Life's Ratchet: How Molecular Machines Extract Order from Chaos (42 page)

Persistent activation requires a switch, which once flipped, stays on for a long time. At the same time, the switch should not react too easily. After all, creating a permanent memory or turning a stem cell into a brain has serious consequences. One would not want these things to happen unless they were absolutely necessary. Therefore, the switch needs to flip on only if the signal is strong enough and persistent enough. Could simple molecular switches do the job? Molecular switches do not typically send sustained signals. Once they are switched on, they send their signal (releasing a molecule, for example), and that’s it.

A better strategy is to have a self-activating feedback loop. This is what Bhalla and Iyengar found. When signaling networks interact in certain ways, they can create a situation where a chemical signal can become locked into a high-activity state—or in other words, where a signaling molecule is continuously produced in high numbers for a long time. This will only happen in response to strong-enough chemical signals. Once the network is activated, the activation is persistent, that is, it will stay activated until another signal switches it off. This
bistability
(in which the network has two stable states: low and high), the duration of the on state, and the threshold concentration needed to activate the network are emergent properties of the interacting networks. Like linking electronic transistors into a larger network in a computer, linking molecular switches together in an interacting network can create more complex functionality.

We have broken down life to its smallest parts: DNA, proteins, enzymes, molecular machines. The idea that we can understand how something works by reducing it to its parts is natural for a physicist. Some consider
physics to ultimately be the quest to break things down to smaller and smaller constituents, until we find the one constituent or equation that explains everything. Biologists know that this approach does not work when studying life. There is no “life atom” or one formula to explain life.

As we have seen, with the help of statistical mechanics and nanoscience, we can decipher how the directed activity of molecular machines
emerges
from the underlying atomic chaos. But understanding these machines is still a long way from providing a full understanding of how a living cell works. The next step is to understand how these machines interact in complex signaling and regulation networks. Moving to this level of understanding brings with it its own emergent properties, moving us closer to understanding how life works.

Understanding the parts is crucial, but parts by themselves are not always sufficient to explain the whole. Complex interactions between parts create new processes, structures and principles that, while based materially on the underlying parts, are conceptually independent of them. This insight is what we call holism.

For reasons mysterious to me, there exists a great debate between scientists of various stripes of what the correct approach to science should be—reductionism or holism? As I hope this book has shown, reductionism is essential if we want to understand life. Without it, scientists would have long ago stopped looking at smaller and smaller scales and would have missed the marvels of molecular machinery. At the same time, molecular machines don’t explain everything. Scientists must still answer the questions of how these machines interact and what roles they play in the complexity of the cell. The ultimate goal is always to explain the totality of life’s processes, from molecules to cells to organisms. Having taken the toy apart, we want to put it back together again. This is the way we learn how things work. Thus reductionism and holism are two sides of the same coin—they are both parts of what good science ought to be.

The battle between holism and reductionism is, in some sense, the modern extension of the ancient battle of the atomists and vitalists. Postulating the existence of perpetually moving atoms, the ancient atomists explained the activity and change they saw in the world as the ultimately impenetrable interactions between atoms. The vitalists adopted a top-down view and declared that it is impossible to reduce life to physical
forces, because seen from the outside, life appeared so different and so mysterious compared with the inanimate world. The fault lines of reductionism and holism run through all of science, but especially biology. Ecologists, for example, must think holistically about the interactions of many organisms in a complex environment, while at the other end of the spectrum, molecular biologists and biophysicists look at the smallest possible units of life.

Ernst Mayr was a staunch defender of biological holism and one of the great evolutionary biologists of the twentieth century. Among his many achievements, he provided the best modern definition of species, the idea that species are separated by the inability to interbreed. Mayr wrote a number of wonderful books on the history of biology and evolution and was one of the most spirited defenders of Darwin’s theory. But he had (in my opinion) one curious flaw: He hated physicists.

More generally, Mayr deeply disliked any reductionist approaches to biology. In a 2004 paper, he went as far as to make this claim: “To the best of my knowledge, none of the great discoveries made by physics in the twentieth century has contributed anything to an understanding of the living world.” Considering the advances we have discussed in this book, which involve twentieth-century physics such as fluorescence spectroscopy, nanotechnology, and X-ray diffraction, this is a curiously uninformed statement by such a great scientist. It seems that he was genuinely concerned that his beloved biology might be taken over by physicists. This fear was and remains unfounded.

In all fairness, Mayr was able to explain more clearly than anyone else why there are differences between biology and physics. For him these differences were in the degree of complexity, the role of chance, the importance of evolutionary history, and the treatment of species as populations. As we have seen, chance and complexity are basic attributes of life. He was quite correct, for example, that much of biology is a question of contingency, of frozen accidents. Biophysics, for example, may explain how a ribosome translates the genetic code into a protein product, but the actual genetic code seems to be a pure accident. There seems to be no reducible physical reason why the genetic letters UUG (corresponding to the RNA molecular bases uracil-uracil-guanine), should translate into a leucine protein subunit, while UGU should translate into cysteine. In most of physics,
we don’t have such frozen historical accidents. Let copper crystallize from a melt, and it will always crystallize into a face-centered cubic crystal structure. The energy levels in every hydrogen atom are identical. The superconducting transition temperature of mercury is always the same. These things can be predicted from doing quantum mechanics. They happen in accord with fixed laws.

But then again, there are many nonbiological frozen accidents in our universe. Our sun, the earth, the moon, and every mountain on our planet are the result of the vagaries of history. But none of them lies outside a physical explanation. We know the mechanisms that form stars, planets, and mountains. We just cannot predict that a particular mountain will be in a particular place a billion years from now.

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.

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?