetrating the mystery of mysteries. But we have come much, much closer.

  If we do not yet completely understand life, it is because life is incredibly complex. How does one combine the fundamental parts of life—DNA, enzymes, molecular machines—to create a Shakespeare or an Einstein? Faced with such mysteries, many people want to throw up their hands like Darwin and declare that it is not possible to explain life after all. Yet, as we have seen throughout this book, science can turn darkness into light and can reveal deep secrets of life. We have seen that life is governed by chance and necessity.

  Glossary

  actin A long, fibrous protein that is part of the “skeleton” of a cell. Also acts as track for myosin and forms the fibers on which myosin II pulls in muscles.

  activation barrier Energy barrier that molecules have to overcome when they change shape or react with one another.

  ADP (adenosine diphosphate) Product of removal of one phosphate group from ATP, an energy-carrying molecule that is used in cells to move chemical energy around. ADP consists of a nucleotide (adenine) with two phosphate groups attached.

  allostery The ability of some enzymes to change shape and functionality in response to binding a control molecule. Allostery constitutes the basis of regulation in cells.

  amino acid Smallest unit of a protein. Proteins consist of a various combinations of the twenty amino acids that are used in nature.

  amphiphilic A molecule that has both hydrophilic and hydrophobic characteristics.

  animism The belief that everything has a soul and is alive.

  atomic force microscopy (AFM) Type of scanning probe microscopy, which measures small forces between a sharp tip and a surface. AFM can provide high-resolution images or can be used to measure forces between molecules.

  atomism The belief that everything is made of small, indivisible, and perpetually moving particles.

  atoms Smallest chemical units, composed of a nucleus (made of protons and neutrons) and a cloud of electrons. Electrons are responsible for chemical bonding.

  ATP (adenosine triphosphate) Energy-carrying molecule, used in cells to move chemical energy around. Consists of a nucleotide (adenine) with three phosphate groups attached.

  ATP hydrolysis Reaction of ATP with water, which detaches one of its phosphate groups and liberates a large amount of energy. End product: ADP (adenosine diphosphate).

  ATP synthase Sophisticated rotary molecular machine located in mitochondria. Uses a proton gradient to recharge ATP.

  ATPase Enzyme that breaks down ATP. Part of almost all molecular machines.

  bit Minimum quantity of information; information contained in a “yes” or “no” answer (or “1” and “0”).

  Brownian motion The random motion of small particles as the result of many collisions with molecules in the air or in a liquid.

  Brownian ratchet A molecular machine that moves in a specific direction via a directed diffusion process. Does not violate the second law of thermodynamics because in order to work, energy is supplied to the ratchet to periodically detach the machine from the track on which it moves. This energy is then dissipated.

  chance and necessity The basic principles responsible for everything there is. Chance arises from quantum mechanics and the molecular storm, while necessity is due to physical laws.

  chaperonin Proteins that help other proteins fold into the correct shape.

  chromosome A bundle of DNA in the cell nucleus.

  codon A “word” in the genetic code; consists of three nucleotide letters. Each codon encodes one amino acid according to the genetic code.

  collagen Fibrous proteins. Part of the extracellular matrix, giving structure to animal bodies.

  complexity Attribute of a system that is composed of many interacting parts and that exhibits emergent properties.

  cooperativity The property of some processes wherein several parts must act together simultaneously for the process to occur.

  diffusion Random motion of molecules or atoms. On average, diffusion leads to the movement of particles from a region of high concentration to a region of low concentration.

  dissipation Degradation of usable (free) energy into unusable energy (heat).

  DNA (deoxyribonucleic acid) A long, double-helical molecule located in the cell nucleus; stores the sequences to make
proteins and directs the development of the cell.

  domain Part of a large molecule.

  dynein Family of molecular motors that move on microtubules.

  emergence Arising of properties resulting from the interaction of many parts; the emergent properties are not properties of the parts by themselves.

  energy A propensity to perform work. The unit of energy is the joule (J).

  energy landscape Conceptual idea of a multidimensional landscape representing how the energy of a protein changes as it changes shape. Each location in the landscape corresponds to a specific protein shape, while the height of the landscape represents the energy associated with the shape.

  energy transformation The change of energy from one type into another, for example, from chemical to kinetic energy, as in a car.

  entropic forces Forces that are not due to the reduction in energy, but are due to an increase in entropy. Examples are depletion forces and hydrophobic forces.

  entropy The degree to which energy is dispersed. Often equated with “disorder.”

  enzyme Protein-based catalyst; protein that can facilitate a reaction by lowering the reaction’s activation barrier.

  equilibrium In thermodynamics, the state at which entropy is maximum, free energy is minimum, and no more useful work can be extracted from a system. Characterized by uniform temperature and pressure.